Sample records for soluble activin type

  1. Activins bind and signal via bone morphogenetic protein receptor type II (BMPR2) in immortalized gonadotrope-like cells.

    PubMed

    Rejon, Carlis A; Hancock, Mark A; Li, Yining N; Thompson, Thomas B; Hébert, Terence E; Bernard, Daniel J

    2013-12-01

    TGF? superfamily ligands greatly outnumber their receptors. Thus, receptors are shared between ligands and individual ligands can bind multiple receptors. Bone morphogenetic proteins (BMPs) bind and signal via both BMP type II (BMPR2) and activin type II (ACVR2) receptors. We hypothesized that, in addition to its canonical receptor ACVR2, activin A might similarly bind and signal via BMPR2. First, using surface plasmon resonance, we showed that activin A binds to the BMPR2 extracellular domain (ECD), though with lower affinity compared to the ACVR2-ECD. We confirmed these results in cells, where radiolabeled activin A bound to ACVR2 and BMPR2, but not to other type II receptors (AMHR2 or TGFBR2). Using homology modeling and site-directed mutagenesis, we identified key residues in BMPR2 that mediate its interaction with activin A. The soluble ECDs of ACVR2 or BMPR2 dose-dependently inhibited activin A-, but not TGF?-induced signaling in cells, suggesting that activin binding to BMPR2 could have functional consequences. To address this idea, we altered BMPR2 expression levels in immortalized murine gonadotrope-like cells, L?T2, in which activins potently stimulate follicle-stimulating hormone ? (Fshb) subunit transcription. BMPR2 expression potentiated activin A responses whereas depletion of endogenous BMPR2 with short interfering RNAs attenuated activin A-stimulated Fshb transcription. Additional data suggest, for the first time, that BMPR2 may form functional complexes with the canonical activin type I receptor, activin receptor-like kinase 4. Collectively, our data show that BMPR2, along with ACVR2, functions as a bona fide activin type II receptor in gonadotrope-like cells, thereby broadening our understanding of mechanisms of activin action. PMID:24018044

  2. Characterization of the Ligand Binding Functionality of the Extracellular Domain of Activin Receptor Type IIB

    PubMed Central

    Sako, Dianne; Grinberg, Asya V.; Liu, June; Davies, Monique V.; Castonguay, Roselyne; Maniatis, Silas; Andreucci, Amy J.; Pobre, Eileen G.; Tomkinson, Kathleen N.; Monnell, Travis E.; Ucran, Jeffrey A.; Martinez-Hackert, Erik; Pearsall, R. Scott; Underwood, Kathryn W.; Seehra, Jasbir; Kumar, Ravindra

    2010-01-01

    The single transmembrane domain serine/threonine kinase activin receptor type IIB (ActRIIB) has been proposed to bind key regulators of skeletal muscle mass development, including the ligands GDF-8 (myostatin) and GDF-11 (BMP-11). Here we provide a detailed kinetic characterization of ActRIIB binding to several low and high affinity ligands using a soluble activin receptor type IIB-Fc chimera (ActRIIB.Fc). We show that both GDF-8 and GDF-11 bind the extracellular domain of ActRIIB with affinities comparable with those of activin A, a known high affinity ActRIIB ligand, whereas BMP-2 and BMP-7 affinities for ActRIIB are at least 100-fold lower. Using site-directed mutagenesis, we demonstrate that ActRIIB binds GDF-11 and activin A in different ways such as, for example, substitutions in ActRIIB Leu79 effectively abolish ActRIIB binding to activin A yet not to GDF-11. Native ActRIIB has four isoforms that differ in the length of the C-terminal portion of their extracellular domains. We demonstrate that the C terminus of the ActRIIB extracellular domain is crucial for maintaining biological activity of the ActRIIB.Fc receptor chimera. In addition, we show that glycosylation of ActRIIB is not required for binding to activin A or GDF-11. Together, our findings reveal binding specificity and activity determinants of the ActRIIB receptor that combine to effect specificity in the activation of distinct signaling pathways. PMID:20385559

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

    E-print Network

    Mayo, Kelly E.

    , Weiss et al. 1995, Pernasetti et al. 2001, Suszko et al. 2003). Activins' actions are not limited, including the type I GnRH receptor (Gnrhr) and the activin bioneutralizing protein, follistatin (FST

  4. Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

    PubMed Central

    Wu, Hui; Wu, Michael; Chen, Yi; Allan, Carolyn A.; Phillips, David J.; Hedger, Mark P.

    2012-01-01

    Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined. Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein. Results. Serum levels of activin A (93.3 ± 27.0?pg/mL, mean ± SD), B (81.8 ± 30.8?pg/mL), or follistatin (6.52 ± 3.15?ng/mL) were not different (P > 0.05) between subjects with normal OGTT (n = 39), impaired glucose tolerance and/or fasting glucose (n = 17), or T2D (n = 36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P < 0.001), fasting insulin (P = 0.02), glycated hemoglobin (P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.001). Follistatin was positively correlated with HOMA-IR alone (P = 0.01). Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease. PMID:23304117

  5. 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.

  6. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy.

    PubMed

    Lach-Trifilieff, Estelle; Minetti, Giulia C; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji; Glass, David J

    2014-02-01

    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings. PMID:24298022

  7. Presence of Activin, Inhibin, and Follistatin in Epithelial Ovarian Carcinoma

    Microsoft Academic Search

    CORRINE K. WELT; GERALYN LAMBERT-MESSERLIAN; WENXIN ZHENG; WILLIAM F. CROWLEY; ALAN L. SCHNEYER

    2010-01-01

    Activin induces proliferation in epithelial ovarian carcinoma cell lines, whereas follistatin (FS), an activin binding protein, inhibits this action. To test the hypothesis that activin production, in excess of inhibin and FS, results in cell proliferation in epithelial ovarian tumors, mes- senger RNA (mRNA) expression of the activin family of proteins, FS, and activin type I and II receptors was

  8. Generation of activin receptor type IIB isoform-specific hypomorphic alleles.

    PubMed

    Lee, Young Jae; Hong, Kwon-Ho; Yun, Jihye; Oh, S Paul

    2006-10-01

    Activin receptor type IIB (Acvr2b) mediates multiple signals for transforming growth factor-beta (TGF-beta) family members, including Activin, Nodal, Bmp7, Gdf1, Gdf3, Myostatin (Gdf8), and Gdf11. Mouse Acvr2b gene generates four transcriptional isoforms (Acvr2b(1-4)) via alternative splicing of two sequence domains located at the juxtaposition of the transmembrane domain. To investigate whether these splicing domains are essential for signal transduction of the Acvr2b receptor in vivo, we have generated a strain of mutant mice (Acvr2b(4/4)) which produce only the Acvr2b(4) isoform, which lacks both splicing domains. Most homozygous Acvr2b(4(neo)/4(neo)) mice, in which a neomycin-resistant cassette was inserted in Intron 4 displayed a mild form of anterior vertebral transformations. However, the penetrance of the vertebral defect was dramatically decreased when the neomycin-resistant cassette was deleted. These results suggest that the Acvr2b(4) isoform is capable of compensating for the deficiency of the other three isoforms. In the absence of its subfamily receptor Acvr2a, however, the development of Acvr2b(4/4) mice was arrested at the gastrulation stage, recapitulating the Acvr2a(-/-); Acvr2b(+/-) mutant phenotype. In this study, we demonstrate that this phenomenon is most likely due to the reduction in the expressed Acvr2b(4) levels rather than to the functional deficiency of the Acvr2b(4) isoform itself. PMID:16991118

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

    SciTech Connect

    Nomura, Masatoshi, E-mail: nomura@med.kyushu-u.ac.jp [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tanaka, Kimitaka; Wang, Lixiang; Goto, Yutaka; Mukasa, Chizu; Ashida, Kenji; Takayanagi, Ryoichi [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)] [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    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.

  10. Differential Antagonism of Activin, Myostatin and Growth and Differentiation Factor 11 by Wild-Type and Mutant Follistatin

    Microsoft Academic Search

    Alan L. Schneyer; Yisrael Sidis; Anisha Gulati; Jie L. Sun; Henry Keutmann; Philip A. Krasney

    2008-01-01

    Follistatin binds and neutralizes members of the TGF su- perfamily including activin, myostatin, and growth and dif- ferentiation factor 11 (GDF11). Crystal structure analysis of thefollistatin-activincomplexrevealedextensivecontactsbe- tween follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained un- knownwhetherfollistatinresiduesinvolvedwithmyostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow

  11. Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin.

    PubMed

    Schneyer, Alan L; Sidis, Yisrael; Gulati, Anisha; Sun, Jie L; Keutmann, Henry; Krasney, Philip A

    2008-09-01

    Follistatin binds and neutralizes members of the TGFbeta superfamily including activin, myostatin, and growth and differentiation factor 11 (GDF11). Crystal structure analysis of the follistatin-activin complex revealed extensive contacts between follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained unknown whether follistatin residues involved with myostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow development of myostatin antagonists that would not inhibit activin actions, a desirable feature for development of myostatin antagonists for treatment of muscle-wasting disorders. We tested this hypothesis with our panel of point and domain swapping follistatin mutants using competitive binding analyses and in vitro bioassays. Our results demonstrate that activin binding and neutralization are mediated primarily by FSD2, whereas myostatin binding is more dependent on FSD1, such that deletion of FSD2 or adding an extra FSD1 in place of FSD2 creates myostatin antagonists with vastly reduced activin antagonism. However, these mutants also bind GDF11, indicating that further analysis is required for creation of myostatin antagonists that will not affect GDF11 activity that could potentially elicit GDF11-induced side effects in vivo. PMID:18535106

  12. Differential Antagonism of Activin, Myostatin and Growth and Differentiation Factor 11 by Wild-Type and Mutant Follistatin

    PubMed Central

    Schneyer, Alan L.; Sidis, Yisrael; Gulati, Anisha; Sun, Jie L.; Keutmann, Henry; Krasney, Philip A.

    2008-01-01

    Follistatin binds and neutralizes members of the TGF? superfamily including activin, myostatin, and growth and differentiation factor 11 (GDF11). Crystal structure analysis of the follistatin-activin complex revealed extensive contacts between follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained unknown whether follistatin residues involved with myostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow development of myostatin antagonists that would not inhibit activin actions, a desirable feature for development of myostatin antagonists for treatment of muscle-wasting disorders. We tested this hypothesis with our panel of point and domain swapping follistatin mutants using competitive binding analyses and in vitro bioassays. Our results demonstrate that activin binding and neutralization are mediated primarily by FSD2, whereas myostatin binding is more dependent on FSD1, such that deletion of FSD2 or adding an extra FSD1 in place of FSD2 creates myostatin antagonists with vastly reduced activin antagonism. However, these mutants also bind GDF11, indicating that further analysis is required for creation of myostatin antagonists that will not affect GDF11 activity that could potentially elicit GDF11-induced side effects in vivo. PMID:18535106

  13. Activins and activin antagonists in hepatocellular carcinoma

    PubMed Central

    Deli, Alev; Kreidl, Emanuel; Santifaller, Stefan; Trotter, Barbara; Seir, Katja; Berger, Walter; Schulte-Hermann, Rolf; Rodgarkia-Dara, Chantal; Grusch, Michael

    2008-01-01

    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor ? (TGF?) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo- or heterodimers formed from four different ? subunits termed ?A, ?B, ?C, and ?E, respectively. Activin A, the dimer of two ?A subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis. PMID:18350601

  14. Activin receptor inhibitors--dalantercept.

    PubMed

    Gupta, Shilpa; Gill, David; Pal, Sumanta K; Agarwal, Neeraj

    2015-04-01

    Development of anti-angiogenic therapy including the vascular endothelial growth factor (VEGF) antibodies and VEGF-tyrosine kinase receptors has been a major landmark in cancer therapy leading improvement in survival in several cancers. While anti-angiogenic therapy is effective in some settings, resistance often develops owing to evasive, alternative pathways. Novel targets for anti-angiogenic therapy are urgently required to provide treatment alternatives in patients whose tumors are unresponsive to approved anti-angiogenic agents; one such pathway is the bone morphogenetic proteins (BMP 9 and BMP 10) that activate the type I activin receptor-like kinase-1 (ALK1), which has been implicated in the development of functional vasculature. Dalantercept (ACE-041) is a novel anti-angiogenic agent, which is a soluble form of ALK1, and acts as a ligand trap for BMP 9 and BMP 10, inhibiting their interaction with ALK1, which further disrupts the process of vascular development. This review will discuss the preclinical and clinical development of dalantercept as a novel anti-angiogenic therapy in treating a variety of cancers and its distinct safety profile compared to other anti-VEGF agents. We will also discuss the ongoing and completed studies of dalantercept, including combination studies with other VEGF-directed therapies. PMID:25708802

  15. Molecular cloning, characterization and tissue distribution of six splice variants of activin type IIA receptor (ActRIIA) from grass carp (Ctenopharyngodon idellus).

    PubMed

    Chen, Chao; Song, Chunlei; Wang, Xinyan; Zhou, Hong

    2009-10-01

    Activin type II receptor (ActRII) is crucial for the assembly of the ligand/receptor complex and the activation of downstream cascades in activin signaling pathway. In this study, we identified six variants of grass carp ActRIIA which can be generated through three alternative splicing events (defined as AS1, AS2 and AS3). AS1 induces a spliced segment encoding 14 amino acids located in the external juxtamembrane region of the receptor. However, both AS2 and AS3 occur at the same cleavage site of kinase domain and induce a premature termination codon. Indeed, AS2 inserts a fragment of 79 bp while AS3 generates a new 3' terminal of cDNA with poly(A) signals. The full length cDNA of the shortest variant was shown to be 2001 bp encoding 514 amino acids with sequence identity of 79-95% to counterparts in other species. Homology modeling studies showed grass carp ActRIIA exhibits a characteristic three-finger toxin fold in the extracellular domain and a conserved bilobal architecture in the intracellular kinase domain. Semi-quantitative RT-PCR analysis revealed that six variants showed different expression patterns in selected tissues of grass carp. This study will be helpful for a better understanding of the physiological role of activin signaling in lower vertebrates. PMID:20154420

  16. Differential Muscle Hypertrophy Is Associated with Satellite Cell Numbers and Akt Pathway Activation Following Activin Type IIB Receptor Inhibition in Mtm1 p.R69C Mice

    PubMed Central

    Lawlor, Michael W.; Viola, Marissa G.; Meng, Hui; Edelstein, Rachel V.; Liu, Fujun; Yan, Ke; Luna, Elizabeth J.; Lerch-Gaggl, Alexandra; Hoffmann, Raymond G.; Pierson, Christopher R.; Buj-Bello, Anna; Lachey, Jennifer L.; Pearsall, Scott; Yang, Lin; Hillard, Cecilia J.; Beggs, Alan H.

    2015-01-01

    X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1?4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials. PMID:24726641

  17. Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

    PubMed Central

    Maeshima, Akito; Mishima, Keiichiro; Yamashita, Shin; Miya, Masaaki; Sakurai, Noriyuki; Sakairi, Toru; Hiromura, Keiju; Hasegawa, Yoshihisa; Kojima, Itaru; Nojima, Yoshihisa

    2014-01-01

    Activin, a member of the TGF-? superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO). The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial ?-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of ?-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression. PMID:24883308

  18. Role of activin A in carbon tetrachloride-induced acute liver injury

    PubMed Central

    Wang, Dong-Hui; Wang, Yi-Nan; Ge, Jing-Yan; Liu, Hai-Yan; Zhang, Hong-Jun; Qi, Yan; Liu, Zhong-Hui; Cui, Xue-Ling

    2013-01-01

    AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expression pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type IIA receptor (ActRIIA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 ?g/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P < 0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, compared with that in control mice (P < 0.01). Activin A protein expression in hepatocytes not within the necrotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRIIA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P < 0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is involved in CCl4-induced acute liver injury. Blocking activin A actions may be a therapeutic approach for acute liver injury. PMID:23840118

  19. Proteomic identification and functional validation of activins and bone morphogenetic protein 11 as candidate novel muscle mass regulators.

    PubMed

    Souza, Tatyana A; Chen, Xuan; Guo, Yongjing; Sava, Parid; Zhang, Jimin; Hill, Jennifer J; Yaworsky, Paul J; Qiu, Yongchang

    2008-12-01

    Myostatin is a secreted TGF-beta family member that controls skeletal muscle growth. Humans, cattle, and dogs carrying natural loss-of-function mutations in the myostatin gene and myostatin knockout mice exhibit significant increases in skeletal muscle mass. Treatment of adult mice with antimyostatin antibodies also resulted in significant muscle mass increases. However, myostatin-knockout mice that were treated with a soluble form of the activin type II receptor (ActRII) B increased their muscle mass by an additional 15-25%, indicating that there is at least one additional ligand, in addition to myostatin, that functions to limit muscle growth. Here, both soluble ActRII and -IIB fragment-crystallizable proteins were used to affinity purify their native ligands from human and mouse sera. Using mass spectrometry-based proteomics and in vitro binding assays we have identified and confirmed that a number of TGF-beta family members, including myostatin, activins-A, -B, and -AB, bone morphogenetic proteins (BMPs) -9, -10, and -11, bind to both ActRIIs. Many of these factors, such as BMPs-11, -9, and -10 were discovered in systemic circulation for the first time, indicating that these ligands may also act in an endocrine fashion. Using a promoter-specific gene reporter assay, we demonstrated that soluble ActRIIB fragment-crystallizable proteins can inhibit the canonical signaling induced by these ligands. In addition, like myostatin, these factors were able to block the differentiation of myoblast cells into myotubes. However, in addition to myostatin, only BMP-11, and activins-A, -B, and -AB could be blocked from inhibiting the myoblast-to-myotube differentiation with both soluble ActRIIs, thus implicating them as potential novel regulators of muscle growth. PMID:18927237

  20. Anteroposterior neural tissue specification by activin-induced?mesoderm

    PubMed Central

    Green, Jeremy B. A.; Cook, T. Les; Smith, J. C.; Grainger, Robert M.

    1997-01-01

    The transforming growth factor ? superfamily member, activin, is able to induce mesodermal tissues in animal cap explants from Xenopus laevis blastula stage embryos. Activin can act like a morphogen of the dorsoventral axis in that lower doses induce more ventral, and higher doses more dorsal, tissue types. Activin has also previously been reported to induce neural tissues in animal caps. From cell mixing experiments it was inferred that this might be an indirect effect of induced mesoderm signaling to uninduced ectoderm. Here we demonstrate directly that neural tissues do indeed arise by the action of induced mesoderm on uninduced ectoderm. Dorsal mesoderm is itself subdivided into posterior and anterior domains in vivo, but this had not been demonstrated for induced mesoderm. We therefore tested whether different concentrations of activin recreate these different anteroposterior properties as well. We show that the anteroposterior positional value of induced mesoderm, including its neuroinductive properties, depends on the dose of activin applied to the mesoderm, with lower doses inducing more posterior and higher doses giving more anterior markers. We discuss the implications of these results for patterning signals and the relationship between anteroposterior and dorsoventral axes. PMID:9238022

  1. Activation of signalling by the activin receptor complex.

    PubMed Central

    Attisano, L; Wrana, J L; Montalvo, E; Massagué, J

    1996-01-01

    Activin exerts its effects by simultaneously binding to two types of p rotein serine/threonine kinase receptors, each type existing in various isoforms. Using the ActR-IB and ActR-IIB receptor isoforms, we have investigated the mechanism of activin receptor activation. ActR-IIB are phosphoproteins with demonstrable affinity for each other. However, activin addition strongly promotes an interaction between these two proteins. Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB. Mutation of conserved serines and threonines in the GS domain, a region just upstream of the kinase domain in ActR-IB, abrogates both phosphorylation and signal propagation, suggesting that this domain contains phosphorylation sites required for signalling. ActR-IB activation can be mimicked by mutation of Thr-206 to aspartic acid, which yields a construct, ActR-IB(T206D), that signals in the absence of ligand. Furthermore, the signalling activity of this mutant construct is undisturbed by overexpression of a dominant negative kinase-defective ActR-IIB construct, indicating that ActR-IB(T206D) can signal independently of ActR-IIB. The evidence suggests that ActR-IIB acts as a primary activin receptor and ActR-IB acts as a downstream transducer of activin signals. PMID:8622651

  2. Activin A Mediates Growth Inhibition and Cell Cycle Arrest through Smads in Human Breast Cancer Cells

    Microsoft Academic Search

    Joanna E. Burdette; Jacqueline S. Jeruss; Sarah J. Kurley; Eun Jig Lee; Teresa K. Woodruff

    The transforming growth factor-B (TGF-B) superfamily of growth factors is responsible for a variety of physiologic actions, including cell cycle regulation. Activin is a member of the TGF-B superfamily that inhibits the proliferation of breast cancer cells. Activin functions by interacting with its type I and type II receptors to induce phosphorylation of intra- cellular signaling molecules known as Smads.

  3. Antibacterial activity of soluble pyridinium-type polymers.

    PubMed Central

    Kawabata, N; Nishiguchi, M

    1988-01-01

    Cross-linked poly(N-benzyl-4-vinylpyridinium halide) (designated insoluble BVP) was previously reported to capture bacterial cells alive by contact with them. The corresponding linear polymer poly(N-benzyl-4-vinylpyridinium salt) (designated soluble BVP) was found to exhibit antibacterial activity. This soluble pyridinium-type polymer showed strong antibacterial activity against gram-positive bacteria, whereas it was less active against gram-negative bacteria. The antibacterial activity of this cationic, polymeric disinfectant was considerably greater than that of the corresponding monomeric compound and was approximately equal to that of conventional disinfectants such as benzalkonium chloride and chlorohexidine. PMID:3202632

  4. Activin inhibits telomerase activity in cancer

    SciTech Connect

    Katik, Indzi; Mackenzie-Kludas, Charley; Nicholls, Craig [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia); Jiang, Fang-Xu [Centre for Diabetes Research, Western Australian Institute for Medical Research and The University of Western Australia, Perth (Australia)] [Centre for Diabetes Research, Western Australian Institute for Medical Research and The University of Western Australia, Perth (Australia); Zhou, Shufeng [School of Health Sciences, RMIT University, Melbourne (Australia)] [School of Health Sciences, RMIT University, Melbourne (Australia); Li, He [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia); Liu, Jun-Ping, E-mail: jun-ping.liu@med.monash.edu.au [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia)

    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.

  5. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer.

    PubMed

    Tsuchida, Kunihiro; Nakatani, Masashi; Uezumi, Akiyoshi; Murakami, Tatsuya; Cui, Xueling

    2008-03-01

    Activin, myostatin and other members of the TGF-beta superfamily signal through a combination of type II and type I receptors, both of which are transmembrane serine/threonine kinases. Activin type II receptors, ActRIIA and ActRIIB, are primary ligand binding receptors for activins, nodal, myostatin and GDF11. ActRIIs also bind a subset of bone morphogenetic proteins (BMPs). Type I receptors that form complexes with ActRIIs are dependent on ligands. In the case of activins and nodal, activin receptor-like kinases 4 and 7 (ALK4 and ALK7) are the authentic type I receptors. Myostatin and GDF11 utilize ALK5, although ALK4 could also be activated by these growth factors. ALK4, 5 and 7 are structurally and functionally similar and activate receptor-regulated Smads for TGF-beta, Smad2 and 3. BMPs signal through a combination of three type II receptors, BMPRII, ActRIIA, and ActRIIB and four type I receptors, ALK1, 2, 3, and 6. BMPs activate BMP-specific Smads, Smad1, 5 and 8. Smad proteins undergo multimerization with co-mediator Smad, Smad4, and translocated into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. The signal transduction pathway through activin type II receptors, ActRIIA and ActRIIB, with type I receptors is involved in various human diseases. In this review, we discuss the role of signaling through activin receptors as therapeutic targets of intractable neuromuscular diseases, endocrine disorders and cancers. PMID:17878607

  6. Ulipristal acetate modulates the expression and functions of activin a in leiomyoma cells.

    PubMed

    Ciarmela, Pasquapina; Carrarelli, Patrizia; Islam, Md Soriful; Janjusevic, Milijana; Zupi, Errico; Tosti, Claudia; Castellucci, Mario; Petraglia, Felice

    2014-09-01

    Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age and represents the single most common indication for hysterectomy. A development of new treatments is necessary for a medical management, and in this direction, several hormonal drugs are under investigation. Ulipristal acetate (UPA; a selective progesterone receptor modulator) is considered as one of the most promising because progesterone has a critical role in development and growth of uterine leiomyoma. The effect of steroids is partly mediated by growth factors like activin A which increases extracellular matrix expression contributing to the growth of leiomyoma. The present study aimed to test whether UPA acts on leiomyoma cells affecting expression and functions of activin A system. Cultured myometrial and leiomyoma cells were treated with UPA, and messenger RNA (mRNA) expression levels of activin A (inhibin ?A [INHBA] subunits), its binding proteins (follistatin [FST] and FST-related gene), and its receptors (activin receptor-like kinase 4 [ALK4], activin receptor type [ActR] II, and ActRIIB) were evaluated. The effect of UPA on activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells was also studied. Ulipristal acetate decreased INHBA, FST, ActRIIB, and Alk4 mRNA expressions in leiomyoma cultured cells. In addition, UPA was able to block the activin A-induced increase in fibronectin or VEGF-A mRNA expression in myometrial and in leiomyoma cultured cells. The present data show that UPA inhibits activin A expression and functions in leiomyoma cells, and this may represent a possible mechanism of action of the drug on uterine leiomyoma. PMID:25001022

  7. Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone beta subunit transcription.

    PubMed

    Lee, Katharine B; Khivansara, Vishal; Santos, Michelle M; Lamba, Pankaj; Yuen, Tony; Sealfon, Stuart C; Bernard, Daniel J

    2007-02-01

    Transforming growth factor beta superfamily ligands regulate pituitary FSH production and secretion. The best-described examples are the activins and inhibins, which respectively stimulate and hinder Fshb subunit transcription in gonadotrope cells. More recently, members of the bone morphogenetic protein (BMP) sub-family were shown to regulate FSH production in a manner analogous to the activins. Here, we used the murine gonadotrope cell line, LbetaT2, to investigate mechanisms through which BMP2 regulates the Fshb gene. Although expressed at low levels in LbetaT2 cells, Bmp2 mRNA was readily detected in adult murine pituitary gland. Recombinant BMP2 stimulated Fshb promoter-reporter activity, although its effects were weaker than those of equimolar activin A or B. BMP4 stimulated transcription comparably with BMP2, but BMPs 6 and 7 were about tenfold less potent. Remarkably, BMP2 and activin A synergistically upregulated Fshb transcription and endogenous Fshb mRNA levels in LbetaT2 cells. Although functionally cooperative, the two ligands appeared to use distinct intracellular mechanisms to mediate their responses because neither ligand altered the timing or magnitude of the other's effects. Receptor overexpression analyses suggested that BMP2 may preferentially signal through complexes of the type II receptor, BMPR2, and the type I receptor, activin receptor like kinase (ALK2; Acvr1), to stimulate Fshb transcription. BMP2 rapidly activated the Smad1/5/8 intracellular signaling cascade and Smad8 overexpression potentiated BMP2's effects. In summary, BMPs regulate Fshb transcription in LbetaT2 cells and can amplify the already robust effects of the activins through a distinct signaling mechanism. Because BMP2 is expressed in the adult mouse pituitary, it may act as critical paracrine co-regulator of FSH synthesis by gonadotropes. PMID:17293449

  8. VIRTUALLY SOLUBLE GROUPS OF TYPE FP CONCHITA MARTINEZ-PEREZ AND BRITA E.A. NUCINKIS

    E-print Network

    Nucinkis, Brita

    VIRTUALLY SOLUBLE GROUPS OF TYPE FP CONCHITA MARTINEZ-P´EREZ AND BRITA E.A. NUCINKIS Abstract. We prove that a virtually soluble group G of type FP admits a finitely dominated model for EG of dimension the Hirsch length of G. This implies in particular that the Brown conjecture is satisfied for virtually

  9. Morphological differences in Xenopus embryonic mesodermal cells are specified as an early response to distinct threshold concentrations of activin.

    PubMed

    Symes, K; Yordán, C; Mercola, M

    1994-08-01

    The involution of presumptive mesoderm that occurs during amphibian gastrulation is a complex process requiring the coordinated action of a diverse range of cells. We show that cells with distinct morphologies, resembling each of those normally found in the involuting tissue of the Xenopus embryo, are induced in dispersed animal pole cells by different doses of the potent mesoderm-inducing factor activin. Each cell type is induced within a restricted dose range of activin concentrations, the boundaries of which are well demarcated shortly after activin treatment. In contrast, Brachyury and goosecoid, two genes thought to pattern the presumptive mesoderm, and the gene encoding platelet-derived growth factor receptor alpha, which is expressed in the mesoderm of gastrula stage embryos, are induced by broad, overlapping ranges of high activin concentrations at such early times. Similarly, the response of the gene encoding platelet-derived growth factor A, which is expressed normally in ectoderm of gastrula stage embryos, diminishes gradually as the activin concentration increases. Dose windows for the expression of these four genes narrow and become distinct from one another in cell aggregates after several hours in culture, suggesting that activin prompts a dynamic program of gene expression in induced mesoderm. PMID:7925034

  10. Activins and follistatins: Emerging roles in liver physiology and cancer

    PubMed Central

    Kreidl, Emanuel; Öztürk, Deniz; Metzner, Thomas; Berger, Walter; Grusch, Michael

    2009-01-01

    Activins are secreted proteins belonging to the TGF-? family of signaling molecules. Activin signals are crucial for differentiation and regulation of cell proliferation and apoptosis in multiple tissues. Signal transduction by activins relies mainly on the Smad pathway, although the importance of crosstalk with additional pathways is increasingly being recognized. Activin signals are kept in balance by antagonists at multiple levels of the signaling cascade. Among these, follistatin and FLRG, two members of the emerging family of follistatin-like proteins, can bind secreted activins with high affinity, thereby blocking their access to cell surface-anchored activin receptors. In the liver, activin A is a major negative regulator of hepatocyte proliferation and can induce apoptosis. The functions of other activins expressed by hepatocytes have yet to be more clearly defined. Deregulated expression of activins and follistatin has been implicated in hepatic diseases including inflammation, fibrosis, liver failure and primary cancer. In particular, increased follistatin levels have been found in the circulation and in the tumor tissue of patients suffering from hepatocellular carcinoma as well as in animal models of liver cancer. It has been argued that up-regulation of follistatin protects neoplastic hepatocytes from activin-mediated growth inhibition and apoptosis. The use of follistatin as biomarker for liver tumor development is impeded, however, due to the presence of elevated follistatin levels already during preceding stages of liver disease. The current article summarizes our evolving understanding of the multi-faceted activities of activins and follistatins in liver physiology and cancer. PMID:21160961

  11. Activin A and TGF-beta stimulate phosphorylation of focal adhesion proteins and cytoskeletal reorganization in rat aortic smooth muscle cells.

    PubMed

    Riedy, M C; Brown, M C; Molloy, C J; Turner, C E

    1999-08-25

    Activin A and Transforming Growth Factor-beta (TGF-beta) are members of a common family of cytokines that bind to and stimulate serine/threonine kinase receptors. Activin A and TGF-beta are important during embryonic development exerting both positive and negative effects on cell growth. In the adult organism, they function in processes such as tissue repair, cellular proliferation, and differentiation. Although activin A and TGF-beta often induce opposite functional outcomes in specific cells; proliferation or differentiation, both were found to stimulate the formation of actin stress fibers and focal adhesions in serum-starved rat aortic smooth muscle (RASM) cells. These structural changes were accompanied by phosphorylation of the focal adhesion proteins, paxillin, and p130(cas). Similar cytoskeletal and biochemical changes were observed with the vasoactive agonist angiotensin II. Activation of the ERK/MAP kinase pathway has been implicated in the migration in certain cell types. However, while activin A, TGF-beta, and angiotensin II all stimulated ERK activity in RASM cells, only activin A and angiotensin II stimulated migration. TGF-beta failed to illicit a chemotactic response. Furthermore, pharmacologic inhibition of MEK activity failed to block migration in response to activin A and angiotensin II, indicating RASM migration can occur independent of ERK activity. These results suggest that TGF-beta and activin A share several signaling pathways with angiotensin II leading to cytoskeletal remodeling and ERK activation, but there are distinct differences regarding the effect of these agonists on cellular migration. PMID:10438585

  12. 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

  13. Activins and Leydig Cell Development Differentiation, and Disease

    Microsoft Academic Search

    Gail P. Risbridger; Christopher Butler

    During development and differentiation of many tissues and organs, activins are potent stimulatory or inhibitory factors,\\u000a but generally during Leydig cell development they are inhibitory. Thus, the decline in activin bioactivity at puberty, corresponds\\u000a with the emergence of the adult Leydig cell population and differentiation from Leydig cell precursors. Once established,\\u000a activins inhibit steroidogenesis and oppose or balance luteinizing hormone

  14. Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior

    Microsoft Academic Search

    F Zheng; H Adelsberger; M R Müller; J-M Fritschy; S Werner; C Alzheimer

    2009-01-01

    Activin, a member of the transforming growth factor-? superfamily, affords neuroprotection in acute brain injury, but its physiological functions in normal adult brain are largely unknown. Using transgenic (tg) mice expressing a dominant-negative activin receptor mutant under the control of the CaMKII? promoter in forebrain neurons, we identified activin as a key regulator of ?-aminobutyric acid (GABA)ergic synapses and anxiety-like

  15. Activin signaling as an emerging target for therapeutic interventions

    Microsoft Academic Search

    Kunihiro Tsuchida; Masashi Nakatani; Keisuke Hitachi; Akiyoshi Uezumi; Yoshihide Sunada; Hiroshi Ageta; Kaoru Inokuchi

    2009-01-01

    After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic

  16. Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis

    Microsoft Academic Search

    Eric Ballot; Jean Claude Homberg; Catherine Johanet

    2000-01-01

    Background\\/Aims: Auto-immune hepatitis patients are divided into two well-defined subgroups on the basis of immunoserological markers, i.e. anti-actin cable and\\/or anti-nuclear antibodies for the auto-immune hepatitis type 1, anti-liver\\/kidney microsome type 1 and\\/or anti-liver cytosol type 1 for the autoimmune hepatitis type 2. Controversial antibodies to a soluble liver antigen have been proposed as a diagnostic marker for the putative

  17. Increased serum activin a differentiates alcoholic from cirrhosis of other aetiologies

    Microsoft Academic Search

    A Voumvouraki; G Notas; M Koulentaki; M Georgiadou; S Klironomos; C Coucoutsi; E Kouroumalis

    2011-01-01

    Introduction, background and aimActivin A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are very few. The authors therefore studied serum levels of Activin A in chronic liver diseases. To identify the origin of Activin A, levels in the hepatic vein were estimated and expression

  18. Preparation of a Foam Spray Dried Whole Milk Type Product with Good Sinkability, Dispersibility, and Solubility

    Microsoft Academic Search

    A. Tamsma; A. Kontson

    1974-01-01

    Foam spray dried powder of whole milk type with good sinkability was pre- Fared by combining three influential fac- tors in the preparation procedure: (1) use of liquid milk fat, (2) high pressure homogenization, and (3) low foaming with carbon dioxide. A 26% liquid milk fat powder has somewhat adverse dis- persibility and solubility, but lowering the fat content to

  19. Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor.

    PubMed

    Shikone, T; Matzuk, M M; Perlas, E; Finegold, M J; Lewis, K A; Vale, W; Bradley, A; Hsueh, A J

    1994-08-01

    Inhibin-alpha-deficient mutant mice have been generated by a targeted deletion of the inhibin-alpha gene through homologous recombination in murine embryonic stem cells. Essentially all of the homozygous mutants develop gonadal sex cord-stromal tumors. To investigate their endocrine and proliferative characteristics, gonadal tumor cells were maintained in vitro. Cells from inhibin-alpha-deficient mice multiplied poorly; however, cells from mice deficient in both inhibin-alpha and p53 proliferated rapidly and showed higher saturation density and plating efficiency, thus allowing the establishment of clonal tumor cell lines. Although negligible estrogen and testosterone was produced by the clonal cells, high levels of progesterone were secreted. A clonal testis tumor cell line (inhibin-alpha/p53 deficient) showed no response to exogenous FSH, human CG (hCG), or inhibin A but exhibited a 6- to 8-fold increase in progesterone production in response to forskolin treatment. The stimulatory effect of forskolin was, however, partially blocked by activin treatment. Northern blot analysis revealed inhibin beta A and beta B mRNA expression in these cells. Furthermore, Western blot analyses indicated the secretion of the beta A-subunit protein. We further tested the role of activin on tumor cell growth. Treatment with follistatin, an activin-binding protein, inhibited tumor cell replication in a dose-dependent manner. In contrast, treatment with activin A stimulated tumor cell growth by itself and partially blocked follistatin action. Incorporation of thymidine into DNA of these cells was also stimulated by activin. In addition, treatment with antiactivin A serum inhibited tumor cell replication and blocked the stimulatory action of activin on cell growth. The activin action is likely mediated by specific receptors because cross-linking of [125]activin to the 50-55 kilodalton type I and 75-80 kilodalton type II receptors was found using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Northern blot analysis also revealed follistatin mRNA expression in the tumor cells, suggesting these cells are related to granulosa cells. Our findings indicate that activin can act as an autocrine growth factor in stimulating the proliferation of gonadal tumor cell lines derived from inhibin-alpha and p53-deficient mice and inhibits progesterone production. These tumor cell lines are useful for studies on the regulation of gonadal cell proliferation and steroidogenesis as well as the signaling pathway mediating activin action. PMID:7997239

  20. The Drosophila Activin receptor Baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development

    PubMed Central

    Brummel, Ted; Abdollah, Shirin; Haerry, Theodor E.; Shimell, Mary Jane; Merriam, John; Raftery, Laurel; Wrana, Jeffrey L.; O’Connor, Michael B.

    1999-01-01

    The TGF-? superfamily of growth and differentiation factors, including TGF-?, Activins and bone morphogenetic proteins (BMPs) play critical roles in regulating the development of many organisms. These factors signal through a heteromeric complex of type I and II serine/threonine kinase receptors that phosphorylate members of the Smad family of transcription factors, thereby promoting their nuclear localization. Although components of TGF-?/Activin signaling pathways are well defined in vertebrates, no such pathway has been clearly defined in invertebrates. In this study we describe the role of Baboon (Babo), a type I Activin receptor previously called Atr-I, in Drosophila development and characterize aspects of the Babo intracellular signal-transduction pathway. Genetic analysis of babo loss-of-function mutants and ectopic activation studies indicate that Babo signaling plays a role in regulating cell proliferation. In mammalian cells, activated Babo specifically stimulates Smad2-dependent pathways to induce TGF-?/Activin-responsive promoters but not BMP-responsive elements. Furthermore, we identify a new Drosophila Smad, termed dSmad2, that is most closely related to vertebrate Smads 2 and 3. Activated Babo associates with dSmad2 but not Mad, phosphorylates the carboxy-terminal SSXS motif and induces heteromeric complex formation with Medea, the Drosophila Smad4 homolog. Our results define a novel Drosophila Activin/TGF-? pathway that is analogous to its vertebrate counterpart and show that this pathway functions to promote cellular growth with minimal effects on patterning. PMID:9887103

  1. Expression of inhibin/activin system messenger ribonucleic acids and proteins in ovarian follicles from women with polycystic ovarian syndrome.

    PubMed

    Roberts, V J; Barth, S; el-Roeiy, A; Yen, S S

    1994-11-01

    The role of inhibin, activin, and follistatin in the pathophysiology of polycystic ovary syndrome (PCOS) was investigated by examining the expression of human inhibin/activin subunit, follistatin, and type II activin receptor (ActRII and -IIB) messenger ribonucleic acid (mRNA) signals (via in situ hybridization) and encoded proteins (via immunocytochemistry) in ovarian follicles (n = 42) from 6 women diagnosed with PCOS. The localization patterns in cellular compartments were compared to those in small antral follicles of comparable size (3-7 mm; n = 40) from 17 normal human ovaries. In small antral follicles of both normal and PCOS ovaries, mRNA signals for all three subunits of inhibin and activin (alpha, beta a, and beta b) were expressed in granulosa cells, whereas in the thecal cell layer, only alpha-subunit mRNA was expressed. The relative intensity of the alpha-subunit mRNA signal was distinctly different in granulosa and thecal cells between PCOS and normal follicles; in small antral follicles of normal ovaries, the alpha-subunit mRNA signal was stronger in the granulosa cell layer than in the thecal cells, and the reverse was found in the polycystic follicles. A light follistatin mRNA signal was found in the granulosa cells of normal small antral follicles, but no follistatin mRNA was detected in any cell type of PCOS follicles. ActRII and -IIB mRNAs were not detected in any cell layer in either normal or PCOS follicles. There were no notable differences in the protein localization pattern of the inhibin/activin system between the PCOS and normal ovaries. In both types of follicles, follistatin and alpha-, beta a-, and beta b-subunit cytoplasmic staining were observed in granulosa cells, as were their corresponding messages, with the exception of the undetectable follistatin mRNA signal in the PCOS follicles. In both normal and PCOS follicles, follistatin and beta a-subunit cytoplasmic staining were occasionally found in thecal interna cells, with no corresponding localization of mRNA, and alpha-subunit protein was not detected in thecal cells despite the presence of the alpha-subunit mRNA. ActRII and -IIB protein localizations were not examined due to the lack of available antisera. These results suggest that granulosa cells of small antral follicles are less active in polycystic than in normal ovaries with respect to inhibin alpha-subunit and follistatin mRNA expression. A consequence of these differences could be an increase in the availability of activin, relative to inhibin, in the arrested follicles in PCOS. PMID:7962340

  2. XSmad2 directly activates the activin-inducible, dorsal mesoderm gene XFKH1 in Xenopus embryos.

    PubMed Central

    Howell, M; Hill, C S

    1997-01-01

    Transforming growth factor (TGF)-beta family members play a central role in mesoderm induction during early embryogenesis in Xenopus. Although a number of target genes induced as an immediate-early response to activin-like members of the family have been described, little is known about the molecular mechanisms involved. Our systematic analysis of the activin induction of the target gene XFKH1 reveals two regions that mediate activin-responsive transcription: one, in the first intron, is targeted directly by the activin-signalling pathway; the other, in the 5' flanking sequences, responds to activin indirectly, possibly being required for maintenance of gene expression. We demonstrate that a 107 bp region of the XFKH1 first intron acts as an enhancer and confers activin inducibility onto a minimal uninducible promoter in the absence of new protein synthesis. It bears little sequence similarity to other activin responsive sequences. We further demonstrate that overexpression of a constitutively active derivative of Xenopus Smad2 (XSmad2), which has been implicated as a component of the activin signalling pathway, is sufficient for direct activation of transcription via this enhancer. Moreover, we show that XSmad2 acts indirectly on the proximal promoter element induced by activin via an indirect mechanism. These results establish the XFKH1 intron enhancer as a direct nuclear target of the activin signalling pathway in Xenopus embryos, and provide strong new evidence that XSmad2 is a transducer of activin signals. PMID:9405370

  3. Activin A regulates proliferation, invasion and migration in osteosarcoma cells.

    PubMed

    Zhu, Jianwei; Liu, Fan; Wu, Quanming; Liu, Xiancheng

    2015-06-01

    Activin A is a member of the TGF?? superfamily. Previous studies have demonstrated that activin A exhibited pluripotent effects in several tumours. However, the roles of activin A signaling in osteosarcoma pathogenesis have not been previously investigated. Therefore, the present study aimed to investigate the effects of activin A on osteosarcoma cell proliferation, invasion and migration. Firstly, the expression of activin A in osteosarcoma cell lines (MG63, SaOS?2 and U2OS) and a human osteoblastic cell line (hFOB1.19) was detected using reverse transcription quantitative polymerase chain reaction and western blotting. Activin A was upregulated in osteosarcoma cell lines compared with hFOB1.19 cells. To investigate the effects of activin A on osteosarcoma cell proliferation, invasion and migration, MG63 cells were generated in which activin A was either overexpressed or depleted. MTT staining, propidium iodide staining and a Transwell assay were used to analyze the cell cycle, proliferation, invasion and migration of MG63 cells, respectively. The results of the present study revealed that the abilities of proliferation, invasion and migration were suppressed in MG63 cells in which activin A was depleted, while they were enhanced in activin A-overexpressing cells. In conclusion, the results of the present study suggested that activin A may facilitate proliferation, invasion and migration of osteosarcoma cells, and it may therefore be a potential target for the treatment of osteosarcoma. PMID:25634369

  4. High levels of fetal membrane activin ?A and activin receptor IIB mRNAs and augmented concentration of amniotic fl uid activin A in women in term or preterm labor

    Microsoft Academic Search

    F PETRAGLIA; A M Di Blasio; P Florio; R GalIo; A R Genazzani; T K Woodruff; W Vale

    The aim of the present study was to evaluate whether spontaneous labor at term and pathological preterm labor are associated with changes in the expression of activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic fl

  5. Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Moriyama, Hiroyoshi; Shinozaki, Junichi; Nakane, Takahisa; Masuda, Kazuo; Bagchi, Manashi

    2013-11-01

    Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-?1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells. PMID:24175655

  6. Mechanism of protection by soluble epoxide hydrolase inhibition in type 2 diabetic stroke.

    PubMed

    Zuloaga, Kristen L; Krasnow, Stephanie M; Zhu, Xinxia; Zhang, Wenri; Jouihan, Sari A; Shangraw, Robert E; Alkayed, Nabil J; Marks, Daniel L

    2014-01-01

    Inhibition of soluble epoxide hydrolase (sEH) is a potential target of therapy for ischemic injury. sEH metabolizes neuroprotective epoxyeicosatrienoic acids (EETs). We recently demonstrated that sEH inhibition reduces infarct size after middle cerebral artery occlusion (MCAO) in type 1 diabetic mice. We hypothesized that inhibition of sEH would protect against ischemic injury in type 2 diabetic mice. Type 2 diabetes was produced by combined high-fat diet, nicotinamide and streptozotocin in male mice. Diabetic and control mice were treated with vehicle or the sEH inhibitor t-AUCB then subjected to 60-min MCAO. Compared to chow-fed mice, high fat diet-fed mice exhibited an upregulation of sEH mRNA and protein in brain, but no differences in brain EETs levels were observed between groups. Type 2 diabetic mice had increased blood glucose levels at baseline and throughout ischemia, decreased laser-Doppler perfusion of the MCA territory after reperfusion, and sustained larger cortical infarcts compared to control mice. t-AUCB decreased fasting glucose levels at baseline and throughout ischemia, improved cortical perfusion after MCAO and significantly reduced infarct size in diabetic mice. We conclude that sEH inhibition, as a preventative treatment, improves glycemic status, post-ischemic reperfusion in the ischemic territory, and stroke outcome in type 2 diabetic mice. PMID:24824753

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

    E-print Network

    Mayo, Kelly E.

    in Mu¨llerian inhibiting substance promoter (MIS)-Smad2 dominant negative mice that have impaired activin signaling through Smad2, and small inter- fering RNAs targeting Smad2 or Smad3 suppressed ER pro- moter activation, suggesting that Smad2 and Smad3 are involved in regulating ER levels. Therefore

  8. Drug delivery system for poorly water-soluble compounds using lipocalin-type prostaglandin D synthase.

    PubMed

    Fukuhara, Ayano; Nakajima, Hidemitsu; Miyamoto, Yuya; Inoue, Katsuaki; Kume, Satoshi; Lee, Young-Ho; Noda, Masanori; Uchiyama, Susumu; Shimamoto, Shigeru; Nishimura, Shigenori; Ohkubo, Tadayasu; Goto, Yuji; Takeuchi, Tadayoshi; Inui, Takashi

    2012-04-10

    Lipocalin-type prostaglandin D synthase (L-PGDS) is a member of the lipocalin superfamily and a secretory lipid-transporter protein, which binds a wide variety of hydrophobic small molecules. Here we show the feasibility of a novel drug delivery system (DDS), utilizing L-PGDS, for poorly water-soluble compounds such as diazepam (DZP), a major benzodiazepine anxiolytic drug, and 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX), an ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist and anticonvulsant. Calorimetric experiments revealed for both compounds that each L-PGDS held three molecules with high binding affinities. By mass spectrometry, the 1:3 complex of L-PGDS and NBQX was observed. L-PGDS of 500?M increased the solubility of DZP and NBQX 7- and 2-fold, respectively, compared to PBS alone. To validate the potential of L-PGDS as a drug delivery vehicle in vivo, we have proved the prospective effects of these compounds via two separate delivery strategies. First, the oral administration of a DZP/L-PGDS complex in mice revealed an increased duration of pentobarbital-induced loss of righting reflex. Second, the intravenous treatment of ischemic gerbils with NBQX/L-PGDS complex showed a protective effect on delayed neuronal cell death at the hippocampal CA1 region. We propose that our novel DDS could facilitate pharmaceutical development and clinical usage of various water-insoluble compounds. PMID:22226778

  9. Activin A expression in esophageal carcinoma and its association with tumor aggressiveness and differentiation

    PubMed Central

    WANG, ZHENHUA; ZHANG, NING; SONG, RUIFENG; FAN, RUITAI; YANG, LIUQIN; WU, LIPING

    2015-01-01

    The aim of the present study was to investigate the expression of activin A in esophageal carcinoma and its association with tumor differentiation and metastasis. A total of 57 esophageal carcinoma patients and 36 controls were included in the current study. The mRNA and protein expression levels of activin A in esophageal tumors or normal esophageal tissues were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis. In addition, the association of activin A expression with esophageal carcinoma differentiation, metastasis and recurrence postoperatively was analyzed. The mRNA and protein expression levels of activin A in esophageal carcinoma were significantly higher compared with those in normal esophageal tissues (P<0.05). The expression of activin A was higher in poorly-/moderately-differentiated esophageal tumor tissues compared with that of well-differentiated or control tissues (P<0.05). Furthermore, the expression of activin A in poorly-differentiated esophageal tumor tissues was higher compared with that of moderately-differentiated tissues (P<0.05). A positive correlation was also observed between differentiation degree and activin A expression. The expression of activin A was higher in patients with lymph node metastasis compared with those without metastasis (P<0.05). The cumulative survival rate of patients with a high expression of activin A at 1, 2 and 3 years postoperatively was significantly decreased compared with that of patients with a lower expression of activin A (P<0.05); by contrast, the cumulative recurrence rate was significantly higher in patients with a lower activin A expression (P<0.05). In conclusion, abnormal expression of activin A was detected in esophageal tumor tissues, which was correlated with the tumor differentiation, metastasis, survival and recurrence. In conclusion, activin A may be used as an auxiliary index in the diagnosis and prognosis of clinical esophageal carcinoma.

  10. Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells

    PubMed Central

    2014-01-01

    Background Activin A, an important member of transforming growth factor-? superfamily, is reported to inhibit proliferation of mature hepatocyte. However, the effect of activin A on growth of hepatic progenitor cells is not fully understood. To that end, we attempted to evaluate the potential role of activin A in the regulation of hepatic progenitor cell proliferation. Results Using the 2-acetaminofluorene/partial hepatectomy model, activin A expression decreased immediately after partial hepatectomy and then increased from the 9th to 15th day post surgery, which is associated with the attenuation of oval cell proliferation. Activin A inhibited oval cell line LE6 growth via activating the SMAD signaling pathway, which manifested as the phosphorylation of SMAD2/3, the inhibition of Rb phosphorylation, the suppression of cyclinD1 and cyclinE, and the promotion of p21WAF1/Cip1 and p15INK4B expression. Treatment with activin A antagonist follistatin or blocking SMAD signaling could diminish the anti-proliferative effect of activin A. By contrast, inhibition of the MAPK pathway did not contribute to this effect. Antagonizing activin A activity by follistatin administration enhanced oval cell proliferation in the 2-acetylaminofluorene/partial hepatectomy model. Conclusion Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells. PMID:24628936

  11. Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation.

    PubMed

    Martins da Silva, S J; Bayne, R A L; Cambray, N; Hartley, P S; McNeilly, A S; Anderson, R A

    2004-02-15

    The formation of the essential functional unit of the ovary, the primordial follicle, occurs during fetal life in humans. Factors regulating oogonial proliferation and interaction with somatic cells before primordial follicle formation are largely unknown. We have investigated the expression, localisation and functional effects of activin and its receptors in the human fetal ovary at 14-21 weeks gestation. Expression of mRNA for the activin betaA and betaB subunits and the activin receptors ActRIIA and ActRIIB was demonstrated by RT-PCR. Expression of betaA mRNA increased 2-fold across the gestational range examined. Activin subunits and receptors were localised by immunohistochemistry. The betaA subunit was expressed by oogonia, and the betaB subunit and activin receptors were expressed by both oogonia and somatic cells. BetaA expression was increased in larger oogonia at later gestations, but was low in oocytes within newly formed primordial follicles. Treatment of ovary fragments with activin A in vitro increased both the number of oogonia present and oogonial proliferation, as detected by bromodeoxyuridine (BrdU) incorporation. These data indicate that activin may be involved in the autocrine and paracrine regulation of germ cell proliferation in the human ovary during the crucial period of development leading up to primordial follicle formation. PMID:14738881

  12. Neuroendocrine regulation of Drosophila metamorphosis requires TGFbeta/Activin signaling.

    PubMed

    Gibbens, Ying Y; Warren, James T; Gilbert, Lawrence I; O'Connor, Michael B

    2011-07-01

    In insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGF?/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGF?/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla. PMID:21613324

  13. Bone morphogenetic protein 2 acts via inhibitor of DNA binding proteins to synergistically regulate follicle-stimulating hormone beta transcription with activin A.

    PubMed

    Ho, Catherine C; Bernard, Daniel J

    2010-07-01

    We recently reported that bone morphogenetic proteins (BMPs) 2 and 4 can stimulate FSHbeta-subunit (Fshb) transcription alone and in synergy with activins. We further showed that BMP2 signals via the BMP type IA receptor (or activin receptor-like kinase 3) to mediate its effects. However, the intracellular mechanisms through which BMP2 regulates Fshb are unknown. In the current study, we used cDNA microarray analyses (and validation by real-time quantitative RT-PCR) to identify BMP2 target genes in the murine gonadotrope cell line, LbetaT2. Short-interfering RNA-mediated knockdown, overexpression, and coimmunoprecipitation experiments were used to examine the potential functional roles of selected gene products. Quantitative RT-PCR analysis largely confirmed the results of the array analyses, and inhibitors of DNA binding 1, 2, and 3 (Id1, Id2, and Id3) were selected for functional analyses. Knockdown of endogenous Id2 or Id3, but not Id1, diminished the synergistic effects of BMP2 and activin A on Fshb transcription. Overexpression of Id1, Id2, or Id3 alone had no effect, but all three potentiated activin A or mothers against decapentaplegic homolog (SMAD)3 induction of Fshb transcription. Though the precise mechanism through which Ids produce their effects are not yet known, we observed physical interactions between Id1, Id2, or Id3 and SMAD3. Collectively, the data suggest that BMP2 synergistically regulates Fshb transcription with activins, at least in part, through the combined actions of Ids 2 or 3 and SMAD3. PMID:20463050

  14. Soluble HLA-G serum levels depend on allergy type and IgE levels

    PubMed Central

    DeAmici, Mara

    2014-01-01

    Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. Two different studies evidenced that both patients with seasonal AR (SAR) and patients with perennial AR (PAR) had higher sHLA-G levels than normal controls. The aim of this study was to compare sHLA-G serum levels in SAR and PAR patients, also considering allergen-specific IgE. One hundred sixty-eight AR patients were enrolled, 94 with SAR and 74 with PAR. A group of 116 healthy subjects was considered as control. sHLA-G and allergen-specific IgE serum levels were determined by immunoenzymatic method. SAR patients had significantly higher levels of sHLA-G than PAR patients (p = 0.0194). sHLA-G was moderately related to allergen-specific IgE both in SAR (r = 0.497) and in PAR patients (r = 0.584). The present study provides evidence that sHLA-G serum levels depend on the type of allergy and are related to allergen-specific IgE serum levels. These findings may suggest that sHLA-G could be a biomarker of allergic reaction. PMID:24612937

  15. Soluble HLA-G serum levels depend on allergy type and IgE levels.

    PubMed

    Ciprandi, Giorgio; DeAmici, Mara

    2014-03-01

    Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. Two different studies evidenced that both patients with seasonal AR (SAR) and patients with perennial AR (PAR) had higher sHLA-G levels than normal controls. The aim of this study was to compare sHLA-G serum levels in SAR and PAR patients, also considering allergen-specific IgE. One hundred sixty-eight AR patients were enrolled, 94 with SAR and 74 with PAR. A group of 116 healthy subjects was considered as control. sHLA-G and allergen-specific IgE serum levels were determined by immunoenzymatic method. SAR patients had significantly higher levels of sHLA-G than PAR patients (p = 0.0194). sHLA-G was moderately related to allergen-specific IgE both in SAR (r = 0.497) and in PAR patients (r = 0.584). The present study provides evidence that sHLA-G serum levels depend on the type of allergy and are related to allergen-specific IgE serum levels. These findings may suggest that sHLA-G could be a biomarker of allergic reaction. PMID:24612937

  16. 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

  17. Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus.

    PubMed

    Tan, Kathryn C B; Shiu, Sammy W M; Wong, Ying; Leng, Lin; Bucala, Richard

    2008-07-01

    The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). We have determined serums LOX-1 in type 2 diabetes and evaluated the effect of glucose and advanced glycation end products (AGEs) on sLOX-1 in vitro and in vivo. Endothelial cells were incubated with glucose or AGEs, and sLOX-1 in cell medium was measured. Serum sLOX-1 was measured in 219 diabetic patients and 187 controls by ELISA. The effect of lowering glucose and AGEs on sLOX-1 was determined in 38 poorly controlled diabetic patients after improvement in glycemic control. Incubation of endothelial cells with AGE-BSA led to a dose-dependent increase in sLOX-1, whereas the effect of glucose on sLOX-1 was less marked. Serum sLOX-1 was 9% higher in diabetic patients compared with controls (P<0.01). In the poorly controlled patients, serum sLOX-1 decreased by 12.5% after improvement in glycemic control (P<0.05). The magnitude of reduction in sLOX-1 correlated with the improvement in hemoglobin A1c and AGEs but not with the reduction in oxidized LDL. sLOX-1 level is increased in type 2 diabetes. Both glucose and AGEs are important determinants of LOX-1 expression, and lowering glucose and AGEs leads to a reduction in sLOX-1. PMID:18408244

  18. Poly(Pyridinium Phenylene)s: Water-Soluble N-Type Polymers

    E-print Network

    Swager, Timothy Manning

    Poly(pyridinium phenylene) conjugated polymers are synthesized by a cross-coupling and cyclization sequence. These polyelectrolytes are freely soluble in water and display high degrees of electroactivity. When reduced ...

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

    E-print Network

    Ibáñez, Carlos

    , while activin A displayed the opposite effects. The downstream mediator Smad3 responded preferentially distinct signal- ling effects of the two activins. In line with this, overexpres- sion of Smad3]. The best known signalling pathway downstream of TGF- superfamily receptors in- volves phosphorylation

  20. Soluble IFN receptor potentiates in vivo type I IFN signaling and exacerbates TLR4-mediated septic shock.

    PubMed

    Samarajiwa, Shamith A; Mangan, Niamh E; Hardy, Matthew P; Najdovska, Meri; Dubach, Daphne; Braniff, Susie-Jane; Owczarek, Catherine M; Hertzog, Paul J

    2014-05-01

    Circulating levels of a soluble type I IFNR are elevated in diseases, such as chronic inflammation, infections, and cancer, but whether it functions as an antagonist, agonist, or transporter is unknown. In this study, we elucidate the in vivo importance of the soluble type I IFNAR, soluble (s)IFNAR2a, which is generated by alternative splicing of the Ifnar2 gene. A transgenic mouse model was established to mimic the 10-15-fold elevated expression of sIFNAR2a observed in some human diseases. We generated transgenic mouse lines, designated SolOX, in which the transgene mRNA and protein-expression patterns mirrored the expression patterns of the endogenous gene. SolOX were demonstrated to be more susceptible to LPS-mediated septic shock, a disease model in which type I IFN plays a crucial role. This effect was independent of "classical" proinflammatory cytokines, such as TNF-? and IL-6, whose levels were unchanged. Because the increased levels of sIFNAR2a did not affect the kinetics of the increased interferonemia, this soluble receptor does not potentiate its ligand signaling by improving IFN pharmacokinetics. Mechanistically, increased levels of sIFNAR2a are likely to facilitate IFN signaling, as demonstrated in spleen cells overexpressing sIFNAR2a, which displayed quicker, higher, and more sustained activation of STAT1 and STAT3. Thus, the soluble IFNR is an important agonist of endogenous IFN actions in pathophysiological processes and also is likely to modulate the therapeutic efficacy of clinically administered IFNs. PMID:24696235

  1. Safety and toxicological evaluation of a novel, water-soluble undenatured type II collagen.

    PubMed

    Yoshinari, Orie; Marone, Palma Ann; Moriyama, Hiroyoshi; Bagchi, Manashi; Shiojima, Yoshiaki

    2013-09-01

    This study was conducted to determine the broad-spectrum safety of a novel, water-soluble undenatured type II collagen (NEXT-II) derived from chicken sternum cartilage. The presence of epitope in NEXT-II was confirmed by using a commercial kit. The acute oral LD?? of NEXT-II was found to be greater than 5000?mg/kg bw in rats, while the single-dose acute dermal LD?? was greater than 2000?mg/kg bw. The primary dermal irritation index (PDII) of NEXT-II was found to be 1.8 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score (MMTS) of NEXT-II was observed to be 7.3 and classified as minimally irritating to the eye. Long-term safety studies were conducted in dogs over a period of 150?d, and no significant changes were observed in body weight, heart rate, respiration rate and blood chemistry. NEXT-II does not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Furthermore, two experiments were conducted to assess the potential of NEXT-II to induce mutations with and without metabolic activation at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. No biologically relevant increase of mutants was observed. Also, no dose-dependent toxicity was observed. Furthermore, colony sizing showed no clastogenic effects induced by NEXT-II under the experimental conditions. These studies demonstrated the broad spectrum of safety of NEXT-II. PMID:23477501

  2. 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.

  3. Hydrogen Peroxide Enhances Shedding of Type I Soluble Tumor Necrosis Factor Receptor from Pulmonary Epithelial Cells

    Microsoft Academic Search

    Toshihiko Hino; Hidenori Nakamura; Shuichi Abe; Hiroshi Saito; Minoru Inage; Kyoko Terashita; Shuichi Kato; Hitonobu Tomoike

    1999-01-01

    Reactive oxygen intermediates (ROIs) are among the important mediators in the pathogenesis of lung dis- eases in which tumor necrosis factor (TNF) plays a pivotal role. However, the effects of ROIs on the TNF- TNF receptor system remain unclear. Effects of hydrogen peroxide on the shedding of soluble tumor necrosis factor receptor (sTNF-R) were investigated in a pulmonary epithelial cell

  4. Constitutively Active FOXO1 Diminishes Activin Induction of Fshb Transcription in Immortalized Gonadotropes

    PubMed Central

    Park, Chung Hyun; Skarra, Danalea V.; Rivera, Alissa J.; Arriola, David J.; Thackray, Varykina G.

    2014-01-01

    In the present study, we investigate whether the FOXO1 transcription factor modulates activin signaling in pituitary gonadotropes. Our studies show that overexpression of constitutively active FOXO1 decreases activin induction of murine Fshb gene expression in immortalized L?T2 cells. We demonstrate that FOXO1 suppression of activin induction maps to the ?304/?95 region of the Fshb promoter containing multiple activin response elements and that the suppression requires the FOXO1 DNA-binding domain (DBD). FOXO1 binds weakly to the ?125/?91 region of the Fshb promoter in a gel-shift assay. Since this region of the promoter contains a composite SMAD/FOXL2 binding element necessary for activin induction of Fshb transcription, it is possible that FOXO1 DNA binding interferes with SMAD and/or FOXL2 function. In addition, our studies demonstrate that FOXO1 directly interacts with SMAD3/4 but not SMAD2 in a FOXO1 DBD-dependent manner. Moreover, we show that SMAD3/4 induction of Fshb-luc and activin induction of a multimerized SMAD-binding element-luc are suppressed by FOXO1 in a DBD-dependent manner. These results suggest that FOXO1 binding to the proximal Fshb promoter as well as FOXO1 interaction with SMAD3/4 proteins may result in decreased activin induction of Fshb in gonadotropes. PMID:25423188

  5. Role of activins and inducible nitric oxide in the pathogenesis of ectopic pregnancy in patients with or without Chlamydia trachomatis infection.

    PubMed

    Refaat, Bassem; Al-Azemi, Majedah; Geary, Ian; Eley, Adrian; Ledger, William

    2009-10-01

    Chlamydia trachomatis infection can lead to pelvic inflammatory disease, ectopic pregnancy (EP), infertility, and chronic pelvic pain in women. Activins and inducible nitric oxide synthase (iNOS) are produced by the human fallopian tube, and we speculate that tubal activins and iNOS may be involved in the immune response to C. trachomatis in humans and their pathological alteration may result in tubal pathology and the development of EP. Blood and fallopian tubes were collected from 14 women with EP. Sera were analyzed by enzyme-linked immunosorbent assay to detect antibodies against chlamydial heat shock protein 60 (chsp60) and the major outer membrane protein of C. trachomatis. Confirmation of C. trachomatis serology was made using the microimmunofluorescence test. The patients were classified into three groups according to their serological results, and immunohistochemistry and quantitative reverse transcription-PCR were performed to investigate the expression of candidate molecules by tubal epithelial cells among the three groups. This is the first study to show an increase in the expression of activin betaA subunit, type II receptors, follistatin, and iNOS within the human fallopian tube of EP patients who were serologically positive for C. trachomatis. A similar expression profile was observed in the fallopian tubes with detectable antibodies only against chsp60. These results were shown at the mRNA and protein levels. We suggest that tubal activin A, its type II receptors, follistatin, and NO could be involved in the microbial-mediated immune response within the fallopian tube, and their pathological expression may lead to tubal damage and the development of EP. PMID:19692623

  6. Association of soluble epoxide hydrolase gene polymorphism with insulin resistance in type 2 diabetic patients

    Microsoft Academic Search

    Kentaro Ohtoshi; Hideaki Kaneto; Koichi Node; Yumiko Nakamura; Toshihiko Shiraiwa; Munehide Matsuhisa; Yoshimitsu Yamasaki

    2005-01-01

    The insulin resistance found in diabetes is influenced by vascular tone and local blood flow. Endothelial-derived hyperpolarizing factor (EDHF) functions as a potent vasodilator to regulate vascular tone, and its production is regulated by soluble epoxide hydrolase (sEH). In this study, we examined the genotype distribution and allele frequency of sEH gene G860A (Arg287Gln) polymorphism in Japanese subjects (n=499) (non-diabetic

  7. Activin receptor signaling regulates cocaine-primed behavioral and morphological plasticity.

    PubMed

    Gancarz, Amy M; Wang, Zi-Jun; Schroeder, Gabrielle L; Damez-Werno, Diane; Braunscheidel, Kevin M; Mueller, Lauren E; Humby, Monica S; Caccamise, Aaron; Martin, Jennifer A; Dietz, Karen C; Neve, Rachael L; Dietz, David M

    2015-07-01

    Activin receptor signaling, including the transcription factor Smad3, was upregulated in the rat nucleus accumbens (NAc) shell following withdrawal from cocaine. Direct genetic and pharmacological manipulations of this pathway bidirectionally altered cocaine seeking while governing morphological plasticity in NAc neurons. Thus, Activin/Smad3 signaling is induced following withdrawal from cocaine, and such regulation may be a key molecular mechanism underlying behavioral and cellular plasticity in the brain following cocaine self-administration. PMID:26030849

  8. 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

  9. Characterization of the soluble domain of the ABC7 type transporter Atm1.

    PubMed

    Chen, Chun-An; Cowan, J A

    2003-12-26

    Atm1 is an ABC transporter that is located in yeast mitochondria and has previously been implicated in the maturation of cytosolic iron-sulfur cluster proteins. The soluble nucleotide binding domain of Atm1 (Atm1-C) has been overexpressed in Escherichia coli, purified, and characterized. Dissociation constants (KD) for Atm1-C binding of ATP (KD approximately 97 microm, pH 7.3, and approximately 102 microm, pH 10.0) and ADP (KD approximately 43 microm, pH 7.3, and 92 microm, pH 10.0) were measured by fluorimetry. The higher binding affinity for ADP suggests that the transmembrane-spanning domain may be required to promote a structural change in the nucleotide binding domain to facilitate substrate export and ADP release. ADP also had an inhibitory effect on Atm1-C with an IC50 of 10 mm. The Michaelis-Menten constants Vmax, KM, and kcat of Atm1-C were measured as 1.822 microm min(-1), 513 microm, and 0.055 min(-1), respectively. The metal dependence of Atm1-C ATPase demonstrated a reactivity order of Mn2+ > Mg2+ > Co2+, while Mg2+ and Co2+ were both found to be inhibitory at higher concentrations. The pH profile and structural comparison with HisP are consistent with a role for His and Lys in promoting the ATPase activity. Structural analysis of Atm1-C by CD spectroscopy suggested a similarity of secondary structure to that found for a prokaryotic homologue (HisP), whereas modeling of the Atm1-C tertiary structure using HisP as a template is also consistent with a similarity in tertiary structure. Atm1-C tends to form a dimer or higher aggregation state at higher concentration; however, the concentration dependence of Atm1-C on ATPase activity and the results of a Hill analysis (napp = 1.1) demonstrated that there was essentially no cooperativity in ATP hydrolysis, in contrast to observations for the prokaryotic HisP transporter, which demonstrated full cooperativity for both full-length and the soluble domains. Accordingly, any cooperative response must be mediated through the transmembrane domain in the case of the eukaryotic Atm1 transporter. PMID:14514697

  10. SLURP-1 Modulates Corneal Homeostasis by Serving as a Soluble Scavenger of Urokinase-Type Plasminogen Activator

    PubMed Central

    Swamynathan, Sudha; Swamynathan, Shivalingappa K.

    2014-01-01

    Purpose. Our previous study revealed the immunomodulatory property of the secreted lymphocyte antigen (Ly6)/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP1), abundantly expressed in the cornea and associated with the hyperkeratotic disorder Mal de Meleda. Here, we test the hypothesis that SLURP1 modulates the functions of membrane-tethered uPAR by acting as a soluble scavenger of its ligand urokinase-type plasminogen activator (uPA). Methods. Human corneal limbal epithelial (HCLE) and mouse corneal stromal fibroblast MK/T-1 cells were employed to examine the effect of SLURP1 on cell proliferation and migration. Human corneal limbal epithelial cell clones stably expressing SLURP1 under the control of cytomegalovirus (CMV) promoter were generated using lentiviral vectors. Recombinant 6× His-mouse Slurp1 and maltose-binding protein (MBP)-mouse uPA were expressed in Escherichia coli and partially purified using nickel-ion and amylose columns, respectively. Slurp1 interaction with uPA was detected using ligand blots, ELISA, pull-down assays, and immunofluorescent staining. Results. Stable expression of SLURP1 in HCLE cells was confirmed by immunoblots and immunofluorescent staining. Human corneal limbal epithelial and MK/T-1 cell proliferation and migration rates were suppressed by exogenous SLURP1. Ligand blots, ELISA, and pull-down assays indicated that Slurp1 efficiently interacts with uPA. Immunofluorescent staining demonstrated that exogenous SLURP1 decreased the amount of cell surface–bound uPA in the leading edges of migrating cells. In gap-filling assays, wild-type HCLE cells responded to uPA by increasing their velocity and closing larger area, while the SLURP1-expressing HCLE cells failed to do so. Conclusions. SLURP1 modulates corneal homeostasis by serving as a soluble scavenger of uPA and regulating the uPA-dependent functions of uPAR. PMID:25168896

  11. [The typing of tick-borne encephalitis virus strains by the soluble antigen].

    PubMed

    Zlobin, V I; Drokin, D A; Mansurov, P G; Kalmin, O B; Iakimenko, V V

    1991-01-01

    Sucrose-acetone-treated antigens (SAA) and soluble antigens (SA) prepared from them by treatment with 8 M urea for eight TBE virus strains isolated in different parts of the virus distribution area were studied in cross CFT with immune ascitic fluids (IAF) for these strains as well as for OHF and Powassan viruses. With SAA, the difference in titres with homologous and heterologous IAFs, as a rule, did not exceed twofold, whereas with SA was 32-fold. It was also noted that in the homologous system the titre of SA decreased not more than 4-fold as compared with that of the initial SAA while in the heterologous system it declined from 4- to 16-fold or more. The level of antigenic relationship of strains was expressed by the formula HAg = SA titre/SA titre X 100%. It was shown that at HAg greater than or equal to 25% the strains used for antigen and antibody generation were closely related and at HAg less than or equal to 6.25% belonged to different subtypes. The analysis of the data suggested the existence of a fourth, "Urals-Siberian" antigenic variant of TBE virus. Using the developed criteria, the 20 strains under study (with one exception) were alloted into one of the four antigenic variants or qualified as intermediate. PMID:1650063

  12. Novel oral formulation approach for poorly water-soluble drug using lipocalin-type prostaglandin D synthase.

    PubMed

    Mizoguchi, Masashi; Nakatsuji, Masatoshi; Inoue, Haruka; Yamaguchi, Keisuke; Sakamoto, Atsushi; Wada, Koichi; Inui, Takashi

    2015-07-10

    Lipocalin-type prostaglandin D synthase (L-PGDS), a member of the lipocalin superfamily, possesses the function of forming complexes together with various small lipophilic molecules. In this study, we chose telmisartan as a model drug due to its pH dependent poor water solubility, and developed and characterized a novel solubilized formulation of telmisartan using a complex formulation with L-PGDS. The solid state of the complex formulation was prepared using a spray-drying process. The spray-dried formulation of telmisartan/L-PGDS powder showed a typical spray-dried particle without any change in the secondary and tertiary structures of L-PGDS. Furthermore, the complex formulation showed a high rate and level of drug release in pH 1.2, 5.0, and 6.8 solutions in comparison with the active pharmaceutical ingredient (API) and commercial product. To validate the potential for oral administration of the telmisartan/L-PGDS complex in vivo, the pharmacokinetic and pharmacodynamic profiles were assessed in spontaneous hypertensive rats. An animal study revealed that the complex formulation led to a significant improvement of AUC and Cmax as compared with API, and the prolonged pharmacologic effect on blood pressure reduction was comparable with the commercial product. These results, taken together, demonstrate that this novel approach is feasible for the solubilized solid oral formulation and it can be applied to poorly water-soluble drugs to enhance oral bioavailability. PMID:25906910

  13. Serum activin A and B, and follistatin in critically ill patients with influenza A(H1N1) infection

    PubMed Central

    2014-01-01

    Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P?>?0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P?

  14. Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells.

    PubMed

    Fukuchi, Y; Kizaki, M; Yamato, K; Kawamura, C; Umezawa, A; Hata Ji; Nishihara, T; Ikeda, Y

    2001-02-01

    Activin A, one member of the transforming growth factor (TGF)-beta superfamily, is known to be a commitment factor for cell death and differentiation. In the present study, we demonstrate that human chronic myeloid leukemia (CML) cell lines, KU812 and K562 cells, either induced apoptosis or differentiation, respectively, by treatment with activin A. During these cell fate decisive events caused by activin A, rapid and transient up-regulation of Mcl-1 was observed in both cell lines. In activin A-induced apoptosis of KU812 cells, continuous up-regulation of Bax was observed. After the decrease in Mcl-1 expression had occurred, activation of caspase-9 and caspase-3 and cleavage of DFF45 were shown to take place in KU812 cells, resulting in the fragmentation of the genomic DNA of the cells. In contrast, the down-regulation of Mcl-1 without up-regulation of Bax caused accumulation of hemoglobin (Hb) contents in activin A-treated K562 cells. Interestingly, erythropoietin (EPO) prevented activin A-induced apoptosis with continuous expression of Mcl-1 and caused KU812 cells to undergo erythroid differentiation. To address the role of Mcl-1 in activin A-treated CML cells, KU812 and K562 cells were stably transfected with cDNA encoding Mcl-1 (designated as KU812/mcl and K562/mcl cells). As in combined effect of activin A and EPO on the parental KU812 cells, activin A induced differentiation, but not apoptosis, of KU812/mcl cells without modulating Bax levels. Activin A-treated K562/mcl cells, as well as parental cells, were only differentiated to erythroid cells. These results suggest that Mcl-1 is an early inducible gene activated by the activin A signaling pathway for both cellular differentiation and apoptosis, and continuous expression of Mcl-1 may be contributed to differentiation signals to the erythroid lineage in CML cells. PMID:11314004

  15. Runt-related transcription factors impair activin induction of the follicle-stimulating hormone {beta}-subunit gene.

    PubMed

    Breen, Kellie M; Thackray, Varykina G; Coss, Djurdjica; Mellon, Pamela L

    2010-06-01

    Synthesis of the FSH beta-subunit (FSHbeta) is critical for normal reproduction in mammals, and its expression within the pituitary gonadotrope is tightly regulated by activin. Here we show that Runt-related (RUNX) proteins, transcriptional regulators known to interact with TGFbeta signaling pathways, suppress activin induction of FSHbeta gene expression. Runx2 is expressed within the murine pituitary gland and dramatically represses activin-induced FSHbeta promoter activity, without affecting basal expression in LbetaT2 cells, an immortalized mouse gonadotrope cell line. This repressive effect is specific, because RUNX2 induces LHbeta transcription (with or without activin) and does not interfere with GnRH induction of either gonadotropin beta-subunit gene. Analysis of the murine FSHbeta promoter by transfection and gel shift assays reveals that RUNX2 repression localizes to a Runx-binding element at -159/-153, which is adjacent to a previously recognized region critical for activin induction. Mutation of this -153 activin-response element or, indeed, any of the five activin-responsive regions prevents activin induction and, in fact, RUNX2 suppression, instead converting RUNX2 to an activator of the FSHbeta gene. Although the Runx-binding element is required for RUNX2-mediated repression of FSHbeta induction by either activin or Smad3, confirming a functional role of this novel site, protein interactions in addition to those between RUNX2 and Smads are necessary to account for full repression of activin induction. In summary, the present study provides evidence for Runx2-mediated repression of activin-induced FSHbeta gene expression and reveals the context dependence of Runx2 action in hormonal regulation of the gonadotropin genes. PMID:20357224

  16. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine ?-thalassemia

    PubMed Central

    Suragani, Rajasekhar N. V. S.; Cawley, Sharon M.; Li, Robert; Wallner, Samantha; Alexander, Mark J.; Mulivor, Aaron W.; Gardenghi, Sara; Rivella, Stefano; Grinberg, Asya V.; Pearsall, R. Scott

    2014-01-01

    In ?-thalassemia, unequal production of ?- and ?-globin chains in erythroid precursors causes apoptosis and inhibition of late-stage erythroid differentiation, leading to anemia, ineffective erythropoiesis (IE), and dysregulated iron homeostasis. Here we used a murine model of ?-thalassemia intermedia (Hbbth1/th1 mice) to investigate effects of a modified activin receptor type IIB (ActRIIB) ligand trap (RAP-536) that inhibits Smad2/3 signaling. In Hbbth1/th1 mice, treatment with RAP-536 reduced overactivation of Smad2/3 in splenic erythroid precursors. In addition, treatment of Hbbth1/th1 mice with RAP-536 reduced ?-globin aggregates in peripheral red cells, decreased the elevated reactive oxygen species present in erythroid precursors and peripheral red cells, and alleviated anemia by promoting differentiation of late-stage erythroid precursors and reducing hemolysis. Notably, RAP-536 treatment mitigated disease complications of IE, including iron overload, splenomegaly, and bone pathology, while reducing erythropoietin levels, improving erythrocyte morphology, and extending erythrocyte life span. These results implicate signaling by the transforming growth factor-? superfamily in late-stage erythropoiesis and reveal potential of a modified ActRIIB ligand trap as a novel therapeutic agent for thalassemia syndrome and other red cell disorders characterized by IE. PMID:24795345

  17. Xenopus axis formation: induction of goosecoid by injected Xwnt-8 and activin mRNAs.

    PubMed

    Steinbeisser, H; De Robertis, E M; Ku, M; Kessler, D S; Melton, D A

    1993-06-01

    In this study, we compare the effects of three mRNAs-goosecoid, activin and Xwnt-8- that are able to induce partial or complete secondary axes when injected into Xenopus embryos. Xwnt-8 injection produces complete secondary axes including head structures whereas activin and goosecoid injection produce partial secondary axes at high frequency that lack head structures anterior to the auditory vesicle and often lack notochord. Xwnt-8 can activate goosecoid only in the deep marginal zone, i.e., in the region in which this organizer-specific homeobox gene is normally expressed on the dorsal side. Activin B mRNA, however, can turn on goosecoid in all regions of the embryo. We also tested the capacity of these gene products to restore axis formation in embryos in which the cortical rotation was blocked by UV irradiation. Whereas Xwnt-8 gives complete rescue of anterior structures, both goosecoid and activin give partial rescue. Rescued axes including hindbrain structures up to level of the auditory vesicle can be obtained at high frequency even in the absence of notochord structures. The possible functions of Wnt-like and activin-like signals and of the goosecoid homeobox gene, and their order of action in the formation of Spemann's organizer are discussed. PMID:7900991

  18. Activin A stimulates mouse macrophages to express APRIL via the Smad3 and ERK\\/CREB pathways

    Microsoft Academic Search

    Hwa-Joung Lee; Goo-Young Seo; Jae-Hee Kim; Mi-Ra Lee; Pyeung-Hyeun Kim

    2011-01-01

    A proliferation-inducing ligand (APRIL) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we investigated the role and signaling mechanisms of activin A in APRIL expression by mouse macrophages. Activin A markedly enhanced APRIL expression in mouse macrophages at both the transcriptional and protein levels. Overexpression of

  19. Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells

    Microsoft Academic Search

    Yumi Fukuchi; Masahiro Kizaki; Kenji Yamato; Chiharu Kawamura; Akihiro Umezawa; Jun-ichi Hata; Tatsuji Nishihara; Yasuo Ikeda

    2001-01-01

    Activin A, one member of the transforming growth factor (TGF)-? superfamily, is known to be a commitment factor for cell death and differentiation. In the present study, we demonstrate that human chronic myeloid leukemia (CML) cell lines, KU812 and K562 cells, either induced apoptosis or differentiation, respectively, by treatment with activin A. During these cell fate decisive events caused by

  20. Soluble ?-Klotho as a Novel Biomarker in the Early Stage of Nephropathy in Patients with Type 2 Diabetes

    PubMed Central

    Lee, Ji-Sung; Kim, In Joo; Song, Sang Heon; Cha, Seung-Kuy; Park, Kyu-Sang; Kang, Jeong Suk; Chung, Choon Hee

    2014-01-01

    Objective Although ?-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble ?-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary ?-klotho levels are associated with albuminuria in kidney disease in diabetes. Research Design and Methods A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of ?-klotho were analyzed by enzyme-linked immunosorbent assay. Results Plasma ?-klotho (572.4 pg/mL [95% CI, 541.9–604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9–545.5 pg/mL]) and urinary ?-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6–82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7–45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma ?-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9–659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5–608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7–581.7 pg/mL] (p for trend ?=?0.0081), while urinary ?-klotho levels were remained constantly high with increasing urinary albumin excretion. Conclusions Soluble ?-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury. PMID:25084095

  1. The Association of Soluble IGF2R and IGF2R Gene Polymorphism with Type 2 Diabetes

    PubMed Central

    Chanprasertyothin, Suwannee; Jongjaroenprasert, Wallaya

    2015-01-01

    The aim of this study is to investigate the insulin-like growth factor type 2 (IGF2R) gene and circulating soluble IGF2R in relation to type 2 diabetes (T2DM). Six hundred fifty-four subjects without history of diabetes were screened for diabetes by oral glucose tolerance test. In addition, 145 subjects with known diabetes were recruited from a local diabetes clinic. Circulating IGF2R levels were measured by ELISA method; plasma glucose was measured by colorimetric method; insulin levels were determined by chemiluminescent method; IGF2R gene rs416572 was genotyped using real-time PCR. The distributions of IGF2R genotypes were 69.2% CC, 27.8% CT, and 3.0% TT. The C allele was more commonly found in diabetes subjects, with a significant difference (P < 0.01). In the presence of the T allele, circulating IGF2R levels were significantly lower (P < 0.05). There was no significant difference in other potential confounders including age, sex, and BMI. Only circulating IGF2R, age, and BMI were independently associated with the degree of insulin resistance, as assessed by the HOMA model. It was found that age, sex, and BMI were associated with beta cell function. In conclusion, IGF2R gene polymorphism and circulating IGF2R are associated with T2DM. PMID:25922844

  2. Collaboration between a soluble C-type lectin and calreticulin facilitates white spot syndrome virus infection in shrimp.

    PubMed

    Wang, Xian-Wei; Xu, Yi-Hui; Xu, Ji-Dong; Zhao, Xiao-Fan; Wang, Jin-Xing

    2014-09-01

    White spot syndrome virus (WSSV) mainly infects crustaceans through the digestive tract. Whether C-type lectins (CLs), which are important receptors for many viruses, participate in WSSV infection in the shrimp stomach remains unknown. In this study, we orally infected kuruma shrimp Marsupenaeus japonicus to model the natural transmission of WSSV and identified a CL (designated as M. japonicus stomach virus-associated CL [MjsvCL]) that was significantly induced by virus infection in the stomach. Knockdown of MjsvCL expression by RNA interference suppressed the virus replication, whereas exogenous MjsvCL enhanced it. Further analysis by GST pull-down and coimmunoprecipitation showed that MjsvCL could bind to viral protein 28, the most abundant and functionally relevant envelope protein of WSSV. Furthermore, cell-surface calreticulin was identified as a receptor of MjsvCL, and the interaction between these proteins was a determinant for the viral infection-promoting activity of MjsvCL. The MjsvCL-calreticulin pathway facilitated virus entry likely in a cholesterol-dependent manner. This study provides insights into a mechanism by which soluble CLs capture and present virions to the cell-surface receptor to facilitate viral infection. PMID:25070855

  3. Relationship of Soluble RAGE with Insulin Resistance and Beta Cell Function during Development of Type 2 Diabetes Mellitus

    PubMed Central

    Biswas, Subrata Kumar; Mohtarin, Sabreena; Mudi, Sonchita Rani; Anwar, Taznuva; Banu, Laila Anjuman; Alam, Sheikh Md. Khorshed; Fariduddin, Md.; Arslan, M. Iqbal

    2015-01-01

    This study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed T2DM. The control subjects (n = 40) and people with prediabetes (n = 52) and diabetes (n = 66) were similar in terms of age, sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found significantly higher in people with diabetes than control subjects (p < 0.001) and people with prediabetes (p = 0.005); and HOMA-%B was found significantly deteriorated in people with diabetes (p < 0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did not show any significant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate analyses did not identify any significant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM.

  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. Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate.

    PubMed

    Gokoffski, Kimberly K; Wu, Hsiao-Huei; Beites, Crestina L; Kim, Joon; Kim, Euiseok J; Matzuk, Martin M; Johnson, Jane E; Lander, Arthur D; Calof, Anne L

    2011-10-01

    Studies of the olfactory epithelium model system have demonstrated that production of neurons is regulated by negative feedback. Previously, we showed that a locally produced signal, the TGF? superfamily ligand GDF11, regulates the genesis of olfactory receptor neurons by inhibiting proliferation of the immediate neuronal precursors (INPs) that give rise to them. GDF11 is antagonized by follistatin (FST), which is also produced locally. Here, we show that Fst(-/-) mice exhibit dramatically decreased neurogenesis, a phenotype that can only be partially explained by increased GDF11 activity. Instead, a second FST-binding factor, activin ?B (ACT?B), inhibits neurogenesis by a distinct mechanism: whereas GDF11 inhibits expansion of INPs, ACT?B inhibits expansion of stem and early progenitor cells. We present data supporting the concept that these latter cells, previously considered two distinct types, constitute a dynamic stem/progenitor population in which individual cells alternate expression of Sox2 and/or Ascl1. In addition, we demonstrate that interplay between ACT?B and GDF11 determines whether stem/progenitor cells adopt a glial versus neuronal fate. Altogether, the data indicate that the transition between stem cells and committed progenitors is neither sharp nor irreversible and that GDF11, ACT?B and FST are crucial components of a circuit that controls both total cell number and the ratio of neuronal versus glial cells in this system. Thus, our findings demonstrate a close connection between the signals involved in the control of tissue size and those that regulate the proportions of different cell types. PMID:21852401

  6. Key role for activin B in cellular transformation after loss of the von Hippel-Lindau tumor suppressor.

    PubMed

    Wacker, Ingrid; Sachs, Martin; Knaup, Karl; Wiesener, Michael; Weiske, Jörg; Huber, Otmar; Akçetin, Ziya; Behrens, Jürgen

    2009-04-01

    The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor (HIF)-mediated gene transcription. Several VHL/HIF targets, such as glycolysis, angiogenesis, cell growth, and chemotaxis of tumor cells, have been implicated in the transformed phenotype of RCC-regulating properties. Here, we show that VHL suppresses key features of cell transformation through downregulation of the HIF-dependent expression of activin B, a member of the transforming growth factor beta superfamily. Activin B expression is repressed by restoration of VHL in VHL-deficient RCC cells and upregulated by hypoxia. RCC tumor samples show increased expression of activin B compared to that in the normal kidney. VHL increases cell adhesion to the extracellular matrix, promotes cell flattening, and reduces invasiveness. These effects are completely phenocopied by RNA interference-mediated knockdown of activin B and reverted by treatment with recombinant activin B. Finally, knockdown of activin B reduces tumor growth of RCC cells in nude mice. Our data indicate that activin B is a key mediator of VHL/HIF-induced transformation in RCC. PMID:19158274

  7. Key Role for Activin B in Cellular Transformation after Loss of the von Hippel-Lindau Tumor Suppressor ? †

    PubMed Central

    Wacker, Ingrid; Sachs, Martin; Knaup, Karl; Wiesener, Michael; Weiske, Jörg; Huber, Otmar; Akçetin, Ziya; Behrens, Jürgen

    2009-01-01

    The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor (HIF)-mediated gene transcription. Several VHL/HIF targets, such as glycolysis, angiogenesis, cell growth, and chemotaxis of tumor cells, have been implicated in the transformed phenotype of RCC-regulating properties. Here, we show that VHL suppresses key features of cell transformation through downregulation of the HIF-dependent expression of activin B, a member of the transforming growth factor ? superfamily. Activin B expression is repressed by restoration of VHL in VHL-deficient RCC cells and upregulated by hypoxia. RCC tumor samples show increased expression of activin B compared to that in the normal kidney. VHL increases cell adhesion to the extracellular matrix, promotes cell flattening, and reduces invasiveness. These effects are completely phenocopied by RNA interference-mediated knockdown of activin B and reverted by treatment with recombinant activin B. Finally, knockdown of activin B reduces tumor growth of RCC cells in nude mice. Our data indicate that activin B is a key mediator of VHL/HIF-induced transformation in RCC. PMID:19158274

  8. Water-soluble LYNX1 Residues Important for Interaction with Muscle-type and/or Neuronal Nicotinic Receptors*

    PubMed Central

    Lyukmanova, Ekaterina N.; Shulepko, Mikhail A.; Buldakova, Svetlana L.; Kasheverov, Igor E.; Shenkarev, Zakhar O.; Reshetnikov, Roman V.; Filkin, Sergey Y.; Kudryavtsev, Denis S.; Ojomoko, Lucy O.; Kryukova, Elena V.; Dolgikh, Dmitry A.; Kirpichnikov, Mikhail P.; Bregestovski, Piotr D.; Tsetlin, Victor I.

    2013-01-01

    Human LYNX1, belonging to the Ly6/neurotoxin family of three-finger proteins, is membrane-tethered with a glycosylphosphatidylinositol anchor and modulates the activity of nicotinic acetylcholine receptors (nAChR). Recent preparation of LYNX1 as an individual protein in the form of water-soluble domain lacking glycosylphosphatidylinositol anchor (ws-LYNX1; Lyukmanova, E. N., Shenkarev, Z. O., Shulepko, M. A., Mineev, K. S., D'Hoedt, D., Kasheverov, I. E., Filkin, S. Y., Krivolapova, A. P., Janickova, H., Dolezal, V., Dolgikh, D. A., Arseniev, A. S., Bertrand, D., Tsetlin, V. I., and Kirpichnikov, M. P. (2011) NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J. Biol. Chem. 286, 10618–10627) revealed the attachment at the agonist-binding site in the acetylcholine-binding protein (AChBP) and muscle nAChR but outside it, in the neuronal nAChRs. Here, we obtained a series of ws-LYNX1 mutants (T35A, P36A, T37A, R38A, K40A, Y54A, Y57A, K59A) and examined by radioligand analysis or patch clamp technique their interaction with the AChBP, Torpedo californica nAChR and chimeric receptor composed of the ?7 nAChR extracellular ligand-binding domain and the transmembrane domain of ?1 glycine receptor (?7-GlyR). Against AChBP, there was either no change in activity (T35A, T37A), slight decrease (K40A, K59A), and even enhancement for the rest mutants (most pronounced for P36A and R38A). With both receptors, many mutants lost inhibitory activity, but the increased inhibition was observed for P36A at ?7-GlyR. Thus, there are subtype-specific and common ws-LYNX1 residues recognizing distinct targets. Because ws-LYNX1 was inactive against glycine receptor, its “non-classical” binding sites on ?7 nAChR should be within the extracellular domain. Micromolar affinities and fast washout rates measured for ws-LYNX1 and its mutants are in contrast to nanomolar affinities and irreversibility of binding for ?-bungarotoxin and similar snake ?-neurotoxins also targeting ?7 nAChR. This distinction may underlie their different actions, i.e. nAChRs modulation versus irreversible inhibition, for these two types of three-finger proteins. PMID:23585571

  9. Activin Regulation of the Follicle-Stimulating Hormone -Subunit Gene Involves Smads and the

    E-print Network

    Mellon, Pamela L.

    . Consensus DNA-binding sequences for Smad2/4 and Smad3/4 complexes have been identified, which contain the palindrome GTCTAGAC, half-sites of this sequence, or CAGA motifs (6­9). Smad3/4 complexes are capa- ble family members, activin signals through receptor serine/threonine kinases, which, in turn, phosphorylate

  10. Activin Regulates Luteinizing Hormone -Subunit Gene Expression through Smad-Binding and

    E-print Network

    Mellon, Pamela L.

    Activin Regulates Luteinizing Hormone -Subunit Gene Expression through Smad-Binding and Homeobox within 24 h after dispersion in culture. Fur- thermore, male mice deficient in Smad3, and there- fore growth response (Egr) site found in this region of the promoter. Juxta- posed to the HB are three Smad

  11. Roles of Inhibins, Activins, and Follistatin in the Female Reproductive System

    Microsoft Academic Search

    P. G. Knight

    1996-01-01

    Some 10 years have elapsed since inhibins were first isolated from ovarian follicular fluid and characterized as disulphide-linked dimeric glycoproteins capable of selectively suppressing the synthesis and secretion of follicle-stimulating hormone (FSH) by pituitary gonadotropes. There have been numerous surprises subsequent to this breakthrough, including the discovery and molecular characterization of activins and follistatins, proteins which share with inhibin an

  12. Evaluation of soluble CD200 levels in type 2 diabetic foot and nephropathic patients: Association with disease activity

    PubMed Central

    Arik, Hasan Onur; Yalcin, Arzu Didem; Celik, Betul; Seyman, Derya; Tetik, Gulsum; Gursoy, Bensu; Kose, Sukran; Gumuslu, Saadet

    2014-01-01

    Background CD200 (OX-2) is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum (s OX-2), which acts to regulate inflammatory and acquired immune responses. Material/Methods We planned this study to evaluate the sOX-2 levels of type 2 diabetic foot (group B), and compare it with that of healthy controls (group A). The patient group had the following values: DM period: 27.9±10.3 year [mean ±SD], HbA1c: 9.52±2.44% [mean ±SD]. Results Blood samples for sCD200 measurement were always taken in the morning between 8 and 10 A.M.. The results were reported as means of duplicate measurements. Concentrations of sOX-2 in the serum samples were quantified using an ELISA kit. Serum hs-CRP levels were measured using an hs-CRP assay kit. The sOX-2 level in group B was 173.8±3.1 and in group A was 70.52±1.2 [p<0.0001). In subgroup analysis of T2DM-DFI patients, we noticed that sOX-2 levels were higher in WGS (Wagner grading system) I and II patients than in WGS III and IV patients. The HbA1c, BUN, creatinine, hs-CRP levels, and sedimentation rates were higher in the patient group (p<0.0001, p<0.001, p<0.001, p<0.005, and p<0.0001, respectively). Conclusions We suggest that there are vascular, immunologic, and neurologic components in DFI, whereas autoimmune diseases and inflammatory skin disorders have only an immunologic component. This is possibly evidence of a pro-inflammatory effect seen in DFI as a vascular complication. PMID:24964809

  13. Effect of type of fiber, site of fermentation, and method of analysis on digestibility of soluble and insoluble fiber in rabbits.

    PubMed

    Abad-Guamán, R; Carabaño, R; Gómez-Conde, M S; García, J

    2015-06-01

    The effect of type of fiber, site of fermentation, method for quantifying insoluble and soluble dietary fiber, and their correction for intestinal mucin on fiber digestibility were examined in rabbits. Three diets differing in soluble fiber were formulated (8.5% soluble fiber, on DM basis, in the low soluble fiber [LSF] diet; 10.2% in the medium soluble fiber [MSF] diet; and 14.5% in the high soluble fiber [HSF] diet). They were obtained by replacing half of the dehydrated alfalfa in the MSF diet with a mixture of beet and apple pulp (HSF diet) or with a mix of oat hulls and soybean protein (LSF diet). Thirty rabbits with ileal T-cannulas were used to determine ileal and fecal digestibility. Cecal digestibility was determined by difference between fecal and ileal digestibility. Insoluble fiber was measured as NDF, insoluble dietary fiber (IDF), and in vitro insoluble fiber, whereas soluble fiber was calculated as the difference between total dietary fiber (TDF) and NDF (TDF-NDF), IDF (TDF-IDF), and in vitro insoluble fiber (TDF-in vitro insoluble fiber). The intestinal mucin content was used to correct the TDF and soluble fiber digestibility. Ileal and fecal concentration of mucin increased from the LSF to the HSF diet group ( < 0.01). Once corrected for intestinal mucin, ileal and fecal digestibility of TDF and soluble fiber increased whereas cecal digestibility decreased ( < 0.01). Ileal digestibility of TDF increased from the LSF to the HSF diet group (12.0 vs. 28.1%; < 0.01), with no difference in the cecum (26.4%), resulting in a higher fecal digestibility from the LSF to the HSF diet group ( < 0.01). Ileal digestibility of insoluble fiber increased from the LSF to the HSF diet group (11.3 vs. 21.0%; < 0.01), with no difference in the cecum (13.9%) and no effect of fiber method, resulting in a higher fecal digestibility for rabbits fed the HSF diet compared with the MSF and LSF diet groups ( < 0.01). Fecal digestibility of NDF was higher compared with IDF or in vitro insoluble fiber ( < 0.01). Ileal soluble fiber digestibility was higher for the HSF than for the LSF diet group (43.6 vs. 14.5%; < 0.01) and fiber method did not affect it. Cecal soluble fiber digestibility decreased from the LSF to the HSF diet group (72.1 vs. 49.2%; < 0.05). The lowest cecal and fecal soluble fiber digestibility was measured using TDF-NDF ( < 0.01). In conclusion, a correction for intestinal mucin is necessary for ileal TDF and soluble fiber digestibility whereas the selection of the fiber method has a minor relevance. The inclusion of sugar beet and apple pulp increased the amount of TDF fermented in the small intestine. PMID:26115273

  14. 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

  15. Codon optimization of the human papillomavirus type 58 L1 gene enhances the expression of soluble L1 protein in Saccharomyces cerevisiae.

    PubMed

    Kim, Hyoung Jin; Kwag, Hye-Lim; Kim, Hong-Jin

    2013-03-01

    The effect of codon optimization of L1 gene on the production of the L1 protein of human papillomavirus (HPV) was investigated in a yeast expression system. Saccharomyces cerevisiae was transformed with a plasmid containing either the wild type (WS)-HPV type 58 L1 (HPV58 L1) gene or a codon-optimized (MO)-HPV58 L1 gene. The proportion of soluble L1 protein expressed from MO-HPV58 L1 was significantly higher than that expressed from WS-HPV58 L1. Moreover, the amount of purified MO-HPV58 L1 protein recovered was 2.5-fold higher than the amount of WS-HPV58 L1 protein. Codon optimization of HPV58 L1 gene thus increases the proportion of soluble L1 protein and the amount of purified product that can be used as antigen to generate vaccines. PMID:23183918

  16. 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

  17. Soluble and nuclear type I and II androgen-binding sites in benign hyperplasia and cancer of the human prostate

    Microsoft Academic Search

    L. Castagnetta; G. Carruba; E. Fecarotta; M. Lo Casto; R. Cusimano; M. Pavone-Macaluso

    1992-01-01

    This paper presents an approach for the assessment of the androgen receptor (AR) status in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues. Evaluation of AR was carried out in both soluble and nuclear fractions by a standard competition method, using tritiated mibolerone as radioligand. Based on our experience with breast and endometrial cancer, this approach focused on both

  18. Solubility study of Yb in n-type skutterudites YbxCo4Sb12 and their enhanced thermoelectric properties

    E-print Network

    Yang, J.

    The solubility of Yb in Yb[subscript x]Co[subscript 4]Sb[subscript 12 was reported to be 0.19 in bulk skutterudites made by melting and slow cooling method. Surprisingly we increased x close to 0.5 by a special sample ...

  19. Different small, acid-soluble proteins of the alpha/beta type have interchangeable roles in the heat and uv (ultraviolet) radiation resistance of Bacillus subtilis spores

    SciTech Connect

    Mason, J.M.; Setlow, P.

    1987-08-01

    Spores of Bacillus subtilis strains which carry deletion mutations in one gene (sspA) or two genes (sspA and sspB) which code for major alpha/beta-type small, acid-soluble spore proteins (SASP) are known to be much more sensitive to heat and UV radiation than wild-type spores. This heat- and UV-sensitive phenotype was cured completely or in part by introduction into these mutant strains of (i) one or more copies of the sspA or sspB genes themselves; (ii) multiple copies of the B. subtilis sspD gene, which codes for a minor alpha/beta-type SASP; or (iii) multiple copies of the SASP-C genes, which codes for a major alpha/beta-type SASP of Bacillus megaterium. These findings suggest that alpha-beta-type SASP play interchangeable roles in the heat and UV radiation resistance of bacterial spores.

  20. Different small, acid-soluble proteins of the alpha/beta type have interchangeable roles in the heat and UV radiation resistance of Bacillus subtilis spores

    SciTech Connect

    Mason, J.M.; Setlow, P.

    1987-08-01

    Spores of Bacillus subtilis strains which carry deletion mutations in one gene (sspA) or two genes (sspA and sspB) which code for major alpha/beta-type small, acid-soluble spore proteins (SASP) are known to be much more sensitive to heat and UV radiation than wild-type spores. This heat- and UV-sensitive phenotype was cured completely or in part by introduction into these mutant strains of one or more copies of the sspA or sspB genes themselves; multiple copies of the B. subtilis sspD gene, which codes for a minor alpha/beta-type SASP; or multiple copies of the SASP-C gene, which codes for a major alpha/beta-type SASP of Bacillus megaterium. These findings suggest that alpha/beta-type SASP play interchangeable roles in the heat and UV radiation resistance of bacterial spores.

  1. 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.

  2. Maternal Serum Activin A at 11–13 Weeks of Gestation in Hypertensive Disorders of Pregnancy

    Microsoft Academic Search

    Ranjit Akolekar; Adolfo Etchegaray; Yi Zhou; Nerea Maiz; Kypros H. Nicolaides

    2009-01-01

    Objectives: To investigate whether the maternal serum concentration of activin A at 11–13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-? receptor-1 (TNF-R1). Material

  3. Resistance of primary isolates of human immunodeficiency virus type 1 to soluble CD4 is independent of CD4-rgp120 binding affinity.

    PubMed Central

    Ashkenazi, A; Smith, D H; Marsters, S A; Riddle, L; Gregory, T J; Ho, D D; Capon, D J

    1991-01-01

    The infection of human cells by laboratory strains of human immunodeficiency virus type 1 (HIV-1) can be blocked readily in vitro by recombinant soluble CD4 and CD4-immunoglobulin hybrid molecules. In contrast, infection by primary isolates of HIV-1 is much less sensitive to blocking in vitro by soluble CD4-based molecules. To investigate the molecular basis for this difference between HIV-1 strains, we isolated the gp120-encoding genes from several CD4-resistant and CD4-sensitive HIV-1 strains and characterized the CD4-binding properties of their recombinant gp120 (rgp120) products. Extensive amino acid sequence variation was found between the gp120 genes of CD4-resistant and CD4-sensitive HIV-1 isolates. However, the CD4-binding affinities of rgp120 from strains with markedly different CD4 sensitivities were essentially the same, and only small differences were observed in the kinetics of CD4 binding. These results suggest that the lower sensitivity of primary HIV-1 isolates to neutralization by CD4-based molecules is not due to lower binding affinity between soluble CD4 and free gp120. PMID:1871120

  4. Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition.

    PubMed

    Kanamaru, C; Yasuda, H; Takeda, M; Ueda, N; Suzuki, J; Tsuchida, T; Mashima, H; Ohnishi, H; Fujita, T

    2001-12-01

    Activin A induces growth arrest of rat hepatocytes in vitro and in vivo. The alpha(1)-adrenergic agonist, norepinephrine (NE), enhances epidermal growth factor-stimulated DNA synthesis and inhibits activin A-induced growth inhibition, but the mechanisms of these actions are unclear. Smad proteins have recently been identified as intracellular signaling mediators of transforming growth factor-beta family members. In the present study, we explored how NE modulates the Smad signaling pathway in rat cultured hepatocytes. We demonstrate that NE inhibits activin A-induced nuclear accumulation of Smad2/3 and that NE rapidly induces inhibitory Smad7 mRNA expression. Infection of Smad7 adenovirus into rat hepatocytes inhibited activin A-induced nuclear accumulation of Smad2/3, enhanced epidermal growth factor-stimulated DNA synthesis, and abolished the growth inhibitory effect of activin A. We also demonstrated that the induction of Smad7 by NE is dependent on nuclear factor-kappa B (NF-kappa B). The amount of active NF-kappa B complex rapidly increased after NE treatment. Preincubation of the cells with an NF-kappa B pathway inhibitor N-tosyl-l-phenylalanine chloromethyl ketone or infection of the cells with an adenovirus expressing an I kappa B super-repressor (Ad5I kappa B) abolished the NE-induced Smad7 expression. These results indicate a mechanism of transmodulation between the Smad and trimeric G protein signaling pathways in rat hepatocytes. PMID:11551920

  5. A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells

    PubMed Central

    Hansson, Mattias; Olesen, Dorthe R.; Peterslund, Janny M. L.; Engberg, Nina; Kahn, Morten; Winzi, Maria; Klein, Tino; Maddox-Hyttel, Poul; Serup, Palle

    2009-01-01

    Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous findings on the ability of increasing concentrations of activin to progressively induce more ES cell progeny to anterior PS and endodermal fates. We find that the number of Sox17- and Gsc-expressing cells increases with increasing activin concentration while the highest number of T-expressing cells is found at the lowest activin concentration. The expression of Gsc and other anterior markers induced by activin is prevented by treatment with BMP4, which induces T expression and subsequent mesodermal development. We show that canonical Wnt-signaling is required only during late stages of activin-induced development of Sox17-expressing endodermal cells. Furthermore, Dkk1 treatment is less effective in reducing development of Sox17+ endodermal cells in adherent culture than in aggregate culture and appears to inhibit nodal-mediated induction of Sox17+ cells more effectively than activin-mediated induction. Notably, activin-induction of Gsc-GFP+ cells appears refractory to inhibition of canonical Wnt signaling but shows a dependence on early as well as late FGF signaling. Additionally, we find a late dependence on FGF signaling during induction of Sox17+ cells by activin while BMP4-induced T expression requires FGF signaling in adherent but not aggregate culture. Lastly, we demonstrate that activin-induced definitive endoderm derived from mouse ES cells can incorporate into the developing foregut endoderm in vivo and adopt a mostly anterior foregut character after further culture in vitro. PMID:19358838

  6. Activin A and TGF-? promote TH9 cell–mediated pulmonary allergic pathology

    PubMed Central

    Jones, Carla P.; Gregory, Lisa G.; Causton, Benjamin; Campbell, Gaynor A.; Lloyd, Clare M.

    2012-01-01

    Background IL-9-secreting (TH9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain. Objective To define a functional phenotype for TH9-driven pathology in vivo. Methods We used fluorescence-activated cell sorting to identify circulating TH9 cells in atopic and nonatopic subjects. In mice we utilized a model of allergic airways disease induced by house dust mite to determine TH9 cell function in vivo and the role of activin A in TH9 generation. Results Allergic patients have elevated TH9 cell numbers in comparison to nonatopic donors, which correlates with elevated IgE levels. In a murine model, allergen challenge with house dust mite leads to rapid TH9 differentiation and proliferation, with much faster kinetics than for TH2 cell differentiation, resulting in the specific recruitment and activation of mast cells. The TGF-? superfamily member activin A replicates the function of TGF-?1 in driving the in vitro generation of TH9 cells. Importantly, the in vivo inhibition of TH9 differentiation induced by allergen was achieved only when activin A and TGF-? were blocked in conjunction but not alone, resulting in reduced airway hyperreactivity and collagen deposition. Conversely, adoptive transfer of TH9 cells results in enhanced pathology. Conclusion Our data identify a distinct functional role for TH9 cells and outline a novel pathway for their generation in vitro and in vivo. Functionally, TH9 cells promote allergic responses resulting in enhanced pathology mediated by the specific recruitment and activation of mast cells in the lungs. PMID:22277204

  7. Soluble urokinase-type plasminogen activator receptor is over-expressed in uterine endometrium from women with endometriosis.

    PubMed

    Sillem, M; Prifti, S; Monga, B; Buvari, P; Shamia, U; Runnebaum, B

    1997-12-01

    Extracellular matrix degradation by secreted proteases, e.g. plasmin, is essential for endometrial functions such as blastocyst implantation and menstruation. We investigated whether the expression of plasmin(ogen) activating or inhibiting factors in endometrial cells from women with endometriosis was different from women without the disease. Endometrial biopsies were obtained from 10 patients with and 16 women without endometriosis. Cells were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12 supplemented with diethylstilboestrol (10(-10) M) alone or combined with promegestone (5 x 10(-8) or 5 x 10(-6) M). Urokinase plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1 and -2, and soluble uPA receptor (suPA-R) concentrations were assayed by enzyme-linked immunosorbent assay (ELISA) in the conditioned media. uPA and PAI-2 concentrations were not influenced by steroid treatment and did not differ between women with and without endometriosis, whereas PAI-1 was significantly up-regulated by promegestone in both groups. In contrast, suPA-R expression was not influenced by steroid treatment but was significantly higher in cells from endometriosis patients. This is the first report on suPA-R secretion in endometrial cells and the results indicate an altered activation of plasmin(ogen) in endometrium from women with endometriosis that could lead to a higher proteolytic potential of retrogradely menstruated endometrial fragments with consecutive development of endometriotic foci. PMID:9464855

  8. 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 ...

  9. Water-soluble Ag:ZnSe nanocrystals with excellent stability via internal doping of donor-type cation impurity

    NASA Astrophysics Data System (ADS)

    Xu, Shuhong; Wang, Chunlei; Sun, Qingfeng; Wang, Zhuyuan; Cui, Yiping

    2014-03-01

    Aqueous internally doped ZnSe nanocrystals (NCs) are a recent promising Cd-free NC system. One major problem for this NC system is the intrinsic poor stability of NCs in aqueous environments due to the promoted oxidation of NC surface ligands by acceptor-type impurity. In this work, we successfully solve this problem by doping a donor-type Ag impurity instead of an acceptor-type impurity inside aqueous ZnSe NCs. Proper doping ratio and solution pH are keys for preparing high quality Ag:ZnSe NCs. Under similar synthesis conditions, as-prepared Ag:ZnSe NCs show quite different optical properties from acceptor-type impurity-doped ZnSe NCs, suggesting the donor nature of Ag impurity. In comparison to the weak stability of acceptor-type impurity-doped ZnSe NCs moreover, as-prepared Ag:ZnSe NCs show strong photochemical and luminescent stability, making this new type of NCs available for LED, optical coding, multicolor bio-imaging and so on.

  10. 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

  11. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells.

    PubMed

    Arber, Charles; Precious, Sophie V; Cambray, Serafí; Risner-Janiczek, Jessica R; Kelly, Claire; Noakes, Zoe; Fjodorova, Marija; Heuer, Andreas; Ungless, Mark A; Rodríguez, Tristan A; Rosser, Anne E; Dunnett, Stephen B; Li, Meng

    2015-04-01

    The efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening and cell therapy for Huntington's disease. GABAergic medium-sized spiny neurons (MSNs) are the principal projection neurons of the striatum and specifically degenerate in the early phase of Huntington's disease. Here we report that activin A induces lateral ganglionic eminence (LGE) characteristics in nascent neural progenitors derived from hESCs and hiPSCs in a sonic hedgehog-independent manner. Correct specification of striatal phenotype was further demonstrated by the induction of the striatal transcription factors CTIP2, GSX2 and FOXP2. Crucially, these human LGE progenitors readily differentiate into postmitotic neurons expressing the striatal projection neuron signature marker DARPP32, both in culture and following transplantation in the adult striatum in a rat model of Huntington's disease. Activin-induced neurons also exhibit appropriate striatal-like electrophysiology in vitro. Together, our findings demonstrate a novel route for efficient differentiation of GABAergic striatal MSNs from human pluripotent stem cells. PMID:25804741

  12. 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

  13. Lipid accumulation impairs adiponectin-mediated induction of activin A by increasing TGFbeta in primary human hepatocytes

    Microsoft Academic Search

    Josef Wanninger; Markus Neumeier; Claus Hellerbrand; Doris Schacherer; Sabrina Bauer; Thomas S. Weiss; Hanna Huber; Andreas Schäffler; Charalampos Aslanidis; Jürgen Schölmerich; Christa Buechler

    2011-01-01

    Fatty liver is commonly detected in obesity and has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of liver diseases. Transforming growth factor beta (TGF?) and activin A, both members of the TGF? superfamiliy, are central regulators in liver fibrosis and regeneration, and the effect of hepatocyte lipid accumulation on the release

  14. Ultraviolet irradiation of DNA complexed with. alpha. /. beta. -type small, acid-soluble proteins from spores of Bacillus or Clostridium species makes spore photoproduct but not thymine dimers

    SciTech Connect

    Nicholson, W.L.; Setlow, B.; Setlow, P. (Univ. of Connecticut Health Center, Farmington (United States))

    1991-10-01

    UV irradiation of complexes of DNA and an {alpha}/{beta}-type small, acid-soluble protein (SASP) from Bacillus subtilis spores gave decreasing amounts of pyrimidine dimers and increasing amounts of spore photoproduct as the SASP/DNA ratio was increased. The yields of pyrimidine dimers and spore photoproduct were < 0.2% and 8% of total thymine, respectively, when DNA saturated with SASP was irradiated at 254 nm with 30 kJ/m{sup 2}; in the absence of SASP the yields were reversed - 4.5% and 0.3%, respectively. Complexes of DNA with {alpha}/{beta}-type SASP from Bacillus cereus, Bacillus megaterium, or Clostridium bifermentans spores also gave spore photoproduct upon UV irradiation. However, incubation of these SASPs with DNA under conditions preventing complex formation or use of mutant SASPs that do not form complexes did not affect the photoproducts formed in vitro. These results suggest that the UV photochemistry of bacterial spore DNA in vivo is due to the binding of {alpha}/{beta}-type SASP, a binding that is known to cause a change in DNA conformation in vitro from the B form to the A form. The yields of spore photoproduct in vitro were significantly lower than in vivo, perhaps because of the presence of substances other than SASP in spores. It is suggested that as these factors diffuse out in the first minutes of spore germination, spore photoproduct yields become similar to those observed for irradiation of SASP/DNA complexes in vitro.

  15. 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

  16. Differential reduction in soluble and membrane-bound c-type cytochrome contents in a Paracoccus denitrificans mutant partially deficient in 5-aminolevulinate synthase activity.

    PubMed Central

    Page, M D; Ferguson, S J

    1994-01-01

    A mutant of Paracoccus denitrificans, DP104, unable to grow anaerobically with nitrate as the terminal electron acceptor or aerobically with methanol as the electron donor and staining negatively in the dimethylphenylene diamine oxidation (Nadi) test, was isolated by transposon Tn5::phoA mutagenesis. P. denitrificans DP104 grown aerobically with succinate or choline had very low levels (2 to 3% of the wild-type levels) of spectroscopically detectable soluble c-type cytochromes. In contrast, membrane cytochromes of the a, b, and c types were present at 50% of the levels found in the wild type. The apo form of cytochrome c550, at an approximately 1:1 molar ratio with the holo form, was found in the periplasm of DP104. The TnphoA element was shown to be inserted immediately upstream of the translational start of hemA, the gene coding for 5-aminolevulinate synthase, which was sequenced. Low-level expression of this gene, driven off an incidental promoter provided by TnphoA-cointegrated suicide vector DNA, is the basis of the phenotype which could be complemented by the addition of 5-aminolevulinate to growth media. Disruption of the hemA gene generated a P. denitrificans strain auxotrophic for 5-aminolevulinate, establishing that there is no hemA-independent pathway of heme synthesis in this organism. The differential deficiency in periplasmic c-type cytochromes relative to membrane cytochromes in DP104 is suggested to arise from unequal competition for the restricted supply of heme which results from the effects of the transposon insertion. Images PMID:7928952

  17. 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, E-mail: sandhu.hardip@gmail.co [Department of Clinical Experimental Research, Glostrup Research Institute, Ndr. Ringvej 69, 2600 Glostrup (Denmark); Xu, Cang Bao [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, University Hospital of Lund, Lund (Sweden); Edvinsson, Lars [Department of Clinical Experimental Research, Glostrup Research Institute, Ndr. Ringvej 69, 2600 Glostrup (Denmark); Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, University Hospital of Lund, Lund (Sweden)

    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.

  18. 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

  19. Salts & Solubility

    NSDL National Science Digital Library

    2012-12-27

    In this online interactive simulation, learners will add different salts to water and then watch the salts dissolve and achieve a dynamic equilibrium with solid precipitate. Learners will also compare the number of ions in NaCl to other slightly soluble salts, and they will relate the charges on ions to the number of ions in the formula of a salt. Learners will also learn how to calculate Ksp values. This activity includes an online simulation, sample learning goals, a teacher's guide, and translations in over 20 languages.

  20. A Novel Soluble Immune-Type Receptor (SITR) in Teleost Fish: Carp SITR Is Involved in the Nitric Oxide-Mediated Response to a Protozoan Parasite

    PubMed Central

    Ribeiro, Carla M. S.; Bird, Steve; Raes, Geert; Ghassabeh, Gholamreza H.; Schijns, Virgil E. J. C.; Pontes, Maria J. S. L.; Savelkoul, Huub F. J.; Wiegertjes, Geert F.

    2011-01-01

    Background The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways. Methodology/Principal Findings Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production. Conclusion/Significance We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite. PMID:21305002

  1. Combinatorial actions of Tgf? and Activin ligands promote oligodendrocyte development and CNS myelination

    PubMed Central

    Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

    2014-01-01

    In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-? (Tgf?) family and signal canonically via Smads 1/5/8. Tgf? ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgf? ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgf? ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgf?1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgf?1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb?/? embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3?/? mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgf? ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

  2. Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats.

    PubMed

    Petri, J B; Schurk, S; Gebauer, S; Haustein, U F

    1998-03-01

    Cyclosporine A is a powerful immunosuppressive agent which is widely used for the prevention of allograft rejection and for the treatment of autoimmune diseases. Clinical and experimental data show that it may also act on connective tissue. We investigated the influence of cyclosporine A on granulation tissue formation and wound healing. Using an in vitro approach, we followed the time course of rat dermal fibroblasts during wound repair. Granulation fibroblasts were compared to dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming growth factor beta1, keratinocyte growth factor and activin betaA. The most pronounced effect in cyclosporine-treated rats was the strong down-regulation of activin beta expression. In cryo-sections of granulation tissue from the same rats, the distribution and expression intensity of intercellular adhesion molecule and its receptors were investigated by immunohistology. Clearly, a time course was detectable. Tissue from CsA-treated animals showed a delay of three days compared to untreated animals. Apoptosis was also delayed in CsA-treated rats by around three days. Furthermore, we investigated the effect of CsA on the expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes in dermal fibroblasts from untreated donors. No changes in the mRNA steady state levels of these genes were revealed after direct addition of different doses of CsA to fibroblast cultures. Our data suggest that CsA may interfere with the complicated net of interactions between connective tissue and the immune system by down-regulation of the inflammatory phase by modulation of cytokines and a subsequent delay of tissue repair. PMID:9649703

  3. Clinical Value of Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Term Neonates with Infection or Sepsis: A Prospective Study

    PubMed Central

    Siahanidou, Tania; Margeli, Alexandra; Charoni, Stavroula; Giannaki, Maria; Vavourakis, Eustathios; Charisiadou, Athina; Papassotiriou, Ioannis

    2014-01-01

    Background. suPAR, the soluble form of the urokinase-type plasminogen activator receptor, has been identified as a biomarker of infection in adults but its properties in neonatal infection are not known. Methods. Plasma suPAR levels were determined by ELISA in 47 term neonates with infection (19 bacterial and 28 viral) and in 18 healthy neonates as controls. Thirteen out of 47 infected neonates were septic. In all infected neonates, suPAR levels were repeated at 24 hours, 48 hours, 3–5 days, and 7–10 days following admission. Results. Plasma suPAR levels were significantly increased in infected neonates upon admission, whereas they were highest in septic neonates, in comparison with controls (P < 0.001) and correlated positively with serum CRP levels (P = 0.001). At infection subsidence, suPAR concentrations decreased significantly in comparison with baseline (P < 0.001) but remained higher than in controls (P = 0.01). Receiver operating characteristic analysis resulted in significant areas under the curve for detecting either infected or septic neonates, but not for discriminating between bacterial and viral cause of infection. Conclusions. suPAR is a diagnostic biomarker of infection or sepsis in term neonates; however, it cannot discriminate bacterial from viral infections and also its utility for monitoring the response to treatment is questioned. PMID:24882949

  4. 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

  5. The structure of the homopolymeric O-specific chain from the phenol soluble LPS of the Rhizobium loti type strain NZP2213

    Microsoft Academic Search

    R. Russa; T. Urbanik-Sypniewska; A. S. Shashkov; H. Kochanowski; H. Mayer

    1995-01-01

    The O-specific polysaccharide of the phenol soluble lipopolysaccharide (LPS) (LPS-P) of the Rhizobium loti NZP2213 strain consists of a homopolymeric chain of ?-1, 3-linked units of 2-O-acetyl-6-deoxy-l-talopyranose, very probably terminated by a single unit of 2-O-acetyl-6-deoxy-l-talopyranose. The hydrophobic character of the long O-chains explains the phenol solubility of LPS-P, in contrast to the water solubility of LPS-W, which is of

  6. Activin A Efficiently Specifies Definitive Endoderm from Human Embryonic Stem Cells Only When Phosphatidylinositol 3Kinase Signaling Is Suppressed

    Microsoft Academic Search

    Amanda B. McLean; Kevin A. D'Amour; Karen L. Jones; Malini Krishnamoorthy; Michael J. Kulik; David M. Reynolds; Alan M. Sheppard; Huiqing Liu; Ying Xu; Emmanuel E. Baetge; Stephen Dalton

    2007-01-01

    Human ESCs (hESCs) respond to signals that determine their pluripotency, proliferation, survival, and differentiation status. In this report, we demonstrate that phosphatidylinositol 3-ki- nase (PI3K) antagonizes the ability of hESCs to differentiate in response to transforming growth factor family members such as Activin A and Nodal. Inhibition of PI3K signaling efficiently promotes differentiation of hESCs into mes- endoderm and then

  7. 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

  8. 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 ...

  9. Increased peripheral T cell reactivity to microbial antigens and collagen type II in rheumatoid arthritis after treatment with soluble TNF? receptors

    PubMed Central

    Berg, L; Lampa, J; Rogberg, S; van Vollenhoven, R; Klareskog, L

    2001-01-01

    OBJECTIVE—Peripheral T cells from patients with rheumatoid arthritis (RA) are hyporesponsive when stimulated with antigen or mitogen in vitro, possibly owing to increased production of proinflammatory cytokines such as tumour necrosis factor ? (TNF?). This study sought to find out if and how RA T cell reactivity is affected during treatment with etanercept (Enbrel), a soluble TNF? receptor.?METHODS—Heparinised blood was collected from patients with RA at baseline, after four and eight weeks of etanercept treatment, and from healthy controls. After density separation spontaneous production of interferon ? (IFN?), TNF?, interleukin 6 (IL6), and IL10 by peripheral blood mononuclear cells (PBMC) was detected by ELISPOT. For detection of T cell reactivity, PBMC were stimulated in vitro with mitogen (phytohaemagglutinin (PHA)), microbial antigens (purified protein derivative (PPD), influenza), or an autoantigen, collagen type II (CII). Supernatants were analysed for IFN? and IL2 content by enzyme linked immunosorbent assay (ELISA).?RESULTS—In RA the number of cells spontaneously producing IFN? was significantly increased after four, but not eight weeks' treatment with etanercept. T cell reactivity, as measured by IFN? production to PPD, influenza, and CII was significantly increased after four and sustained after eight weeks' treatment, whereas IFN? production induced by PHA remained unchanged. TNF? production was significantly higher in patients with RA than in controls and did not change during etanercept treatment.?CONCLUSION—Treatment of patients with RA with etanercept may lead to increased peripheral T cell reactivity both to microbial antigens and to self antigens such as CII. These findings indicate that TNF? blockade may not only suppress but also stimulate certain aspects of antimicrobial immune defence and autoimmunity.?? PMID:11156546

  10. Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.

    PubMed

    Bertero, Alessandro; Madrigal, Pedro; Galli, Antonella; Hubner, Nina C; Moreno, Inmaculada; Burks, Deborah; Brown, Stephanie; Pedersen, Roger A; Gaffney, Daniel; Mendjan, Sasha; Pauklin, Siim; Vallier, Ludovic

    2015-04-01

    Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin-SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs. PMID:25805847

  11. Embryonic stem cells of the non-human primate Callithrix jacchus can be differentiated into definitive endoderm by Activin-A but not IDE-1/2.

    PubMed

    Diekmann, Ulf; Naujok, Ortwin; Blasczyk, Rainer; Müller, Thomas

    2015-04-01

    Pluripotent stem cells hold great promise for regenerative medicine, due to their unlimited self-renewal potential and the ability to differentiate into all somatic cell types. Differences between the rodent disease models and the situation in humans can be narrowed down with non-human primate models. The common marmoset monkey (Callithrix jacchus) is an interesting model for biomedical research because these animals are easy to breed, get relatively old (? 13 years), are small in size, are relatively cost-effective and have a high genetic proximity to the human. In particular, diseases of the liver and pancreas are interesting for cell replacement therapies but the in vitro differentiation of ESCs into the definitive endoderm germ layer is still a demanding task. Membrane-permeable, chemically defined small molecules can possibly replace recombinant growth factors used in most directed differentiation protocols. However, the potent small molecules IDE-1 and IDE-2 were not able to induce definitive endoderm-like cells when ESCs from the common marmoset were treated with these compounds, whereas the recombinant growth factor Activin A could force the differentiation into this lineage. Our results indicate that ESCs from the common marmoset are less sensitive or even insensitive to these small molecules. Thus, differences between the species of human ESCs and ESCs of this non-human primate might be a useful model to further evaluate the exact mode of action of these compounds. PMID:23418163

  12. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in ?-thalassemia.

    PubMed

    Dussiot, Michael; Maciel, Thiago T; Fricot, Aurélie; Chartier, Céline; Negre, Olivier; Veiga, Joel; Grapton, Damien; Paubelle, Etienne; Payen, Emmanuel; Beuzard, Yves; Leboulch, Philippe; Ribeil, Jean-Antoine; Arlet, Jean-Benoit; Coté, Francine; Courtois, Geneviève; Ginzburg, Yelena Z; Daniel, Thomas O; Chopra, Rajesh; Sung, Victoria; Hermine, Olivier; Moura, Ivan C

    2014-04-01

    The pathophysiology of ineffective erythropoiesis in ?-thalassemia is poorly understood. We report that RAP-011, an activin receptor IIA (ActRIIA) ligand trap, improved ineffective erythropoiesis, corrected anemia and limited iron overload in a mouse model of ?-thalassemia intermedia. Expression of growth differentiation factor 11 (GDF11), an ActRIIA ligand, was increased in splenic erythroblasts from thalassemic mice and in erythroblasts and sera from subjects with ?-thalassemia. Inactivation of GDF11 decreased oxidative stress and the amount of ?-globin membrane precipitates, resulting in increased terminal erythroid differentiation. Abnormal GDF11 expression was dependent on reactive oxygen species, suggesting the existence of an autocrine amplification loop in ?-thalassemia. GDF11 inactivation also corrected the abnormal ratio of immature/mature erythroblasts by inducing apoptosis of immature erythroblasts through the Fas-Fas ligand pathway. Taken together, these observations suggest that ActRIIA ligand traps may have therapeutic relevance in ?-thalassemia by suppressing the deleterious effects of GDF11, a cytokine which blocks terminal erythroid maturation through an autocrine amplification loop involving oxidative stress and ?-globin precipitation. PMID:24658077

  13. Soluble Radicals Rebecca Waldecker

    E-print Network

    Waldecker, Rebecca

    Soluble Radicals Rebecca Waldecker Let G be a finite group and let sol(G) denote the soluble radical of G, i.e. the largest normal soluble subgroup of G. Paul Flavell conjectured in 2001 that sol(G) coincides with the set of all elements x G such that for any y G the subgroup x, y is soluble

  14. A decatungstate-type polyoxoniobate with centered manganese: [H2Mn(IV)Nb10O32]8- as a soluble tetramethylammonium salt.

    PubMed

    Son, Jung-Ho; Casey, William H

    2013-10-01

    A highly symmetric Mn(IV)-centered polyoxoniobate [H2Mn(IV)Nb10O32](8-) was synthesized via hydrothermal methods as a soluble tetramethylammonium salt. The structure is similar to decatungstate structure [W10O32](4-), except for the central heteroatom. The cluster is stable between 4 < pH < 10, as was characterized with ESI-MS and UV-Vis spectroscopy. PMID:23942463

  15. 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

  16. 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

  17. Postnatal regulation of germ cells by activin: the establishment of the initial follicle pool.

    PubMed

    Bristol-Gould, Sarah K; Kreeger, Pamela K; Selkirk, Christina G; Kilen, Signe M; Cook, Robert W; Kipp, Jingjing L; Shea, Lonnie D; Mayo, Kelly E; Woodruff, Teresa K

    2006-10-01

    Mammalian females enter puberty with follicular reserves that exceed the number needed for ovulation during a single lifetime. Follicular depletion occurs throughout reproductive life and ends in menopause, or reproductive senescence, when the follicle pool is exhausted. The mechanisms regulating the production of a species-specific initial follicle pool are not well understood. However, the establishment of a follicular reserve is critical to defining the length of reproductive cyclicity. Here we show that activin A (rh-ActA), a known regulator of follicle formation and growth in vitro, increased the number of postnatal mouse primordial follicles by 30% when administered to neonatal animals during the time of germline cyst breakdown and follicle assembly. This expansion in the initial follicle pool was characterized by a significant increase in both germ cell and granulosa cell proliferation. However, the excess follicles formed shortly after birth did not persist into puberty and both adult rh-ActA- and vehicle-treated animals demonstrated normal fertility. A follicle atresia kinetic constant (k(A)) was modeled for the two groups of animals, and consistent with the empirical data, the k(A) for rh-ActA-treated was twice that of vehicle-treated animals. Kinetic constants for follicle formation, follicle loss and follicle expansion from birth to postnatal day 19 were also derived for vehicle and rh-ActA treatment conditions. Importantly, introduction of exogenous rh-ActA revealed an intrinsic ovarian quorum sensing mechanism that controls the number of follicles available at puberty. We propose that there is an optimal number of oocytes present at puberty, and when the follicle number is exceeded, it occurs at the expense of oocyte quality. The proposed mechanism provides a means by which the ovary eliminates excess follicles containing oocytes of poor quality prior to puberty, thus maintaining fertility in the face of abnormal hormonal stimuli in the prepubertal period. PMID:16930587

  18. Differential expression and regulation by activin of the neurotrophins BDNF and NT4 during human and mouse ovarian development.

    PubMed

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

    2010-04-01

    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. PMID:20175187

  19. Mesenchymal stromal cell delivery of full-length tumor necrosis factor–related apoptosis-inducing ligand is superior to soluble type for cancer therapy

    PubMed Central

    Yuan, ZhengQiang; Kolluri, Krishna K.; Sage, Elizabeth K.; Gowers, Kate H.C.; Janes, Sam M.

    2015-01-01

    Background aims Mesenchymal stromal cell (MSC) delivery of pro-apoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an attractive strategy for anticancer therapy. MSCs expressing full-length human TRAIL (flT) or its soluble form (sT) have previously been shown to be effective for cancer killing. However, a comparison between the two forms has never been performed, leaving it unclear which approach is most effective. This study addresses the issue for the possible clinical application of TRAIL-expressing MSCs in the future. Methods MSCs were transduced with lentiviruses expressing flT or an isoleucine zipper-fused sT. TRAIL expression was examined and cancer cell apoptosis was measured after treatment with transduced MSCs or with MSC-derived soluble TRAIL. Results The transduction does not adversely affect cell phenotype. The sT-transduced MSCs (MSC-sT) secrete abundant levels of soluble TRAIL but do not present the protein on the cell surface. Interestingly, the flT-transduced MSCs (MSC-flT) not only express cell-surface TRAIL but also release flT into medium. These cells were examined for inducing apoptosis in 20 cancer cell lines. MSC-sT cells showed very limited effects. By contrast, MSC-flT cells demonstrated high cancer cell-killing efficiency. More importantly, MSC-flT cells can overcome some cancer cell resistance to recombinant TRAIL. In addition, both cell surface flT and secreted flT are functional for inducing apoptosis. The secreted flT was found to have higher cancer cell-killing capacity than either recombinant TRAIL or MSC-secreted sT. Conclusions These observations demonstrate that MSC delivery of flT is superior to MSC delivery of sT for cancer therapy. PMID:25888191

  20. Altered Sex Hormone Concentrations and Gonadal mRNA Expression Levels of Activin Signaling Factors in Hatchling Alligators From a Contaminated Florida Lake

    PubMed Central

    MOORE, BRANDON C.; KOHNO, SATOMI; COOK, ROBERT W.; ALVERS, ASHLEY L.; HAMLIN, HEATHER J.; WOODRUFF, TERESA K.; GUILLETTE, LOUIS J.

    2014-01-01

    Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin ?A subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly. PMID:20166196

  1. Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception

    Microsoft Academic Search

    R. L. Jones; L. A. Salamonsen; H. O. D. Critchley; P. A. W. Rogers; B. Affandi; J. K. Findlay

    2000-01-01

    Inhibins and activins are dimeric hormones which share common subunits and which have diverse endocrine and paracrine roles in regulating reproductive function. Endometrial expression of inhibin ?, ?A and ?B subunits was examined by immunohistochemistry and in-situ hybridization, across the menstrual cycle and in early pregnancy. All three subunits were found to be expressed in endometrium, primarily by glandular epithelium

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

    SciTech Connect

    Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)] [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

    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.

  3. Follicular Development and Expression of the Messenger Ribonucleic Acid for the Inhibin\\/Activin Subunits in Two Genetic Lines of Turkey Hens that Differ in Total Egg Production

    Microsoft Academic Search

    J. B. Hoffman; A. P. Benson; V. L. Christensen; B. D. Fairchild; A. J. Davis

    The characterization of the follicular hier- archy and the expression of the mRNA for the inhibin\\/ activin subunits was investigated in the follicles of 2 lines of turkey hens selected for over 40 generations for in- creased egg production (Egg line) or increased body weight (Growth line). The follicular hierarchies of 6 hens from the Egg and Growth lines were

  4. Exogenous supplementation of Activin A enhances germ cell differentiation of human embryonic stem cells†.

    PubMed

    Duggal, Galbha; Heindryckx, Björn; Warrier, Sharat; Taelman, Jasin; Van der Jeught, Margot; Deforce, Dieter; Chuva de Sousa Lopes, Susana; De Sutter, Petra

    2015-05-01

    Human embryonic stem cells (hESCs) derived in the presence of Activin A (ActA) demonstrate an increased differentiation propensity toward the germ cell lineage. In addition, mouse epiblast stem cells and mouse epiblast-like cells are poised toward germ cell differentiation and are derived in the presence of ActA. We therefore investigated whether supplementation with ActA enhances in vitro hESC differentiation toward germ cell lineage. ActA up-regulated early primordial germ cell (PGC) genes STELLA/DPPA3 (developmental pluripotency associated 3) and tyrosine kinase receptor cKIT in both ActA-derived and standard-derived hESCs indicating its role in priming hESCs toward the PGC lineage. Indeed, ActA plus bone morphogenic protein 4 (BMP4) strongly increased germ cell differentiation potential of hESCs based on the high expression of late PGC markers DAZL (deleted in azoospermia-like) and VASA/DDX4 (DEAD-box polypeptide 4) at mRNA and protein level. Hence, the combination of ActA with BMP4 provides an additional boost for hESCs to develop into postmigratory germ cells. Together with increased VASA expression in the presence of ActA and BMP4, we also observed up-regulation of endoderm-specific genes GATA4 (GATA binding protein 4) and GATA6. Finally, we were able to further mature these in vitro-derived PGC-like cells (PGCLCs) by culturing them in in vitro maturation (IVM) medium, resulting in the formation of germ cell-like clusters and induction of meiotic gene expression. In conclusion, we demonstrate for the first time a synergism between ActA and BMP4 in facilitating germ cell-directed differentiation of hESCs, which is enhanced by extended culture in IVM medium, as shown by cytoplasmic VASA-expressing PGCLCs. We propose a novel relationship between the endoderm and germ cell lineage during hESC differentiation. PMID:25634576

  5. What Variables Affect Solubility?

    ERIC Educational Resources Information Center

    Baker, William P.; Leyva, Kathryn

    2003-01-01

    Helps middle school students understand the concept of solubility through hands-on experience with a variety of liquids and solids. As they explore factors that affect solubility and saturation, students gain content mastery and an understanding of the inquiry process. Also enables teachers to authentically assess student performance on several…

  6. Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen

    PubMed Central

    1992-01-01

    Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-beta (TGF- beta) family. Both BMP 2B and activin A, but not TGF-beta 1, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited approximately 2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, including fibronectin, laminin, and collagen type IV potentiated the activity of BMP and activin A, with the latter being the most active. Direct experiments demonstrated that radioiodinated BMP 2B bound to collagen type IV better than to either laminin or fibronectin. These data demonstrate a common neurotrophic activity of both BMP 2B and activin A, and suggest that these regulatory molecules alone and in conjunction with extracellular matrix components may play a role in both the development and repair of nervous tissue. PMID:1469059

  7. Immunization of Rabbits with Highly Purified, Soluble, Trimeric Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces a Vigorous B Cell Response and Broadly Cross-Reactive Neutralization

    PubMed Central

    Quinnan, Gerald V.; Onabajo, Olusegun; Zhang, Pengfei; Yan, Lianying; Mattapallil, Joseph J.; Zhang, Zhiqiang; Dong, Ming; Lu, Min; Montefiori, David; LaBranche, Celia; Broder, Christopher C.

    2014-01-01

    Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction. PMID:24846288

  8. What Should We Teach Beginners about Solubility and Solubility Products?

    ERIC Educational Resources Information Center

    Hawkes, Stephen J.

    1998-01-01

    Argues that consideration should be given to whether teaching solubility product calculations is at all useful. Claims that experienced teachers seriously misunderstand and misuse solubility product calculations. (DDR)

  9. 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

  10. Stimulation of Activin A\\/Nodal signaling is insufficient to induce definitive endoderm formation of cord blood-derived unrestricted somatic stem cells

    Microsoft Academic Search

    Caitlin E Filby; Robert Williamson; Peter van Kooy; Alice Pébay; Mirella Dottori; Ngaire J Elwood; Faten Zaibak

    2011-01-01

    Introduction  Unrestricted somatic stem cells (USSC) derived from umbilical cord blood are an attractive alternative to human embryonic\\u000a stem cells (hESC) for cellular therapy. USSC are capable of forming cells representative of all three germ line layers. The\\u000a aim of this study was to determine the potential of USSC to form definitive endoderm following induction with Activin A, a\\u000a protein known

  11. Activin-A stimulates, while transforming growth factor ? 1 inhibits,chorionic gonadotrophin production and aromatase activity in cultured human placental trophoblasts

    Microsoft Academic Search

    Y. Song; J. Keelan; J. T. France

    1996-01-01

    Transforming growth factor-beta (TGF-?) and activin-A, two members of a ubiquitous family of regulators of growth,differentiation and hormonogenesis, are produced by the human placenta. Their effects on placental hCG, inhibin, and oestrogen production in vitro, either alone or in combination, were investigated using cultured Percoll-purified placental trophoblasts. Inhibin and hCG were measured by immunoassay, while aromatase activity (i.e. oestrogen production)

  12. 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

  13. Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific activation of the early response gene XFD-1' in Xenopus laevis embryos.

    PubMed Central

    Kaufmann, E; Paul, H; Friedle, H; Metz, A; Scheucher, M; Clement, J H; Knöchel, W

    1996-01-01

    Transcription of the early response gene XFD-1' (XFKH1) in the dorsal lip (Spemann organizer) of Xenopus embryos is activated by dorsal mesoderm inducing factors. Promoter studies revealed the presence of an activin A response element (ARE) which is both necessary and sufficient for transcriptional activation of reporter genes in animal cap explants incubated with activin A. Surprisingly, this ARE is also active within vegetal explants in the absence of exogenously added inducers, but an additional inhibitory response element prevents transcription of the XFD-1' gene in the ventral/vegetal region of the embryo in vivo. This element is located upstream of the ARE, it responds to bone morphogenic proteins 2 and 4 (BMP-2/4) triggered signals and it overrides the activating properties of the ARE. Expression patterns of BMP-2 and BMP-4 in the late blastula stage embryo and, especially, their absence from the dorsal blastopore lip may thus control the spatial transcription of the XFD-1' gene. Accordingly, the temporal activation and the spatial restriction of XFD-1' gene activity to the Spemann organizer is regulated by antagonistic actions of two distinct members of the TGF-beta family (activin and BMP) which act on different promoter elements. Images PMID:8978699

  14. 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

  15. Tiling of R7 Axons in the Drosophila Visual System is Mediated Both by Transduction of an Activin Signal to the Nucleus and by Mutual Repulsion

    PubMed Central

    Ting, Chun-Yuan; Herman, Tory; Yonekura, Shinichi; Gao, Shuying; Wang, Jian; Serpe, Mihaela; O’Connor, Michael B.; Zipursky, S. Lawrence; Lee, Chi-Hon

    2009-01-01

    Summary The organization of neuronal wiring into layers and columns is a common feature of both vertebrate and invertebrate brains. In the Drosophila visual system, each R7 photoreceptor axon projects within a single column to a specific layer of the optic lobe. We refer to the restriction of terminals to single columns as tiling. In a genetic screen based on an R7-dependent behavior, we identified the Activin receptor Baboon and the nuclear import adaptor Importin-?3 as being required to prevent R7 axon terminals from overlapping with the terminals of R7s in neighboring columns. This tiling function requires the Baboon ligand, dActivin, the transcription factor, dSmad2, and retrograde transport from the growth cone to the R7 nucleus. We propose that dActivin is an autocrine signal that restricts R7 growth cone motility, and we demonstrate that it acts in parallel with a paracrine signal that mediates repulsion between R7 terminals. PMID:18054857

  16. 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

  17. 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

  18. A novel simple method to purify recombinant soluble human complement receptor type 1 (sCR1) from CHO cell culture

    Microsoft Academic Search

    Hisamune Kato; Takehiro Inoue; Noriyuki Ishii; Yoshinobu Murakami; Masatoshi Matsumura; Tsukasa Seya; Pi-Chao Wang

    2002-01-01

    The human complement receptor type 1 (CR1, C3 b\\/C4b receptor) is a polymorphic membrane glycoprotein expressed on human erythrocytes,\\u000a peripheral leukocytes, plasma and renal glomerular podocytes, which consists of transmembrane and cytoplasmic domains with\\u000a 30 repeating homologous protein domains knows as short consensus repeats (SCR). CR1 has been used as an inhibitor for inflammatory\\u000a and immune system for the past

  19. 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.

  20. Water soluble perforation pack

    SciTech Connect

    Mondshine, T.C.

    1986-11-11

    This patent describes a well completion and workover method wherein a subterranean formation in a well is perforated to provide channels for fluids within the formation to flow to the well bore, the steps comprising: (a) pumping a first treating fluid into the well and contacting the perforation channels with the first treating fluid. The first treating fluid comprises a saturated aqueous saline solution with at least one water soluble particulate sized salt which is substantially insoluble in the saturated aqueous saline solution; (b) filling the perforation channels with the water soluble particulate sized salt which is substantially insoluble in the first treating fluid. The water soluble particulate sized salt has a particle size range such that the perforation channels filled with the water soluble salt have a permeability sufficiently high to affect the easy removal of the water soluble particulate sized salt from the perforation channels when desired; (c) forming a bridge and seal on the surface of the filled perforation channels to bridge and seal off the filled perforation channels by contacting the filled perforation channels with a second treating fluid. The second treating fluid comprises a saturated aqueous saline solution in which the water soluble particulate sized salt filled within the perforation channels is substantially insoluble having suspended therein at least one particulate bridging material having a particle size range such that a low permeability seal of the filled perforation channels is obtained; and thereafter when desired.

  1. 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 [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States); Franti, Michael [Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Dey, Antu K. [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States); Kirschner, Marc [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States); Iyer, Sai Prasad N. [Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Fisch, Danielle C. [Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Ketas, Thomas [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States); Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Yuste, Eloisa [New England Primate Research Center, Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, MA 01772 (United States); Desrosiers, Ronald C. [New England Primate Research Center, Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, MA 01772 (United States); Klasse, Per Johan [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States); Maddon, Paul J. [Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Olson, William C. [Progenics Pharmaceuticals, Inc. Tarrytown, New York, NY 10591 (United States); Moore, John P. [Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021 (United States)]. 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.

  2. Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/activin/nodal signaling using SB-431542.

    PubMed

    Mahmood, Amer; Harkness, Linda; Schrøder, Henrik Daa; Abdallah, Basem M; Kassem, Moustapha

    2010-06-01

    Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor beta (TGF-beta)/activin/nodal signaling during embryoid body (EB) formation using SB-431542 (SB) in serum-free medium markedly upregulated paraxial mesodermal markers (TBX6, TBX5) and several myogenic developmental markers, including early myogenic transcriptional factors (Myf5, Pax7), as well as myocyte-committed markers [NCAM, CD34, desmin, MHC (fast), alpha-smooth muscle actin, Nkx2.5, cTNT]. Continuous inhibition of TGF-beta signaling in EB outgrowth cultures (SB-OG) enriched for myocyte progenitor cells; markers were PAX7(+) (25%), MYOD1(+) (52%), and NCAM(+) (CD56) (73%). DNA microarray analysis revealed differential upregulation of 117 genes (>2-fold compared with control cells) annotated to myogenic development and function. Moreover, these cells showed the ability to contract (80% of the population) and formed myofibers when implanted intramuscularly in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSCs): CD44(+) (100%), CD73(+) (98%), CD146(+) (96%), and CD166(+) (88%) with the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Furthermore, microarray analysis of these cells revealed downregulation of genes related to myogenesis: MYH3 (-167.9-fold), ACTA1 (-161-fold), MYBPH (-139-fold), ACTC (-100.3-fold), MYH8 (-45.5-fold), and MYOT (-41.8-fold) and marked upregulation of genes related to mesoderm-derived cell lineages. In conclusion, our data provides a simple and versatile protocol for directing the differentiation of hESCs into a myogenic lineage and then further into mesenchymal progenitors by blocking the TGF-beta signaling pathway. PMID:20200949

  3. Nickel solubility in intrinsic and doped silicon

    SciTech Connect

    Istratov, A.A.; Zhang, P.; McDonald, R.J.; Smith, A.R.; Seacrist, M.; Moreland, J.; Shen, J.; Wahlich, R.; Weber, E.R. [Department of Materials Science and Engineering, University of California, and Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720-8253 (United States); Nuclear Physics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); MEMC Electronic Materials, St. Peters, Missouri 63376 (United States); Siltronic Corp., Portland, Oregon 97210 (United States); Siltronic AG, Burghausen (Germany); Department of Materials Science and Engineering, 374 Hearst Mining Building, University of California, Berkeley California 94720-1760 (United States)

    2005-01-15

    Solubility of nickel in intrinsic, moderately, and heavily doped n-type and p-type silicon was determined using instrumental neutron activation analysis. The solubility data for intrinsic silicon were found to be in good agreement with the literature data. In heavily doped p-type silicon the enhancement of nickel solubility, if present, was close to the error margins of the experiment, indicating that interstitial nickel is predominantly neutral in silicon and suggesting that its donor level lies close to the valence band edge, if not within the valence band itself. No dependence of nickel solubility on doping level of the samples was observed in n-type silicon. This is consistent with the model reported in the literature of two acceptor levels of substitutional nickel located in the upper half of the band gap, one of the levels close to the conduction band edge. Consequently, unlike copper or iron, nickel does not segregate in heavily p-type or n-type doped areas of silicon wafers.

  4. Cloning and characterization of the activin like receptor 1 homolog (Pf-ALR1) in the pearl oyster, Pinctada fucata.

    PubMed

    Zhou, Yujuan; He, Zuoxin; Huang, Jing; Gong, Ningping; Yan, Zhenguang; Liu, Xiaojun; Sun, Juan; Wang, Hongzhong; Zhang, Guiyou; Xie, Liping; Zhang, Rongqing

    2010-07-01

    The signal transduction mechanisms in mollusks are still elusive since the genome information is incomplete and cell lines are not available. In previous study, we cloned a highly conserved Smad3 homolog (designated as Pf-Smad3) from the pearl oyster, Pinctada fucata. It seems that transforming growth factor beta (TGFbeta) signaling may play similar roles in the oyster as in vertebrate. Here we report a cDNA encoding an activin like receptor 1 homolog (designated as Pf-ALR1) of the oyster, another kind of TGFbeta superfamily member. Compared to the activin receptor-like kinases (ALK) in human, the amino acid sequence of Pf-ALR1 is more similar to that of ALK1, especially the L45 loop. Reverse transcription-polymerase chain reaction results indicate that Pf-ALR1 mRNA is expressed ubiquitously in the adult oyster. Thus, Pf-ALR1 may be important for many physiological processes in the oyster. To lay a basis for further investigation of the TGFbeta signal pathway functions in the oyster shell formation, in this report, the Pf-ALR1 mRNA expression in the oyster mantle was detected by in situ hybridization. The results show that Pf-ALR1 in the oyster mantle is mainly expressed at the inner epithelial cells of the outer fold and the outer epithelial cells of the middle fold, similarly as Pf-Smad3. The mRNA levels of Pf-ALR1 and Pf-Smad3 are all changed after shell notching. These results indicate that both Pf-ALR1 and Pf-Smad3 may take part in shell formation and repair. The results of drug treatment experiments with in-vitro cultured oyster mantle tissue cells demonstrate that the mRNA expression levels of Pf-Smad3, Pf-ALR1 and two oyster nuclear factor-kappaB (NF-kB) members can be adjusted and correlated. All our observations suggest that there should be similar TGFbeta signal pathways in the oyster and vertebrate. However, the potential functions of Pf-ALR1 and the relations of TGFbeta and NF-kB members in the oyster all need to be thoroughly investigated. PMID:20226263

  5. The Balance of Cell Surface and Soluble Type III TGF-? Receptor Regulates BMP Signaling in Normal and Cancerous Mammary Epithelial Cells1

    PubMed Central

    Gatza, Catherine E.; Elderbroom, Jennifer L.; Oh, Sun Young; Starr, Mark D.; Nixon, Andrew B.; Blobe, Gerard C.

    2014-01-01

    Bone morphogenetic proteins (BMPs) are members of the TGF-? superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-? receptor (T?RIII) mediates BMP signaling. While T?RIII expression is lost during breast cancer progression, the role of T?RIII in regulating BMP signaling in normal mammary epithelium and breast cancer cells has not been examined. Restoring T?RIII expression in a 4T1 murine syngeneic model of breast cancer suppressed Smad1/5/8 phosphorylation and inhibited the expression of the BMP transcriptional targets, Id1 and Smad6, in vivo. Similarly, restoring T?RIII expression in human breast cancer cell lines or treatment with sT?RIII inhibited BMP-induced Smad1/5/8 phosphorylation and BMP-stimulated migration and invasion. In normal mammary epithelial cells, shRNA-mediated silencing of T?RIII, T?RIII over-expression, or treatment with sT?RIII inhibited BMP-mediated phosphorylation of Smad1/5/8 and BMP induced migration. Inhibition of T?RIII shedding through treatment with TAPI-2 or expression of a non-shedding T?RIII mutant rescued T?RIII mediated inhibition of BMP induced Smad1/5/8 phosphorylation and BMP induced migration and/or invasion in both in normal mammary epithelial cells and breast cancer cells. Conversely, expression of a T?RIII mutant, which exhibited increased shedding, significantly reduced BMP-mediated Smad1/5/8 phosphorylation, migration, and invasion. These data demonstrate that T?RIII regulates BMP-mediated signaling and biological effects, primarily through the ligand sequestration effects of sT?RIII in normal and cancerous mammary epithelial cells and suggest that the ratio of membrane bound versus sT?RIII plays an important role in mediating these effects. PMID:25077702

  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. (Univ. Hospital Leiden (Netherlands))

    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. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells.

    PubMed Central

    Moore, J P; Sattentau, Q J; Klasse, P J; Burkly, L C

    1992-01-01

    The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion. Images PMID:1378510

  8. Solid solubilities of oxygen, carbon, and nitrogen in yttrium

    Microsoft Academic Search

    O. N. Carlson; R. R. Lichtenberg; J. C. Warner

    1974-01-01

    The solid solubilities were investigated and a partial diagram is ; proposed for the Y --YN system. The temperature dependence of the solubility of ; each solute in alpha yttrium was fitted empirically to Arrhenius-type ; equations, and the heats of solution for the coexisting oxide, carbide, or ; nitride phase were found to be 6.8 plus or minus 0.4,

  9. Influence of dispersants on the solubility of calcined kaolin

    Microsoft Academic Search

    Jun Yuan; William L Garforth; Robert J Pruett

    1998-01-01

    The solubility of calcined kaolin relative to different aqueous solution chemistries is important to its industrial application. When used in paper-making, a calcined kaolin product is required to have good flow characteristics and viscosity stability, both of which are largely controlled by the type and level of soluble salts in the kaolin suspension. In this study, five common dispersing agents

  10. Understanding Solubility and Density

    NSDL National Science Digital Library

    2010-01-01

    Understanding Solubility and Density is a graduate-level professional development course designed to enhance your understanding and teaching of physical science. In two sessions, you will investigate physical science topics using hands-on activities and online resources including video segments, interactive activities, readings, and other multimedia materials. These resources are drawn from Teachers' Domain, WGBH's digital library service.

  11. Pluripotency Gene Expression and Growth Control in Cultures of Peripheral Blood Monocytes during Their Conversion into Programmable Cells of Monocytic Origin (PCMO): Evidence for a Regulatory Role of Autocrine Activin and TGF-?

    PubMed Central

    Ungefroren, Hendrik; Hyder, Ayman; Hinz, Hebke; Groth, Stephanie; Lange, Hans; El-Sayed, Karim M. Fawzy; Ehnert, Sabrina; Nüssler, Andreas K.; Fändrich, Fred; Gieseler, Frank

    2015-01-01

    Previous studies have shown that peripheral blood monocytes can be converted in vitro to a stem cell-like cell termed PCMO as evidenced by the re-expression of pluripotency-associated genes, transient proliferation, and the ability to adopt the phenotype of hepatocytes and insulin-producing cells upon tissue-specific differentiation. However, the regulatory interactions between cultured cells governing pluripotency and mitotic activity have remained elusive. Here we asked whether activin(s) and TGF-?(s), are involved in PCMO generation. De novo proliferation of PCMO was higher under adherent vs. suspended culture conditions as revealed by the appearance of a subset of Ki67-positive monocytes and correlated with down-regulation of p21WAF1 beyond day 2 of culture. Realtime-PCR analysis showed that PCMO express ActRIIA, ALK4, T?RII, ALK5 as well as TGF-?1 and the ?A subunit of activin. Interestingly, expression of ActRIIA and ALK4, and activin A levels in the culture supernatants increased until day 4 of culture, while levels of total and active TGF-?1 strongly declined. PCMO responded to both growth factors in an autocrine fashion with intracellular signaling as evidenced by a rise in the levels of phospho-Smad2 and a drop in those of phospho-Smad3. Stimulation of PCMO with recombinant activins (A, B, AB) and TGF-?1 induced phosphorylation of Smad2 but not Smad3. Inhibition of autocrine activin signaling by either SB431542 or follistatin reduced both Smad2 activation and Oct4A/Nanog upregulation. Inhibition of autocrine TGF-? signaling by either SB431542 or anti-TGF-? antibody reduced Smad3 activation and strongly increased the number of Ki67-positive cells. Furthermore, anti-TGF-? antibody moderately enhanced Oct4A/Nanog expression. Our data show that during PCMO generation pluripotency marker expression is controlled positively by activin/Smad2 and negatively by TGF-?/Smad3 signaling, while relief from growth inhibition is primarily the result of reduced TGF-?/Smad3, and to a lesser extent, activin/Smad2 signaling. PMID:25707005

  12. 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

  13. 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.

  14. A Perspective on Solubility Rules.

    ERIC Educational Resources Information Center

    Monroe, Manus; Abrams, Karl

    1984-01-01

    Presents four generalizations about solubilities. These generalizations (rules), are useful in introducing the dynamic topics of solubility and in helping high school and introductory college chemistry students make some order out of the tremendous number of facts available. (JN)

  15. 5, 58095839, 2005 Water soluble

    E-print Network

    Paris-Sud XI, Université de

    ACPD 5, 5809­5839, 2005 Water soluble inorganic compounds in the Zurich area R. Fisseha et al and Physics Discussions Seasonal and diurnal characteristics of water soluble inorganic compounds in the gas­5839, 2005 Water soluble inorganic compounds in the Zurich area R. Fisseha et al. Title Page Abstract

  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. 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…

  18. Activin/Nodal Inhibition Alone Accelerates Highly Efficient Neural Conversion from Human Embryonic Stem Cells and Imposes a Caudal Positional Identity

    PubMed Central

    Patani, Rickie; Compston, Alastair; Puddifoot, Clare A.; Wyllie, David J. A.; Hardingham, Giles E.; Allen, Nicholas D.; Chandran, Siddharthan

    2009-01-01

    Background Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using Noggin and SB431542 (an inhibitor of activin/nodal signaling). Previous studies have also determined a role for activin/nodal signaling in development of the neural plate and anterior fate specification. We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions. Methodology/Principal Findings We show that in non-adherent culture conditions, treatment with SB431542 alone for 8 days is sufficient for highly efficient and accelerated neural conversion from hESCs with negligible mesendodermal, epidermal or trophectodermal contamination. In addition the resulting neural progenitor population has a predominantly caudal identity compared to the more anterior positional fate of non-SB431542 treated cultures. Finally we demonstrate that resulting neurons are electro-physiologically competent. Conclusions This study provides a platform for the efficient generation of caudal neural progenitors under defined conditions for experimental study. PMID:19806200

  19. 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

  20. 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

  1. The maturation-inducing hormone 17a-20b-dihydroxy-4pregnen-3-one regulates gene expression of inhibin A and bambi (bone morphogenetic protein and activin membrane bound inhibitor) in the rainbow trout ovary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transforming growth factor-beta (TGFb) superfamily members are important paracrine and autocrine regulators of ovarian development and steroidogenesis in mammals and birds, but their reproductive roles in fish are not well understood. The activin system, Tgfb, and bone morphogenetic protein 15 (Bmp...

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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%.

  7. 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%.

  8. 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%.

  9. Microemulsion formulation for enhanced absorption of poorly soluble drugs

    Microsoft Academic Search

    Kohsaku Kawakami; Takayoshi Yoshikawa; Yasushi Moroto; Eri Kanaoka; Koji Takahashi; Yoshitaka Nishihara; Kazuyoshi Masuda

    2002-01-01

    Microemulsion formulations, which can be used to improve the bioavailability of poorly soluble drugs, were designed using only pharmaceutical excipients. Several types of oils and surfactants were tested and it was found that propyleneglycol monoalkyl ester and glycerol monoalkyl ester were solubilized easily in an aqueous medium by various types of surfactants. Although propyleneglycol dialkyl ester was difficult to be

  10. Phenylated Polyimides With Greater Solubility

    NASA Technical Reports Server (NTRS)

    Harris, Frank W.

    1991-01-01

    In experiments, 3,6-diphenylpyromellitic dianhydride monomer prepared and polymerized with several different diamines. Polyimides with pendent phenyl groups along polymer backbones considerably more soluble than PMDA-based materials. Increased solubility eases processing, providing increased potential use in variety of applications. Because most polymers soluble in organic solvents, usable in microelectronics applications. Excellent thermal stabilities and high transition temperatures make them ideally suited. Many polymers extremely rigid and useful as reinforcing polymers in molecular composites. More flexible compositions useful as matrix resins in carbon-reinforced composites.

  11. Mineral oil soluble borate compositions

    SciTech Connect

    Dulat, J.

    1981-09-15

    Alkali metal borates are reacted with fatty acids or oils in the presence of a low hlb value surfactant to give a stable mineral oil-soluble product. Mineral oil containing the borate can be used as a cutting fluid.

  12. Method for estimating solubility parameter

    NASA Technical Reports Server (NTRS)

    Lawson, D. D.; Ingham, J. D.

    1973-01-01

    Semiempirical correlations have been developed between solubility parameters and refractive indices for series of model hydrocarbon compounds and organic polymers. Measurement of intermolecular forces is useful for assessment of material compatibility, glass-transition temperature, and transport properties.

  13. water-soluble fluorocarbon coating

    NASA Technical Reports Server (NTRS)

    Nanelli, P.

    1979-01-01

    Water-soluble fluorocarbon proves durable nonpolluting coating for variety of substrates. Coatings can be used on metals, masonry, textiles, paper, and glass, and have superior hardness and flexibility, strong resistance to chemicals fire, and weather.

  14. Water-soluble vitamins.

    PubMed

    Konings, Erik J M

    2006-01-01

    Simultaneous Determination of Vitamins.--Klejdus et al. described a simultaneous determination of 10 water- and 10 fat-soluble vitamins in pharmaceutical preparations by liquid chromatography-diode-array detection (LC-DAD). A combined isocratic and linear gradient allowed separation of vitamins in 3 distinct groups: polar, low-polar, and nonpolar. The method was applied to pharmaceutical preparations, fortified powdered drinks, and food samples, for which results were in good agreement with values claimed. Heudi et al. described a separation of 9 water-soluble vitamins by LC-UV. The method was applied for the quantification of vitamins in polyvitaminated premixes used for the fortification of infant nutrition products. The repeatability of the method was evaluated at different concentration levels and coefficients of variation were <6.5%. The concentrations of vitamins found in premixes with the method were comparable to the values declared. A disadvantage of the methods mentioned above is that sample composition has to be known in advance. According to European legislation, for example, foods might be fortified with riboflavin phosphate or thiamin phosphate, vitamers which are not included in the simultaneous separations described. Vitamin B2.--Viñas et al. elaborated an LC analysis of riboflavin vitamers in foods. Vitamin B2 can be found in nature as the free riboflavin, but in most biological materials it occurs predominantly in the form of 2 coenzymes, flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). Several methods usually involve the conversion of these coenzymes into free riboflavin before quantification of total riboflavin. According to the authors, there is growing interest to know flavin composition of foods. The described method separates the individual vitamers isocratically. Accuracy of the method is tested with 2 certified reference materials (CRMs). Vitamin B5.-Methods for the determination of vitamin B5 in foods are limited because of their low sensitivity and poor selectivity. Pakin et al. proposed a post-column derivatization of pantothenic acid as a fluorescent compound and used this principle in a specific and sensitive method for the determination of free and bound pantothenic acid in a large variety of foods. A French laboratory invited European laboratories to participate in a series of collaborative studies for this method, which will be carried out in 2005/2006. A more sophisticated method was described by Mittermayer et al. They developed an LC-mass spectrometry (LC/MS) method for the determination of vitamin B5 in a wide range of fortified food products. Application of the method to various samples showed consistent results with those obtained by microbiology. Vitamin B6.-Method 2004.07, an LC method for the analysis of vitamin B6 in reconstituted infant formula, was published by Mann et al. In contrast with this method, which quantifies vitamin B6 after converting the phosphorylated and free vitamers into pyridoxine, Viñas et al. published an LC method which determines 6 vitamin B6 related compounds, the 3 B6 vitamers, their corresponding phosphorylated esters, and a metabolite. Accuracy was determined using 2 CRMs. Results were within the certified ranges. Vitamin C.-Franke et al. described an extensive study to vitamin C and flavonoid levels of fruits and vegetables consumed in Hawaii. Vitamin C was determined by measuring ascorbic acid in its reduced state by LC and coulometric detection along with UV absorbance detection at 245 nm. No attempts were made to assess levels of dehydroascorbic acid. Most recent research revealed that cell uptake of dehydroascorbic acid is unlikely to play a major role, which may explain the very low vitamin C activity of orally administered L-dehydroascorbic acid in rats. The food levels found by Franke et al. are variably lower, higher, or equal in comparison to other studies. Iwase described a method for the determination of ascorbic acid in foods using L-methionine for the pre-analysis sample stabilization. Electrochemical detection wa

  15. Hydrotropic Nanocarriers for Poorly Soluble Drugs

    Microsoft Academic Search

    Tooru Ooya; Sang Cheon Lee; Kang Moo Huh

    Delivery of poorly water-soluble drugs remains as one of the most difficult challenges in the pharmaceutics and drug delivery areas. One of the recent approaches of increasing the water-solubility of poorly soluble drugs has been to utilize polymeric hydrotropic agents. Hydrotropic agents in nanocarrier forms, such as dendrimers and polymer micelles, increase the water solubility by orders of magnitude. The

  16. The ellipsoidal model of the solubility volume

    Microsoft Academic Search

    Ivica Gusi?; Helena Jasna Mencer

    2003-01-01

    Generally, the solubility of polymers in different solvents may be described by the so-called solubility volume in the Hansen's three-dimensional solubility (parameter) space. The solubility volume is usually modeled by the sphere or, less commonly, by the inclined ellipsoid. In this paper, the ellipsoidal model is revised. The procedure for the calculation of model parameters is given in details for

  17. [Preliminary study on correlation between diversity of soluble proteins and producing area of Cordyceps sinensis].

    PubMed

    Ren, Yan; Qiu, Yi; Wan, De-Guang; Lu, Xian-Ming; Guo, Jin-Lin

    2013-05-01

    To analyze the content and type of soluble proteins in Cordyceps sinensis from different producing areas and processed with different methods with bradford method and 2-DE technology, in order to discover significant differences in soluble proteins in C. sinensis processed with different methods and from different producing areas. The preliminary study indicated that the content and diversity of soluble proteins were related to producing areas and processing methods to some extent. PMID:23944072

  18. 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

  19. Soluble ST2 in Ventricular Dysfunction.

    PubMed

    Lupu, Silvia; Agoston-Coldea, Lucia

    2015-01-01

    Heart failure is a commonly encountered condition associated with increased morbidity, mortality, and healthcare cost. For years, its management has been strongly influenced by the use of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide biomarkers. In some cases, this approach does not always identify patients with heart failure accurately and may not provide the best prognostic assessment, particularly in the presence of comorbidities. Biomarkers that help refine diagnosis and risk stratification are needed. Soluble ST2, a peptide belonging to the interleukin-1 receptor family, is secreted when cardiomyocytes and cardiac fibroblasts are subjected to mechanical strain. Although preliminary results on this novel biomarker are encouraging, additional and more comprehensive studies are clearly needed to establish its role in the management of patients with heart failure. The purpose of this chapter is to provide an overview of data currently available. PMID:25934361

  20. 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

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

    PubMed

    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

  2. Activin receptor-like kinase 7 mediates high glucose-induced H9c2 cardiomyoblast apoptosis through activation of Smad2/3.

    PubMed

    Liu, Lin; Ding, Wen-yuan; Zhao, Jing; Wang, Zhi-hao; Zhong, Ming; Zhang, Wei; Chen, Yu-guo; Zhang, Yun; Li, Li; Tang, Meng-xiong

    2013-09-01

    Cardiomyocyte apoptosis is an important pathological change of diabetic cardiomyopathy. How the elevated glucose levels cause cell apoptosis remains unknown. The aim of our study was to investigate whether activin receptor-like kinase 7 (ALK7)-Smad2/3 signaling pathway plays an important role in high glucose-induced cardiomyocyte apoptosis. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes were treated with 33mmol/l glucose. The expression of ALK7, Smad2 and Smad3 were inhibited by small interfering RNA respectively. The level of ALK7, total Smad2/3, phosphorylated Smad2/3, B-cell lymphoma-2 (Bcl-2) and cleaved Caspase3 were evaluated using western blot. The apoptosis rate was detected by flow cytometer. High glucose treatment caused the apoptosis of H9c2 cardiomyocyte and the inhibition of Smad2 or Smad3 attenuated this apoptosis. ALK7 existed in both H9c2 cardiomyoblasts and neonatal rat cardiomyocytes and high ambient glucose upregulated its expression. The increased expression level of cleaved Caspase3 and apoptosis rate and decreased expression of Bcl-2 were reversed after ALK7 was inhibited. The expression of phosphorylated Smad2/3 also decreased after the knockdown of ALK7. Our findings suggest that ALK7 mediates high ambient glucose-induced H9c2 cardiomyoblasts apoptosis through the activation of Smad2/3. PMID:23830891

  3. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes

    PubMed Central

    Yoon, Jeong-Hwan; Jung, Su Myung; Park, Seok Hee; Kato, Mitsuyasu; Yamashita, Tadashi; Lee, In-Kyu; Sudo, Katsuko; Nakae, Susumu; Han, Jin Soo; Kim, Ok-Hee; Oh, Byung-Chul; Sumida, Takayuki; Kuroda, Masahiko; Ju, Ji-Hyeon; Jung, Kyeong Cheon; Park, Seong Hoe; Kim, Dae-Kee; Mamura, Mizuko

    2013-01-01

    Varieties of transforming growth factor-? (TGF-?) antagonists have been developed to intervene with excessive TGF-? signalling activity in cancer. Activin receptor-like kinase5 (ALK5) inhibitors antagonize TGF-? signalling by blocking TGF-? receptor-activated Smad (R-Smad) phosphorylation. Here we report the novel mechanisms how ALK5 inhibitors exert a therapeutic effect on a mouse B16 melanoma model. Oral treatment with a novel ALK5 inhibitor, EW-7197 (2.5 mg/kg daily) or a representative ALK5 inhibitor, LY-2157299 (75 mg/kg bid) suppressed the progression of melanoma with enhanced cytotoxic T-lymphocyte (CTL) responses. Notably, ALK5 inhibitors not only blocked R-Smad phosphorylation, but also induced ubiquitin-mediated degradation of the common Smad, Smad4 mainly in CD8+ T cells in melanoma-bearing mice. Accordingly, T-cell-specific deletion of Smad4 was sufficient to suppress the progression of melanoma. We further identified eomesodermin (Eomes), the T-box transcription factor regulating CTL functions, as a specific target repressed by TGF-? via Smad4 and Smad3 in CD8+ T cells. Thus, ALK5 inhibition enhances anti-melanoma CTL responses through ubiquitin-mediated degradation of Smad4 in addition to the direct inhibitory effect on R-Smad phosphorylation. PMID:24127404

  4. Biochemical and physiological studies of soluble esterases from Drosophila melanogaster

    Microsoft Academic Search

    Marion J. Healy; Mira M. Dumancic; John G. Oakeshott

    1991-01-01

    Twenty-two soluble esterases have been identified inD. melanogaster by combining the techniques of native polyacrylamide gel electrophoresis and isoelectric focusing. The sensitivity of each isozyme to three types of inhibitors (organophosphates, eserine sulfate, and sulfydryl reagents) identified 10 as carboxylesterases, 6 as cholinesterases, and 3 as acetylesterases. Three isozymes could not be classified and no arylesterases were identified. The carboxyl-

  5. Regulatory role of suppressor T cells in the expression of delayed-type hypersensitivity in mice. II. Soluble factor from thymic suppressor cells stimulated with antigen in vitro and its possible interaction with macrophages.

    PubMed Central

    Kojima, A; Tamura, S I; Egashira, Y

    1979-01-01

    Thymus cells from mice primed s.c. with a high dose (10 mg) of lysozyme (Lys) specifically suppressed delayed footpad reaction (FPR) in mice previously immuned with lipid-conjugated lysozyme (D.Lys), and also suppressed the transfer of FPR by D.Lys-immune spleen cells into normal mice. Furthermore, they inhibited antigen-stimulated DNA synthesis of D.Lys-immune spleen cells in vitro. If the suppressor thymus cells were cultured with Lys in vitro, they produced soluble factor which depressed the ability of D.Lys-immune spleen cells to transfer FPR. Both supernatant of culture without Lys and extract of suppressor thymus cells were inactive in supression of FPR. The suppressor factor was antigen-specific because its suppressive activity was absorbed with Lys but not with an unrelated antigen lactalbumin. The factor failed to depress the ability of D.Lys-immune spleen cells to transfer FPR when the spleen cells were depleted of glass-adherent cells. In addition, incubation of peritoneal exudate cells from normal mice with the factor rendered the cells suppressive for passive transfer of FPR. These results suggest that the suppressor factor depresses the effector function of T cells responsible for FPR possibly via macrophage. PMID:91573

  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. 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

  8. FOXL2 Is Involved in the Synergy between Activin and Progestins on the Follicle-Stimulating Hormone -

    E-print Network

    Mellon, Pamela L.

    , the type I receptor phosphorylates SMA/mothers against decapentaplegic homologs (SMAD) 2 and SMAD3, which), and PR are required. Furthermore, we demonstrate that FOXL2 can physically interact with PR and SMAD3 receptor leads to heterodimerization and phosphorylation of the type I receptor (18). Subsequently

  9. 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.

  10. 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...

  11. The Solubility Parameters of Ionic Liquids

    PubMed Central

    Marciniak, Andrzej

    2010-01-01

    The Hildebrand’s solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated. PMID:20559495

  12. bFGF and Activin A function to promote survival and proliferation of single iPS cells in conditioned half-exchange mTeSR1 medium.

    PubMed

    Guo, Xiaoling; Lian, Ruiling; Guo, Yonglong; Liu, Qing; Ji, Qingshan; Chen, Jiansu

    2015-07-01

    Human induced pluripotent stem (iPS) cells can be well maintained by clonal growth. The pluripotent growth of single iPS cells is limited by low survival. To facilitate robust single iPS cells cultured in vitro, half-exchange mTeSR1 medium (HM), whole-exchange medium (WM) and iPS cell-derived conditioned medium (iPS-CM) culture were used. The effects of bFGF and Activin A on the growth of single iPS cells were explored. The dissociation and propagation of single iPS cells also included Accutase enzymatic isolation, Rho-associated protein kinase (ROCK) inhibitor Y27632 protection and high-density single-cell seeding (1 × 10(6) cells/well). CCK-8 assays demonstrated that the viability of clonal iPS cells in mTeSR1 medium and single iPS cells in HM, iPS-CM or WM supplemented with 100 ng/ml bFGF and 10 ng/ml Activin A was significantly higher than that in WM. Annexin v and propidium iodide (PI) assay, Calcein AM and EthD-III double staining also confirmed the similar results. ELISA assays showed that the levels of bFGF and Activin A of single iPS cells in HM and iPS-CM were higher than single iPS cells in WM. Meanwhile, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), quantitative Polymerase Chain Reaction (qPCR), Western Blotting (WB), Immunofluorescence (IF) and karyotype analysis revealed that HM culture was able to maintain undifferentiated markers of Nanog, Klf4, Sox2, Oct4, and did not affect the karyotype of iPS cells. Undifferentiated single iPS cells in HM displayed homogenized growth. These findings demonstrate that bFGF and Activin A are important for the survival and growth of single iPS cells. HM culture system combined Accutase, Y27632 and high-density single-cell seeding can facilitate short-term growth of single iPS cells in vitro. PMID:25754839

  13. Presentation of Solubility Data: Units and Applications

    E-print Network

    CHAPTER 2 Presentation of Solubility Data: Units and Applications Stephen Schwartz Atmosphetic Sciences Division, Brookhaven National Laboratoty, Upton, NY, USA The solubility of gases in water such as the intracellular fluids of plants and animals. It is also pertinent to sampling of soluble atmospheric gases

  14. Protein solubility: sequence based prediction and experimental

    Microsoft Academic Search

    Pawel Smialowski; Antonio J. Martin-Galiano; Aleksandra Mikolajka; Tobias Girschick; Tad A. Holak; Dmitrij Frishman

    Motivation: Obtaining soluble proteins in sufficient concentrations is a recurring limiting factor in various experimental studies. Solubility is an individual trait of proteins which, under a given set of experi- mental conditions, is determined by their amino acid sequence. Accurate theoretical prediction of solubility from sequence is instru- mental for setting priorities on targets in large-scale proteomics pro- jects. Results:

  15. Solubility assessment for fertilizer containing phosphate rock

    Microsoft Academic Search

    S. H. Chien

    1993-01-01

    Various methods have been used worldwide for measuring the solubility of phosphate rock (PR) and fertilizers containing PR. In this review, chemical, mineralogical, and physical factors affecting various measurements of PR solubility are discussed. The most important factors are (1) PR solubility expression, (2) mineralogical composition of PR, (3) free carbonate (calcite dolomite) effect, (4) effect of apatite crystallinity and

  16. Effect of milk solids concentration on the pH, soluble calcium and soluble phosphate levels

    E-print Network

    Boyer, Edmond

    Note Effect of milk solids concentration on the pH, soluble calcium and soluble phosphate levels and equilibrium states of calcium and inorganic phosphate, are considered to be important in the stabilityH and the concentrations of soluble calcium (Casol) and soluble inorganic phosphate (Psol). At any given temperature

  17. BMP signaling mediated by constitutively active Activin type 1 receptor (ACVR1) results in ectopic bone formation localized to distal extremity joints.

    PubMed

    Agarwal, Shailesh; Loder, Shawn J; Brownley, Cameron; Eboda, Oluwatobi; Peterson, Jonathan R; Hayano, Satoru; Wu, Bingrou; Zhao, Bin; Kaartinen, Vesa; Wong, Victor C; Mishina, Yuji; Levi, Benjamin

    2015-04-15

    BMP signaling mediated by ACVR1 plays a critical role for development of multiple structures including the cardiovascular and skeletal systems. While deficient ACVR1 signaling impairs normal embryonic development, hyperactive ACVR1 function (R206H in humans and Q207D mutation in mice, ca-ACVR1) results in formation of heterotopic ossification (HO). We developed a mouse line, which conditionally expresses ca-ACVR1 with Nfatc1-Cre(+) transgene. Mutant mice developed ectopic cartilage and bone at the distal joints of the extremities including the interphalangeal joints and hind limb ankles as early as P4 in the absence of trauma or exogenous bone morphogenetic protein (BMP) administration. Micro-CT showed that even at later time points (up to P40), cartilage and bone development persisted at the affected joints most prominently in the ankle. Interestingly, this phenotype was not present in areas of bone outside of the joints - tibia are normal in mutants and littermate controls away from the ankle. These findings demonstrate that this model may allow for further studies of heterotopic ossification, which does not require the use of stem cells, direct trauma or activation with exogenous Cre gene administration. PMID:25722188

  18. 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.

  19. Differential subcellular localization of endogenous and transfected soluble epoxide hydrolase in mammalian cells: evidence for isozyme variants

    Microsoft Academic Search

    Robert T Mullen; Richard N Trelease; Heike Duerk; Michael Arand; Bruce D Hammock; Franz Oesch; David F Grant

    1999-01-01

    Endogenous, constitutive soluble epoxide hydrolase in mice 3T3 cells was localized via immunofluorescence microscopy exclusively in peroxisomes, whereas transiently expressed mouse soluble epoxide hydrolase (from clofibrate-treated liver) accumulated only in the cytosol of 3T3 and HeLa cells. When the C-terminal Ile of mouse soluble epoxide hydrolase was mutated to generate a prototypic putative type 1 PTS (-SKI to -SKL), the

  20. Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and non-alcoholic fatty liver disease in high-fructose diet-fed rats.

    PubMed

    Chang, Wan-Ching; Jia, Huijuan; Aw, Wanping; Saito, Kenji; Hasegawa, Sumio; Kato, Hisanori

    2014-09-14

    Jerusalem artichoke (JA) has the potential to attenuate lipid disturbances and insulin resistance (IR), but the underlying mechanisms are not well understood. In the present study, we elucidated the physiological responses and mechanisms of JA intervention with a comprehensive transcriptome analysis. Wistar rats were fed a control diet, a 60 % fructose-enriched diet (FRU), or a FRU with 10 % JA (n 6-7) for 4 weeks. An oral glucose tolerance test was carried out on day 21. Liver samples were collected for biochemical and global gene expression analyses (GeneChip® Rat Genome 230 2.0 Array, Affymetrix). Fructose feeding resulted in IR and hepatic TAG accumulation; dietary JA supplementation significantly improved these changes. Transcriptomic profiling revealed that the expression of malic enzyme 1 (Me1), associated with fatty acid synthesis; decorin (Dcn), related to fibrosis; and cytochrome P450, family 1, subfamily a, polypeptide 2 (Cyp1a2) and nicotinamide phosphoribosyltransferase (Nampt), associated with inflammation, was differentially altered by the FRU, whereas dietary JA supplementation significantly improved the expression of these genes. We established for the first time the molecular mechanisms driving the beneficial effects of JA in the prevention of type 2 diabetes and non-alcoholic fatty liver disease. We propose that 10 % JA supplementation may be beneficial for the prevention of the onset of these diseases. PMID:24968200

  1. Pharmacokinetics of a Water-Soluble Fullerene in Rats

    Microsoft Academic Search

    PRABHU RAJAGOPALAN; FRED WUDL; RAYMOND F. SCHINAZI; DOUGLAS BOUDINOT

    1996-01-01

    Fullerenes are the recently discovered third allotropic form of carbon. The biological activities of these compounds are being studied for various purposes. The bis(monosuccinimide) derivative ofp,p*-bis(2-amino- ethyl)-diphenyl-C60 (MSAD-C60) is a water-soluble fullerene derivative. MSAD-C60 has been shown to have antiviral activity against human immunodeficiency virus types 1 and 2 in vitro and to have virucidal and anti-human immunodeficiency virus protease

  2. Enhancement of solubility of dexibuprofen applying mixed hydrotropic solubilization technique.

    PubMed

    El-Houssieny, Boushra Mohamed; El-Dein, Esmat Zein; El-Messiry, Hussien Mohamed

    2014-08-01

    Dexibuprofen, is a practically water-insoluble nonsterodial anti-inflammatory drug which has a better anti-inflammatory effect than ibuprofen. A mixed hydrotropic solubilization technique was applied in order to improve the aqueous solubility and dissolution rate of dexibuprofen. Nine formulae were prepared using different concentrations of hydrotropic agents (sodium citrate dihydrate and urea). The prepared formulae were inspected visually for color and odor. Hygroscopicity, micromeretic properties, solubility, and pH for 1% aqueous solutions were determined. In-vitro dissolution studies of the different prepared formulae were performed adopting the USP XXII dissolution method type I basket apparatus method. The prepared formulae were characterized by infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The prepared formulae were a white color, odorless, slightly hygroscopic and exhibited good flow properties. Formulae containing higher amounts of hydrotropic agents exhibited an increase in the pH, solubility, rate and amount of dexibuprofen released from the dissolution medium. The highest dissolution rate was achieved from the F9 formula at drug:sodium citrate dihydrate:urea ratio (1:3:7.5). IR and DSC thermograph of dexibuprofen, hydrotropic agents and prepared formulae indicated the presence of intermolecular interaction between drug and hydrotropic agents which increased solubility and dissolution rate of drug, also, there is no chemical interaction confirming the stability of the drug with hydrotropic agents. PMID:25262596

  3. Enhanced solubility of petroleum hydrocarbons using biosurfactants 

    E-print Network

    Page, Cheryl Ann

    1997-01-01

    . . Saturation Model Development. . . . . 9 . . . 11 . . . 12 13 RESULTS AND DISCUSSION OF PAH SOLUBILITY EXPERIMENT. . . 14 IV RESULTS AND DISCUSSION OF ALKANE SOLUBILITY EXPERIMENT V CONCLUSIONS AND RECOMMENDATIONS. . . . . . 46 PAH Solubility... hydrocarbons (PAHs) was evaluated by temporal monitoring of the WAF concentrations of the compounds in the absence of surfactants, in the presence of a biosurfactant, and in the presence of a synthetic surfactant. The second study involved the temporal...

  4. 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.

  5. Soluble ?-synuclein is a novel modulator of Alzheimer’s disease pathophysiology

    PubMed Central

    Larson, Megan E.; Sherman, Mathew A.; Greimel, Susan; Kuskowski, Michael; Schneider, Julie A.; Bennett, David A.; Lesné, Sylvain E.

    2012-01-01

    Recent evidence has emphasized soluble species of amyloid-? (A?) and tau as pathogenic effectors in AD. Despite the fact that A?, tau and ?-synuclein (?Syn) can promote each other’s aggregation, the potential contribution of soluble ?Syn to Alzheimer’s disease (AD) pathogenesis is unknown. Here, we found a ~2-fold increase over controls in soluble ?Syn levels in AD brains in the absence of LB cytopathology. Importantly, soluble ?Syn levels were a quantitatively stronger correlate of cognitive impairment than soluble A? and tau levels. To examine a putative role for ?Syn in modulating cognitive function, we used the Barnes circular maze to assess spatial reference memory in transgenic mice overexpressing human wild-type ?Syn. The results revealed that a ~3-fold elevation of ?Syn in vivo induced memory deficits similar to those observed in AD mouse models. The neurobiological changes associated with this elevation of soluble ?Syn included decreases in selected synaptic vesicle proteins and an alteration of the protein composition of synaptic vesicles. Finally, a synergism between A?/APP and human tau appears to be responsible for the abnormal elevation of soluble ?Syn in transgenic mice. Altogether, our data reveal an unexpected role for soluble, intraneuronal ?Syn in AD pathophysiology. PMID:22836259

  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. Characterization of a soluble polyimide

    NASA Technical Reports Server (NTRS)

    Young, Philip R.; Wakelyn, N. T.; Chang, A. C.

    1985-01-01

    The solid phase thermal imidization of a soluble 4,4-prime-bis (3,4-dicarboxyphynoxy) diphenyl sulfide dianhydride plus 2,2-bis 4-(4-aminophenoxyl)phenyl hexafluoropropane (BDSDA-BDAF) polyimide precursor staged between 40 and 325 C was characterized by gel permeation chromatography, inherent viscosity, and number average molecular weight measurements. The information obtained indicated that this polyamic acid experienced an initial reduction in molecular weight during cure before achieving its ultimate molecular weight as a polyimide. The event was most likely related to the development of an anhydride band that appeared in the infrared spectrum around 1850/cm as the material cured. Correlation through infrared spectroscopy with a previous study dealing with several common, but insoluble, polyimide precursors, suggested that polyimides, in general, exhibit this trend in molecular weight behavior.

  8. Spreadsheet Techniques for Evaluating the Solubility of Sparingly Soluble Salts of Weak Acids

    Microsoft Academic Search

    José L. Guinón; José García-Antón; Valentín Pérez-Herranz

    1999-01-01

    A spreadsheet of Microsoft Excel for determining the solubility of sparingly soluble salts is described. The chart and worksheet are shown simultaneously on the screen. The worksheet can be used for any salt by merely changing the data for the solubility product constant and ionization constants. Practical examples of calculations are given and discussed.

  9. Limiting Solubilities and lonization Constants of Sparingly Soluble Compounds: Determination from Aqueous Potentiometric Titration Data Only

    Microsoft Academic Search

    Adriaan P. IJzerman

    1988-01-01

    A new method is described for the concomitant determination of limiting solubilities and ionization constants of sparingly soluble compounds, i.e., drugs. Aqueous potentiometric titration data were recorded both before and after precipitation of the compound and subjected to computer-assisted analysis. Limiting solubilities and ionization constants were obtained for nucleoside transport inhibitors, viz., dilazep, soluflazine, and hexobendine. The method was validated

  10. Quantification of soluble HLA class I gene products by an enzyme linked immunosorbent assay

    Microsoft Academic Search

    Ilias Doxiadis; Ulrike Westhoff; Hans Grosse-Wilde

    1989-01-01

    A simplified enzyme linked immunosorbent assay utilizing an HLA class I frameworkspecific monoclonal antibody and a polyclonal enzyme linked beta-2 microglobulin specific antiserum has been established for the quantitative measurement of soluble HLA class I molecules. A total of 219 unrelated healthy individuals and 137 members of 28 families typed for HLA were analyzed for their non-membrane bound, i.e. soluble

  11. Phase Selectively Soluble Polystyrene-Supported Organocatalysts 

    E-print Network

    Khamatnurova, Tatyana

    2014-08-10

    increase in phase selective solubility in thermomorphic and latent biphasic systems. The advantage of alkyl-substituted polystyrenes is that they are phase-selectively soluble which means that a polymer-bound catalyst can be separated from products in a...

  12. Wet removal of highly soluble gases

    Microsoft Academic Search

    Peter Brimblecombe; G. A. Dawson

    1984-01-01

    Partition, not kinetics, ultimately determines the concentration of highly soluble gases in cloud droplets. Partition equations are formulated and applied to idealized air-mass thunderclouds and precipitating stratus. Contribution to aqueous concentrations from sub-cloud scavenging of highly soluble gases is estimated at between 10 and 20% under relatively unpolluted conditions. Data indicate that evaporation can produce enhancements in concentration of as

  13. 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

  14. 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…

  15. Airway exchange of highly soluble gases.

    PubMed

    Hlastala, Michael P; Powell, Frank L; Anderson, Joseph C

    2013-03-01

    Highly blood soluble gases exchange with the bronchial circulation in the airways. On inhalation, air absorbs highly soluble gases from the airway mucosa and equilibrates with the blood before reaching the alveoli. Highly soluble gas partial pressure is identical throughout all alveoli. At the end of exhalation the partial pressure of a highly soluble gas decreases from the alveolar level in the terminal bronchioles to the end-exhaled partial pressure at the mouth. A mathematical model simulated the airway exchange of four gases (methyl isobutyl ketone, acetone, ethanol, and propylene glycol monomethyl ether) that have high water and blood solubility. The impact of solubility on the relative distribution of airway exchange was studied. We conclude that an increase in water solubility shifts the distribution of gas exchange toward the mouth. Of the four gases studied, ethanol had the greatest decrease in partial pressure from the alveolus to the mouth at end exhalation. Single exhalation breath tests are inappropriate for estimating alveolar levels of highly soluble gases, particularly for ethanol. PMID:23305981

  16. 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)

  17. A new nondamaging acid soluble weighting material

    Microsoft Academic Search

    J. P. Jr. Sloan; J. P. Brooks; S. F. Dear

    1974-01-01

    Discovery of a new, acid soluble weighting material, iron carbonate, promises significant reduction of formation damage caused by fluids weighted up to 19 lb\\/gal. Two primary causes of such damage, particulate invasion and filter cake buildup, were virtually eliminated in laboratory permeability studies, which also compared performance with barite mixtures. The new material is soluble in dilute HCl and HCOOH,

  18. Determination of ozone solubility in polymeric materials

    Microsoft Academic Search

    Maarten Dingemans; Jo Dewulf; Wouter Van Hecke; Herman Van Langenhove

    2008-01-01

    The transport of a gas or vapour through a dense, nonporous membrane can be described in terms of a solution-diffusion mechanism, which states that the permeability is determined by its diffusivity and solubility. The solubility of many different molecules in many different polymers has been measured and can be found in the literature. However, very little information can be found

  19. Solubility of aceclofenac in polyamidoamine dendrimer solutions

    PubMed Central

    Patel, Jaydeep; Garala, Kevin; Basu, Biswajit; Raval, Mihir; Dharamsi, Abhay

    2011-01-01

    In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs. PMID:23071935

  20. Solubility of aceclofenac in polyamidoamine dendrimer solutions.

    PubMed

    Patel, Jaydeep; Garala, Kevin; Basu, Biswajit; Raval, Mihir; Dharamsi, Abhay

    2011-07-01

    In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs. PMID:23071935

  1. Phase selectively soluble polymer supports to facilitate homogeneous catalysis 

    E-print Network

    Ortiz-Acosta, Denisse

    2009-05-15

    Soluble polymers that have phase selective solubility are useful in synthesis because they simplify purification and separation. Such selectively soluble polymers simplify catalyst, reagent, and product recovery and enable the use of Green chemistry...

  2. 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

  3. Residual nilpotence and residual solubility of groups

    NASA Astrophysics Data System (ADS)

    Mikhailov, R. V.

    2005-12-01

    The properties of the residual nilpotence and the residual solubility of groups are studied. The main objects under investigation are the class of residually nilpotent groups such that each central extension of these groups is also residually nilpotent and the class of residually soluble groups such that each Abelian extension of these groups is residually soluble. Various examples of groups not belonging to these classes are constructed by homological methods and methods of the theory of modules over group rings. Several applications of the theory under consideration are presented and problems concerning the residual nilpotence of one-relator groups are considered.

  4. 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

  5. Studies of phase separable soluble polymers 

    E-print Network

    Furyk, Steven Michael

    2006-08-16

    but suffer from problems inherent to their heterogeneous nature. A solution to these problems has been to utilize phase separable soluble polymers in the design of Â?smartÂ? responsive systems that offer the option of homogenous reaction conditions...

  6. Studies of Soluble Polymer-supported Organocatalysts 

    E-print Network

    Yang, Yun-Chin

    2012-10-19

    soluble polymer-supported phosphines and electronically similar low molecular weight phosphine ligands. The phosphine-silver complexes supported on terminally functionalized polyisobutylene (PIB) and poly(ethylene glycol) show similar kinetic behavior...

  7. An Introduction to the Understanding of Solubility.

    ERIC Educational Resources Information Center

    Letcher, Trevor M.; Battino, Rubin

    2001-01-01

    Explores different solubility processes and related issues, including the second law of thermodynamics and ideal mixtures, real liquids, intermolecular forces, and solids in liquids or gases in liquids. (Contains 22 references.) (ASK)

  8. Soluble levels of cytosolic tubulin regulate ciliary length control

    PubMed Central

    Sharma, Neeraj; Kosan, Zachary A.; Stallworth, Jannese E.; Berbari, Nicolas F.; Yoder, Bradley K.

    2011-01-01

    The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control. PMID:21270438

  9. Cell-mediated immunity to soluble and particulate inhaled antigens

    PubMed Central

    Hill, J. O.; Burrell, R.

    1979-01-01

    In order to determine the influence of an antigen's physical properties on the development of cell-mediated immunity (CMI) in the lung following aerosol immunization, human serum albumin (HSA) was prepared in either a soluble or a particulate form, the latter being coupled to respirable, carboxylated latex beads. Antigen was administered via an aerosol to groups of guinea-pigs, twice weekly for up to 4 weeks. Additional groups of animals served as unexposed and unconjugated latex controls. Lymphoid cells for CMI assays were isolated from the lung by bronchopulmonary lavage and from blood for use in mitogen- and antigen-induced lymphocyte transformation assays, as well as indirect macrophage migration inhibition tests. Particulate HSA-exposed animals yielded the highest numbers of free lung cells containing predominantly macrophages, with up to 33% lymphocytes. These were followed by the latex control, soluble HSA and unexposed control groups, respectively. Only the animals exposed to particulate HSA had evidence of antigen reactivation in the lung cell populations as measured by lymphocyte stimulation assays. In contrast, a response to polyclonal mitogens was found only in animals exposed to antigen in a soluble form. Data from macrophage depletion experiments suggest that the antigenicity of inhaled antigens may be due to the types and numbers of cells responding to the stimulus, and the subsequent role the alveolar macrophage may play in the modulation of cellular immunity. PMID:393444

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

    PubMed

    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

  11. Structural Characterization of Cleaved, Soluble HIV-1 Envelope Glycoprotein Trimers

    PubMed Central

    Khayat, Reza; Lee, Jeong Hyun; Julien, Jean-Philippe; Cupo, Albert; Klasse, Per Johan; Sanders, Rogier W.; Moore, John P.; Wilson, Ian A.

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is a significant global public health problem for which development of an effective prophylactic vaccine remains a high scientific priority. Many concepts for a vaccine are focused on induction of appropriate titers of broadly neutralizing antibodies (bNAbs) against the viral envelope (Env) glycoproteins gp120 and gp41, but no immunogen has yet accomplished this goal in animals or humans. One approach to induction of bNAbs is to design soluble, trimeric mimics of the native viral Env trimer. Here, we describe structural studies by negative-stain electron microscopy of several variants of soluble Env trimers based on the KNH1144 subtype A sequence. These Env trimers are fully cleaved between the gp120 and gp41 components and stabilized by specific amino acid substitutions. We also illustrate the structural consequences of deletion of the V1/V2 and V3 variable loops from gp120 and the membrane-proximal external region (MPER) from gp41. All of these variants adopt a trimeric configuration that appropriately mimics native Env spikes, including the CD4 receptor-binding site and the epitope for the VRC PG04 bNAb. These cleaved, soluble trimer designs can be adapted for use with multiple different env genes for both vaccine and structural studies. PMID:23824817

  12. Measurement of Protein Solubility in Common Feedstuffs

    Microsoft Academic Search

    J. E. Wohlt; C. J. Sniffen; W. H. Hoover

    1973-01-01

    Percent total soluble nitrogen of casein and soy protein (25 mg nitrogen\\/100 ml solvent) was determined at three pH's (5.5, 6.5, and 7.5) over four intervals (30, 60, 90, and 120 min) and in two solvents at 40 C. A comparison cf means (46 vs. 477O) showed that solubility in autoclaved rumen fluid was significantly less than in mineral buffer.

  13. Correlation of Catalytic Rates With Solubility Parameters

    NASA Technical Reports Server (NTRS)

    Lawson, Daniel D.; England, Christopher

    1987-01-01

    Catalyst maximizes activity when its solubility parameter equals that of reactive species. Catalytic activities of some binary metal alloys at maximum when alloy compositions correspond to Hildebrand solubility parameters equal to those of reactive atomic species on catalyst. If this suggestive correlation proves to be general, applied to formulation of other mixed-metal catalysts. Also used to identify reactive species in certain catalytic reactions.

  14. GELATION OF ALFALFA SOLUBLE LEAF PROTEINS

    Microsoft Academic Search

    B. P. Lamsal; R. G. Koegel; S. Gunasekaran

    Various alfalfa soluble leaf protein concentrates were prepared by freeze-drying acid-precipitated proteins (pH 3.5), resolubilized proteins (pH 7), and membrane-concentrated clarified alfalfa juice. Dilute leaf protein solutions were prepared by dissolving these concentrates in water. Storage modulus (G ) of soluble leaf protein solutions as they gel was monitored with a cone-and-plate probe during temperature sweep from 25°C to 90°C

  15. 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.

  16. 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

  17. Oil-soluble corrosion inhibitor packages of the third generation

    SciTech Connect

    Shkol'nikov, V.M.; Shekhter, Yu.N.; Pospelov, M.V.; Furman, A.Ya.; Kardash, N.V.

    1988-05-01

    Oil-soluble corrosion inhibitors of different chemical classes and certain combined inhibitors have been investigated to determine their influence on specific forms of corrosion attack and corrosive-mechanical wear. Data are presented to illustrate the influence of combined inhibitors on the functional properties of oils in test-stand units and in full-scale carburetor and diesel engines in various types of automotive vehicles. It is shown that of all the inhibitors investigated, the best results in terms of the entire set of properties are shown by molybdenum-containing surfactants. Theoretical principles are set forth as guidelines in selecting components for corrosion inhibitors of the third generation.

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

    E-print Network

    Magee, Joseph W.

    Institute of Physics and the American Chemical Society. Reprints available from ACS; see Reprints List, of thermodynamic data related to the solubility of gases in polymers at different temperatures and pressures to represent variations of solubility with changes in gas pressure and temperature. Refer- enced works

  19. Melt extrusion with poorly soluble drugs.

    PubMed

    Shah, Sejal; Maddineni, Sindhuri; Lu, Jiannan; Repka, Michael A

    2013-08-30

    Melt extrusion (ME) over recent years has found widespread application as a viable drug delivery option in the drug development process. ME applications include taste masking, solid-state stability enhancement, sustained drug release and solubility enhancement. While ME can result in amorphous or crystalline solid dispersions depending upon several factors, solubility enhancement applications are centered around generating amorphous dispersions, primarily because of the free energy benefits they offer. In line with the purview of the current issue, this review assesses the utility of ME as a means of enhancing solubility of poorly soluble drugs/chemicals. The review describes major processing aspects of ME technology, definition and understanding of the amorphous state, manufacturability, analytical characterization and biopharmaceutical performance testing to better understand the strength and weakness of this formulation strategy for poorly soluble drugs. In addition, this paper highlights the potential advantages of employing a fusion of techniques, including pharmaceutical co-crystals and spray drying/solvent evaporation, facilitating the design of formulations of API exhibiting specific physico-chemical characteristics. Finally, the review presents some successful case studies of commercialized ME based products. PMID:23178213

  20. Solubility of pllutonium in alkaline salt solutions

    SciTech Connect

    Hobbs, D.T.; Edwards, T.B.

    1993-02-26

    Plutonium solubility data from several studies have been evaluated. For each data set, a predictive model has been developed where appropriate. In addition, a statistical model and corresponding prediction intervals for plutonium solubility as a quadratic function of the hydroxide concentration have been developed. Because of the wide range of solution compositions, the solubility of plutonium can vary by as much as three orders of magnitude for any given hydroxide concentration and still remain within the prediction interval. Any nuclear safety assessments that depend on the maximum amount of plutonium dissolved in alkaline salt solutions should use concentrations at least as great as the upper prediction limits developed in this study. To increase the confidence in the prediction model, it is recommended that additional solubility tests be conducted at low hydroxide concentrations and with all of the other solution components involved. To validate the model for application to actual waste solutions, it is recommended that the plutonium solubilities in actual waste solutions be determined and compared to the values predicted by the quadratic model.

  1. 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.

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

    PubMed

    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

  3. Solubility of Mg-containing beta-tricalcium phosphate at 25 degrees C.

    PubMed

    Li, Xia; Ito, Atsuo; Sogo, Yu; Wang, Xiupeng; LeGeros, R Z

    2009-01-01

    The equilibrium solubility of Mg-containing beta-tricalcium phosphate (betaMgTCP) with various magnesium contents was determined by immersing betaMgTCP powder for 27 months in a CH(3)COOH-CH(3)COONa buffer solution at 25 degrees C under a nitrogen gas atmosphere. The negative logarithm of the solubility product (pK(sp)) of betaMgTCP was expressed as pK(sp)=28.87432+1.40348C-0.3163C(2)+0.04218C(3)-0.00275C(4)+0.0000681659C(5), where C is the magnesium content in betaMgTCP (mol.%). The solubility of betaMgTCP decreased with increasing magnesium content owing to the increased structural stability and possible formation of a whitlockite-type phase on the surface. As a result, betaMgTCP with 10.1 mol.% magnesium had a lower solubility than that of hydroxyapatite below pH 6.0. betaMgTCP was found to be more soluble than zinc-containing beta-tricalcium phosphate given the same molar content of zinc or magnesium. The solubility of betaMgTCP and release rate of magnesium from betaMgTCP can be controlled by adjusting the Mg content by selecting the appropriate pK(sp). PMID:18644755

  4. Kinesin Spindle Protein Inhibitors with Diaryl Amine Scaffolds: Crystal Packing Analysis for Improved Aqueous Solubility

    PubMed Central

    2014-01-01

    Diaryl amine derivatives have been designed and synthesized as novel kinesin spindle protein (KSP) inhibitors based on planar carbazole-type KSP inhibitors with poor aqueous solubility. The new generation of inhibitors was found to show comparable inhibitory activity and high selectivity for KSP, and this was accompanied with improved solubility. Kinetic analysis and molecular modeling studies suggested that these inhibitors work in an ATP-competitive manner via binding to the secondary allosteric site formed by ?4 and ?6 helices of KSP. Comparative structural investigations on a series of compounds revealed that the higher solubility of diaryl amine-type inhibitors was attributed to fewer van der Waals interactions in the crystal packing and the hydrogen-bond acceptor nitrogen of the aniline moiety for favorable solvation. PMID:24900881

  5. 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

  6. 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.

  7. AW-101 entrained solids - Solubility versus temperature

    SciTech Connect

    GJ Lumetta; RC Lettau; GF Piepel

    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 AW-101 low-activity waste (LAW) sample. BNFL requested Battelle to dilute the AW-1-1 sample using de-ionized water to mimic expected plant operating conditions. BNFL further requested Battelle to assess the solubility of the solids present in the diluted AW-101 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. The work was conducted according to test plan BNFL-TP-29953-7, Rev. 0, Determination of the Solubility of LAW Entrained Solids. The test went according to plan, with no deviations from the test plan.

  8. Aqueous slurry blasting composition containing an aliphatic amine salt and a water soluble inorganic perchlorate

    Microsoft Academic Search

    H. G. Jr

    1971-01-01

    Inorganic oxidizer salt blasting compositions of the aqueous slurry type are provided which contain a combination of an aliphatic amine salt and a water- soluble inorganic perchlorate as a sensitizer component. Preferably, each of the amine salt and perchlorate is present in the sensitizer combination in a proportion at least stoichiometrically equivalent to that required for reaction with the other

  9. 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...

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

    SciTech Connect

    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.

  11. Increased plasma soluble endoglin levels as an indicator of cardiovascular alterations in hypertensive and diabetic patients

    Microsoft Academic Search

    Ana M Blázquez-Medela; Luis García-Ortiz; Manuel A Gómez-Marcos; José I Recio-Rodríguez; Angel Sánchez-Rodríguez; José M López-Novoa; Carlos Martínez-Salgado

    2010-01-01

    BACKGROUND: Endoglin is involved in the regulation of endothelial function, but there are no studies concerning its relation with hypertension- and diabetes-associated pathologies. Thus, we studied the relationship between plasma levels of soluble endoglin and cardiovascular alterations associated with hypertension and diabetes. METHODS: We analyzed 288 patients: 64 with type 2 diabetes, 159 with hypertension and 65 healthy patients. We

  12. Structure of the Soluble Domain of Cytochrome f from the Cyanobacterium Phormidium laminosum,

    E-print Network

    Cramer, William A.

    Structure of the Soluble Domain of Cytochrome f from the Cyanobacterium Phormidium laminosum ABSTRACT: Cytochrome f from the photosynthetic cytochrome b6f complex is unique among c-type cytochromes of cytochrome f from the thermophilic cyanobacterium Phormidium laminosum demonstrates that an unusual buried

  13. Abstract. Soluble epoxide hydrolase (sEH) hydrolyses/ inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs)

    E-print Network

    Hammock, Bruce D.

    the development of many types of cancers (1, 2). A typical example is inflammatory bowel disease (IBD) that comes active inflammatory process in the gut and includes two diseases: ulcerative colitis (UC) and CrohnAbstract. Soluble epoxide hydrolase (sEH) hydrolyses/ inactivates anti-inflammatory

  14. Best-basis estimates of solubility of selected radionuclides in sludges in Hanford single-shell tanks

    SciTech Connect

    HARMSEN, R.W.

    1999-02-24

    The Hanford Defined Waste (HDW) model (Rev. 4) (Agnew et al. 1997) projects inventories (as of January 1, 1994) of 46 radionuclides in the Hanford Site underground waste storage tanks. To model the distribution of the 46 radionuclides among the 177 tanks, it was necessary for Agnew et al. to estimate the solubility of each radionuclide in the various waste types originally added to the single-shell tanks. Previous editions of the HDW model used single-point solubility estimates. The work described in this report was undertaken to provide more accurate estimates of the solubility of all 46 radionuclides in the various wastes.

  15. Partially soluble organics as cloud condensation nuclei: Role of trace soluble and surface active species

    NASA Astrophysics Data System (ADS)

    Broekhuizen, K.; Kumar, P. Pradeep; Abbatt, J. P. D.

    2004-01-01

    The ability of partially soluble organic species to act as cloud condensation nuclei (CCN) has been studied. A Köhler model incorporating solute solubility and droplet surface tension describes the behavior of solid adipic and succinic acid particles, whereas solid azelaic acid activates much more efficiently that predicted. In addition, it was shown that trace levels of either sulfate or surface active species have a dramatic effect on the activation of adipic acid, a moderately soluble organic, as predicted by the full Köhler model. For internally mixed particles in the atmosphere, these effects will greatly enhance the role of organic aerosols as CCN.

  16. Towards a Molecular Understanding of Protein Solubility 

    E-print Network

    Kramer, Ryan 1984-

    2011-05-31

    be used to obtain comparative solubility measurements, and they fall into three broad classes: salts, long-chain polymers, and organic solvents. Our group has used a model protein, RNase Sa, to create 20 variants that differ by the residues at a single...

  17. Soluble arsenic removal at water treatment plants

    SciTech Connect

    McNeill, L.S.; Edwards, M. [Univ. of Colorado, Boulder, CO (United States). Dept. of Civil Engineering

    1995-04-01

    Arsenic profiles were obtained from full-scale conventional treatment (coagulation, Fe-Mn oxidation, or softening) plants, facilitating testing of theories regarding arsenic removal. Soluble As(V) removal efficiency was controlled primarily by pH during coagulation, be Fe{sup +2} oxidation and Fe(OH){sub 3} precipitation during Fe-Mn oxidation, and by Mg(OH){sub 2} formation during softening. Insignificant soluble As(V) removal occurred during calcite precipitation at softening plants or during Mn{sup +2} oxidation-precipitation at Fe-Mn oxidation plants. The extent of soluble As(V) removal during coagulation and softening treatments was lower than expected. Somewhat surprisingly, during coagulation As(V) removal efficiencies were limited by particulate aluminum formation and removal, because much of the added coagulant was not removed by 0.45-{mu}m-pore-size filters. At one utility, reducing the coagulation pH from 7.4 to 6.8 (at constant alum dose) improved removal of particulate aluminum, thereby enhancing soluble As(V) removal during treatment.

  18. Advanced soluble hydroliquefaction and hydrotreating catalysts

    SciTech Connect

    Laine, R.M. (Michigan Univ., Ann Arbor, MI (United States). Dept. of Materials Science and Engineering); Stoebe, T. (Washington Univ., Seattle, WA (United States). Dept. of Materials Science and Engineering)

    1991-11-22

    The purpose of the present program is to develop soluble analogs of surface confined catalysts that can be impregnated directly into the coal structure at low temperatures. This approach should avoid problems related to surface area dependence, a two phase (surface-liquid) reaction system and, mass transport limitations.

  19. Advanced soluble hydroliquefaction and hydrotreating catalysts

    SciTech Connect

    Laine, R.M. (Michigan Univ., Ann Arbor, MI (United States). Dept. of Materials Science and Engineering); Stoebe, T. (Washington Univ., Seattle, WA (United States). Dept. of Materials Science and Engineering)

    1992-01-31

    The purpose of the present program is to develop soluble analogs of surface confined catalysts that can be impregnated directly into the coal structure at low temperatures. This approach should avoid problems related to surface area dependence, a two phase (surface- liquid) reaction system and, mass transport limitations.

  20. Precipitation and solubility of some polonium compounds

    Microsoft Academic Search

    L. Zikovsky

    1998-01-01

    Polonium was precipitated from dilute solutions with metaarsenites, dichromates, iodides, molybdates, sulphites, sulphates\\u000a and metavanadates. The solubility products of polonium iodide, molybdate, sulphite and sulphate were determined to be 1.92,\\u000a 3.7, 3.3 and 0.9 respectively.

  1. A new silver sulfadiazine water soluble gel

    Microsoft Academic Search

    Andrew J. L. Gear; Timothy B. Hellewell; Heather R. Wright; Peter M. Mazzarese; Peter B. Arnold; George T. Rodeheaver; Richard F. Edlich

    1997-01-01

    Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice

  2. 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.

  3. Solubility Screening Kit Table of Contents

    E-print Network

    Lebendiker, Mario

    and insoluble proteins. RoboPop Solubility Screening Kit together with Novagen's RoboPop Purification Kits (2) allow rapid optimization of the host-vector combinations, expression conditions, and purification PopCulture in a room temperature water bath with gentle swirling or inversion to redissolve. Lysonase

  4. Absorption of water-soluble vitamins.

    PubMed

    Halsted, Charles H

    2003-03-01

    Water-soluble vitamins are required as enzyme cofactors in a wide variety of metabolic reactions. Riboflavin, niacin, and vitamin C are essential in redox reactions; thiamine and biotin are involved in macronutrient metabolism; and folate, vitamin B12, pyridoxine, and riboflavin play important roles in the regulation of S-adenosylmethionine production and DNA synthesis. Each of the water-soluble vitamins appears to require its own membrane transport process for absorption across the enterocyte. The absorption of vitamin B12, or cobalamin (Cbl), is unique in requiring multiple processes from the stomach to the ileum that involve at least four different binding proteins. Whereas all water-soluble vitamins are absorbed from the small intestine, folate, biotin, and riboflavin can be transported across colonic epithelial cells, with uncertain clinical significance. This article reviews recent studies on the requirement, metabolism, and deficiency state of each water-soluble vitamin, followed by a discussion of current knowledge on the regulation of its intestinal absorption. PMID:15703550

  5. Assessing Students' Conceptual Understanding of Solubility Equilibrium.

    ERIC Educational Resources Information Center

    Raviolo, Andres

    2001-01-01

    Presents a problem on solubility equilibrium which involves macroscopic, microscopic, and symbolic levels of representation as a resource for the evaluation of students, and allows for assessment as to whether students have acquired an adequate conceptual understanding of the phenomenon. Also diagnoses difficulties with regard to previous…

  6. Evaluating soluble toxicants in contaminated soils

    Microsoft Academic Search

    J. R. Pratt; P. V. McCormick; K. W. Pontasch; J. Cairns

    1988-01-01

    Complex mixtures of water soluble materials from contaminated soils can move into groundwater and surface water by leaching, percolation, and runoff. We evaluated the potential toxicity of leachable materials from seven soils. Five soil samples were obtained at designated toxic or hazardous waste sites, and two additional soils samples were obtained from a coal storage area and from an agricultural

  7. Free and water soluble chloride in concrete

    Microsoft Academic Search

    M. N. Haque; O. A. Kayyali

    1995-01-01

    Two methods were used to determine the ‘free’ and ‘water soluble’ chloride ions concentration in four differing strength grade concretes. Each grade of concrete had varying concentration of Cl? admixed as NaCl. In all 24 different batches of concretes were made with admixed Cl? concentration varying from 0.2 to 2%, by weight of cement. The first method was the analysis

  8. 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.

  9. Structure and solubility of natural silk fibroin

    Microsoft Academic Search

    E. S. Sashina; A. M. Bochek; N. P. Novoselov; D. A. Kirichenko

    2006-01-01

    The solubility of silk fibroin in aqueous-salt, aqueous-organic, and organic media is analyzed. Factors affecting the formation\\u000a of the secondary structural organization of fibroin in solutions and in the solid state after the recovery from solutions\\u000a are analyzed.

  10. Measurements and correlation of effect of cosolvents on the solubilities of complex molecules in supercritical carbon dioxide

    Microsoft Academic Search

    Min Jeong Noh; Tae Gyun Kim; In Kwon Hong; Ki-Pung Yoo

    1995-01-01

    A new transparent microscale circulation-type high pressure equilibrium cell with on-line sampling was devised. With this\\u000a apparatus, experimental solubility of molecularly complex species such as steroids (cholesterol, stigmasterol and ergosterol)\\u000a and fatty acids (palmitic acid and stearic acid) in supercritical carbon dioxide(sc-C02) were measured. Also, to find an appropriate substance for enhancing both the polarity and the solubility power of

  11. 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.

  12. Solubility of ?-diketonate complexes for cobalt(III) and chromium(III) in supercritical carbon dioxide

    Microsoft Academic Search

    Masashi Haruki; Fumiya Kobayashi; Masaaki Okamoto; Shin-ichi Kihara; Shigeki Takishima

    2010-01-01

    The solubilities of tris(2,2,6,6-tetramethyl-3,5-heptanedionate) cobalt(III) (Co(thd)3) and chromium(III) (Cr(thd)3) in supercritical carbon dioxide (scCO2) were measured at temperatures ranging from 313 to 343K. The measurements were carried out using a circulation-type apparatus with a UV–vis spectrometer. The solubilities of both Co(thd)3 and Cr(thd)3 increased as both the density of scCO2 and the temperature increased, which has the same tendency as

  13. Properties of spores of Bacillus subtilis strains which lack the major small, acid-soluble protein

    SciTech Connect

    Hackett, R.H.; Setlow, P.

    1988-03-01

    Bacillus subtilis strains containing a deletion in the gene coding for the major small, acid-soluble, spore protein (SASP-gamma) grew and sporulated, and their spores initiated germination normally, but outgrowth of SASP-gamma- spores was significantly slower than that of wild-type spores. The absence of SASP-gamma had no effect on spore protoplast density or spore resistance to heat or radiation. Consequently, SASP-gamma has a different function in spores than do the other major small, acid-soluble proteins.

  14. Soluble extensions of the Dirac oscillator with exact and broken supersymmetry

    SciTech Connect

    Castanos, O.; Frank, A.; Lopez, R.; Urrutia, L.F. (Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Circuito Exterior, C. U., Apartado Postal 70-543, 04510 Mexico, Distrito Federal, Mexico (MX))

    1991-01-15

    We consider a large class of Dirac oscillator-type couplings that exhibit a three-dimensional hidden supersymmetry. A subclass of exactly soluble cases is determined by using the Infeld and Hull procedure. We find that the corresponding spectra possess a high degree of unphysical degeneracy, similar to the Dirac oscillator case. This difficulty is overcome by proposing a further generalization of this coupling, which breaks supersymmetry but retains exact solubility. We also discuss the covariance properties of the new coupling together with its Poincare-invariant extension to the many-particle case.

  15. Glucose and insulin responses to whole grain breakfasts varying in soluble fiber, ?-glucan

    Microsoft Academic Search

    Hyunsook Kim; Kim S. Stote; Kay M. Behall; Karen Spears; Bryan Vinyard; Joan M. Conway

    2009-01-01

    Background  A high intake of whole grains containing soluble fiber has been shown to lower glucose and insulin responses in overweight\\u000a humans and humans with type 2 diabetes.\\u000a \\u000a \\u000a \\u000a Aim of the study  We investigated the linearity of this response after consumption of 5 breakfast cereal test meals containing wheat and\\/or\\u000a barley to provide varying amounts of soluble fiber, ?-glucan (0, 2.5, 5,

  16. Plasma Soluble Fas and Soluble Fas Ligand in ChronicGlomerulo nephritis

    Microsoft Academic Search

    Hirotake Sano; Kiyoji Asano; Shinya Minatoguchi; Jitsuko Hiraoka; Koh Fujisawa; Kazuhiko Nishigaki; Norio Yasuda; Hirokazu Kumada; Masao Takemura; Hiroshige Ohashi; Mitsuru Seishima; Takako Fujiwara; Hisayoshi Fujiwara

    1998-01-01

    It has been reported that glomerular cells with apoptosis and positive Fas immunoreactivity are seen in proliferative glomerulonephritis (PGN). Fas induces apoptosis when it binds to Fas ligand (Fas-L) or soluble Fas-L (sFas-L). However, soluble Fas (sFas) blocks apoptosis by inhibiting binding between Fas and Fas-L or sFas-L. That is, Fas, Fas-L, and sFas-L are inducers of apoptosis, but sFas

  17. Solubility constants and free enthalpies of metal sulphides, part 6: A new solubility cell

    Microsoft Academic Search

    Roland Heindl; Heinz Gamsjäger

    1977-01-01

    A solubility cell which can be operated continuously over the temperature range 5–95 °C has been developed. The solubility of Fe0.88S (monoclinic pyrrhotite) in solutions\\u000a$$S_0 = ([H^ + ]) = H{\\\\text{ }}m,{\\\\text{ }}[Na^ + ] = (1.00---H) m,{\\\\text{ }}[ClO_{4^ - } ] = 1.00 m)$$\\u000a at fixed partial pressures of H2S has been investigated at 50.7 °C. The hydrogen

  18. Binding of Soluble Yeast ?-Glucan to Human Neutrophils and Monocytes is Complement-Dependent

    PubMed Central

    Bose, Nandita; Chan, Anissa S. H.; Guerrero, Faimola; Maristany, Carolyn M.; Qiu, Xiaohong; Walsh, Richard M.; Ertelt, Kathleen E.; Jonas, Adria Bykowski; Gorden, Keith B.; Dudney, Christine M.; Wurst, Lindsay R.; Danielson, Michael E.; Elmasry, Natalie; Magee, Andrew S.; Patchen, Myra L.; Vasilakos, John P.

    2013-01-01

    The immunomodulatory properties of yeast ?-1,3/1,6 glucans are mediated through their ability to be recognized by human innate immune cells. While several studies have investigated binding of opsonized and unopsonized particulate ?-glucans to human immune cells mainly via complement receptor 3 (CR3) or Dectin-1, few have focused on understanding the binding characteristics of soluble ?-glucans. Using a well-characterized, pharmaceutical-grade, soluble yeast ?-glucan, this study evaluated and characterized the binding of soluble ?-glucan to human neutrophils and monocytes. The results demonstrated that soluble ?-glucan bound to both human neutrophils and monocytes in a concentration-dependent and receptor-specific manner. Antibodies blocking the CD11b and CD18 chains of CR3 significantly inhibited binding to both cell types, establishing CR3 as the key receptor recognizing the soluble ?-glucan in these cells. Binding of soluble ?-glucan to human neutrophils and monocytes required serum and was also dependent on incubation time and temperature, strongly suggesting that binding was complement-mediated. Indeed, binding was reduced in heat-inactivated serum, or in serum treated with methylamine or in serum reacted with the C3-specific inhibitor compstatin. Opsonization of soluble ?-glucan was demonstrated by detection of iC3b, the complement opsonin on ?-glucan-bound cells, as well as by the direct binding of iC3b to ?-glucan in the absence of cells. Binding of ?-glucan to cells was partially inhibited by blockade of the alternative pathway of complement, suggesting that the C3 activation amplification step mediated by this pathway also contributed to binding. PMID:23964276

  19. IUPAC-NIST Solubility Data Series 69. Ternary Alcohol-Hydrocarbon-Water Systems

    NASA Astrophysics Data System (ADS)

    Skrzecz, Adam; Shaw, David G.; Maczynski, Andrzej; Skrzecz, Adam

    1999-07-01

    The mutual solubilities of ternary systems containing alcohols, hydrocarbons and water are reviewed. An exhaustive search of the literature was attempted for numerical data on all alcohols and hydrocarbons which are liquid at STP. Data were found for alcohols with up to nine carbon atoms, but mostly with fewer than four carbons. Data for a variety of hydrocarbon structural types were found including alkane, alkene, and arene. A total of 205 original studies treating 116 ternary systems which have been published through 1992 are compiled. For 47 systems sufficient data were available to allow critical evaluation. All solubility data are expressed as mass and mole fractions as well as the originally reported units. Similar reviews of the related binary systems have previously been prepared for the Solubility Data Series.

  20. 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.

  1. Phase selectively soluble polymers for homogeneously supported catalysts 

    E-print Network

    Sung, Shayna D

    2006-10-30

    Soluble polymer supports that could be used in thermomorphic and latent biphasic systems have been prepared and analyzed for their potential application as supports for facilitated synthesis and catalysis. Phase selective solubilities were evaluated...

  2. Enhancement of Solubility and Bioavailability of -Lapachone Using

    E-print Network

    Gao, Jinming

    Enhancement of Solubility and Bioavailability of -Lapachone Using Cyclodextrin Inclusion Complexes. To explore the use of cyclodextrins (CD) to form inclusion complexes with -lapachone ( -lap) to overcome solubility and bioavailability. KEY WORDS: -lapachone; cyclodextrin; inclusion complex; solu- bility

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

    SciTech Connect

    Yin Hui [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Huang Baojun [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Department of Immunology, Anhui Medical University, Hefei 230032 (China); Yang Heng [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Huang Yafei [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Xiong Ping [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Zheng Fang [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Chen Xiaoping [Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Chen Yifa [Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China)]. E-mail: yfchen@tjh.tjmu.edu.cn; Gong Feili [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China)]. 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.

  4. Effects of solubility properties of solvents and biomass on biomass pretreatment.

    PubMed

    Weerachanchai, Piyarat; Kwak, Sang Kyu; Lee, Jong-Min

    2014-10-01

    Hildebrand solubility parameters of biomasses and pretreatment solvents were examined by a method of intrinsic viscosity. This is to be used as basic information in selecting a suitable solvent for biomass pretreatment processes. The effects of mixing1-ethyl-3-methylimidazolium acetate (EMIM-AC) and different solvents, lignin content in a pretreatment solvent, and biomass type on the Hildebrand solubility parameter and thermodynamic properties were carried out and calculated in this work. The Hildebrand solubility parameters of the mixtures are according to those of organic solvents: ?H[EMIM-AC/DMA]=25.07solubility parameters of biomass compositions (microcrystalline cellulose, xylan and alkali lignin) and biomasses (cassava pulp residue and rice straw) vary in the ranges of 25.14-26.13. The increases of lignin content in the pretreatment solvents lead to the Hildebrand solubility parameter becoming closer to that of lignin. PMID:25129231

  5. The Solubility of Ionic Solids and Molecular Liquids

    Microsoft Academic Search

    Carl Baer; Sheila M. Adamus

    1999-01-01

    Solubility is a ubiquitous concept in chemistry, but usually only sparingly soluble salts are examined in the introductory chemistry laboratory. With this two-part experiment, students study more common solubility phenomena. First, solubilities of three ionic salts (NaCl, PbCl2, and KAl(SO4)2.12H2O) in water are measured at four temperatures. The concept of recrystallization is introduced as students cool a high-temperature solution and

  6. [Distributional difference of fat-soluble compounds in the roots, stems and leaves of four Salvia plants].

    PubMed

    Li, Jin Tong; Dong, Juan E; Liang, Zong Suo; Shu, Zhi Ming; Wan, Guo Wei

    2008-02-01

    To illustrate distribution of fat-soluble compounds in the roots, stems and leaves of four Salvia plants, the methods of Histochemistry and HPLC were adopted to analyze different parts of the four Salvia plants in this paper. The results showed that distribution was differential, and following as this: the roots, stems and leaves of four Salvia plants contained fat-soluble compounds, moreover, the fat-soluble compounds of the roots located in periderm and the stems and leaves in epidermis. The main components of the fat-soluble compounds were Tanshinone IIA, Tanshinone I and Dihydrotanshinone I in the toots of Salvia miltiorrhiza Bunge and Salvia miltiorrhiza bge. f. alba, yet there were only Tanshinone IIA in the roots of Salvia japonica and Salvia officinalis. And fat-soluble compounds were not Tanshinone IIA, Tanshinone I and Dihydrotanshinone I in the stems and leaves of four Salvia plants. The type and content of fat-soluble compounds related to the species and introduction regions, they changed with the species and introduction regions. The conclusion clarified the accurate distribution of fat-soluble compounds in the different parts of four Salvia plants, and provided some theoretical basis for the application of Chinese herbs. PMID:18464589

  7. 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

  8. 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.

  9. Preparation of Soluble Proteins from Escherichia coli.

    PubMed

    Wingfield, Paul T

    2014-01-01

    Purification of human IL-1? is used in this unit as an example of the preparation of a soluble protein 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. In addition, the purification procedure serves as an example of how to use classical protein purifications methods, which may also be used in conjunction with the affinity-based methods now more commonly used. © 2014 by John Wiley & Sons, Inc. PMID:25367009

  10. Nomenclature for mammalian soluble glutathione transferases.

    PubMed

    Mannervik, Bengt; Board, Philip G; Hayes, John D; Listowsky, Irving; Pearson, William R

    2005-01-01

    The nomenclature for human soluble glutathione transferases (GSTs) is extended to include new members of the GST superfamily that have been discovered, sequenced, and shown to be expressed. The GST nomenclature is based on primary structure similarities and the division of GSTs into classes of more closely related sequences. The classes are designated by the names of the Greek letters: Alpha, Mu, Pi, etc., abbreviated in Roman capitals: A, M, P, and so on. (The Greek characters should not be used.) Class members are distinguished by Arabic numerals and the native dimeric protein structures are named according to their subunit composition (e.g., GST A1-2 is the enzyme composed of subunits 1 and 2 in the Alpha class). Soluble GSTs from other mammalian species can be classified in the same manner as the human enzymes, and this chapter presents the application of the nomenclature to the rat and mouse GSTs. PMID:16399376

  11. Computational design of a water-soluble analog of phospholamban

    E-print Network

    Summa, Christopher M.

    Computational design of a water-soluble analog of phospholamban AVRAM M. SLOVIC,1 CHRISTOPHER M September 24, 2002) Abstract Membrane proteins and water-soluble proteins share a similar core their lipid-exposed residues. We have developed computational tools to design water-soluble variants

  12. The Solubility of Sulphur in Hydrous Rhyolitic Melts

    E-print Network

    Paris-Sud XI, Université de

    The Solubility of Sulphur in Hydrous Rhyolitic Melts BEATRICE CLEMENTE, BRUNO SCAILLET AND MICHEL to hydrous metaluminous rhyolite bulk compositions, were used to constrain the solubility of sulphur in rhyolite melts. The results show that fS2 exerts a dominant control on the sulphur solubility in hydrous

  13. 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

  14. 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

  15. Improving drug solubility for oral delivery using solid dispersions

    Microsoft Academic Search

    Christian Leuner; Jennifer Dressman

    2000-01-01

    The solubility behaviour of drugs remains one of the most challenging aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Although solid solutions have tremendous potential for improving drug solubility, 40 years of research have resulted in only a few marketed products using this approach.

  16. Solubility of carbon in tetragonal ferrite in equilibrium with austenite

    E-print Network

    Cambridge, University of

    Solubility of carbon in tetragonal ferrite in equilibrium with austenite Jae Hoon Jang a H. K. D. H carbon is mobile. To explain this, we report the first calculations of the solubility of carbon in tetragonal ferrite that is in equilibrium with austenite. It is found that the solubility is dramatically

  17. 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

  18. ENTROPY OF SOLUBILITY OF SUBSTITUTIONAL IMPURITIES IN SOLID COMPOUNDS

    E-print Network

    Paris-Sud XI, Université de

    L-177 ENTROPY OF SOLUBILITY OF SUBSTITUTIONAL IMPURITIES IN SOLID COMPOUNDS F. BÉNIÈRE Physique des. Abstract. 2014 The vibrational solubility entropy, 0394Ssol, is evaluated for vanishingly low solid solubilities in a very simplified calculation. 0394Ssol is thus simply related to the Einstein frequencies

  19. Selection for intrabody solubility in mammalian cells using GFP fusions

    E-print Network

    Paris-Sud XI, Université de

    - 1 - Selection for intrabody solubility in mammalian cells using GFP fusions Laurence Guglielmi1 and VD contributed equally to this work. running title: Soluble intrabody selection in mammalian cells soluble expression levels in E. coli cytoplasm, have different behaviours in mammalian cells. When over

  20. LOCAL SOLUBILITY AND HEIGHT BOUNDS FOR COVERINGS OF ELLIPTIC CURVES

    E-print Network

    Fisher, Tom

    LOCAL SOLUBILITY AND HEIGHT BOUNDS FOR COVERINGS OF ELLIPTIC CURVES T.A. FISHER AND G.F. SILLS#cient algorithms for testing local solubility and modify the classical formulae for the covering maps so. An n­descent cal­ culation computes equations for the everywhere locally soluble n­coverings of E

  1. DEMULSIFICATION OF WATER IN OIL EMULSIONS USING WATER SOLUBLE DEMULSIFIERS

    Microsoft Academic Search

    C. S. Shetty; A. D. Nikolov; D. T. Wasan; B. R. Bhattacharyya

    1992-01-01

    The possibility of using a water soluble,as opposed to the conventional oil soluble demulsifier, to destabilize a w\\/o emulsion in crude oil has been explored. It was found experimentally that a surfactant soluble in the water (dispersed) phase could destabilize the emulsion. Polymer molecules with varying HLB's and molecular weights and structure were synthesized and these compounds were added to

  2. 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

  3. Solubility enhancement of celecoxib using ?-cyclodextrin inclusion complexes

    Microsoft Academic Search

    Swati Rawat; Sanjay K Jain

    2004-01-01

    Celecoxib has very low water solubility. It forms a complex with ?-cyclodextrin (?CD) both in aqueous and in solid state. It was observed that due to formation of the inclusion complex, the solubility and dissolution rate of celecoxib were enhanced. The formation of 1:1 complex with ?CD in solution was confirmed by phase solubility and spectral shift studies. The apparent

  4. Solubility of Pa(V) in solutions of thiocyanic acid

    Microsoft Academic Search

    V. V. Nekrasova; E. S. Palshin; B. F. Myasoedov

    1974-01-01

    The solubility of Pa(V) and Ta(V) hydroxides in HSCN as well as HCl ; solutions containing thiocyanato ions was studied. At equal concentrations of ; the acids the solubility of Pa(V) is higher in HSCN solutions than in HCl ; solutions. In 1M HSCN the Pa(V) solubility is 0.05 g\\/l. (auth);

  5. Soluble Aromatic Polyimides For Film Coating

    NASA Technical Reports Server (NTRS)

    St. Clair, Anne K.; St. Clair, Terry L.

    1989-01-01

    Because of toughness, flexibility, and remarkable thermal stability, linear all-aromatic polyimides excellent candidate film and coating materials for advanced electronic circuitry and wires. Study determined effects on solubility of changing isomeric points of attachment of phenoxy units in diamine portions of several all-aromatic polyimides. Tough, flexible, transparent films produced by thermally converting polyamic acids to polyimides at 300 degree C in air. Potential for electronic applications excellent.

  6. Polymorphisms in Human Soluble Epoxide Hydrolase

    Microsoft Academic Search

    BEATA D. PRZYBYLA-ZAWISLAK; PUNIT K. SRIVASTAVA; JOHANA V ´ AZQUEZ-MATIAS; HARVEY W. MOHRENWEISER; JOSEPH E. MAXWELL; BRUCE D. HAMMOCK; J. ALYCE BRADBURY; AHMED E. ENAYETALLAH; DARRYL C. ZELDIN; DAVID F. GRANT

    2003-01-01

    Human soluble epoxide hydrolase (hsEH) metabolizes a variety of epoxides to the corresponding vicinal diols. Arachidonic and linoleic acid epoxides are thought to be endogenous substrates for hsEH. Enzyme activity in humans shows high interindividual variation (e.g., 500-fold in liver) suggesting the existence of regulatory and\\/or structural gene polymorphisms. We rese- quenced each of the 19 exons of the hsEH

  7. Murine lung immunity to a soluble antigen

    SciTech Connect

    Weissman, D.N.; Bice, D.E.; Siegel, D.W.; Schuyler, M.R. (Albuquerque Veterans Administration Medical Center, NM (United States) Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States))

    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.

  8. Finite simply reducible groups are soluble

    SciTech Connect

    Kazarin, Lev S; Chankov, Evgenii I [P.G. Demidov Yaroslavl State University, Yaroslavl (Russian Federation)

    2010-06-29

    A finite group G is called simply reducible (briefly, an SR-group) if it has the following two properties: every element of this group is conjugate to its inverse; the tensor product of any two irreducible representations decomposes into a sum of irreducible representations of the group G with multiplicities not exceeding 1. It is proved that finite SR-groups are soluble. Bibliography: 13 titles.

  9. Solubility of plutonium and waste evaporation

    SciTech Connect

    Karraker, D.G.

    1993-10-22

    Chemical processing of irradiated reactor elements at the Savannah River Site separates uranium, plutonium and fission products; fission products and process-added chemicals are mixed with an excess of NaOH and discharged as a basic slurry into large underground tanks for temporary storage. The slurry is composed of base-insoluble solids that settle to the bottom of the tank; the liquid supemate contains a mixture of base-soluble chemicals--nitrates, nitrites aluminate, sulfate, etc. To conserve space in the waste tanks, the supemate is concentrated by evaporation. As the evaporation proceeds, the solubilities of some components are exceeded, and these species crystallize from solution. Normally, these components are soluble in the hot solution discharged from the waste tank evaporator and do not crystallize until the solution cools. However, concern was aroused at West Valley over the possibility that plutonium would precipitate and accumulate in the evaporator, conceivably to the point that a nuclear accident was possible. There is also a concern at SRS from evaporation of sludge washes, which arise from washing the base-insoluble solids ({open_quote}sludge{close_quote}) with ca. 1M NaOH to reduce the Al and S0{sub 4}{sup {minus}2} content. The sludge washes of necessity extract a low level of Pu from the sludge and are evaporated to reduce their volume, presenting the possibility of precipitating Pu. Measurements of the solubility of Pu in synthetic solutions of similar composition to waste supernate and sludge washes are described in this report.

  10. Solubility of nitrous oxide in amine solutions

    SciTech Connect

    Bensetiti, Z.; Iliuta, I.; Larachi, F.; Grandjean, B.P.A. [Laval Univ., Quebec (Canada)] [Laval Univ., Quebec (Canada)

    1999-01-01

    The solubility of nitrous oxide (N{sub 2}O) in 13 amine solvents and solutions was correlated to amine mole fractions and temperature using feedforward neural networks. This general correlation, using a massive database, predicted N{sub 2}O solubility at temperatures between 283 and 398 K in pure solvents [H{sub 2}O, monoethanolamine (MEA), diethanolamine (DEA), methyldiethanolamine (MDEA), and 2-amino-2-methyl-1-propanolamine (AMP)], in binary aqueous amine solutions [H{sub 2}O/MEA, H{sub 2}O/DEA, H{sub 2}O/MDEA, and H{sub 2}O/AMP], and in ternary aqueous amine blends [AMP/MDEA/H{sub 2}O, AMP/DEA/H{sub 2}O, DEA/MDEA/H{sub 2}O, MDEA/MEA/H{sub 2}O, and AMP/MEA/H{sub 2}O]. Combined with the N{sub 2}O analogy, this present improved correlation can be advantageously implemented in amine plant design software and procedures for the prediction of CO{sub 2} solubility in amine blend solutions over wide temperature and concentration ranges.

  11. 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.

  12. Improved water-soluble polymers for enhanced recovery of oil

    SciTech Connect

    Martin, F.D.; Hatch, M.J.; Shepitka, J.S.; Ward, J.S.

    1983-01-01

    Two principal types of polymers have been used extensively for enhanced recovery of crude oil: partially hydrolyzed polyacrylamide (HPAM) and xanthan gum. Because of its lower cost, HPAM is being used in a majority of the field projects when water-soluble polymers are applied. However, HPAM does lose viscosity in brines, particularly when divalent ions are present, and is susceptible to mechanical degradation under high shear conditions. Although many different polymer structures were evaluated in the laboratory tests, the main focus consisted of modifying the structure of HPAM and observing the effects on brine and shear stability. Testing of these analogs provided a systematic correlation of polymer structure with polymer performance so that improved compounds could be developed. 33 references.

  13. Biodegradable fibre scaffolds incorporating water-soluble drugs and proteins.

    PubMed

    Ma, J; Meng, J; Simonet, M; Stingelin, N; Peijs, T; Sukhorukov, G B

    2015-07-01

    A new type of biodegradable drug-loaded fibre scaffold has been successfully produced for the benefit of water-soluble drugs and proteins. Model drug loaded calcium carbonate (CaCO3) microparticles incorporated into poly(lactic acid-co-glycolic acid) (PLGA) fibres were manufactured by co-precipitation of CaCO3 and the drug molecules, followed by electrospinning of a suspension of such drug-loaded microparticles in a PLGA solution. Rhodamine 6G and bovine serum albumin were used as model drugs for our release study, representing small bioactive molecules and protein, respectively. A bead and string structure of fibres was achieved. The drug release was investigated with different drug loadings and in different pH release mediums. Results showed that a slow and sustained drug release was achieved in 40 days and the CaCO3 microparticles used as the second barrier restrained the initial burst release. PMID:26155976

  14. Solubility and solubility constant of barium sulfate in aqueous sodium sulfate solutions between 0 and 80°C

    Microsoft Academic Search

    Chengfa Jiang

    1996-01-01

    The solubilities of barium sulfate in aqueous solutions of sodium sulfate were studied at ionic strengths from 0.0005 to 0.02 mol-kg-1 and at 0, 20, 40, 60, and 80°C. The solubility data were used to calculate the solubility constants using an extrapolation method. The solubility constant obtained were in good agreement with literature data. The mean activity coefficients of barium

  15. Solubility of Lysozyme in the Presence of Aqueous Chloride Salts: Common-Ion Effect and Its Role on Solubility and

    E-print Network

    Benedek, George B.

    Solubility of Lysozyme in the Presence of Aqueous Chloride Salts: Common-Ion Effect and Its Role on Solubility and Crystal Thermodynamics Onofrio Annunziata,* Andrew Payne, and Ying Wang Department protein solubility is important for a rational design of the conditions of protein crystallization. We

  16. 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.

  17. The Solubility of Oxygen and Ozone in Liquids

    NASA Astrophysics Data System (ADS)

    Battino, Rubin; Rettich, Timothy R.; Tominaga, Toshihiro

    1983-04-01

    This review covers the solubility of oxygen and ozone in liquids as a function of temperature and pressure. Solubility data for individual systems were critically evaluated and recommended or tentative values presented in many cases. The trend of solubilities in homologous series or related solvents is discussed. Liquids include water; seawater; aqueous salt solutions; mixed solvents; hydrocarbons; organic compounds containing oxygen, halogen, sulfur, nitrogen, or silicon; olive oil; and human blood. For ozone, only its solubility in water is presented. Key words: aqueous solutions; biological fluids; gas solubility; hydrocarbons; mixed solvents; organic solvents; oxygen; ozone; seawater; water.

  18. 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.

  19. Changes in soluble carbohydrates during phytochrome-regulated petiole elongation in watermelon seedlings

    E-print Network

    Decoteau, Dennis R.

    Changes in soluble carbohydrates during phytochrome-regulated petiole elongation in watermelon, Phytochrome, Soluble carbohydrates Abstract Changes in soluble carbohydrate composition and concentration, and soluble carbohydrate concentration and composition in leaves and petioles were determined after 3 and 6

  20. Carbollide solubility and chemical compatibility summary

    SciTech Connect

    McCabe, D.J.

    1993-08-17

    This report examines the value of the cobalt dicarbollide anion as an effective form of in-tank precipitation. The cobalt dicarbollide anion (CDC) has been investigated for the possible replacement of tetraphenyl borate anion (TPB) for precipitation of cesium in SRS High Level Waste (HLW). The solubility of the cesium CDC in 5 M salt solutions and the reactivity with caustic have been studied extensively. The solubility of CSCDC in a mixture of 4 M sodium nitrate and 1 m sodium hydroxide is {approximately}2 {times} 10{sup {minus}3} M at 40{degrees}C. Furthermore, the CDC decomposes in 1 M sodium hydroxide solution with apparent first order kinetics with a half-life of 7.3 days at 60 {degrees}C and 94 days at 40{degrees}C. Tank temperatures are currently estimated to approach 60{degrees}C during the ITP filtration cycle. This solubility and rapid decomposition of the CDC under highly alkaline conditions and high temperature would require increasing the quantity of CDC and nonradioactive cesium which must be added, increasing the cost of production. Increasing the quantity of CDC would necessitate recovery of the material, probably using a solvent extraction system. Due to the large amount of nonradioactive cesium which must be added, the total amount of precipitate formed exceeds that for TPB precipitation. Also, formation of sodium and/or potassium precipitates compete with cesium salt precipitation in 5 M salt solutions at lower temperature (<30{degrees}C). Decomposition generates hydrogen, which may lead to process complications.

  1. 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.

  2. Sulfide solubilities in Alteration-controlled Systems

    USGS Publications Warehouse

    Hemley, J.J.; Meyer, C.; Hodgson, C.J.; Thatcher, A.B.

    1967-01-01

    Solubilities of sphalerite (ZnS) and galena (PbS) were determined at 300?? to 500??C and 1000 bars total pressure in a chemical environment buffered by silicate mineral equilibria. Chloride solutions and muscovite-bearing assemblages characteristic of hydrothermal wall-rock alteration were used; weak acidities at temperature were therefore involved. The metal concentrations encountered tended to be higher than those observed in high bisulfide-H2S systems at neutral to weakly basic pH used in most previous experimentation; the chemical conditions of the work, although not completely satisfactory, are geologically more realistic than previous experimentation done in the basic-pH region.

  3. Advanced, soluble hydroliquefaction and hydrotreating catalysts

    SciTech Connect

    Laine, R.M. (Michigan Univ., Ann Arbor, MI (United States). Dept. of Materials Science and Engineering); Stoebe, T. (Washington Univ., Seattle, WA (United States). Dept. of Materials Science and Engineering)

    1992-09-08

    Present hydroliquefaction of coal suffers from required high temperatures and high hydrogen pressures. Surface confined, organometallic catalysists are effective for hydrogenation and HDN of coal model compounds such as quinoline, but not of coal itself. Purpose of this program is to develop soluble analogs of surface confined catalysts that can be impregnated directly into the coal structure at low temperatures. The program consists of 3 major tasks: preparation of candidate HPA (heteropolyanion) precatalysts, HDN and HDO modeling studies, and direct liquefaction studies. During this period, preparation of [PRuMo[sub 11]O[sub 39

  4. 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.

  5. Solubility of HFCs in pentaerythritol tetraalkyl esters

    SciTech Connect

    Wahlstroem, A.; Vamling, L.

    2000-02-01

    The solubilities of difluoromethane (HFC32), 1,1,1,2,2-pentafluoroethane (HFC125), 1,1,1,2-tetrafluoroethane (HFC134a), 1,1,1-trifluoroethane (HFC143a) and 1,1-difluoroethane (HFC152a) in pentaerythritol tetranonanoate, pentaerythritol tetra-2-ethylbutanoate, and pentaerythritol tetra-2-ethylhexanoate have been measured at temperatures between 303 and 363 K and pressures between 0.07 and 2.1 MPa. Henry's constant and the activity coefficient for HFCs at infinite dilution were derived for measurements below 0.34 MPa. The measurements were made by an isochoric method with an uncertainty of <2% for Henry's constant and <3% at high pressure. Within the investigated temperature range, solubilities for HFCs in pentaerythritol tetraalkyl esters decrease in the following order: HFC152a > HFC134a > HFC32 > HFC125 > HFC143a. The experimental data have been correlated with a Flory-Huggins model with an extended temperature dependence, which is able to describe the data with a deviation from measured data of <2.7%.

  6. 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

  7. Soluble adenylyl cyclase in health and disease.

    PubMed

    Schmid, Andreas; Meili, Dimirela; Salathe, Matthias

    2014-12-01

    The second messenger cAMP is integral for many physiological processes. Soluble adenylyl cyclase (sAC) was recently identified as a widely expressed intracellular source of cAMP in mammalian cells. sAC is evolutionary, structurally, and biochemically distinct from the G-protein-responsive transmembranous adenylyl cyclases (tmAC). The structure of the catalytic unit of sAC is similar to tmAC, but sAC does not contain transmembranous domains, allowing localizations independent of the membranous compartment. sAC activity is stimulated by HCO(3)(-), Ca²? and is sensitive to physiologically relevant ATP fluctuations. sAC functions as a physiological sensor for carbon dioxide and bicarbonate, and therefore indirectly for pH. Here we review the physiological role of sAC in different human tissues with a major focus on the lung. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease, guest edited by J. Buck and L.R. Levin. PMID:25064591

  8. Soluble Mediators Regulating Immunity in Early Life

    PubMed Central

    Pettengill, Matthew Aaron; van Haren, Simon Daniël; Levy, Ofer

    2014-01-01

    Soluble factors in blood plasma have a substantial impact on both the innate and adaptive immune responses. The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. Levels of these innate effector proteins are generally lower in neonatal circulation at term delivery than in adults, and lower still at preterm delivery. The extracellular environment also has a critical influence on immune cell maturation, activation, and effector functions, and many of the factors in plasma, including hormones, vitamins, and purines, have been shown to influence these processes for leukocytes of both the innate and adaptive immune systems. The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. Accordingly, we survey here a number of soluble mediators in plasma for which age-dependent differences in abundance may influence the ontogeny of immune function, particularly direct innate interaction and skewing of adaptive lymphocyte activity in response to infectious microorganisms and adjuvanted vaccines. PMID:25309541

  9. Fissile solubility and monosodium titanate loading tests

    SciTech Connect

    Hobbs, D.T.; Fleischman, S.D.

    1993-02-12

    The solubilities of plutonium and uranium have been determined for alkaline salt solutions having compositions which bound those which will be processed in the In-Tank Precipitation (ITP) process. Loadings of plutonium and uranium onto monosodium titanate (MST) have been determined at temperatures bounding those expected to occur during ITP and using a salt solution which was determined to have the maximum solubility for uranium and plutonium. Fissile loadings increase with decreasing amounts of MST in contact with the salt solutions saturated in plutonium and uranium. At MST concentrations bounding those which are planned for the ITP process, expressions for the maximum loadings (wt %) are determined to be 0.29 - 0.20x[MST] for plutonium and 1.8 - 0.29x[MST] for uranium, where [MST] is the concentration of MST in grams/liter. These expressions are valid over the range of MST concentrations from 0.05 to 0.51 g/L and temperatures of 17[degrees]--74[degrees]C. These loadings are below the individual infinitely safe limits for plutonium and uranium. Additional confirmatory experiments are planned to verify the effects of temperature and multiple contacts of the MST with fresh salt solution on the fissile loadings.

  10. Fissile solubility and monosodium titanate loading tests

    SciTech Connect

    Hobbs, D.T.; Fleischman, S.D.

    1993-02-12

    The solubilities of plutonium and uranium have been determined for alkaline salt solutions having compositions which bound those which will be processed in the In-Tank Precipitation (ITP) process. Loadings of plutonium and uranium onto monosodium titanate (MST) have been determined at temperatures bounding those expected to occur during ITP and using a salt solution which was determined to have the maximum solubility for uranium and plutonium. Fissile loadings increase with decreasing amounts of MST in contact with the salt solutions saturated in plutonium and uranium. At MST concentrations bounding those which are planned for the ITP process, expressions for the maximum loadings (wt %) are determined to be 0.29 - 0.20x[MST] for plutonium and 1.8 - 0.29x[MST] for uranium, where [MST] is the concentration of MST in grams/liter. These expressions are valid over the range of MST concentrations from 0.05 to 0.51 g/L and temperatures of 17{degrees}--74{degrees}C. These loadings are below the individual infinitely safe limits for plutonium and uranium. Additional confirmatory experiments are planned to verify the effects of temperature and multiple contacts of the MST with fresh salt solution on the fissile loadings.

  11. One-pot synthesis of water-soluble polymeric photoinitiator via thioxanthonation and sulfonation process

    Microsoft Academic Search

    Gokhan Temel; Nergis Arsu

    2009-01-01

    One-pot synthesis of water-soluble side chain thioxanthone polystyrene (PSt-TX-WS) was achieved, and photoinduced polymerization of acrylamide (AAm) in water was performed with PSt-TX-WS in the presence of a tertiary amine. Since the amine is necessary for photopolymerization to occur, it is likely that PSt-TX-WS initiates polymerization of AAm according to the Norrish Type II reaction. The fluorescence quantum yield of

  12. Soluble derivatives of perylene and naphthalene diimide for n-channel organic field-effect transistors

    Microsoft Academic Search

    Th. B. Singh; S. Erten; S. Günes; C. Zafer; G. Turkmen; B. Kuban; Y. Teoman; N. S. Sariciftci; S. Icli

    2006-01-01

    Solution-processed n-type organic field-effect transistors (OFETs) have been fabricated using soluble derivatives of perylene diimide and naphthalene diimide. We report the synthesis of the organic semiconductors and the fabrication of bottom gate OFET devices using solution-processed organic dielectrics. Surface morphology studies reveal films with layered textures and liquid crystalline-like structure. Devices show field-effect electron mobilities of 10?2cm2\\/Vs and 10?3cm2\\/Vs for

  13. Cathodic electro-deposition of low-temperature curable water-soluble polyepoxide coatings

    Microsoft Academic Search

    P. Kumar; M. K. Trivedi

    2000-01-01

    Epoxidised phenol-novolac (EPN) type of polyepoxide resin was used for developing water-soluble cathodically electro-depositable coatings which could be self-curable without using any external\\/additional cross-linking agent. The self-curing of cathodically deposited films could be effected at a low temperature of 80°C in 30min, as compared to 150–170°C in 30min practised presently in many commercial cathodic electro-deposition (CED) installations. In this work,

  14. Determination of phase diagrams of eutectic binary alloys with partial solid solubility

    Microsoft Academic Search

    L. J. Gallego; J. A. Somoza; J. A. Alonso; J. M. Lopez

    1988-01-01

    Using a semi-empirical theory largely based on the heat of formation model developed by Miedema and co-workers, we have constructed the phase diagram of the alloy CuAg, a prototypical example of a system of eutectic type with appreciable solid solubility and no intermetallic compounds. This is an advance on the simpler kind of phase diagrams we considered in a previous

  15. A general approach to creating soluble catalytic polymers heterogenized in microcapsules.

    PubMed

    Mason, Brian P; Bogdan, Andrew R; Goswami, Anandarup; McQuade, D Tyler

    2007-08-16

    A general method for preparing site-isolated polymeric catalysts is presented. Linear chloromethyl and azide polymers have been sequestered within polyurea microcapsules and small molecule catalysts soaked through the shell walls to functionalize the soluble polymers. Reaction onto each type of support is quantitative and MacMillan, DMAP, and TEMPO test catalysts are shown to have faster reaction rates than the analogous resin-supported catalysts. PMID:17645350

  16. Aqueous solubility of crystalline and amorphous drugs: Challenges in measurement.

    PubMed

    Murdande, Sharad B; Pikal, Michael J; Shanker, Ravi M; Bogner, Robin H

    2011-06-01

    Measurement of drug solubility is one of the key elements of active pharmaceutical ingredient (API) characterization during the drug discovery and development process. This report is a critical review of experimental methods reported in the literature for the measurement of aqueous solubility of amorphous, partially crystalline and crystalline organic compounds. A summary of high-throughput automated methods used in early drug discovery research is also provided in this report. This review summarizes the challenges that are encountered during solubility measurement and the complexities that are often overlooked. Even though there is an advantage in using the amorphous form of a drug due to its higher solubility, measurement of its solubility with useful accuracy is still a practical problem. Therefore, this review provides recommendations of preferred methods and precautions in using these methods to determine the aqueous solubility of amorphous and crystalline new molecular entities, with emphasis on the physico-chemical characterization of the solid state of the test substance. PMID:20429826

  17. Comparison of solubility databases used for HLW performance assessment

    NASA Astrophysics Data System (ADS)

    McKinley, Ian G.; Savage, David

    1996-02-01

    Elemental solubility limits are employed in many performance assessment studies of the disposal of high-level radioactive waste. A comparison of solubility databases used in a number of recent assessments from Canada, Finland, Japan, Sweden, Switzerland and the U.S.A. is presented. Despite similarities in the chemical conditions under which such solubilities are defined, there are very large ranges in the values selected for most elements (several orders of magnitude). In some cases, differences in solubilities can be attributed to differences in the thermodynamic databases used but, due to generally incomplete documentation, both of such databases and the criteria for data selection, detailed analysis of the reason for such discrepancies is precluded. A key factor, however, is the fairly subjective choice of the solid phase considered to be "solubility-limiting". Procedures are recommended which would increase the transparency of solubility database compilation in future analyses.

  18. Solubility of multi-component biodiesel fuel systems

    Microsoft Academic Search

    Violeta Makareviciene; Egle Sendzikiene; Prutenis Janulis

    2005-01-01

    Solubility of biodiesel fuel components in fossil diesel fuel–methanol–rapeseed oil methyl ester, fossil diesel fuel–ethanol–rapeseed oil methyl ester and fossil diesel fuel–ethanol–rapeseed oil ethyl ester systems was investigated. The solubility of components in the fossil diesel fuel–ethanol–rapeseed oil methyl ester system at 20 °C was substantially higher than in the fossil diesel fuel–methanol–rapeseed oil methyl ester system. The solubility of

  19. Soluble aromatic polyimides for film and coating applications

    NASA Technical Reports Server (NTRS)

    St. Clair, Anne K.; St. Clair, Terry L.

    1987-01-01

    The effect of changing isomeric points of attachment of phenoxy units in the diamine portion of several all-aromatic polyimide systems on the solubility of these materials were investigated. It was found that solubility could be enhanced by the presence of meta and ortho isomer links in the diamine portion of the molecule. The soluble phenoxy-linked polyimides yield tough flexible colorless to pale-yellow transparent films from solutions of chlorinated solvents, with high potential for use in electronic applications.

  20. BWIP data package for reference solubility and Kd values

    SciTech Connect

    Salter, P.F.; Jacobs, G.K.

    1983-01-06

    This data package defines the solubility and Kd values to be used for all modeling activities related to the migration of radionuclides through the geologic setting, or any other path where the geochemical conditions are appropriate. The set of conservative and expected solubilities and Kd values for modeling purposes are compared to available thermodynamic calculations and experimental data, respectively. Where no data or calculations are available, estimates of solubilities and Kd values have been made. 11 refs., 2 tabs.

  1. Miscible flooding process using improved soluble oil compositions

    Microsoft Academic Search

    Holm

    1970-01-01

    Soluble oil surfactant slugs were designed for enhanced oil recovery. The slugs contained Petronate CR (mixed alkyl aryl petroleum monosulfonates), Illinois crude oil, water (less than 5,000 ppM TDS), and isopropyl alcohol or butyl Cellosolve (2-butoxyethanol). The Cellosolve causes the surface active component of the soluble oil to be more effective and improves the stability of the resulting soluble oil

  2. Miscible flooding process using improved soluble oil compositions

    Microsoft Academic Search

    Holm

    1969-01-01

    Soluble oil surfactant slugs were designed for enhanced oil recovery. The slugs contained Petronate CR (mixed alkyl aryl petroleum monosulfonates), Illinois crude oil, water (less than 5,000 ppM TDS), and isopropyl alcohol or butyl Cellosolve (2-butoxyethanol). The Cellosolve causes the surface active component of the soluble oil to be more effective and improves the stability of the resulting soluble oil

  3. Soluble Phosphorus Released by Poultry Wastes in Acidified Aqueous Extracts

    Microsoft Academic Search

    Armando S. Tasistro; Miguel L. Cabrera; Yebin B. Zhao; David E. Kissel; Kang Xia; Dorcas H. Franklin

    2007-01-01

    Research has shown that measured water?soluble phosphorus (WSP) from poultry litter might have been less than that released in the field. The effects of acidified extractions on soluble P (SP) concentrations were studied, and a buffer was selected to measure SP at pH 6.0, which is a target value for soil management in Georgia.Soluble P concentrations were extracted from poultry

  4. Aqueous solubilities of phenol derivatives by conductivity measurements

    SciTech Connect

    Achard, C.; Jaoui, M.; Schwing, M.; Rogalski, M. [Univ. de Metz (France). Lab. de Thermodynamique et d`Analyse Chimique] [Univ. de Metz (France). Lab. de Thermodynamique et d`Analyse Chimique

    1996-05-01

    The aqueous solubilities of five chlorophenols and three nitrophenols were measured by conductimetry at temperatures between 15 and 48C. The solubilities of 2-chlorophenol, 4-chlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophenol, pentachlorophenol, 2-nitrophenol, 4-nitrophenol, and 2,4-dinitrophenol were studied. Automatic conductivity measurements allow the determination of the solute concentration and, hence, the determination of the solubility. Emulsion formation can also be followed. Results obtained are in good agreement with literature values.

  5. Solubility of 2,4,6-trinitrotoluene (TNT) in water

    Microsoft Academic Search

    Kyoung S. Ro; Asha Venugopal; D. Dean Adrian; David Constant; K. T. Valsaraj; L. J. Thibodeaux; K. Qaisi; Dipak Roy

    1996-01-01

    Current literature values of 2,4,6-trinitrotoluene (TNT) solubility in water vary widely from 100 to 200 mg\\/L at room temperature. The authors investigated the effects of temperature and pH on the solubility of both reference TNT and field neat TNT obtained from the Alabama Army Ammunition Plant (AAAP), Childersburg, AL. The TNT solubility determined from this study was significantly lower than

  6. 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

  7. 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.

  8. Rare earth and yttrium phosphate solubilities in aqueous solution

    NASA Astrophysics Data System (ADS)

    Liu, Xuewu; Byrne, Robert H.

    1997-04-01

    Rare earth and yttrium phosphate solubility products range over more than 1 order of magnitude. Minimum solubilities are observed for light rare earths between Ce and Sm. For the elements Ce, Pr, Nd, and Sm solubility products (log Ksp0 ( M) = log ([ Mi3+] [PO 43-])) at zero ionic strength and 25°C can be approximated as log Ksp0,( M) = -26.3 ± 0.2. Rare earth phosphate solubility products for well-aged, coarse precipitates increase substantially between Sm and Lu, with log Ksp0(Lu) estimated as -24.7. The solubility product of Y is similar to that of Ho (log Ksp0 (Y) = -25.0) and is much higher than those of all light rare earths. The solubility product of La is substantially larger than that of Cc (log Ksp 0(La) - log Ksp0 (Ce) ? 0.5). Solubility products are strongly dependent on the conditions of solid phase formation. Fresh precipitates are much more soluble than slowly formed, well-aged, coarse precipitates. The pattern of rare earth and yttrium phosphate solubility products is generally similar to the fractionation patterns which are developed during phosphate coprecipitation.

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

    SciTech Connect

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. (Centre de Neurochimie du C.N.R.S., Strasbourg, (France))

    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.

  10. 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.

  11. Soluble variants of human recombinant glutaminyl cyclase.

    PubMed

    Castaldo, Cristiana; Ciambellotti, Silvia; de Pablo-Latorre, Raquel; Lalli, Daniela; Porcari, Valentina; Turano, Paola

    2013-01-01

    Recombinant human Glutaminyl Cyclase expressed in E. coli is produced as inclusion bodies. Lack of glycosylation is the main origin of its accumulation in insoluble aggregates. Mutation of single isolated hydrophobic amino acids into negative amino acids was not able to circumvent inclusion bodies formation. On the contrary, substitution with carboxyl-terminal residues of two or three aromatic residues belonging to extended hydrophobic patches on the protein surface provided soluble but still active forms of the protein. These mutants could be expressed in isotopically enriched forms for NMR studies and the maximal attainable concentration was sufficient for the acquisition of (1)H-(15)N HSQC spectra that represent the starting point for future drug development projects targeting Alzheimer's disease. PMID:23977104

  12. Water-soluble vitamins: research update.

    PubMed

    Bruno, Eugene J; Ziegenfuss, Tim N

    2005-08-01

    For more than 50 years, the Food and Nutrition Board of the National Academy of Sciences has been reviewing nutrition research and defining nutrient requirements for healthy people, referred to as the recommended dietary allowances (RDA). As new nutrition research is published, the importance of vitamins as vital nutrients is underscored, and new physiologic roles and applications to human health are examined and considered with regard to updating the RDA. Each year a substantial amount of research is published on vitamins. This article examines and summarizes noteworthy research published on individual water-soluble vitamins (excluding vitamin C) in the past 12 months, provides relevant background information on these vitamins, and offers critical reviews as appropriate. PMID:16004830

  13. Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

    PubMed Central

    Hwang, Sung Hee; Tsai, Hsing-Ju; Liu, Jun-Yan; Morisseau, Christophe; Hammock, Bruce D.

    2008-01-01

    A series of N,N?-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane ? to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 ± 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models. PMID:17616115

  14. 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.

  15. [Soluble epoxide hydrolase and lipid metabolism].

    PubMed

    Ma, Xin-Xin; Liu, Yan; Zhu, Yi

    2010-08-01

    Soluble epoxide hydrolase (sEH) is widely distributed in mammalian tissues. Epoxyeicosatrienoic acids (EETs), as metabolites of arachidonic acid, are degraded by sEH. EETs may function as antihypertensive and antiarthrosclerotic mediators for vasculature. Therefore, sEH is closely related with cardiovascular diseases and inflammation. Recent studies indicate that sEH is also involved in the regulation of lipid metabolism, and different functions of its C-terminal epoxide hydrolase domain and N-terminal phosphatase domain are revealed. Here we review the progress on the aspects of the different enzyme activity of the two terminals of sEH and the mechanisitic study on the regulation of lipid metabolism by sEH. PMID:21416942

  16. 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.

  17. A Census of Human Soluble Protein Complexes

    PubMed Central

    Havugimana, Pierre C.; Hart, G. Traver; Nepusz, Tamás; Yang, Haixuan; Turinsky, Andrei L.; Li, Zhihua; Wang, Peggy I.; Boutz, Daniel R.; Fong, Vincent; Phanse, Sadhna; Babu, Mohan; Craig, Stephanie A.; Hu, Pingzhao; Wan, Cuihong; Vlasblom, James; Dar, Vaqaarun-Nisa; Bezginov, Alexander; Clark, Gregory W.; Wu, Gabriel C.; Wodak, Shoshana J.; Tillier, Elisabeth R.M.; Paccanaro, Alberto; Marcotte, Edward M.; Emili, Andrew

    2012-01-01

    SUMMARY Cellular processes often depend on stable physical associations between proteins. Despite recent progress, knowledge of the composition of human protein complexes remains limited. To close this gap, we applied an integrative global proteomic profiling approach, based on chromatographic separation of cultured human cell extracts into more than one thousand biochemical fractions which were subsequently analyzed by quantitative tandem mass spectrometry, to systematically identify a network of 13,993 high-confidence physical interactions among 3,006 stably-associated soluble human proteins. Most of the 622 putative protein complexes we report are linked to core biological processes, and encompass both candidate disease genes and unnanotated proteins to inform on mechanism. Strikingly, whereas larger multi-protein assemblies tend to be more extensively annotated and evolutionarily conserved, human protein complexes with 5 or fewer subunits are far more likely to be functionally un-annotated or restricted to vertebrates, suggesting more recent functional innovations. PMID:22939629

  18. Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies

    Microsoft Academic Search

    Laura Ribeiro; Rui A. Carvalho; Domingos C. Ferreira; Francisco J. B. Veiga

    2005-01-01

    This work deals with multicomponent complex formation of vinpocetine (VP) with ?-cyclodextrin (?CD), sulfobutyl ether ?-cyclodextrin (SBE?CD) and tartaric acid (TA), in the presence or absence of water-soluble polymers, in aqueous solution. Complexation was monitored by phase-solubility and proton nuclear magnetic resonance (1H NMR) studies. TA demonstrated a synergistic effect on VP solubility, and in the complexation efficiency of ?CD

  19. 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

  20. The coagulation characteristics of humic acid by using acid-soluble chitosan, water-soluble chitosan, and chitosan coagulant mixtures.

    PubMed

    Chen, Chih-Yu; Wu, Chung-Yu; Chung, Ying-Chien

    2015-05-01

    Chitosan is a potential substitute for traditional aluminium salts in water treatment systems. This study compared the characteristics of humic acid (HA) removal by using acid-soluble chitosan, water-soluble chitosan, and coagulant mixtures of chitosan with aluminium sulphate (alum) or polyaluminium chloride (PACl). In addition, we evaluated their respective coagulation efficiencies at various coagulant concentrations, pH values, turbidities, and hardness levels. Furthermore, we determined the size and settling velocity of flocs formed by these coagulants to identify the major factors affecting HA coagulation. The coagulation efficiency of acid- and water-soluble chitosan for 15?mg/l of HA was 74.4% and 87.5%, respectively. The optimal coagulation range of water-soluble chitosan (9-20?mg/l) was broader than that of acid-soluble chitosan (4-8?mg/l). Notably, acid-soluble chitosan/PACl and water-soluble chitosan/alum coagulant mixtures exhibited a higher coagulation efficiency for HA than for PACl or alum alone. Furthermore, these coagulant mixtures yielded an acceptable floc settling velocity and savings in both installation and operational expenses. Based on these results, we confidently assert that coagulant mixtures with a 1:1 mass ratio of acid-soluble chitosan/PACl and water-soluble chitosan/alum provide a substantially more cost-effective alternative to using chitosan alone for removing HA from water. PMID:25362971

  1. Detailed study of precipitation of a poorly water soluble test compound using methodologies as in activity and solubility screening - mixing and automation effects.

    PubMed

    Gillespie, Cheska; Kennedy, Alan R; Edwards, Darren; Dowden, Lee; Daublain, Pierre; Halling, Peter

    2013-09-01

    Storage of pharmaceutical discovery compounds dissolved in dimethylsulfoxide (DMSO) is commonplace within industry. Often, the DMSO stock solution is added to an aqueous system (e.g. in bioassay or kinetic solubility testing)- since most test compounds are hydrophobic, precipitation could occur. Little is known about the factors affecting this precipitation process at the low (µM) concentrations used in screening analyses. Here, a poorly water soluble test compound (tolnaftate) was used to compare manual and automated pipetting, and explore the effect of mixing variables on precipitation. The amount of drug present in the supernatant after precipitation and centrifugation of the samples was quantified. An unusual result was obtained in three different laboratories: results of experiments performed initially were statistically significantly higher than those performed after a few days in the same lab. No significant differences were found between automated and manual pipetting, including in variability. Vortex mixing was found to give significantly lower supernatant amounts compared to milder mixing types. The mixing employed affects the particle growth of the precipitate. These findings are of relevance to discovery stage bioassay and kinetic solubility analyses. PMID:23713459

  2. A consensus neural network-based technique for discriminating soluble and poorly soluble compounds.

    PubMed

    Manallack, David T; Tehan, Benjamin G; Gancia, Emanuela; Hudson, Brian D; Ford, Martyn G; Livingstone, David J; Whitley, David C; Pitt, Will R

    2003-01-01

    BCUT [Burden, CAS, and University of Texas] descriptors, defined as eigenvalues of modified connectivity matrices, have traditionally been applied to drug design tasks such as defining receptor relevant subspaces to assist in compound selections. In this paper we present studies of consensus neural networks trained on BCUTs to discriminate compounds with poor aqueous solubility from those with reasonable solubility. This level was set at 0.1 mg/mL on advice from drug formulation and drug discovery scientists. By applying strict criteria to the insolubility predictions, approximately 95% of compounds are classified correctly. For compounds whose predictions have a lower level of confidence, further parameters are examined in order to flag those considered to possess unsuitable biopharmaceutical and physicochemical properties. This approach is not designed to be applied in isolation but is intended to be used as a filter in the selection of screening candidates, compound purchases, and the application of synthetic priorities to combinatorial libraries. PMID:12653537

  3. Argon solubility in silicate melts at very high pressures. Experimental set-up and preliminary results for silica and anorthite melts

    Microsoft Academic Search

    Eva Chamorro-Perez; Philippe Gillet; Albert Jambon

    1996-01-01

    A CO2 laser-heated diamond anvil cell was used for performing argon solubility experiments in silicate melts. This technique allowed solubility experiments to be carried out at much higher pressures than in a piston-cylinder-type apparatus. When the beam of the CO2 laser is focused on the silicate sample, argon, acting as a pressure-transmitting medium, melts by conductive heating from the molten

  4. Testing of the OMERACT 8 Draft Validation Criteria for a Soluble Biomarker Reflecting Structural Damage in Rheumatoid Arthritis: A Systematic Literature Search on 5 Candidate Biomarkers

    Microsoft Academic Search

    S. W. Syversen; R. Landewe; D. van der HEIJDE; J. M. Bathon; M. Boers; V. P. Bykerk; O. FitzGerald; D. D. Gladman; P. Garnero; P. Geusens; H. El-Gabalawy; R. D. Inman; V. Kraus; T. K. Kvien; P. J. Mease; M. Ostergaard; C. J. Ritchlin; P.-P. TAK; W. J. Taylor; W. P. Maksymowych

    2009-01-01

    Objective. To test the OMERACT 8 draft validation criteria for Soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers. Methods. A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix metalloprotease (MMP-3), urine C-telopeptide of types I and 11 collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT

  5. Soluble Concentrate Material Safety Data Sheet 102381-0002

    E-print Network

    Rollins, Andrew M.

    IDENTIFICATION Product Name Soluble Concentrate (SC) General Use Alkaline detergent for soluble support removal, give oxygen. Call a physician. Skin Contact Remove contaminated clothing. Wash thoroughly with soap is extremely corrosive. Avoid contact with skin and eyes. Wash thoroughly after handling. Remove contaminated

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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.

  11. Microemulsion formulation for enhanced absorption of poorly soluble drugs

    Microsoft Academic Search

    Kohsaku Kawakami; Takayoshi Yoshikawa; Takashi Hayashi; Yoshitaka Nishihara; Kazuyoshi Masuda

    2002-01-01

    Oral administration study of microemulsion formulations, which are known to improve the bioavailability of poorly soluble drugs, was performed using rats. Nitrendipine was used as a poorly soluble model drug, and its absorption was enhanced significantly by employing the microemulsion formulations compared to a suspension or an oil solution. The effect of the fed state on the oral absorption of

  12. Solubility of non-polar gases in electrolyte solutions

    NASA Technical Reports Server (NTRS)

    Walker, R. L., Jr.

    1970-01-01

    Solubility theory describes the effects of both concentration and temperature on solute activity coefficients. It predicts the salting-out effect and the decrease in solubility of non-polar gases with increased electrolyte concentration, and can be used to calculate heats of solution, entropies, and partial molal volumes of dissolved gases

  13. 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°...

  14. Le Chatelier's Principle Applied to the Temperature Dependence of Solubility.

    ERIC Educational Resources Information Center

    Treptow, Richard S.

    1984-01-01

    One effect of temperature is its influence on solubility, and that effect is used as a common example when teaching Le Chatelier's principle. Attempts to clarify the question of whether the principle holds in the case of the solubility of ionic compounds in water by investigating the literature data in detail. (JN)

  15. Assessing Junior High Students' Understanding of Density and Solubility.

    ERIC Educational Resources Information Center

    Gennaro, Eugene D.

    1981-01-01

    Three density questions were administered to 290 ninth-grade students to assess their understanding of this concept. Found two-thirds of students understand displacement and/or density concepts. Three solubility questions were administered to 385 ninth-graders to assess understandings of solubility. Found students have difficulty with some aspects…

  16. Human soluble epoxide hydrolase: Structural basis of inhibition by

    E-print Network

    Hammock, Bruce D.

    Human soluble epoxide hydrolase: Structural basis of inhibition by 4-(3-cyclohexylureido October 3, 2005) Abstract X-ray crystal structures of human soluble epoxide hydrolase (sEH) complexed-site hydrophobic tunnel. Alternative binding orientations observed for this series of inhibi- tors to human s

  17. Cloud condensation nuclei activation of limited solubility organic aerosol

    NASA Astrophysics Data System (ADS)

    Huff Hartz, Kara E.; Tischuk, Joshua E.; Chan, Man Nin; Chan, Chak K.; Donahue, Neil M.; Pandis, Spyros N.

    The cloud condensation nuclei (CCN) activation of 19 organic species with water solubilities ( Csat) ranging from 10 -4 to 10 2 g solute 100 g -1 H 2O was measured. The organic particles were generated by nebulization of an aqueous or an alcohol solution. Use of alcohols as solvents enables the measurement of low solubility, non-volatile organic CCN activity and reduces the likelihood of residual water in the aerosol. The activation diameter of organic species with very low solubility in water ( Csat<0.3 g 100 g -1 H 2O) is in agreement with Köhler theory using the bulk solubility (limited solubility case) of the organic in water. Many species, including 2-acetylbenzoic acid, aspartic acid, azelaic acid, glutamic acid, homophthalic acid, phthalic acid, cis-pinonic acid, and salicylic acid are highly CCN active in spite of their low solubility (0.3 g 100 g -1 H 2O< Csat<1 g 100 g -1 H 2O), and activate almost as if completely water soluble. The CCN activity of most species is reduced, if the particles are produced using non-aqueous solvents. The existence of the particles in a metastable state at low RH can explain the observed enhancement in CCN activity beyond the levels suggested by their solubility.

  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. 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...

  20. The temperature dependence of the solubility product constant of vivianite

    Microsoft Academic Search

    Amal Al-Borno; Mason B. Tomson

    1994-01-01

    Vivianite Fe 3 (PO 4 ) 2 · 8H 2 O is an important phosphate mineral in many natural and environmental aquatic systems. Yet, the solubility product constant of vivianite has been determined only at room temperature. A new apparatus has been designed to facilitate the study of redox sensitive elements. Using this apparatus the solubility product constant of vivianite

  1. SOLUBILITY OF FERMAT EQUATIONS T.D. Browning & R. Dietmann

    E-print Network

    Browning, Tim

    SOLUBILITY OF FERMAT EQUATIONS by T.D. Browning & R. Dietmann Abstract. -- The arithmetic then (d) := 3 (d) 1 - 1 d . All of the implied constants in our work are allowed to depend at most upon d a1xd 1 + a2xd 2 + a3xd 3 + a4xd 4 = 0 is everywhere locally soluble. The following inequality

  2. Soluble inhibitors\\/deactivators of cellulase enzymes from lignocellulosic biomass

    Microsoft Academic Search

    Youngmi Kim; Eduardo Ximenes; Nathan S. Mosier; Michael R. Ladisch

    2011-01-01

    Liquid hot water, steam explosion, and dilute acid pretreatments of lignocellulose generate soluble inhibitors which hamper enzymatic hydrolysis as well as fermentation of sugars to ethanol. Toxic and inhibitory compounds will vary with pretreatment and include soluble sugars, furan derivatives (hydroxymethyl fulfural, furfural), organic acids (acetic, formic and, levulinic acid), and phenolic compounds. Their effect is seen when an increase

  3. Solubility of hydrogen isotopes in stressed hydride-forming metals

    Microsoft Academic Search

    C. E. Coleman; J. F. R. Ambler

    1983-01-01

    Components made from hydride-forming metals can be brittle when particles of hydride are present. The solid solubility limit of hydrogen in these metals needs to be known so that fracture resistance can be properly assessed. Stress affects the solubility of hydrogen in metals. As hydrogen dissolves the metal volume increases, an applied hydrostatic tensile stress supplies work to increase the

  4. Analytical detection of soluble polysulphides in a modified Swagelok cell

    Microsoft Academic Search

    Robert Dominko; Rezan Demir-Cakan; Mathieu Morcrette; Jean-Marie Tarascon

    2011-01-01

    A modified 4-electrode Swagelok cell is proposed as an in situ analytical tool for the detection of soluble polysulphides in the electrolyte during lithium sulphur battery operation. Besides the standard Swagelok configuration, this cell has two additional perpendicular electrodes (wires) placed between two separators. Soluble polysulphides in the electrolyte are reduced on the nickel wire and the cumulative charge in

  5. 2 + 1 dimensional gravity as an exactly soluble system

    Microsoft Academic Search

    Edward Witten

    1988-01-01

    By disentangling the hamiltonian constraint equations, 2 + 1 dimensional gravity (with or without a cosmological constant) is shown to be exactly soluble at the classical and quantum levels. Indeed, it is closely related to Yang-Mills theory with purely the Chern-Simons action, which recently has turned out to define a soluble quantum field theory. 2 + 1 dimensional gravity has

  6. Solubility of airborne radioactive fuel particles from the Chernobyl reactor and implication to dose.

    PubMed

    Garger, E K; Sazhenyuk, A D; Odintzov, A A; Paretzke, H G; Roth, P; Tschiersch, J

    2004-05-01

    Airborne particles of nuclear fuel from the Chernobyl reactor that had been collected on air filters and stored, were characterised using in vitro dissolution tests to assess effective doses after their inhalation. As solvent, the Gamble biological fluid was used to simulate lung fluid. The solubility of the measured radionuclides decreased in the order (137)Cs>(90)Sr>(241)Am>or=(239+240)Pu in the simulated lung fluid. The dissolution rate constant of e.g. (239+249)Pu ranged from 0.72 to 5.4 x 10(-6) g x cm(-2) d(-1) and decreased (for all nuclides) with increasing particle size as predicted from theoretical considerations. Considering the inhalation dose, decreasing dose with size and increasing doses with lower solubility may partly counterbalance each other for (137)Cs and (90)Sr. On the other hand, for (239)Pu and (241)Am larger particles and associated lower solubility both change the resulting dose in the same direction towards lower values. The comparison of the experimentally determined dose coefficients with ICRP values indicates that nuclear fuel particles closely resemble type M material characteristics for (137)Cs and (90)Sr and type S material characteristics for (239)Pu and (241)Am. PMID:14991369

  7. Physicochemical characterization of Capstone depleted uranium aerosols IV: in vitro solubility analysis.

    PubMed

    Guilmette, Raymond A; Cheng, Yung Sung

    2009-03-01

    As part of the Capstone Depleted Uranium (DU) Aerosol Study, the solubility of selected aerosol samples was measured using an accepted in vitro dissolution test system. This static system was employed along with a SUF (synthetic ultrafiltrate) solvent, which is designed to mimic the physiological chemistry of extracellular fluid. Using sequentially obtained solvent samples, the dissolution behavior over a 46-d test period was evaluated by fitting the measurement data to two- or three-component negative exponential functions. These functions were then compared with Type M and S absorption taken from the International Commission on Radiological Protection Publication 66 Human Respiratory Tract Model. The results indicated that there was a substantial variability in solubility of the aerosols, which in part depended on the type of armor being impacted by the DU penetrator and the particle size fraction being tested. Although some trends were suggested, the variability noted leads to uncertainties in predicting the solubility of other DU-based aerosols. Nevertheless, these data provide a useful experimental basis for modeling the intake-dose relationships for inhaled DU aerosols arising from penetrator impact on armored vehicles. PMID:19204487

  8. 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.

  9. 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.

  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. Water and acid soluble trace metals in atmospheric particles

    NASA Technical Reports Server (NTRS)

    Lindberg, S. E.; Harriss, R. C.

    1983-01-01

    Continental aerosols are collected above a deciduous forest in eastern Tennessee and subjected to selective extractions to determine the water-soluble and acid-leachable concentrations of Cd, Mn, Pb, and Zn. The combined contributions of these metals to the total aerosol mass is 0.5 percent, with approximately 70 percent of this attributable to Pb alone. A substantial fraction (approximately 50 percent or more) of the acid-leachable metals is soluble in distilled water. In general, this water-soluble fraction increases with decreasing particle size and with increasing frequency of atmospheric water vapor saturation during the sampling period. The pattern of relative solubilities (Zn being greater than Mn, which is approximately equal to Cd, which is greater than Pb) is found to be similar to the general order of the thermodynamic solubilities of the most probable salts of these elements in continental aerosols with mixed fossil fuel and soil sources.

  12. Classification of binary alloys and their phase diagrams by the type of transformations occurring in them

    Microsoft Academic Search

    G. I. Pogodin-Alekseev

    1967-01-01

    1.Binary alloys crystallizing from homogeneous liquid melts can be divided into alloys of the eutectic, peritectic, and megotectic type, depending on the type of the transformations and structures occurring. Each of them can have complete, limited, or no solubility in the solid state, i.e., have a homogeneous solid solution, a mixture of solid solutions with limited solubility, or a mixture

  13. 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…

  14. 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…

  15. Additional File 2 to Scoring Function to Predict Solubility Mutagenesis Confusion Matrices

    E-print Network

    Krishnamoorthy, Bala

    Additional File 2 to Scoring Function to Predict Solubility Mutagenesis ­ Confusion Matrices Ye classification Increased Solubility Decreased Solubility Predicted as 48/59 15/78 "Increased Solubility" Predicted as 11/59 63/78 "Decreased Solubility" Table 2: Confusion Matrix for SVM (LOOCV) Experimental

  16. Soluble expression and one-step purification of recombinant mouse interferon-?3 in Escherichia coli.

    PubMed

    Wang, Y Q; Zhou, M; Zeng, L M; Gao, Q Y; Yuan, X L; Li, Y; Li, M C

    2015-02-01

    Interferon (IFN)-?3, a member of the type III IFN family, is a pleiotropic cytokine that exhibits potent antiproliferative, antiviral, and immunoregulatory activities. For further functional study of IFN-?3, we developed an efficient procedure that includes cloning, expression, and purification to obtain relatively large quantity of mouse IFN-?3 fusion protein. The mature IFN-?3 protein-coding region was cloned into the prokaryotic expression vector pET-44. IFN-?3 contains a hexahistidine tag at its C-terminus. We used Ni(2+)-nitrilotriacetic acid agarose-affinity chromatography to purify the expressed soluble protein. The purified IFN-?3 inhibited significantly IL-13 production in stimulated RAW264.7 macrophages. Our findings show that the production of soluble IFN-?3 proteins by the pET-44 vector in Escherichia coli is a good alternative for the production of native IFN-?3 and could be useful for the production of other IFN proteins. PMID:25756537

  17. New synthetic routes towards soluble and dissymmetric triphenodioxazine dyes designed for dye-sensitized solar cells.

    PubMed

    Nicolas, Yohann; Allama, Fouzia; Lepeltier, Marc; Massin, Julien; Castet, Frédéric; Ducasse, Laurent; Hirsch, Lionel; Boubegtiten, Zahia; Jonusauskas, Gediminas; Olivier, Céline; Toupance, Thierry

    2014-03-24

    New ?-conjugated structures are constantly the subject of research in dyes and pigments industry and electronic organic field. In this context, the triphenodioxazine (TPDO) core has often been used as efficient photostable pigments and once integrated in air stable n-type organic field-effect transistor (OFET). However, little attention has been paid to the TPDO core as soluble materials for optoelectronic devices, possibly due to the harsh synthetic conditions and the insolubility of many compounds. To benefit from the photostability of TPDO in dye-sensitized solar cells (DSCs), an original synthetic pathway has been established to provide soluble and dissymmetric molecules applied to a suitable design for the sensitizers of DSC. The study has been pursued by the theoretical modeling of opto-electronic properties, the optical and electronic characterizations of dyes and elaboration of efficient devices. The discovery of new synthetic pathways opens the way to innovative designs of TPDO for materials used in organic electronics. PMID:24677330

  18. Synthesis and Antibacterial Evaluation of Novel Water-Soluble Organic Peroxides

    PubMed Central

    Liu, Wenqiu; Liu, Xuejun; Knaebel, David; Luck, Linda; Li, Yuzhou

    1998-01-01

    A set of new water-soluble organic peroxides has been synthesized and evaluated for in vitro antibacterial activity as part of an effort to develop new antibacterial agents for the treatment of acne vulgaris. The water solubility of these new dialkyl peroxides and peroxyesters was achieved by incorporating either a quaternary ammonium group or a polyethylene glycol moiety. These peroxides are effective against both gram-positive and gram-negative bacteria and have a prolonged activity compared to that of benzoyl peroxide and other peroxide-type antiseptic agents. Among them 4-[[(tert-butylperoxy)carbonyl]benzyl]triethylammonium chloride and [10-(tert-butylperoxy)decyl]trimethylammonium bromide have the broadest antimicrobial spectrums. We have shown that the oxidizing properties of the dioxy group of these compounds are responsible for their antibacterial activities. PMID:9559807

  19. 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

  20. [Nickel solubility of dental alloys in the immersions-test and in the mouth].

    PubMed

    Pfeiffer, P; Schwickerath, H

    1991-01-01

    The nickel solubility of 7 different nickel-alloys was tested in vivo and in vitro. The results revealed that the solubility of the alloys, after encasing them in lactic-acid solution of pH 4.2 for a period of seven days, allows to find out those alloys, which will also clinically dissolve small amounts of ions only. The Ni59-65Cr26-23Mo11-9 mass per cent alloys dissolved the smallest quantities of nickel in the in vitro and the in vivo tests and are therefore recommended for clinical use instead of the type Ni74-85Cr15-13Mo5-3 alloys. PMID:1816842

  1. Solubilities of selected organic electronic materials in pressurized hot water and estimations of aqueous solubilities at 298.15 K.

    PubMed

    Karásek, Pavel; Hohnová, Barbora; Planeta, Josef; Št'avíková, Lenka; Roth, Michal

    2013-02-01

    Increasing production and disposal of organic light-emitting diode (OLED) displays for smartphones and tablets may have impact on the environment depending on the aqueous solubility of the pertinent chemicals. Here, aqueous solubilities are presented for several compounds, mostly aromatic amines, used as hole transport materials in the OLED displays. Solute selection includes 1,4-bis(diphenylamino)benzene, tetra-N-phenylbenzidine, 4,4'-bis(N-carbazolyl)-1,1'-biphenyl, 1,3,5-tris(diphenylamino)benzene, and 9,10-bis(phenylethynyl)anthracene. The solubilities are those in pressurized hot water (PHW), i.e., measured at elevated temperature (up to 260 °C) and pressure. The semi-quantitative estimates of room-temperature solubilities of the solutes have been obtained from extrapolations of the solubilities in PHW. For the compounds studied, the estimated aqueous solubilities at room temperature do not exceed 2×10(-11) g of the solute per 1 kg of water. Aqueous solubilities of triphenylamine have also been measured and used to upgrade a recent group-contribution model of aqueous solubilities of organic nonelectrolytes with the parameters for the nitrogen atom in aromatic amines. PMID:23177709

  2. Leaching Soluble Salts Increases Population Densities of Tylenchulus semipenetrans

    PubMed Central

    Mashela, P.; Duncan, L. W.; Graham, J. H.; McSorley, R.

    1992-01-01

    The effect of salinity on population densities of Tylenchulus semipenetrans was measured on 3-month-old salt-tolerant Rangpur lime growing on either loamy sand, sand, or organic mix and on 4-month-old salt-sensitive Sweet lime in organic mix. Salinity treatments were initiated by watering daily with 25 mol/m³ NaCl + 3.3 mol/m³ CaCl? for 3 days and every other day with 50 mol/m³ NaC1 + 6.6 mol/m³ CaC1? for one week, with no salt (NS) treatments as controls. Salinity was discontinued in one treatment (DS) by leaching with tap water prior to inoculation with nematodes, whereas the continuous salinity (CS) treatment remained unchanged. Overall, in Rangpur lime organic soil supported the highest population densities of T. semipenetrans, followed by loamy sand and sand. The DS treatment resulted in the highest (P ? 0.05) mean population densities of T. semipenetrans in the three soil types. Similarly, the DS treatment in Sweet lime resulted in the highest (P ? 0.05) nematode populations. The DS treatment predisposed citrus to nematode infection through accumulated salt stress, whereas leaching soluble salt in soil solution offered nematodes a suitable nonosmotic habitat. Nematode females under the DS treatment also had the highest (P ? 0.05) fecundity. PMID:19283210

  3. 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.

  4. Diclofenac Solubility: Independent Determination of the Intrinsic Solubility of Three Crystal Antonio Llina`s, Jonathan C. Burley, Karl J. Box, Robert C. Glen, and Jonathan M. Goodman*,

    E-print Network

    de Gispert, Adrià

    Diclofenac Solubility: Independent Determination of the Intrinsic Solubility of Three Crystal Forms, East Sussex, RH18 5DW, United Kingdom ReceiVed NoVember 7, 2006 The solubility in water of diclofenac were anhydrous and corresponded to an earlier crystal structure. Separate solubility measurements

  5. Soft typing with conditional types

    Microsoft Academic Search

    Alexander Aiken; Edward L. Wimmers; T. K. Lakshmant

    1994-01-01

    We present a simple and powerful type inference method for dynamically typed languages where no type information is supplied by the user. Type inference is reduced to the problem of solvability of a system of type inclusion constraints over a type language that includes function types, constructor types, union, intersection, and recursive types, and conditional types. Conditional types enable us

  6. Polysaccharide components from the scape of Musa paradisiaca: main structural features of water-soluble polysaccharide component.

    PubMed

    Anjaneyalu, Y V; Jagadish, R L; Raju, T S

    1997-06-01

    Polysaccharide components present in the pseudo-stem (scape) of M. paradisiaca were purified from acetone powder of the scape by delignification followed by extraction with aqueous solvents into water soluble polysaccharide (WSP), EDTA-soluble polysaccharide (EDTA-SP), alkali-soluble polysaccharide (ASP) and alkali-insoluble polysaccharide (AISP) fractions. Sugar compositional analysis showed that WSP and EDTA-SP contained only D-Glc whereas ASP contained D-Glc, L-Ara and D-Xyl in approximately 1:1:10 ratio, respectively, and AISP contained D-Glc, L-Ara and D-Xyl in approximately 10:1:2 ratio, respectively. WSP was further purified by complexation with iso-amylalcohol and characterized by specific rotation, IR spectroscopy, Iodine affinity, ferricyanide number, blue value, hydrolysis with alpha-amylase and glucoamylase, and methylation linkage analysis, and shown to be a amylopectin type alpha-D-glucan. PMID:9249151

  7. Two exactly soluble models of rigidity percolation

    PubMed Central

    Thorpe, M. F.; Stinchcombe, R. B.

    2014-01-01

    We summarize results for two exactly soluble classes of bond-diluted models for rigidity percolation, which can serve as a benchmark for numerical and approximate methods. For bond dilution problems involving rigidity, the number of floppy modes F plays the role of a free energy. Both models involve pathological lattices with two-dimensional vector displacements. The first model involves hierarchical lattices where renormalization group calculations can be used to give exact solutions. Algebraic scaling transformations produce a transition of the second order, with an unstable critical point and associated scaling laws at a mean coordination ?r?=4.41, which is above the ‘mean field’ value ?r?=4 predicted by Maxwell constraint counting. The order parameter exponent associated with the spanning rigid cluster geometry is ?=0.0775 and that associated with the divergence of the correlation length and the anomalous lattice dimension d is d?=3.533. The second model involves Bethe lattices where the rigidity transition is massively first order by a mean coordination ?r?=3.94 slightly below that predicted by Maxwell constraint counting. We show how a Maxwell equal area construction can be used to locate the first-order transition and how this result agrees with simulation results on larger random-bond lattices using the pebble game algorithm. PMID:24379428

  8. 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.

  9. Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition.

    PubMed

    Iqbal, K; Zaidi, T; Thompson, C H; Merz, P A; Wisniewski, H M

    1984-01-01

    A method has been developed for the bulk isolation of Alzheimer neurofibrillary tangles (ANT) of paired helical filaments (PHF) from histopathologically confirmed cases of Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). The fresh or frozen autopsied cerebral cortex affected with Alzheimer neurofibrillary changes is dissociated by homogenization and sieving through nylon bolting cloth and the ANT are separated by a combination of sucrose discontinuous density gradient centrifugation, glass bead column chromatography, and sodium dodecyl sulfate (SDS) treatment. The isolated ANT produce red-green birefringence when viewed through polarized light after staining with Congo red. Ultrastructurally, the isolated PHF are well preserved and have the dimensions of the PHF seen in situ. Two major Populations of ANT which exist in different proportions in AD/SDAT brains are identified on the basis of their solubility in SDS. The ANT I and the ANT II are soluble and insoluble respectively on treatment with 2% SDS at room temperature for 5 min. Solubilization of the ANT II requires several repeated extractions with a solution containing 10% each of SDS and beta-mercaptoethanol (BME) at 100 degrees C for 10 min. Sonication of the ANT II greatly facilitates their solubilization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the isolated ANT reveals the presence of two major polypeptides with molecular weights (MW) of 62,000 and 57,000, several minor polypeptides with MW below 57,000, and a significant amount of material not entering the stacking and the resolving gels. Re-electrophoresis of polypeptides extracted from various areas of the resolving gel or of the material which does not enter the gel generates the same polypeptide profile as on the first gel, suggesting that the PHF material which does not enter the gel may result from the reaggregation of the polypeptides that enter the resolving gel. None of the polypeptides that enter the resolving gel. None of the polpeptides observed in the isolated PHF comigrate in the SDS-PAGE with any of the neurofilament polypeptides, tubulin, actin, or myosin. PMID:6538056

  10. 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.

  11. Uranium (VI) solubility in carbonate-free ERDA-6 brine

    SciTech Connect

    Lucchini, Jean-francois [Los Alamos National Laboratory; Khaing, Hnin [Los Alamos National Laboratory; Reed, Donald T [Los Alamos National Laboratory

    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.

  12. Solubility of 2,4,6-trinitrotoluene (TNT) in water

    SciTech Connect

    Ro, K.S.; Venugopal, A.; Adrian, D.D.; Constant, D.; Valsaraj, K.T.; Thibodeaux, L.J. [Louisiana State Univ., Baton Rouge, LA (United States)] [Louisiana State Univ., Baton Rouge, LA (United States); Qaisi, K. [S and SW, Baton Rouge, LA (United States). Hazardous Substance Research Center] [S and SW, Baton Rouge, LA (United States). Hazardous Substance Research Center; Roy, D. [Polytechnic Univ., Brooklyn, NY (United States). Dept. of Civil and Environmental Engineering] [Polytechnic Univ., Brooklyn, NY (United States). Dept. of Civil and Environmental Engineering

    1996-07-01

    Current literature values of 2,4,6-trinitrotoluene (TNT) solubility in water vary widely from 100 to 200 mg/L at room temperature. The authors investigated the effects of temperature and pH on the solubility of both reference TNT and field neat TNT obtained from the Alabama Army Ammunition Plant (AAAP), Childersburg, AL. The TNT solubility determined from this study was significantly lower than that of Taylor and Rinkenbach, which was cited by several reference chemical handbooks and articles. However, the values reported by the Merck Index and the Lange`s Handbook of Chemistry compared well with the authors` values. TNT solubility dropped rapidly as the pH increased. Three unknown HPLC peaks were observed at high pH, indicating a possibility of forming unknown transformation products. Both reference and field neat TNT solubility agreed well. A semiempirical solubility correlation was developed to predict the solubility of TNT at a temperature range from 6 C to 42 C.

  13. Solubility and dissolution enhancement strategies: current understanding and recent trends.

    PubMed

    Jain, Shashank; Patel, Niketkumar; Lin, Senshang

    2015-06-01

    Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade. PMID:25342479

  14. Structural characterization of minor ampullate spidroin domains and their distinct roles in fibroin solubility and fiber formation.

    PubMed

    Gao, Zhenwei; Lin, Zhi; Huang, Weidong; Lai, Chong Cheong; Fan, Jing-song; Yang, Daiwen

    2013-01-01

    Spider silk is protein fibers with extraordinary mechanical properties. Up to now, it is still poorly understood how silk proteins are kept in a soluble form before spinning into fibers and how the protein molecules are aligned orderly to form fibers. Minor ampullate spidroin is one of the seven types of silk proteins, which consists of four types of domains: N-terminal domain, C-terminal domain (CTD), repetitive domain (RP) and linker domain (LK). Here we report the tertiary structure of CTD and secondary structures of RP and LK in aqueous solution, and their roles in protein stability, solubility and fiber formation. The stability and solubility of individual domains are dramatically different and can be explained by their distinct structures. For the tri-domain miniature fibroin, RP-LK-CTD(Mi), the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTD(Mi) is very stable and soluble, but it cannot stabilize the entire protein against chemical and thermal denaturation while it can keep the entire tri-domain in a highly water-soluble state. In the presence of shear force, protein aggregation is greatly accelerated and the aggregation rate is determined by the stability of folded domains and solubility of the disordered domains. Only the tri-domain RP-LK-CTD(Mi) could form silk-like fibers, indicating that all three domains play distinct roles in fiber formation: LK as a nucleation site for assembly of protein molecules, RP for assistance of the assembly and CTD for regulating alignment of the assembled molecules. PMID:23418525

  15. STRUCTURE OF TYPE 5 ADENOVIRUS

    PubMed Central

    Wilcox, Wesley C.; Ginsberg, Harold S.

    1963-01-01

    Type 5 adenovirus was purified by fluorocarbon (freon 113) treatment followed by banding in a CsCl equilibrium density gradient. This method permitted separation of virus from normal host cell materials and virus-specific soluble antigens. Virus banded in CsCl with a mean bouyant density of 1.3349 gm/cm3. The three virus-specific soluble antigens (group- and type-specific antigens and toxin) banded together with a mean bouyant density of 1.2832 gm/cm3. The group-specific antigen was the predominant antigen of the purified virus particle, whereas the group- and type-specific antigens were present in equal titers in the antigen band. Infectious virus particles were inactivated by prolonged dialysis at pH 10.5. Centrifugation of inactivated virus preparations in a CsCl equilibrium density gradient resulted in separation of virus DNA from specific antigen: the antigens banded with a mean bouyant density of 1.2832 gm/cm3 and the DNA sedimented to the bottom of the tube. The predominant antigen derived from purified virus particles was the group-specific antigen and it was in the same relative proportion to the type-specific antigen as measured in intact particles. The antigens derived from disrupted virus were immunologically identical with the soluble virus antigens present in infected cells. PMID:14074393

  16. 21 CFR 73.3110 - Chlorophyllin-copper complex, oil soluble.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 false Chlorophyllin-copper complex, oil soluble. 73.3110 ...Devices § 73.3110 Chlorophyllin-copper complex, oil soluble. (a) Identity. The color additve is chlorophyllin-copper complex, oil soluble. The...

  17. 21 CFR 73.3110 - Chlorophyllin-copper complex, oil soluble.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 false Chlorophyllin-copper complex, oil soluble. 73.3110 ...Devices § 73.3110 Chlorophyllin-copper complex, oil soluble. (a) Identity. The color additve is chlorophyllin-copper complex, oil soluble. The...

  18. 21 CFR 73.3110 - Chlorophyllin-copper complex, oil soluble.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 false Chlorophyllin-copper complex, oil soluble. 73.3110 ...Devices § 73.3110 Chlorophyllin-copper complex, oil soluble. (a) Identity. The color additve is chlorophyllin-copper complex, oil soluble. The...

  19. TITLE: SOLUBILITY PREDICTION OF WEAK ELECTROLYTE MIXTURES Xiang-Yang Zhang, Gilles Fvottea

    E-print Network

    Paris-Sud XI, Université de

    TITLE: SOLUBILITY PREDICTION OF WEAK ELECTROLYTE MIXTURES Xiang-Yang Zhang, Gilles Févottea , Gang Supérieure des Mines de Saint Etienne, Saint-Étienne, France Keywords: solubility, weak electrolyte, dissociation constant, activity coefficient The solubility of materials is a thermodynamic variable

  20. Thermodynamic model for mineral solubility in aqueous fluids: theory, calibration and application to model

    E-print Network

    Manning, Craig

    Thermodynamic model for mineral solubility in aqueous fluids: theory, calibration and application has been calibrated by experimental solubilities of quartz, corundum, rutile, calcite, apatite show a steady increase in solubility along constant geothermal gradients or water isochores

  1. Thermodynamic Model for ThO2(am) Solubility in Isosaccharinate Solutions

    E-print Network

    Rai, Dhanpat

    2010-01-01

    constant value [15] and the fits to the solubility data ofSolubility, thermodynamics, ThO 2 (am), isosaccharinate, thorium isosaccharinate complexes, complexation constants,constants were then tested to predict ThO 2 (am) solubility

  2. Endocytosis of soluble immune complexes leads to their clearance by Fc?RIIIB but induces neutrophil extracellular traps via Fc?RIIA in vivo.

    PubMed

    Chen, Kan; Nishi, Hiroshi; Travers, Richard; Tsuboi, Naotake; Martinod, Kimberly; Wagner, Denisa D; Stan, Radu; Croce, Kevin; Mayadas, Tanya N

    2012-11-22

    Soluble immune complexes (ICs) are abundant in autoimmune diseases, yet neutrophil responses to these soluble humoral factors remain uncharacterized. Moreover, the individual role of the uniquely human Fc?RIIA and glycophosphatidylinositol (GPI)-linked Fc?RIIIB in IC-mediated inflammation is still debated. Here we exploited mice and cell lines expressing these human neutrophil Fc?Rs to demonstrate that Fc?RIIIB alone, in the absence of its known signaling partners Fc?RIIA and the integrin Mac-1, internalizes soluble ICs through a mechanism used by GPI-anchored receptors and fluid-phase endocytosis. Fc?RIIA also uses this pathway. As shown by intravital microscopy, Fc?RIIA but not Fc?RIIIB-mediated neutrophil interactions with extravascular soluble ICs results in the formation of neutrophil extracellular traps (NETs) in tissues. Unexpectedly, in wild-type mice, IC-induced NETosis does not rely on the NADPH oxidase, myeloperoxidase, or neutrophil elastase. In the context of soluble ICs present primarily within vessels, Fc?RIIIB-mediated neutrophil recruitment requires Mac-1 and is associated with the removal of intravascular IC deposits. Collectively, our studies assign a new role for Fc?RIIIB in the removal of soluble ICs within the vasculature that may serve to maintain homeostasis, whereas Fc?RIIA engagement of tissue soluble ICs generates NETs, a proinflammatory process linked to autoimmunity. PMID:22955924

  3. Aggregation and solubility behavior of asphaltenes and their subfractions.

    PubMed

    Spiecker, P Matthew; Gawrys, Keith L; Kilpatrick, Peter K

    2003-11-01

    Asphaltenes from four different crude oils (Arab Heavy, B6, Canadon Seco, and Hondo) were fractionated in mixtures of heptane and toluene and analyzed chemically, by vapor pressure osmometry (VPO), and by small angle neutron scattering (SANS). Solubility profiles of the asphaltenes and their subfractions indicated strong cooperative asphaltene interactions of a particular subfraction that is polar and hydrogen bonding. This subfraction had lower H/C ratios and modestly higher N, V, Ni, and Fe contents than the less polar and more soluble subfraction of asphaltenes. VPO and SANS studies indicated that the less soluble subfractions formed aggregates that were considerably larger than the more soluble subfractions. In general, asphaltene aggregate size increased with decreasing solvent aromaticity up to the solubility limit, beyond which the aggregate size decreased with heptane addition. The presence of a low wavevector Q feature in the scattering curves at 25 degrees C indicated that the individual aggregates were flocculating; however, the intensity of the feature was diminished upon heating of the samples to 80 degrees C. The solubility mechanism for Canadon Seco asphaltenes, the largest aggregate formers, appears to be dominated by aromatic pi-bonding interactions due to their low H/C ratio and low nitrogen content. B6 and Hondo asphaltenes formed similar-sized aggregates in heptol and the solubility mechanism is most likely driven by polar interactions due to their relatively high H/C ratios and high nitrogen contents. Arab Heavy, the least polar asphaltene, had a H/C ratio similar to Canadon Seco but formed the smallest aggregates in heptol. The enhancement in polar and pi-bonding interactions for the less soluble subfraction indicated by elemental analysis is reflected by the aggregate size from SANS. The less soluble asphaltenes contribute the majority of species responsible for aggregation and likely cause many petroleum production problems such as pipeline deposition and water-in-oil emulsion stabilization. PMID:14554184

  4. Coccidioides immitis vaccine: potential of an alkali-soluble, water-soluble cell wall antigen 

    E-print Network

    Lecara, Grace

    1980-01-01

    -soluble cell wali antigen of C. immitis, C-ASWS, was evaluated for its vaccine potential in mice. Groups of mice were vaccinated with the mycelial-derived antigen, C-ASWS-M, in complete Freund's adjuvant, the spherule-derived antigen, C-ASWS-S, in adjuvant..., or tor controls, phosphate buffered saline in adjuvant. Thirty to forty days post-vaccination, mice were infected intranasally with viable arthro- spores of C. immitis strain Siiveira. Three doses of arthrospores were used: a dose & I LD50 ( & 50...

  5. 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.

  6. Soluble aromatic polyimides for film and coating applications

    NASA Technical Reports Server (NTRS)

    St.clair, Anne K.; St.clair, Terry L.

    1987-01-01

    Linear all-aromatic polyimides have been synthesized and characterized which show much potential as films and coatings for electronic applications. Structure-property relations with regard to methods for obtaining solubility of fully imidized polymers will be discussed. Methods used to obtain solubility include variation of polymer molecular structure, variation of isomerism of the diamine monomer, modification of cure time/temperature and atmosphere. Other properties of soluble polyimides will be presented which include glass transition temperatures, thermooxidative stabilities, UV-visible spectra, and refractive indices.

  7. Exactly Soluble Sector of Quantum Gravity

    E-print Network

    Joy Christian

    2005-11-07

    Cartan's spacetime reformulation of the Newtonian theory of gravity is a generally-covariant Galilean-relativistic limit-form of Einstein's theory of gravity known as the Newton-Cartan theory. According to this theory, space is flat, time is absolute with instantaneous causal influences, and the degenerate `metric' structure of spacetime remains fixed with two mutually orthogonal non-dynamical metrics, one spatial and the other temporal. The spacetime according to this theory is, nevertheless, curved, duly respecting the principle of equivalence, and the non-metric gravitational connection-field is dynamical in the sense that it is determined by matter distributions. Here, this generally-covariant but Galilean-relativistic theory of gravity with a possible non-zero cosmological constant, viewed as a parameterized gauge theory of a gravitational vector-potential minimally coupled to a complex Schroedinger-field (bosonic or fermionic), is successfully cast -- for the first time -- into a manifestly covariant Lagrangian form. Then, exploiting the fact that Newton-Cartan spacetime is intrinsically globally-hyperbolic with a fixed causal structure, the theory is recast both into a constraint-free Hamiltonian form in 3+1-dimensions and into a manifestly covariant reduced phase-space form with non-degenerate symplectic structure in 4-dimensions. Next, this Newton-Cartan-Schroedinger system is non-perturbatively quantized using the standard C*-algebraic technique combined with the geometric procedure of manifestly covariant phase-space quantization. The ensuing unitary quantum field theory of Newtonian gravity coupled to Galilean-relativistic matter is not only generally-covariant, but also exactly soluble.

  8. Uranium solubility studies during waste evaporation

    SciTech Connect

    Karraker, D.G.

    1993-08-16

    The liquid waste streams from chemical processing of reactor-irradiated targets and fuel are neutralized with excess NaOH and discharged to mild steel waste tanks for interim storage. To reduce the number of tanks required, and thus the cost of waste storage, the supernate is evaporated to about 70% solids, discharged while hot into clean waste tanks. As the solution cools, solids crystallize from the saturated solution and form a solid layer on the bottom of the tank. The supernate is re-evaporated to concentrate the volume further. Evaporation and crystallization are continued until, for tank 41, the tank is almost filled with crystallized salts. In the DWPF processing scheme, these salts will be redissolved in water and {sup 137}Cs precipitated with sodium tetraphenylborate in the in-tank precipitation facility. The decontaminated supernate is now mixed with cement and stored as a solid monolith; the precipitated Cs and the base-insoluble solids are encapsulated in glass for permanent storage. Questions have been raised about the nuclear safety of these operations, particularly for tank 41, where the waste source was waste from the H-Area fuel processing. One scenario for a potential nuclear accident considers that the salts in tank 41 would dissolve in water, but the enriched uranium solids would not dissolve. The uranium is hypothesized to settle to the bottom of the tank and become concentrated enough to reach a critical mass. A second scenario, promulgated by West Valley, is that uranium would precipitate in the evaporator and form a critical mass in the evaporator. To shed some light on the probable behavior of U in the waste system, the solubility of U in synthetic waste was studied. The results are reported here.

  9. Poorly water-soluble drug nanoparticles via solvent evaporation in water-soluble porous polymers.

    PubMed

    Roberts, Aled D; Zhang, Haifei

    2013-04-15

    A generic method is described to form poorly water-soluble drug nanoparticles within water-soluble porous polymer by solvent evaporation. The simple dissolution of porous polymer with drug nanoparticles results in stable aqueous drug nanoparticle suspension under the optimized conditions. The porous polymers were prepared by freeze-drying aqueous solutions of polyvinyl alcohol, polyethylene glycol, and a surfactant. They were then used as scaffolds for the formation of nanoparticles by initially soaking them in an organic drug solution, followed with removing the solvent via evaporation under ambient conditions. This process was optimized for an antifungal drug griseofulvin, before being translated to anticonvulsant carbamazepine and antineoplastic paclitaxel via a similar procedure, with an aim to improve the loading of drug nanoparticles. By varying certain process parameters a degree of control over the particle size and surface charge could be attained, as well as the drug to stabilizer ratio (drug payload). Noticeably, aqueous paclitaxel nanoparticles (500 nm) were prepared which used the equivalent of 46% less stabilizer than the formulation Taxol. PMID:23499755

  10. Antigenic heterogeneity of an alkali-soluble, water-soluble cell wall extract of Coccidioides immitis.

    PubMed Central

    Cox, R A; Britt, L A

    1985-01-01

    The antigenic composition of an alkali-soluble, water-soluble cell wall extract of Coccidioides immitis, designated C-ASWS, was assessed by two-dimensional immunoelectrophoresis against goat antisera to C-ASWS and coccidioidin. The results established that C-ASWS from mycelia or spherule cell walls is heterogeneous in composition, containing two distinct antigenic components. One is present as a polymer that is antigenically identical to a polymeric antigen in coccidioidin, designated antigen 2. The other component detected in C-ASWS presented an unusual precipitin pattern in that a cathodal leg was demonstrable in the absence of an anodal leg. This incomplete precipitinogen was also detected in coccidioidin. In addition to the finding that C-ASWS is antigenically heterogeneous, the results provide evidence that the conformational and/or configurational structure of the C-ASWS antigen 2 (or antigen 2-like polymer) is altered during physicochemical extraction. This conclusion is based upon the finding that the immunoelectrophoretic profile of the C-ASWS polymer differs from that of coccidioidin antigen 2. The C-ASWS polymer is characterized by having a small cathodal precipitin peak connected to a large anodal peak, whereas coccidioidin antigen 2 is characterized by a predominant cathodal peak. Images PMID:4055022

  11. 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...

  12. Estimating the Solubility of Gases in Battery Electrolytes

    NASA Technical Reports Server (NTRS)

    Lawson, D. D.; Frank, H. A.

    1984-01-01

    Estimates in excellent agreement with experimental values. Simple method proposed for estimating solubility of gases in electrolytes of lithium batteries using expressions for energy of vaporization and for molar volume.

  13. ANNUAL REPORT. BIOFILTRATION OF VOLATILE POLLUTANTS: SOLUBILITY EFFECTS

    EPA Science Inventory

    This project investigates and collects fundamental partitioning data for a variety of sparingly soluble subsurface contaminants (e.g., TCE, etc.) between vapor, aqueous phase, and matrices containing substantial quantities of biomass and biomass components. Due to the difficulty ...

  14. Analysis of Functional Groups by Solubility and Infrared Analysis.

    ERIC Educational Resources Information Center

    Turek, William N.

    1984-01-01

    An experiment which introduces students to infrared spectroscopy and the solubility behavior of various organic compounds is described. The experiment also serves to integrate some of the basic chemical reactions of functional groups with their spectral properties. (JN)

  15. 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.

  16. 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.

  17. PROGRESS REPORT. BIOFILTRATION OF VOLATILE POLLUTANTS: SOLUBILITY EFFECTS

    EPA Science Inventory

    This project investigates and collects fundamental partitioning data for a variety of sparingly soluble subsurface contaminants (e.g., TCE, etc.) between vapor, aqueous phase, and matrices containing substantial quantities of biomass and biomass components. Due to the difficulty ...

  18. 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.

  19. Metal oxide solubility in eutectic Li/K carbonate melts

    SciTech Connect

    Baumgartner, C.E.

    1984-07-01

    The equilibrium solubility of NiO, CuO, ZnO, LiFeO/sub 2/, and LaNiO/sub 3/ in binary Li/K carbonate was quantitatively measured between 823 and 1223 K under a simulated molten carbonate fuel cell cathode environment. The solubility of all materials, except LaNiO/sub 3/, was found to increase with increasing temperature. Equilibrium solubilities at 923 K, the operating temperature of a molten carbonate fuel cell, were determined to be 13 X 10/sup -6/, 32 X 10/sup -6/, 63 X 10/sup -6/, and 16 X 10/sup -6/ mole fraction for NiO, CuO, ZnO, and LiFeO/sub 2/, respectively. The LaNiO/sub 3/ solubility remained below the quantitative detection limit until the melt's temperature exceeded 1123 K, at which time material decomposition was detected.

  20. 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.

  1. 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.

  2. Development of an ELISA assay for the quantification of soluble huntingtin in human blood cells

    PubMed Central

    2013-01-01

    Background Huntington’s disease (HD) is a monogenic disorder caused by an aberrant expansion of CAG repeats in the huntingtin gene (HTT). Pathogenesis is associated with expression of the mutant (mHTT) protein in the CNS, with its levels most likely related to disease progression and symptom severity. Since non-invasive methods to quantify HTT in the CNS do not exist, measuring amount of soluble HTT in peripheral cells represents an important step in development of disease-modifying interventions in HD. Results An ELISA assay using commercially available antibodies was developed to quantify HTT levels in complex matrices like mammalian cell cultures lysates and human samples. The immunoassay was optimized using a recombinant full-length HTT protein, and validated both on wild-type and mutant HTT species. The ability of the assay to detect significant variations of soluble HTT levels was evaluated using an HSP90 inhibitor that is known to enhance HTT degradation. Once optimized, the bioassay was applied to peripheral blood mononuclear cells (PBMCs) from HD patients, demonstrating good potential in tracking the disease course. Conclusions The method described here represents a validated, simple and rapid bio-molecular assay to evaluate soluble HTT levels in blood cells as useful tool in disease and pharmacodynamic marker identification for observational and clinical trials. PMID:24274906

  3. Novel insights about salting-effects and reactivity of soluble molecules in aqueous aerosols

    NASA Astrophysics Data System (ADS)

    Volkamer, Rainer

    2014-05-01

    Organic carbon in the atmosphere modifies the lifetime of climate active gases such as O3, and CH4 (oxidative capacity), and forms aerosols that affect Earth's radiation balance. Water soluble organic carbon (WSOC) molecules are well established to form secondary organic aerosol (SOA) in cloud water. However, the chemistry and rate of SOA formation in aqueous aerosol is less well known, and is typically ignored in atmospheric models. Aqueous particles provide a very different chemical environment than clouds, i.e., they are the most concentrated aqueous salt solution that can be found on Earth. As a result of high ionic strength, phase separations of inorganic and organic phases, mass transfer limitations and viscosity effects affect the chemistry in aqueous particles, which proceeds via essentially different reaction pathways than in clouds. Of particular importance in this context is the Henry's law partitioning coefficient. Laboratory experiments show activity coefficients of 1/500 for Henry's law partitioning coefficients of glyoxal in concentrated aqueous aerosol- salt solutions. This salting-in mechanism is investigated in laboratory experiments, and shown to be a major driver in the rate of secondary organic aerosol (SOA) formation from the multiphase chemistry of soluble species like glyoxal. This solicited talk will summarize and discuss new experimental findings from simulation chamber experiments, and bulk reactor experiments to assess the Setschenow salting behavior of soluble molecules in different aqueous seed types, and study the effect of anthropogenic triggers such as sulfate and ammonium for the reactivity of multiphase reactions in the aerosol aqueous phase.

  4. 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.

  5. Suppression of experimental lupus nephritis by aberrant expression of the soluble E-selectin gene.

    PubMed

    Takahashi, Satoru; Araki, Kimi; Araki, Masatake; Ito, Mitsuko R; Nakatani, Kimihiko; Fujii, Hiroshi; Izui, Shozo; Vassalli, Pierre; Nose, Masato

    2002-03-01

    Circulating leukocytes, particularly neutrophils and monocytes, are important effector cells in the induction of many forms of glomerulonephritis. Adhesion molecules, especially selectins, are also thought to be critical for the development of this disease. We examined the possible suppressive effect of soluble E-selectin on the development of experimental lupus nephritis induced by the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ-lpr/lpr lupus mouse. This clone produces IgG3 antibodies that induce severe proliferative glomerulonephritis resembling lupus nephritis when injected into normal mice. Transgenic mice with a soluble E-selectin gene were injected intraperitoneally with the hybridoma cells and histopathologically examined on day 15. As a result, the development of glomerulonephritis was significantly suppressed. This suppression was characterized by fewer inflammatory cell infiltrates, compared with non-transgenic litter mates, despite the fact that there were no remarkable differences in immunoglobulin deposits or expression of E-selectin between the two groups. These findings suggest that by controlling inflammatory cell infiltration, soluble E-selectin plays a preventative role in the development of a particular type of lupus nephritis. PMID:11972860

  6. 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.

  7. Sorption, Solubility, Bond Strength and Hardness of Denture Soft Lining Incorporated with Silver Nanoparticles

    PubMed Central

    Chladek, Grzegorz; Kasperski, Jacek; Barszczewska-Rybarek, Izabela; ?mudzki, Jaros?aw

    2013-01-01

    The colonization of denture soft lining material by oral fungi can result in infections and stomatitis of oral tissues. In this study, 0 ppm to 200 ppm of silver nanoparticles was incorporated as an antimicrobial agent into composites to reduce the microbial colonization of lining materials. The effect of silver nanoparticle incorporation into a soft lining material on the sorption, solubility, hardness (on the Shore A scale) and tensile bond strength of the composites was investigated. The data were statistically analyzed using two-way ANOVA and Newman-Keuls post hoc tests or the chi-square Pearson test at the p < 0.05 level. An increase in the nanosilver concentration resulted in a decrease in hardness, an increase in sorption and solubility, a decrease in bond strength and a change in the failure type of the samples. The best combination of bond strength, sorption, solubility and hardness with antifungal efficacy was achieved for silver nanoparticle concentrations ranging from 20 ppm to 40 ppm. These composites did not show properties worse than those of the material without silver nanoparticles and exhibited enhanced in vitro antifungal efficiency. PMID:23271371

  8. Association of Soluble HLA-G with Acute Rejection Episodes and Early Development of Bronchiolitis Obliterans in Lung Transplantation

    PubMed Central

    White, Steven R.; Floreth, Timothy; Liao, Chuanhong; Bhorade, Sangeeta M.

    2014-01-01

    Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of bronchiolitis obliterans syndrome (BOS). Soluble HLA-G, a mediator of adaptive immunity that modulates regulatory T cells and certain classes of effector T cells, may be a useful marker of survival free of BOS. We conducted a retrospective, single-center, pilot review of 38 lung transplant recipients who underwent collection of serum and bronchoalveolar lavage fluid 3, 6 and 12 months after transplantation, and compared soluble HLA-G concentrations in each to the presence of type A rejection and lymphocytic bronchiolitis in the first 12 months and to the presence of BOS at 24 months after transplantation. Lung soluble HLA-G concentrations were directly related to the presence of type A rejection but not to lymphocytic bronchiolitis. Our data demonstrate that soluble HLA-G concentrations in bronchoalveolar lavage but not in serum correlates with the number of acute rejection episodes in the first 12 months after lung transplantation, and thus may be a reactive marker of rejection. PMID:25068264

  9. Solubility of tungsten in copper-nickel melts

    Microsoft Academic Search

    V. N. Eremenko; R. V. Minakova; M. M. Churakov

    1977-01-01

    1.The surface of primary solidification of tungsten in the nickel-copper-tungsten system has been determined.2.It is shown that raising the copper content of a copper-nickel melt sharply decreases the solubility of tungsten in the melt, particularly at low nickel contents.3.Equations have been derived expressing the dependence of the solubility of tungsten on the composition of the melt and temperature.4.An assessment is

  10. Reservoir brines influence soluble-oil flooding process

    Microsoft Academic Search

    L. W. Holm; V. A. Josendal

    1972-01-01

    Oilfield brines appear to exercise control over the effectiveness and properties of micellar solutions, polymers, and surfactants used in secondary and tertiary waterflooding. However, soluble-oil surfactants appear to be more tolerant of brines than aqueous surfactant solutions. The soluble-oil surfactants contain large quantities of monovalent cations (Na\\/sup +\\/, NHâ\\/sup +\\/) that exchange with the multivalent cations present in the reservoir

  11. Polythermal solubility of fullerenes in higher isomeric carboxylic acids

    Microsoft Academic Search

    K. N. Semenov; O. V. Arapov; A. K. Pyartman; V. A. Keskinov; V. V. Lishchuk; N. A. Charykov; N. I. Alekseev

    2007-01-01

    The solubility of individual fullerenes C60 and C70 and a fullerene mixture enriched in higher fullerenes (C60 38.8, C70 33.0, C76–78 5.6, C84 8.6, C90 2.6, and C96 3.3%) in higher isomeric carboxylic acids was studied within the 20–80C temperature range; the corresponding solubility\\u000a polytherms are presented.

  12. Compositional Analysis of Water-Soluble Materials in Corn Stover

    Microsoft Academic Search

    Shou-Feng Chen; Richard A. Mowery; Christopher J. Scarlata; C. Kevin Chambliss

    2007-01-01

    Corn stover is one of the leading feedstock candidates for commodity-scale biomass-to-ethanol processing. The composition of water-soluble materials in corn stover has been determined with greater than 90% mass closure in four of five representative samples. The mass percentage of water-soluble materials in tested stover samples varied from 14 to 27% on a dry weight basis. Over 30 previously unknown

  13. Biochemical and immunological studies on soluble antigens of Entamoeba histolytica

    Microsoft Academic Search

    P. Das; K. Sengupta; S. Pal; D. Das; S. C. Pal

    1993-01-01

    The soluble antigens ofEntamoeba histolytica trophozoites were analysed in detail by biochemical and immunochemical methods. The antigen was highly complex and heterogeneous as revcaled by Sephacryl S-300 column chromatography, which showed four distinct fractions. The molecular mass of fractions FI, FII, FIII and FIV was 660, 170, 65 and 13 kDa, respectively. Protein was the major constituent in crude soluble

  14. Soluble interleukin-2 receptor as a predictor of neonatal sepsis

    Microsoft Academic Search

    Michael L. Spear; John L. Stefano; Paul Fawcett; Roy Proujansky

    1995-01-01

    We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results. (J PEDIATR 1995;126:982-5)

  15. Carbon dioxide solubility in 1-ethyl-3-methylimidazolium trifluoromethanesulfonate

    Microsoft Academic Search

    Allan N. Soriano; Bonifacio T. Doma Jr.; Meng-Hui Li

    2009-01-01

    In this work, we present new solubility results for carbon dioxide in the ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate for temperatures ranging from (303.2 to 343.2)K and pressures up to 5.9MPa using a thermogravimetric microbalance. Carbon dioxide solubilities were determined from absorption saturation (equilibrium) results at each fixed temperature and pressure. The buoyancy effect was accounted for in the evaluation of the

  16. Molecular analysis of the soluble butane monooxygenase from 'Pseudomonas butanovora

    Microsoft Academic Search

    Miriam K. Sluis; Luis A. Sayavedra-Soto; Daniel J. Arp

    2002-01-01

    'Pseudomonas butanovora' is capable of growth with butane via the oxidation of butane to 1-butanol, which is catalysed by a soluble butane monooxygenase (sBMO). In vitro oxidation of ethylene (an alternative substrate for sBMO) was reconstituted in the soluble portion of cell extracts and was NADH-dependent. Butane monooxygenase was separated into three components which were obligately required for substrate oxidation.

  17. Solubility of some solid triazine herbicides in supercritical carbon dioxide

    Microsoft Academic Search

    Željko Knez; Andreja Rižner-Hraš; Klementina Kokot; Davorin Bauman

    1998-01-01

    Supercritical fluids can be applied for decontamination of soils and other solid materials containing residual pesticides. The solubility of solid s-triazine derivatives: ametryne, prometryne, atrazine and simazine in supercritical CO2 were measured by a static–analytic method in the pressure range from 100 to 300 bar at temperatures of 40, 60 and 80°C. The solubilities of atrazine and simazine are lower

  18. Soluble CD40 ligand in acute coronary syndromes

    Microsoft Academic Search

    C. Heeschen; S. Dimmeler; C. W. Hamm; A. M. Zeiher; M. L. Simoons; Brand van den M. J. B. M; H. Boersma

    2003-01-01

    BACKGROUND: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb\\/IIIa receptor inhibition in patients with acute coronary syndromes. METHODS: Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who

  19. Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers

    Microsoft Academic Search

    Juyang Huang; Jeffrey T. Buboltz; Gerald W. Feigenson

    1999-01-01

    In any lipid bilayer membrane, there is an upper limit on the cholesterol concentration that can be accommodated within the bilayer structure; excess cholesterol will precipitate as crystals of pure cholesterol monohydrate. This cholesterol solubility limit is a well-defined quantity. It is a first-order phase boundary in the phospholipid\\/cholesterol phase diagram. There are many different solubility limits in the literature,

  20. Demulsification of bitumen emulsions using water soluble salts of polymers

    SciTech Connect

    McCoy, D.R.; Cuscurida, M.; Speranza, G.P.

    1983-08-02

    A process for recovering bitumen from oil-in-water (O/W) emulsions is disclosed wherein water-soluble demulsifiers are used. These demulsifiers are water-soluble salts of polymers prepared by the reaction between certain polyoxyalkylene diamines with diepoxides. To resolve the bituminous petroleum emulsions, the process is carried out between 25/sup 0/ and 160/sup 0/C. wherein the demulsifier of the invention is contacted with the bituminous emulsion.

  1. Diffusion and solubility of HCHO in ice: preliminary results

    Microsoft Academic Search

    S. Perrier; P. Sassin; F. Domine

    2003-01-01

    The diffusion and solubility of formaldehyde (HCHO) in ice were measured at -15degrees by exposing large single crystals of ice to low vapor pressures of HCHO (P-HCHO) for several days. The solubility was found to be ( 30 +\\/- 3) x 10(-6) mol L-1 at -15degrees under P-HCHO = 1.7 x 10(-2) Pa. The diffusion coefficient is of the order

  2. Determination of petroleum pipe scale solubility in simulated lung fluid

    E-print Network

    Cezeaux, Jason Roderick

    2005-08-29

    tract solubility experiments have been predominantly performed with uranium ore/yellowcake or plutonium oxide dusts. Through a history of trials, certain experimental details have become almost standard. The first experimental component... of concern. Lung fluid dissolution trials have been done for many years. Most work in the past has been centered on uranium yellowcake or plutonium solubility. In these previous works, a standard simulant for SUF was developed. The simulated SUF...

  3. Nitrogen solubility and protein utilization by dairy cows

    E-print Network

    El Majdoub, Abdesselam

    1977-01-01

    NITROGEN SOLUBILITY AND PROTEIN UTILIZATION BY DAIRY COWS A Thesis by ABDESSELAM EL MAJDOUB Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree of MASTER OF SCIENCE August 1977... Major Subject: Animal Nutrition NITROGEN SOLUBILITY AND PROTEIN UTILIZATION BY DAIRY COIAIS A Thesis by ABD ESS ELAM EL MA JDOUB Approved as to style and content by: Chai n of mmittee Head o Depa ment Member Member August 1977 ABSTRACT...

  4. Uncertainty and sensitivity analysis of solubility calculations at elevated temperatures

    SciTech Connect

    Ekberg, C.; Skarnemark, G.; Emren, A.T.; Lunden, I. [Chalmers Univ. of Technology, Gothenburg (Sweden). Dept. of Nuclear Chemistry

    1996-08-01

    Computer simulations are commonly used in many areas to obtain information about a system. It is, however, important to remember that to these models are encumbered with errors of varying magnitude. To investigate the effect of these errors, a sensitivity-uncertainty (s/u) analysis is often made. This paper focuses on how the solubility of a solid phase is affected by uncertainties in the enthalpy of reaction for the species present in the solvent. Usually, thermodynamic data are given for a temperature of 25 C, but calculations are not made at this temperature for many practical applications. It is interesting to know which enthalpies are important and how much given uncertainties in these enthalpies affect the calculated solubility of a solid phase. The solubility calculations were performed by the thermodynamic equilibrium program PHREEQE and the statistical evaluations with a modified version of the SENVAR program. The solubility of e.g. UO{sub 3}{center_dot}2H{sub 2}O at 80 C was investigated. The conclusion was that the solubility ranged from 1E-05 to 4.5E-06 when the enthalpies of reaction for the interesting species were changed within a four kcal/mole wide interval. The maximum solubility, based on an arbitrary distribution, was found to be no greater than 9E-05 with 95% confidence.

  5. Solubility of nitrous oxide in alkanolamine aqueous solutions

    SciTech Connect

    Tsai, T.C.; Ko, J.J.; Wang, H.M.; Lin, C.Y.; Li, M.H.

    2000-04-01

    The solubility of nitrous oxide (N{sub 2}O) in alkanolamine aqueous solutions has been measured at (30, 35, and 40) C. The systems studied are monoethanolamine, diethanolamine, diisopropanolamine, triethanolamine, and 2-amino-2-methyl-1-propanol aqueous solutions. The concentration of amine for monoethanolamine ranges from (1 to 6) kmol/m{sup 3} and for other amines from (0.5 to 3) kmol/m{sup 3}. The accuracy of the measurement is estimated to be {+-}2%. A semiempirical model of the excess Henry's constant proposed by Wang et al. (1992) was used to correlate the solubility of N{sub 2}O in amine solutions. The parameters of the correlation were determined from the measured solubility data and the available data in the open literature. For a wide temperature range from (15 to 75) C, the obtained correlation has been shown to represent reasonably the solubility of N{sub 2}O in six amine aqueous solutions: MEA, DEA, DIPA, TEA, MDEA, and AMP. For the purpose of process design, the obtained correlations are, in general, satisfactory for estimating the solubility of N{sub 2}O in amine solutions, which in turn can be used to estimate the correct free-gas solubility of CO{sub 2} in amines.

  6. Solubility Behavior of Cyanophycin Depending on Lysine Content

    PubMed Central

    Wiefel, Lars

    2014-01-01

    Study of the synthesis of cyanophycin (CGP) in recombinant organisms focused for a long time mostly on the insoluble form of CGP, due to its easy purification and its putative use as a precursor for biodegradable chemicals. Recently, another form of CGP, which, in contrast to the insoluble form, was soluble at neutral pH, became interesting due to its high lysine content, which was also assumed to be the reason for the solubility of the polymer. In this study, we demonstrate that lysine incorporated into insoluble CGP affected the solubility of the polymer in relation to its lysine content. Insoluble CGP can be separated along a temperature gradient of 90°C to 30°C, where CGP showed an increasing lysine content corresponding to a decreasing temperature needed for solubilization. CGP with less than 3 to 4 mol% lysine did not become soluble even at 90°C, while CGP with 31 mol% lysine was soluble at 30°C. In lysine fractions at higher than 31 mol%, CGP was soluble. The temperature separation will be suitable for improving the downstream processing of CGP synthesized in large-scale fermentations, including faster and more efficient purification of CGP, as well as enrichment and separation of dipeptides and CGP with specific amino acid compositions. PMID:24271185

  7. Probing Domain Interactions in Soluble Guanylate Cyclase†

    PubMed Central

    Derbyshire, Emily R.; Winter, Michael B.; Ibrahim, Mohammed; Deng, Sarah; Spiro, Thomas G.; Marletta, Michael A.

    2011-01-01

    Eukaryotic nitric oxide (NO) signaling involves modulation in cyclic GMP (cGMP) levels through activation of the soluble isoform of guanylate cyclase (sGC). sGC is a heterodimeric hemoprotein that contains a Heme-Nitric oxide and OXygen binding (H-NOX) domain, a Per/ARNT/Sim (PAS) domain, a coiled-coil (CC) domain, and a catalytic domain. To evaluate the role of these domains in regulating the ligand binding properties of the heme cofactor of NO-sensitive sGC, chimeras were constructed by swapping the rat ?1 H-NOX domain with the homologous region of H-NOX domain-containing proteins from Thermoanaerobacter tengcongensis, Vibrio cholerae, and Caenorhabditis elegans (TtTar4H, VCA0720, and Gcy-33, respectively). Characterization of ligand binding by electronic absorption and resonance Raman spectroscopy indicates that the other rat sGC domains influence the bacterial and worm H-NOX domains. Analysis of cGMP production in these proteins reveals that the chimeras containing bacterial H-NOXs exhibit guanylate cyclase activity, but this activity is not influenced by gaseous ligand binding to the heme cofactor. The rat-worm chimera containing the atypical sGC Gcy-33 H-NOX domain was weakly activated by NO, CO and O2, suggesting that atypical guanylate cyclases and NO-sensitive guanylate cyclases have a common molecular mechanism for enzyme activation. To probe the influence of the other sGC domains on the mammalian sGC heme environment, heme pocket mutants (Pro118Ala and Ile145Tyr) were generated in the ?1 H-NOX construct (residues 1–194), the ?1 H-NOX-PAS-CC construct (residues 1–385), and the full-length ?1?1 sGC heterodimer (?1 residues 1–619). Spectroscopic characterization of these proteins shows that inter-domain communication modulates the coordination state of the heme-NO complex and the heme oxidation rate. Taken together, these findings have important implications for the allosteric mechanism of regulation within H-NOX containing proteins. PMID:21491957

  8. AN ANALYSIS OF THE RELATIONSHIP BETWEEN SOLUBILITY AND STIMULATING EFFECT IN TARSAL CHEMORECEPTION

    PubMed Central

    Dethier, V. G.; Chadwick, L. E.

    1950-01-01

    The rejection thresholds of the blowfly Phormia regina Meigen for a selected series of substituted aliphatic hydrocarbons have been determined and an analysis made of the effect on stimulation of increasing the number of like substitutions from one to two, of the interaction of different types of substituent, and of the position of the substituent in the molecule. The order of stimulating efficiency (reciprocal of rejection threshold) of the functional groups which have been studied is: Br > Cl ? CH3 ? CHO > C=O > OH. There is a consistent decrease in stimulating effect following the introduction of a second hydroxyl group. The introduction of a second C=O has little effect. Introduction of a second halogen is generally followed by a decrease in threshold. Two different species of functional group, one of which tends to increase water solubility and the other to decrease it, tend to counter-balance each other. A single oxygen-containing functional group on the end of the molecule or two of these groups which are terminal reduce the stimulating effect less than when one or more of such groups are subterminal or located elsewhere within the molecule. Branching of the carbon chain decreases effectiveness. Sulfur and oxygen linkages also decrease effectiveness. In general, the length of the free alkyl group largely determines the stimulating effectiveness. Its power is modified to varying degrees by the nature of the attached polar groups. Of all chemical properties examined, solubility alone agrees consistently with the foregoing data. Threshold varies directly with the molar solubility of the compounds in water. The fact that the threshold values for individual compounds are frequently different from those which would be expected solely on the basis of the correlation between threshold and solubility in water suggests that other factors are also concerned in stimulation. These have not yet been identified. PMID:15422112

  9. 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

  10. Soluble cysteine-rich tick saliva proteins Salp15 and Iric-1 from E. coli.

    PubMed

    Kolb, Philipp; Vorreiter, Jolanta; Habicht, Jüri; Bentrop, Detlef; Wallich, Reinhard; Nassal, Michael

    2015-01-01

    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 Ixodes ricinus. 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 (1)H-(15)N 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 (13)C/(15)N 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

  11. Biophysical comparison of soluble amyloid-?(1-42) protofibrils, oligomers, and protofilaments.

    PubMed

    Nichols, Michael R; Colvin, Benjamin A; Hood, Elizabeth A; Paranjape, Geeta S; Osborn, David C; Terrill-Usery, Shana E

    2015-04-01

    Some of the pathological hallmarks of the Alzheimer's disease brain are senile plaques composed of insoluble amyloid-? protein (A?) fibrils. However, much of the recent emphasis in research has been on soluble A? aggregates in response to a growing body of evidence that shows that these species may be more neurotoxic than fibrils. Within this subset of soluble aggregated A? are protofibrils and oligomers. Although each species has been widely investigated separately, few studies have directly compared and contrasted their physical properties. In this work, we examined well-recognized preparations of A?(1-42) oligomers and protofibrils with multiangle (MALS) and dynamic (DLS) light scattering in line with, or following, size-exclusion chromatography (SEC). Multiple SEC-MALS analyses of protofibrils revealed molecular weight (Mw) gradients ranging from 200 to 2600 kDa. Oligomeric A? species are generally considered to be a smaller and more nascent than protofibrils. However, oligomer Mw values ranged from 225 to 3000 kDa, larger than that for protofibrils. Root-mean-square radius (Rg) values correlated with the Mw trends with protofibril Rg values ranging from 16 to 35 nm, while oligomers produced one population at 40-43 nm with a more disperse population from 22 to 39 nm. Hydrodynamic radius (RH) measurements by DLS and thioflavin T fluorescence measurements indicated that protofibrils and oligomers had commonalities, yet electron microscopy revealed morphological differences between the two. SEC-purified A?(1-42) monomer at lower concentrations was slower to nucleate but formed protofibrils (1500 kDa) or soluble protofilaments (3000 kDa) depending on the buffer type. The findings from these studies shed new light on the similarities and differences between distinct soluble aggregated A? species. PMID:25756466

  12. Soluble CD44 Interacts with Intermediate Filament Protein Vimentin on Endothelial Cell Surface

    PubMed Central

    Päll, Taavi; Pink, Anne; Kasak, Lagle; Turkina, Marina; Anderson, Wally; Valkna, Andres; Kogerman, Priit

    2011-01-01

    CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12–37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells. PMID:22216242

  13. Influence of cosolvent on solubilities of fatty acids and higher alcohols in supercritical carbon dioxide

    Microsoft Academic Search

    Yoshio Koga; Yoshio Iwai; Yoshiaki Hata; Morio Yamamoto; Yasuhiko Arai

    1996-01-01

    Influences of cosolvents on the solubilities of fatty acids (palmitic acid (C15H31COOH) and stearic acid (C17H35COOH)) and higher alcohols (cetyl alcohol (C16H33OH) and stearyl alcohol (C18H37OH)) in supercritical carbon dioxide were measured by using a flow-type apparatus. Experiments were carried out at 308.2 K under 9.9, 14.8 and 19.7 MPa. Ethanol and octane were used as cosolvents. The concentration of

  14. [Nutrition and bone health. The bone and the foods containing many water-soluble vitamins].

    PubMed

    Ishida, Hiromi

    2009-08-01

    On the Dietary Reference Intakes in Japan, nine kinds of water-soluble vitamins are taken up. Those vitamins are supplied from various food. Food from animal sources and vegetable sources are those vitamins source of supply. Vitamin C participates in generation of collagen. Vitamin C is supplied from vegetables or fruits. Since vitamin C is lost by cooking processing, the content of a raw state is not expectable after cooking. Moreover, the vitamin B group of food origin has combined with protein etc., and free types, such as supplement, differ in the bioavailability. PMID:19638705

  15. Chemical constituents from the root of Polygonum multiflorum and their soluble epoxide hydrolase inhibitory activity.

    PubMed

    Sun, Ya Nan; Li, Wei; Kim, Jang Hoon; Yan, Xi Tao; Kim, Ji Eun; Yang, Seo Young; Kim, Young Ho

    2015-06-01

    Fourteen compounds were isolated from a methanol extract of Polygonum multiflorum roots, and their structures were elucidated by comparing spectroscopic data to published spectra. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were then evaluated. Compounds 1-7 inhibited sEH activity potently, with IC50 values ranging from 6.2 ± 0.5 to 48.6 ± 3.1 ?M. Moreover, a kinetic analysis of compounds 1-7 revealed that the inhibitory actions of compounds 1, 3 and 4 were non-competitive, whereas those of compounds 2 and 5-7 were mixed-type. PMID:25413971

  16. Solubility Behavior of Narcotic Analgesics in Aqueous Media: Solubilities and Dissociation Constants of Morphine, Fentanyl, and Sufentanil

    Microsoft Academic Search

    Samir D. Roy; Gordon L. Flynn

    1989-01-01

    The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35°C. Dissociation constants and corresponding pKa' values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa' values of 8.08, 8.99, and 8.51, respectively. Over the pH

  17. Stability of fat-soluble and water-soluble vitamins in artificially prepared, vitamin-enriched, lyophilized serum.

    PubMed

    Ihara, Hiroshi; Hashizume, Naotaka; Matsubayashi, Tadashi; Futaki, Koichi; Yoshida, Masayuki; Sagawa, Naotoshi; Fujisaki, Makoto; Mita, Kazuo; Kadota, Akira

    2004-01-01

    Vitamin-enriched, lyophilized serum (VES) was prepared for an inter-laboratory study to compare vitamin assays. The VES contained water-soluble vitamins (vitamin B1, vitamin B12, vitamin C, and folate), fat-soluble vitamins (vitamin A and vitamin E), and cholesterol. We performed stability studies and determined vitamin concentrations and total cholesterol in VES stored at -20 degrees C for 12 months. Our recovery of the water-soluble vitamins in reconstituted VES was 70-142%, but we recovered only 33-45% of the fat-soluble vitamins. Physicochemical properties, such as specific gravity and viscosity of the reconstituted VES did not affect manual or automated measurements of these vitamins. Vial-to-vial differences found for the VES were the same as the within-day analytical variations. There was no evidence of degradation of vitamin A, vitamin B1, vitamin B12, vitamin C, folate, and cholesterol over 12 months in VES stored at -20 degrees C. Following deproteinization, vitamin C concentration was found to be lower than when not deproteinated. Vitamin E was less stable in VES, however, and the degradation during 12 months was lower than the between-day analytical variation of the assay. Our VES is the first preparation of lyophilized control serum that contains water-soluble and fat-soluble vitamins. PMID:15202117

  18. Solubility of hydrogen isotopes in stressed hydride-forming metals

    SciTech Connect

    Coleman, C.E.; Ambler, J.F.R.

    1983-01-01

    Components made from hydride-forming metals can be brittle when particles of hydride are present. The solid solubility limit of hydrogen in these metals needs to be known so that fracture resistance can be properly assessed. Stress affects the solubility of hydrogen in metals. As hydrogen dissolves the metal volume increases, an applied hydrostatic tensile stress supplies work to increase the solubility. Precipitation of hydrides increases the volume further. A hydrostatic tensile stress promotes the formation of hydrides and tends to reduce the terminal solubility. For materials containing hydrogen in solution in equilibrium with hydrides, the effect of stress on the terminal solubility is given. Hydrogen migrates up tensile stress gradients because of the effect of stress on the solubility and solubility limit. Consequently, hydrogen concentrates at flaws. When hydrides are present in the metal matrix, those remote from the flaw tip will preferentially dissolve in favor of those precipitated at the flaw. If the stress is large enough, at some critical condition the hydrides at the flaw will crack. This is delayed hydrogen cracking. Notched and fatigue-cracked cantilever beam specimens (6) (38 x 4 x 3 mm) were machined from the circumferential direction of several cold-worked Zr-2.5 at. % Nb pressure tubes. The chemical compositions had the ranges (in atomic %) Nb - 2.5 to 2.7; O - 0.58 to 0.71; H - 0.018 to 0.18. The effect of test temperature is for a specimen containing 0.13 at. % protium and 0.29 at .% deuterium. Between 505 K and 530 K was less than 1 hr, between 530 K and 537 K it increased to 25.8 h, while at 538 K no cracking was observed up to the 54 h.

  19. Short Communication CORAL: QSPR model of water solubility based on local and global SMILES attributes

    E-print Network

    Gini, Giuseppina

    Short Communication CORAL: QSPR model of water solubility based on local and global SMILES model for water solubility is described in detail. a r t i c l e i n f o Article history: Received 20 Keywords: Water solubility QSPR Monte Carlo technique CORAL software a b s t r a c t Water solubility

  20. Solubility and partitioning of Ar in anorthite, diopside, forsterite, spinel, and synthetic basaltic liquids

    Microsoft Academic Search

    C. L. Broadhurst; M. J. Drake; B. E. Hagee; T. J. Bernatowicz

    1990-01-01

    The authors have investigated the solubility and partitioning of Ar in natural anorthite, diopside, forsterite, spinel, and synthetic iron-free basaltic melts. The solubility of Ar in the minerals is surprisingly high. In addition, the solubility of Ar in different samples of a particular mineral run in the same experiment varies more than the solubility in the same sample run in