Sample records for soluble activin type

  1. Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects

    PubMed Central

    1995-01-01

    Proteins in the TGF-beta superfamily transduce their effects through binding to type I and type II serine/threonine kinase receptors. Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 or BMP-7), a member of the TGF-beta superfamily which belongs to the BMP subfamily, was found to bind activin receptor type I (ActR-I), and BMP receptors type IA (BMPR-IA) and type IB (BMPR-IB) in the presence of activin receptors type II (ActR-II) and type IIB (ActR-IIB). The binding affinity of OP-1 to ActR-II was two- to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR-II. These results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins. Some of the known biological effects of activin were observed for OP-1, including growth inhibition and erythroid differentiation induction. Compared to activin, OP-1 was shown to be a poor inducer of mesoderm in Xenopus embryos. Moreover, follistatin, an inhibitor of activins, was found to inhibit the effects of OP-1, if added at a 10-fold excess. However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. OP-1 has overlapping binding specificities with activins, and shares certain but not all of the functional effects of activins. Thus, OP-1 may have broader effects in vivo than hitherto recognized. PMID:7790373

  2. 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

  3. Development of novel activin-targeted therapeutics.

    PubMed

    Chen, Justin L; Walton, Kelly L; Al-Musawi, Sara L; Kelly, Emily K; Qian, Hongwei; La, Mylinh; Lu, Louis; Lovrecz, George; Ziemann, Mark; Lazarus, Ross; El-Osta, Assam; Gregorevic, Paul; Harrison, Craig A

    2015-03-01

    Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-? proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys(45), Tyr(96), His(97), and Ala(98); activin A numbering) that confer latency to other TGF-? proteins were incorporated. For the activin A prodomain, these modifications generated a reagent that potently (IC50 5 nmol/l) and specifically inhibited activin A signaling in vitro, and activin A-induced muscle wasting in vivo. Interestingly, the modified activin B prodomain inhibited both activin A and B signaling in vitro (IC50 ~2 nmol/l) and in vivo, suggesting it could serve as a general activin antagonist. Importantly, unlike soluble ActRIIA/IIB, the modified prodomains did not inhibit myostatin or GDF-11 activity. To underscore the therapeutic utility of specifically antagonising activin signaling, we demonstrate that the modified activin prodomains promote significant increases in muscle mass. PMID:25399825

  4. Gonadotropin regulation of activin betaA and activin type IIA receptor expression in the ovarian follicle cells of the zebrafish, Danio rerio.

    PubMed

    Pang, Yefei; Ge, Wei

    2002-02-25

    We have previously demonstrated that both activin and its receptors are expressed in the zebrafish ovary, suggesting paracrine roles for activin in the ovarian functions. Activin significantly stimulated zebrafish oocyte maturation in vitro, and this effect could be blocked by follistatin, an activin-binding protein. Interestingly, follistatin also blocked the stimulatory effect of gonadotropin (hCG) on the oocyte maturation. Taken together, these results have led to a hypothesis that the ovarian activin system may play a role in mediating the actions of gonadotropin in the ovary. To test this hypothesis, the present study was undertaken to investigate if gonadotropin has any effect on the expression of activin betaA subunit and activin type IIA (ActRIIA) receptor in the zebrafish ovary. A primary culture of zebrafish ovarian follicle cells was established in the present study, and the cultured cells expressed both activin betaA and ActRIIA receptor when assayed with RT-PCR. The primary culture consisted of three major types of cells, presumably the fibroblasts, the thecal cells and the granulosa cells, according to the morphological features, histochemical staining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and RT-PCR for aromatase. Using a semi-quantitative RT-PCR with beta-actin as the internal control, we demonstrated that hCG significantly stimulated mRNA expression of both activin betaA and ActRIIA receptor in the cultured follicle cells in a time- and dose-dependent manner. Treatment of the cells with hCG quickly increased the steady-state mRNA levels of activin betaA and ActRIIA receptor, and the effect peaked at 2 h of treatment. The stimulatory effect of gonadotropin diminished with longer treatment and no effect was observed at 8 h of treatment. The effect of hCG also exhibited strong dose dependence when assayed at 2 h of treatment. The levels of activin betaA and ActRIIA receptor mRNA elevated with increasing dose of hCG; however, the effect significantly decreased at dosage higher than 15 IU/ml. Consistent with the stimulatory effect of gonadotropin on the expression of activin betaA and ActRIIA receptor, IBMX, forskolin and 8-Br-cAMP all significantly increased the mRNA levels of activin betaA and ActRIIA receptor. These results suggest that gonadotropin activates the activin system in the zebrafish ovary by increasing the expression of both activin and its receptors. PMID:11911957

  5. Conditional Activin Receptor Type 1B (Acvr1b) Knockout Mice Reveal Hair Loss Abnormality

    Microsoft Academic Search

    Wanglong Qiu; Xiaojun Li; Hongyan Tang; Alicia S Huang; Andrey A Panteleyev; David M Owens; Gloria H Su

    2011-01-01

    The in vivo functions of the activin A receptor type 1b (Acvr1b) have been difficult to study because Acvr1b?\\/? mice die during embryogenesis. To investigate the roles of Acvr1b in the epithelial tissues, we created mice with a conditional disruption of Acvr1b (Acvr1bflox\\/flox) and crossed them with K14-Cre mice. Acvr1bflox\\/flox; K14-Cre mice displayed various degrees of hairlessness at postnatal day

  6. Cycloheximide inhibits follicle-stimulating hormone ? subunit transcription by blocking de novo synthesis of the labile activin type II receptor in gonadotrope cells.

    PubMed

    Rejon, Carlis A; Ho, Catherine C; Wang, Ying; Zhou, Xiang; Bernard, Daniel J; Hébert, Terence E

    2013-06-01

    The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), play essential roles in the regulation of vertebrate reproduction. Activins and inhibins have opposing actions on FSH (but not LH) synthesis, either inducing or inhibiting transcription of the FSH? subunit gene (Fshb). The translational inhibitor cycloheximide (CHX) produces inhibin-like effects in cultured pituitary cells, selectively suppressing FSH production. Using the murine gonadotrope-like cell line, L?T2, as a model, we tested the hypothesis that a component of the activin pathway is highly labile in gonadotrope cells and that its rapid loss following CHX treatment impairs activin-stimulated Fshb transcription. Treatment of cells with CHX for 6h, but not 1h, blocked activin A-stimulated Fshb transcription. Pre-treatment of L?T2 cells with CHX for as few as 2-3h inhibited activin A-stimulated SMAD2/3 phosphorylation without altering total SMAD2/3 protein levels. These data indicated that CHX affects activin signalling upstream of SMAD proteins, most likely at the receptor level. Indeed, CHX rapidly reduced activin A binding to L?T2 cells. We went on to show that activin A signals via the type II receptor ACVR2, rather than ACVR2B, to regulate Fshb transcription and that the receptor has a half life of ~2h in L?T2 cells. The mechanism of ACVR2 turnover remains undefined, but appears to be ligand-, proteasome-, and lysosome-independent. Collectively, these data indicate that CHX produces inhibin-like effects in gonadotropes by preventing de novo synthesis of the highly labile ACVR2, thereby blocking activin signaling to the Fshb promoter. PMID:23499904

  7. 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.

  8. Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer

    PubMed Central

    2014-01-01

    Background Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the SMAD4 gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear. Methods and results We found a homozygous deletion of the activin A receptor, type IB (ACVR1B) gene in 2 out of 8 PC cell lines using array-comparative genomic hybridization, and the absence of ACVR1B mRNA and protein expression was confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth and increased the phosphorylation level of SMAD2 and the expression level of p21CIP1/WAF1 in the Sui66 cell line (wild-type ACVR1B and SMAD4 genes) but not in the Sui68 cell line (homozygous deletion of ACVR1B gene). Stable ACVR1B-knockdown using short hairpin RNA cancelled the effects of activin A on the cellular growth of the PC cell lines. In addition, ACVR1B-knockdown significantly enhanced the cellular growth and colony formation abilities, compared with controls. In a xenograft study, ACVR1B-knockdown resulted in a significantly elevated level of tumorigenesis and a larger tumor volume, compared with the control. Furthermore, in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the ACVR1B gene, while 10 of the 29 samples (34.5%) carried a deletion of the SMAD4 gene. Of note, 5 of the 6 samples with a deletion of the ACVR1B gene also had a deletion of the SMAD4 gene. Conclusion We identified a homozygous deletion of the ACVR1B gene in PC cell lines and clinical samples and proposed that the deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in PC. Our findings provide novel insight into the role of the activin signal in PC. PMID:24886203

  9. 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

  10. Comparative analysis of follistatin-, activin beta A- and activin beta B-mRNA steady-state levels in diverse porcine tissues by multiplex S1 nuclease analysis

    Microsoft Academic Search

    Olaf Schneider; Roland Nau; Uwe Michel

    2000-01-01

    Objective: The relation of activins (dimers of the beta-subunits of inhibin) and follistatin (FS) (their binding protein) affect the growth and differentiation of many cell types. Activin- and FS-mRNAs show a widespread co-expression throughout the organism, indicating an essential role for the FS\\/activin system in diverse physiological processes. The present study was performed to investigate FS-, activin beta A-, and

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

    SciTech Connect

    Cheng, Jung-Chien; Chang, Hsun-Ming; Qiu, Xin; Fang, Lanlan; Leung, Peter C.K., E-mail: peter.leung@ubc.ca

    2014-01-10

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

  12. Activin A regulation under global hypoxia in developing mouse brain.

    PubMed

    Brackmann, Florian A; Link, Andrea S; Jung, Susan; Richter, Mandy; Zoglauer, Daniel; Walkinshaw, Gail; Alzheimer, Christian; Trollmann, Regina

    2013-09-19

    Activin A is a multifunctional growth and differentiation factor with pronounced neuroprotective properties that is strongly up-regulated in various forms of acute brain disorders and injuries including epilepsy, stroke and trauma. In a pediatric context, activin A has been advanced as a potential marker for the severity of perinatal hypoxic-ischemic brain injury. Here we investigated the regulation of activin A under global hypoxia without ischemia in primary cultures of cortical neurons and in neonatal and adult mice of two strains (C57BL/6 and CD-1). From birth to adulthood, activin ?A subunit, activin receptors, and functional activin antagonists were all expressed at roughly similar mRNA levels in the brain of C57BL/6 mice. Independent of mouse line and age, we found both moderate (11% O2, 2h) and severe hypoxia (8%, 6h) to be consistently associated with normal or even reduced levels of activin ?A (Inhba) mRNA. The surprising unresponsiveness of Inhba expression to hypoxia was confirmed at the protein level. In situ hybridization did not indicate regional, hypoxia-related differences in Inhba expression. Pharmacologic stabilization of hypoxia inducible factors with the prolyl hydroxylase inhibitor FG-4497 did not influence Inhba mRNA levels in neonatal mice. Our data indicate that pure hypoxia differs from other, more complex types of brain damage in that it appears not to recruit activin A as an endogenous neuroprotective agent. PMID:23916668

  13. 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

  14. Follistatin, an activin antagonist, ameliorates renal interstitial fibrosis in a rat model of unilateral ureteral obstruction.

    PubMed

    Maeshima, Akito; Mishima, Keiichiro; Yamashita, Shin; Nakasatomi, Masao; Miya, Masaaki; Sakurai, Noriyuki; Sakairi, Toru; Ikeuchi, Hidekazu; 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

  15. Evidence of Selection for Clones Having Genetic Inactivation of the Activin A Type II Receptor (ACVR2) Gene in Gastrointestinal Cancers1

    Microsoft Academic Search

    Paula M. Hempen; Lin Zhang; Ravi K. Bansal; Christine A. Iacobuzio-Donahue; Kathleen M. Murphy; Anirban Maitra; Bert Vogelstein; Robert H. Whitehead; Sanford D. Markowitz; James K. V. Willson; Charles J. Yeo; Ralph H. Hruban; Scott E. Kern

    2003-01-01

    The activin signaling pathway parallels the transforming growth factor (TGF)- pathway. Both use extracellular ligands and cell surface recep- tors that are structurally and functionally related, as well as the same intracellular mediators (SMADs 2- 4) to transmit these signals. Members of both pathways have been characterized previously as tumor suppressor genes on the demonstration of inactivating mutations in human

  16. Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and Bærum Cardiovascular Diabetes (ABCD) cohort study

    PubMed Central

    2013-01-01

    Background Novel and robust cardiovascular (CV) markers are needed to improve CV morbidity and mortality risk prediction in type 2 diabetes (T2D). We assessed the long term predictive value of 4 novel CV risk markers for major CV events and mortality. Methods We included patients with T2D who had cytokines (interleukin [IL]-6 and activin A [actA]), a maximum stress ECG test (evaluated by the normalization pattern in early recovery phase) and echocardiography (evaluated by a measure of the left ventricular filling pressure - E/Em) assessed at baseline. The primary endpoint was time to first of any of the following events: myocardial infarction, stroke, hospitalization for unstable angina pectoris and death. All outcomes were adjudicated by independent experts. We used Cox proportional hazard modeling, Harrell C-statistic and the net reclassification improvement (NRI) to assess the additional value beyond conventional markers (age, gender, prior CV disease, HDL, creatinine, diastolic BP, microalbuminuria). Results At baseline the study cohort (n?=?135, mean age/diabetes duration/HbA1c: 59 yrs/7 yrs/7.6% [59 mmol/mol], 26% females) had moderate elevated CV risk (42% microalbuminuria, mean Framingham 10 year CV-risk 9.6%). During 8.6 yrs/1153.7 person years, 26 patients experienced 36 events. All 4 novel risk markers were significantly associated with increased risk of the primary endpoint, however, only IL-6 and actA improved C-statistic and NRI (+0.119/43.2%, +0.065/20.3% respectively) compared with the conventional CV risk factors. Conclusions IL-6 and actA may provide prognostic information on CV events and mortality in T2D beyond conventional CV risk factors. Trial registration ClinicalTrials.gov: NCT00133718 PMID:23987834

  17. The Interpretation of Position in a Morphogen Gradient as Revealed by Occupancy of Activin Receptors

    Microsoft Academic Search

    Steven Dyson; J. B. Gurdon

    1998-01-01

    Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells

  18. Activins and inhibins: Novel regulators of thymocyte development

    SciTech Connect

    Licona-Limon, Paula; Aleman-Muench, German [Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Circuito Escolar s/n, Mexico, DF 04510 (Mexico); Chimal-Monroy, Jesus [Departamento de Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, UNAM, Mexico, DF (Mexico); Macias-Silva, Marina [Departmento de Biologia Celular, Instituto de Fisiologia Celular, UNAM, Mexico, DF (Mexico); Garcia-Zepeda, Eduardo A. [Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Circuito Escolar s/n, Mexico, DF 04510 (Mexico); Matzuk, Martin M. [Departments of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX (United States); Fortoul, Teresa I. [Departamento de Biologia Celular y Tisular, Facultad de Medicina, UNAM, Mexico, DF (Mexico); Soldevila, Gloria [Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Circuito Escolar s/n, Mexico, DF 04510 (Mexico)], E-mail: soldevi@servidor.unam.mx

    2009-04-03

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

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

    SciTech Connect

    Hashimoto, Osamu [Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan)]. E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki [Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan); Sekiyama, Kazunari [Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan); Yamaguchi, Osamu [Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan); Yoshioka, Kazuki [Laboratory of Veterinary Anatomy, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan); Mutoh, Ken-Ichiro [Laboratory of Veterinary Anatomy, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan); Hasegawa, Yoshihisa [Laboratory of Experimental Animal Science, Faculty of Veterinary Medicine, Kitasato University, School of Veterinary Medicine and Animal Sciences, Towada, Aomori 034-8628 (Japan)

    2006-03-10

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

  20. Activin A Inhibits Antigen-Induced Allergy in Murine Epicutaneous Sensitization

    PubMed Central

    Kypriotou, Magdalini; Rivero, Dianelys; Haller, Sergio; Mariotto, Anita; Huber, Marcel; Acha-Orbea, Hans; Werner, Sabine; Hohl, Daniel

    2013-01-01

    Activin A, a member of the TGF? superfamily, is involved in physiological processes such as cell differentiation, tissue homeostasis, wound healing, reproduction, and in pathological conditions, such as fibrosis, cancer, and asthma. Activin enhances mast cell maturation, as well as regulatory T-cell and Langerhans cell differentiation. In this study we investigated the potential role of activin in epicutaneous sensitization with ovalbumin (OVA), notably with respect to its effect on known Th2-polarization. For this purpose, transgenic mice overexpressing activin in keratinocytes and their wild-type (WT) controls were sensitized epicutaneously with OVA. Skin biopsies were analyzed with regard to histopathological features and mRNA expression of pro-inflammatory and Th1/Th2 cytokines, and Ig levels were measured in the serum. Unexpectedly, activin overexpressing animals were protected from Th2-cytokine expression and induction of OVA-specific IgE levels compared to WT animals. On the other hand, transgenic mice were more susceptible to inflammation compared to WT littermates after tape-stripping and saline (vehicle) or OVA application, as shown by increased pro-inflammatory cytokine mRNA levels and neutrophil accumulation at the site of the treatment. We conclude that activin protects from antigen-induced cutaneous Th2-polarization through modulation of the immune response. These findings highlight the role of activin in cutaneous sensitization, allergy, and in skin homeostasis. PMID:23986758

  1. Solubility

    NSDL National Science Digital Library

    2012-07-19

    Investigate what makes something soluble by exploring the effects of intermolecular attractions and what properties are necessary in a solution to overcome them. Interactive models simulate the process of dissolution, allowing you to experiment with how external factors, such as heat, can affect a substance's solubility.

  2. Activin promotes astrocytic differentiation of a multipotent neural stem cell line and an astrocyte progenitor cell line from murine central nervous system

    Microsoft Academic Search

    Motonobu Satoh; Hiromu Sugino; Touho Yoshida

    2000-01-01

    The effects of activin A were investigated on the development of a multipotent neural stem cell line (MEB5) and an astrocyte progenitor cell line (AP-16) that were established from murine central nervous system (CNS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that each cell line expresses both type I and type II activin receptors and signaling molecules for activin, Smad2,

  3. R-Smad Competition Controls Activin Receptor Output in Drosophila

    PubMed Central

    Shimell, MaryJane; Stefancsik, Ray; Wijayatonge, Ranjula; Herder, Rachel; Raftery, Laurel A.; O'Connor, Michael B.

    2012-01-01

    Animals use TGF-? superfamily signal transduction pathways during development and tissue maintenance. The superfamily has traditionally been divided into TGF-?/Activin and BMP branches based on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture systems, “BMP-specific” Smads can be phosphorylated in response to TGF-?/Activin pathway activation. Using Drosophila cell culture as well as in vivo assays, we find that Baboon, the Drosophila TGF-?/Activin-specific Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors. Wing phenotypes generated by Baboon gain-of-function require Mad, and are partially suppressed by over-expression of dSmad2. In the larval wing disc, activated Baboon cell-autonomously causes C-terminal Mad phosphorylation, but only when endogenous dSmad2 protein is depleted. The Baboon-Mad relationship is thus controlled by dSmad2 levels. Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae, and these levels are normalized in dSmad2; baboon double mutants, indicating that the cross-talk reaction and Smad competition occur with endogenous levels of signaling components in vivo. In addition, we find that high levels of Activin signaling cause substantial turnover in dSmad2 protein, providing a potential cross-pathway signal-switching mechanism. We propose that the dual activity of TGF-?/Activin receptors is an ancient feature, and we discuss several ways this activity can modulate TGF-? signaling output. PMID:22563507

  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. Activin/Nodal signalling in stem cells.

    PubMed

    Pauklin, Siim; Vallier, Ludovic

    2015-02-15

    Activin/Nodal growth factors control a broad range of biological processes, including early cell fate decisions, organogenesis and adult tissue homeostasis. Here, we provide an overview of the mechanisms by which the Activin/Nodal signalling pathway governs stem cell function in these different stages of development. We describe recent findings that associate Activin/Nodal signalling to pathological conditions, focusing on cancer stem cells in tumorigenesis and its potential as a target for therapies. Moreover, we will discuss future directions and questions that currently remain unanswered on the role of Activin/Nodal signalling in stem cell self-renewal, differentiation and proliferation. PMID:25670788

  6. Differences in solubility of two types of heterogeneous fluoridated hydroxyapatites.

    PubMed

    Okazaki, M; Tohda, H; Yanagisawa, T; Taira, M; Takahashi, J

    1998-01-01

    Two types of heterogeneous fluoridated apatites, H-F and F-H, were synthesized by supplying fluoride over the whole range of the degree of fluoridation (X = 0-1.0) during the initial or final half of the experimental period. Although X-ray diffraction patterns and scanning electron microscopy (SEM) photographs of both H-F and F-H type apatites were not significantly different, high-resolution transmission electron microscopy (HR-TEM) showed quite different features; H-F type apatites were elongated hexagons with electron beam damage in the core, while F-H type apatites were rather wider hexagons and approached the typical hexagon of fluorapatite. These results supported the previous speculations on the two different types of heterogeneous fluoridated hydroxyapatites synthesized with fluoride concentration stoichiometrically equivalent to that of fluorapatite: hydroxyapatite covered with fluorapatite and fluorapatite covered with hydroxyapatite. The apparent solubility of H-F type apatites decreased with increases in degree of fluoridation, while that of F-H type apatites decreased markedly and then remained almost constant. PMID:9663733

  7. Activin A induction of FSHbeta subunit transcription requires SMAD4 in immortalized gonadotropes.

    PubMed

    Wang, Ying; Libasci, Vanessa; Bernard, Daniel J

    2010-06-01

    Activins regulate FSH synthesis by stimulating the phosphorylation and nuclear accumulation of SMAD2 and SMAD3, which bind to a consensus SMAD-binding element in the proximal murine FSHbeta (Fshb) subunit gene to drive transcription. Previous over-expression and in vitro DNA binding analyses suggested that SMAD4 participates in complexes with SMAD2 and SMAD3 to regulate Fshb expression. Here, we have characterized the role of endogenous SMAD4 in activin A induction of Fshb transcription in immortalized murine gonadotropes (LbetaT2). We identified five murine Smad4 mRNA isoforms, of which, four are newly described; however, the canonical full-length form predominated at both the mRNA and protein levels. Depletion of endogenous SMAD4 by RNA interference (RNAi) abolished activin A-induced Fshb promoter-reporter activity and greatly attenuated constitutively active activin type IB receptor-stimulated Fshb mRNA levels. The activin A response was rescued with an RNAi-resistant form of wild-type SMAD4, but not with a DNA-binding-deficient (Lys88Arg) SMAD4, suggesting that DNA binding by SMAD4 is necessary for activin induction of the Fshb gene. Though SMAD2 and SMAD3 are generally thought to partner with SMAD4 prior to accumulation in the nucleus, treatment with leptomycin B, an inhibitor of SMAD4 nuclear export, reduced but did not prevent activin A induction of Fshb mRNA levels or promoter activity. In addition, a constitutively nuclear form of SMAD4 rescued the effect of endogenous SMAD4 depletion. Collectively, these data demonstrate a necessary role for SMAD4 in activin A induction of the murine Fshb gene in immortalized gonadotropes. PMID:20371653

  8. Activin Regulates Luteinizing Hormone ?-Subunit Gene Expression through Smad-Binding and Homeobox Elements

    PubMed Central

    Coss, Djurdjica; Thackray, Varykina G.; Deng, Chu-Xia; Mellon, Pamela L.

    2010-01-01

    LH ?-subunit (LH?), which is essential for ovulation and reproductive fitness, is synthesized specifically in pituitary gonadotropes. In this study, we show that LH? gene expression is induced by activin in mouse primary pituitary cells if the cells are treated within 24 h after dispersion in culture. Furthermore, male mice deficient in Smad3, and therefore in activin signaling, have lower expression of both LH? and FSH? mRNAs compared with their wild-type littermates. Using the L?T2 immortalized mouse gonadotrope cell line that endogenously expresses LH, we identify specific elements in the regulatory region of the rat LH? gene necessary for its induction by activin. Activin responsiveness is conferred by a promoter-proximal region located ?121/?86 from the transcriptional start site. Maximal LH? induction by activin requires a homeobox element (HB) and a 5?-early growth response (Egr) site found in this region of the promoter. Juxtaposed to the HB are three Smad-binding elements (SBEs), which are essential for LH? induction. Interestingly, two of the SBEs are also critical for basal expression of the LH? gene. We demonstrate that Smad proteins are necessary and sufficient for activin induction of the LH? gene. Furthermore, Smad proteins can bind one of the identified SBEs. In addition to binding this SBE, Smad proteins interact with pituitary homeobox 1 (Ptx-1) and orthodenticle homeobox 1 (Otx-1), which can bind the HB located close to the Smad-binding site. Thus, activin induction of LH? gene expression requires a combination of several transcription factors, both basal and activin induced, as well as cooperation between multiple DNA elements. PMID:15961509

  9. 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

  10. Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex.

    PubMed Central

    Wrana, J L; Tran, H; Attisano, L; Arora, K; Childs, S R; Massagué, J; O'Connor, M B

    1994-01-01

    A transmembrane protein serine/threonine kinase, Atr-I, that is structurally related to receptors for members of the transforming growth factor-beta (TGF-beta) family has been cloned from Drosophila melanogaster. The spacing of extracellular cysteines and the cytoplasmic domain of Atr-I resemble most closely those of the recently described mammalian type I receptors for TGF-beta and activin. When expressed alone in test cells, Atr-I is unable to bind TGF-beta, activin, or bone morphogenetic protein 2. However, Atr-I binds activin efficiently when coexpressed with the distantly related Drosophila activin receptor Atr-II, with which it forms a heteromeric complex. Atr-I can also bind activin in concert with mammalian activin type II receptors. Two alternative forms of Atr-I have been identified that differ in an ectodomain region encompassing the cysteine box motif characteristic of receptors in this family. Comparison of Atr-I with other type I receptors reveals the presence of a characteristic 30-amino-acid domain immediately upstream of the kinase region in all these receptors. This domain, of unknown function, contains a repeated Gly-Ser sequence and is therefore referred to as the GS domain. Maternal Atr-I transcripts are abundant in the oocyte and widespread during embryo development and in the imaginal discs of the larva. The structural properties, binding specificity, and dependence on type II receptors define Atr-I as an activin type I receptor from D. melanogaster. These results indicate that the heteromeric kinase structure is a general feature of this receptor family. Images PMID:8289834

  11. Conversion of amylase-secreting rat pancreatic AR42J cells to neuronlike cells by activin A.

    PubMed Central

    Ohnishi, H; Ohgushi, N; Tanaka, S; Mogami, H; Nobusawa, R; Mashima, H; Furukawa, M; Mine, T; Shimada, O; Ishikawa, H

    1995-01-01

    When AR42J cells, an amylase-secreting pancreatic exocrine cell line, were treated with activin A, cells extended neuritelike processes, and, concomitantly, amylase-containing vesicles disappeared. Immunofluorescence and immunoelectron microscopy revealed that these processes had neurite-specific cytoskeletal architectures: neurofilaments and microtubule bundles with cross-bridges of microtubule-associated protein 2. In addition to such morphological changes, activin-treated cells exhibited a marked increase in cytoplasmic free calcium concentration in response to depolarizing concentration of potassium. Moreover, activin-treated AR42J cells expressed mRNA for alpha 1 subunit of the neuroendocrine/beta cell-type voltage-dependent calcium channel. In naive AR42J cells, a sulfonylurea compound, tolbutamide, did not affect free calcium concentration, while it induced a marked elevation of free calcium in activin-treated cells. Single channel recording of the membrane patch revealed the existence of ATP-sensitive potassium channel in activin-treated cells. These results indicate that activin A converts amylase-secreting AR42J cells to neuronlike cells. Given that pancreatic endocrine cells possess neuronlike properties and express ATP-sensitive potassium channel as well as neuroendocrine/beta cell-type voltage-dependent calcium channel, activin treatment of AR42J cells may provide an in vitro model system to study the conversion of pancreatic exocrine cells to endocrine cells in islets. Images PMID:7537763

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

    PubMed

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

    2015-01-01

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

  13. Overexpression of activin-A and -B in malignant mesothelioma - Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth.

    PubMed

    Tamminen, Jenni A; Yin, Miao; Rönty, Mikko; Sutinen, Eva; Pasternack, Arja; Ritvos, Olli; Myllärniemi, Marjukka; Koli, Katri

    2015-03-01

    Activin-A and activin-B, members of the TGF-? superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. PMID:25557874

  14. Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis

    PubMed Central

    Wankell, Miriam; Munz, Barbara; Hübner, Griseldis; Hans, Wolfgang; Wolf, Eckhard; Goppelt, Andreas; Werner, Sabine

    2001-01-01

    Recently, we demonstrated a strong upregulation of activin expression after skin injury. Furthermore, overexpression of this transforming growth factor ? family member in the skin of transgenic mice caused dermal fibrosis, epidermal hyperthickening and enhanced wound repair. However, the role of endogenous activin in wound healing has not been determined. To address this question we overexpressed the soluble activin antagonist follistatin in the epidermis of transgenic mice. These animals were born with open eyes, and the adult mice had larger ears, longer tails and reduced body weight compared with non-transgenic littermates. Their skin was characterized by a mild dermal and epidermal atrophy. After injury, a severe delay in wound healing was observed. In particular, granulation tissue formation was significantly reduced, leading to a major reduction in wound breaking strength. The wounds, however, finally healed, and the resulting scar area was smaller than in control animals. These results implicate an important function of endogenous activin in the control of wound repair and scar formation. PMID:11574468

  15. Identification of a Drosophila activin receptor.

    PubMed Central

    Childs, S R; Wrana, J L; Arora, K; Attisano, L; O'Connor, M B; Massagué, J

    1993-01-01

    Activins are cytokines of the transforming growth factor beta superfamily that control various events during vertebrate embryo development and cell differentiation in the adult, and act through transmembrane receptors that contain a cytoplasmic protein-serine/threonine kinase domain. We describe the identification, deduced primary structure, and expression pattern of Atr-II, a receptor serine/threonine kinase found in Drosophila. With the exception of the spacing of 10 cysteine residues, the extracellular domain of Atr-II is very dissimilar from those of vertebrate activin receptors, yet it binds activin with high affinity and specificity. The kinase domain sequence of Atr-II is 60% identical to those of activin receptors from vertebrates, suggesting similarities in their signaling mechanisms. Maternal Atr-II transcript and its product are abundant in the oocyte. During development, the highest levels of Atr-II transcript and protein are observed in the mesoderm and gut. The possible role of an activin signaling system in Drosophila development is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8415726

  16. Diagnostic applications for inhibin and activins.

    PubMed

    McNeilly, Alan S

    2012-08-15

    Inhibin and activins play major roles as paracrine and autocrine signaling molecules in reproduction and development where the main emphasis has been placed in developing potential diagnostic applications. While a role for activin assays in diagnostics has so far been unfounded, ELISAs specific for the biologically active inhibin A and B dimers, and for free inhibin alpha subunits, alone or in combination have found some specific diagnostic applications. Addition of inhibin A to the triple test for Down syndrome in the second trimester of pregnancy, measurement of total inhibin as a marker of certain forms of ovarian cancer in specific circumstances, and inhibin B for male fertility are useful diagnostics. A review of the evidence so far suggests that other applications for inhibin and activin assays have yet to be confirmed, or translated into reliable tools for clinical practice. PMID:21741437

  17. The ESA scenario gets complex: from biosimilar epoetins to activin traps.

    PubMed

    Jelkmann, Wolfgang

    2014-04-19

    Recombinant human erythropoietin (rhEpo, epoetin) has proved beneficial in preventing transfusion-dependent anaemia in patients with chronic kidney disease. Apart from copied epoetins distributed in less regulated markets, 'biosimilar' epoetins have gained currency in many regions, where they compete with the originals and with rhEpo analogues with prolonged survival in circulation ('biobetter'). Recombinant erythropoiesis stimulating agents are potent and well tolerated. However, their production is costly, and they must be administered by the parenteral route. Hence, other anti-anaemia treatments are being evaluated. Clinical trials are being performed with stabilizers of the hypoxia-inducible transcription factors (HIFs), which increase endogenous Epo production. HIF stabilizers are chemical drugs and they are active on oral administration. However, there is fear that they may promote tumour growth. Epo mimetic peptides have also raised expectations. Yet the prototype peginesatide was recalled after just 1 year of its widespread use in the USA because of serious side-effects including cases of death. Most recently, clinical trials have been initiated with sotatercept, a recombinant soluble activin receptor type 2A IgG-Fc fusion protein. Sotatercept binds distinct members of the transforming growth factor-? family, thereby preventing the inhibitory action of these factors in erythropoiesis. Taken together, rhEpo and its long-acting recombinant analogues will likely remain mainstay of anti-anaemia therapies in the near future. PMID:24748667

  18. Differences in solubility of two types of heterogeneous fluoridated hydroxyapatites

    Microsoft Academic Search

    M. Okazaki; H. Tohda; T. Yanagisawa; M. Taira; J. Takahashi

    1998-01-01

    SynopsisTwo types of heterogeneous fluoridated apatites, H-F and F-H, were synthesized by supplying fluoride over the whole range of the degree of fluoridation (X=0–1.0) during the initial or final half of the experimental period. Although X-ray diffraction patterns and scanning electron microscopy (SEM) photographs of both H-F and F-H type apatites were not significantly different, high-resolution transmission electron microscopy (HR-TEM)

  19. Cerebellar Soluble Mutant Ataxin-3 Level Decreases during Disease Progression in Spinocerebellar Ataxia Type 3 Mice

    PubMed Central

    Weber, Jonasz Jeremiasz; Grueninger, Stephan; Riess, Olaf; Weiss, Andreas

    2013-01-01

    Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominantly inherited neurodegenerative disease caused by an expanded polyglutamine stretch in the ataxin-3 protein. A pathological hallmark of the disease is cerebellar and brainstem atrophy, which correlates with the formation of intranuclear aggregates in a specific subset of neurons. Several studies have demonstrated that the formation of aggregates depends on the generation of aggregation-prone and toxic intracellular ataxin-3 fragments after proteolytic cleavage of the full-length protein. Despite this observed increase in aggregated mutant ataxin-3, information on soluble mutant ataxin-3 levels in brain tissue is lacking. A quantitative method to analyze soluble levels will be a useful tool to characterize disease progression or to screen and identify therapeutic compounds modulating the level of toxic soluble ataxin-3. In the present study we describe the development and application of a quantitative and easily applicable immunoassay for quantification of soluble mutant ataxin-3 in human cell lines and brain samples of transgenic SCA3 mice. Consistent with observations in Huntington disease, transgenic SCA3 mice reveal a tendency for decrease of soluble mutant ataxin-3 during disease progression in fractions of the cerebellum, which is inversely correlated with aggregate formation and phenotypic aggravation. Our analyses demonstrate that the time-resolved Förster resonance energy transfer immunoassay is a highly sensitive and easy method to measure the level of soluble mutant ataxin-3 in biological samples. Of interest, we observed a tendency for decrease of soluble mutant ataxin-3 only in the cerebellum of transgenic SCA3 mice, one of the most affected brain regions in Spinocerebellar Ataxia Type 3 but not in whole brain tissue, indicative of a brain region selective change in mutant ataxin-3 protein homeostasis. PMID:23626768

  20. Hypertension in pregnancy: changes in activin A maternal serum concentration.

    PubMed

    Petraglia, F; Aguzzoli, L; Gallinelli, A; Florio, P; Zonca, M; Benedetto, C; Woodruff, K

    1995-07-01

    Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy. PMID:7479615

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  3. 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

  4. Inhibins, activins and follistatin: actions on the testis

    Microsoft Academic Search

    D. M. de Kretser; K. L. Loveland; T. Meehan; M. K. O'Bryan; D. J. Phillips; N. G. Wreford

    2001-01-01

    While the early studies of the inhibins, activins and follistatins concentrated on their role as endocrine regulators of FSH secretion, recent data has emphasized the local actions of the activins and follistatin. Inhibin, through its capacity to suppress FSH secretion can modulate numerous processes within the testis. However, to date, evidence to support a local role for inhibin is limited.

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

    SciTech Connect

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

    2009-03-11

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

  6. Characterization of Soluble N-Ethylmaleimide-Sensitive Fusion Attachment Protein in Alveolar Type II Cells Implications in Lung Surfactant Secretion

    Microsoft Academic Search

    Barack O. Abonyo; Pengcheng Wang; Telugu A. Narasaraju; William H. Rowan; David H. McMillan; Un-Jin Zimmerman; Lin Liu

    N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (-SNAP) are thought to be soluble factors that transiently bind and disassemble SNAP receptor complex during exocytosis in neuronal and endocrine cells. Lung surfactant is secreted via exocytosis of lamellar bodies from alveolar epithelial type II cells. However, the secretion of lung surfactant is a relatively slow process, and involvement of

  7. An activin A/BMP2 chimera, AB204, displays bone-healing properties superior to those of BMP2.

    PubMed

    Yoon, Byung-Hak; Esquivies, Luis; Ahn, Chihoon; Gray, Peter C; Ye, Sang-Kyu; Kwiatkowski, Witek; Choe, Senyon

    2014-09-01

    Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures. PMID:24692083

  8. Neuroendocrine control of female reproductive function by the activin receptor ALK7.

    PubMed

    Sandoval-Guzmán, Tatiana; Göngrich, Christina; Moliner, Annalena; Guo, Tingqing; Wu, Haiya; Broberger, Christian; Ibáñez, Carlos F

    2012-12-01

    Activins are critical components of the signaling network that controls female reproduction. However, their roles in hypothalamus, and the specific functions of their different receptors, have not been elucidated. Here, we investigated the expression and function of the activin receptor ALK7 in the female reproductive axis using Alk7-knockout mice. ALK7 was found in subsets of SF1-expressing granulosa cells in the ovary, FSH gonadotrophs in the pituitary, and NPY-expressing neurons in the arcuate nucleus of the hypothalamus. Alk7-knockout females showed delayed onset of puberty and abnormal estrous cyclicity, had abnormal diestrous levels of FSH and LH in serum, and their ovaries showed premature depletion of follicles, oocyte degeneration, and impaired responses to exogenous gonadotropins. In the arcuate nucleus, mutant mice showed reduced expression of Npy mRNA and lower numbers of Npy-expressing neurons than wild-type controls. Alk7 knockouts showed a selective loss of arcuate NPY/AgRP innervation in the medial preoptic area, a key central regulator of reproduction. These results indicate that ALK7 is an important regulator of female reproductive function and reveal a new role for activin signaling in the control of hypothalamic gene expression and wiring. Alk7 gene variants may contribute to female reproductive disorders in humans, such as polycystic ovary syndrome. PMID:22954591

  9. Anterograde Activin Signaling Regulates Postsynaptic Membrane Potential and GluRIIA/B Abundance at the Drosophila Neuromuscular Junction

    PubMed Central

    Kim, Myung-Jun; O’Connor, Michael B.

    2014-01-01

    Members of the TGF-? superfamily play numerous roles in nervous system development and function. In Drosophila, retrograde BMP signaling at the neuromuscular junction (NMJ) is required presynaptically for proper synapse growth and neurotransmitter release. In this study, we analyzed whether the Activin branch of the TGF-? superfamily also contributes to NMJ development and function. We find that elimination of the Activin/TGF-? type I receptor babo, or its downstream signal transducer smox, does not affect presynaptic NMJ growth or evoked excitatory junctional potentials (EJPs), but instead results in a number of postsynaptic defects including depolarized membrane potential, small size and frequency of miniature excitatory junction potentials (mEJPs), and decreased synaptic densities of the glutamate receptors GluRIIA and B. The majority of the defective smox synaptic phenotypes were rescued by muscle-specific expression of a smox transgene. Furthermore, a mutation in act?, an Activin-like ligand that is strongly expressed in motor neurons, phenocopies babo and smox loss-of-function alleles. Our results demonstrate that anterograde Activin/TGF-? signaling at the Drosophila NMJ is crucial for achieving normal abundance and localization of several important postsynaptic signaling molecules and for regulating postsynaptic membrane physiology. Together with the well-established presynaptic role of the retrograde BMP signaling, our findings indicate that the two branches of the TGF-? superfamily are differentially deployed on each side of the Drosophila NMJ synapse to regulate distinct aspects of its development and function. PMID:25255438

  10. Replica exchange molecular dynamics simulations of an ?/?-type small acid soluble protein (SASP).

    PubMed

    Ojeda-May, P; Pu, Jingzhi

    2013-12-31

    Small acid soluble proteins (SASPs) of ?/?-type play a major role in the resistance of spore DNAs to external assaults. It has been found that ?/?-type SASP exhibits intrinsic disorder on isolation, but it acquires a defined native state upon binding to DNA. This disorder to order transition is not yet understood. Other questions related to the role of the thermodynamics and structure of the individual protein in the complex formation remain elusive. Characterization of the unbound state of ?/?-type SASP in experiments could be a challenging problem because of the heterogeneous nature of the ensemble. Here, computer simulations can help gain more insights into the unbound state of ?/?-type SASP. In the present work, by using replica exchange molecular dynamics (REMD), we simulated an ?/?-type SASP on isolation with an implicit solvent. We found that ?/?-type SASP undergoes a continuous phase transition with a small free energy barrier, a common feature of intrinsically disordered proteins (IDPs). Additionally, we detected the presence of residual ?-helical structures at local level and a high degree of plasticity in the chain which can contribute to the fast disorder to order transition by reducing the fly-casting mechanism. PMID:24029407

  11. Soluble interleukin-15 complexes are generated in vivo by type I interferon dependent and independent pathways.

    PubMed

    Anthony, Scott M; Howard, Megan E; Hailemichael, Yared; Overwijk, Willem W; Schluns, Kimberly S

    2015-01-01

    Interleukin (IL)-15 associates with IL-15R? on the cell surface where it can be cleaved into soluble cytokine/receptor complexes that have the potential to stimulate CD8 T cells and NK cells. Unfortunately, little is known about the in vivo production of soluble IL-15R?/IL-15 complexes (sIL-15 complexes), particularly regarding the circumstances that induce them and the mechanisms responsible. The main objective of this study was to elucidate the signals leading to the generation of sIL-15 complexes. In this study, we show that sIL-15 complexes are increased in the serum of mice in response to Interferon (IFN)-?. In bone marrow derived dendritic cells (BMDC), IFN-? increased the activity of ADAM17, a metalloproteinase implicated in cleaving IL-15 complexes from the cell surface. Moreover, knocking out ADAM17 in BMDCs prevented the ability of IFN-? to induce sIL-15 complexes demonstrating ADAM17 as a critical protease mediating cleavage of IL-15 complexes in response to type I IFNs. Type I IFN signaling was required for generating sIL-15 complexes as in vivo induction of sIL-15 complexes by Poly I:C stimulation or total body irradiation (TBI) was impaired in IFNAR-/- mice. Interestingly, serum sIL-15 complexes were also induced in mice infected with Vesicular stomatitis virus (VSV) or mice treated with agonistic CD40 antibodies; however, sIL-15 complexes were still induced in IFNAR-/- mice after VSV infection or CD40 stimulation indicating pathways other than type I IFNs induce sIL-15 complexes. Overall, this study has shown that type I IFNs, VSV infection, and CD40 stimulation induce sIL-15 complexes suggesting the generation of sIL-15 complexes is a common event associated with immune activation. These findings reveal an unrealized mechanism for enhanced immune responses occurring during infection, vaccination, inflammation, and autoimmunity. PMID:25756182

  12. Soluble Interleukin-15 Complexes Are Generated In Vivo by Type I Interferon Dependent and Independent Pathways

    PubMed Central

    Anthony, Scott M.; Howard, Megan E.; Hailemichael, Yared; Overwijk, Willem W.; Schluns, Kimberly S.

    2015-01-01

    Interleukin (IL)-15 associates with IL-15R? on the cell surface where it can be cleaved into soluble cytokine/receptor complexes that have the potential to stimulate CD8 T cells and NK cells. Unfortunately, little is known about the in vivo production of soluble IL-15R?/IL-15 complexes (sIL-15 complexes), particularly regarding the circumstances that induce them and the mechanisms responsible. The main objective of this study was to elucidate the signals leading to the generation of sIL-15 complexes. In this study, we show that sIL-15 complexes are increased in the serum of mice in response to Interferon (IFN)-?. In bone marrow derived dendritic cells (BMDC), IFN-? increased the activity of ADAM17, a metalloproteinase implicated in cleaving IL-15 complexes from the cell surface. Moreover, knocking out ADAM17 in BMDCs prevented the ability of IFN-? to induce sIL-15 complexes demonstrating ADAM17 as a critical protease mediating cleavage of IL-15 complexes in response to type I IFNs. Type I IFN signaling was required for generating sIL-15 complexes as in vivo induction of sIL-15 complexes by Poly I:C stimulation or total body irradiation (TBI) was impaired in IFNAR-/- mice. Interestingly, serum sIL-15 complexes were also induced in mice infected with Vesicular stomatitis virus (VSV) or mice treated with agonistic CD40 antibodies; however, sIL-15 complexes were still induced in IFNAR-/- mice after VSV infection or CD40 stimulation indicating pathways other than type I IFNs induce sIL-15 complexes. Overall, this study has shown that type I IFNs, VSV infection, and CD40 stimulation induce sIL-15 complexes suggesting the generation of sIL-15 complexes is a common event associated with immune activation. These findings reveal an unrealized mechanism for enhanced immune responses occurring during infection, vaccination, inflammation, and autoimmunity. PMID:25756182

  13. 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

  14. Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

    SciTech Connect

    Tsvitov, Marianna [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Frampton, Arthur R. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Shah, Waris A. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Wendell, Steven K. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Ozuer, Ali [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Kapacee, Zoher [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Goins, William F. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Cohen, Justus B. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Glorioso, Joseph C. [Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1246 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)]. E-mail: glorioso@pitt.edu

    2007-04-10

    Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry and gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.

  15. Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

    PubMed Central

    Trimarchi, Hernán

    2013-01-01

    Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy. PMID:24255893

  16. 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

  17. Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells.

    PubMed

    Fujii, Yasuhisa; Kawakami, Satoru; Okada, Yohei; Kageyama, Yukio; Kihara, Kazunori

    2004-06-01

    Activins are multifunctional growth and differentiation factors and stimulate FSH-beta gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5alpha-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo. PMID:14761877

  18. 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

  19. 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 ...

  20. Soluble AXL: A Possible Circulating Biomarker for Neurofibromatosis Type 1 Related Tumor Burden

    PubMed Central

    Johansson, Gunnar; Peng, Po-Chun; Huang, Po-Yuan; Chien, Hsiung-Fei; Hua, Kuo-Tai; Kuo, Min-Liang; Chen, Chin-Tin; Lee, Ming-Jen

    2014-01-01

    Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and its level was correlated to poor prognosis in patients with renal cancer. Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. Treatment with a newly developed photodynamic therapy, prevented further tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, further supporting the role of sAXL as a marker for NF1 related tumor burden. PMID:25551830

  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. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

    PubMed Central

    Gumus, Aziz; Altintas, Nejat; Cinarka, Halit; Kirbas, Aynur; Haz?roglu, Muge; Karatas, Mevlut; Sahin, Unal

    2015-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations. (AE). During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment. Methods The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. Results We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively). Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=?478, P=0.001). Conclusion suPAR is a marker of acute inflammation. It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment. PMID:25709430

  3. Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction

    PubMed Central

    Andersen, Geir Ø.; Ueland, Thor; Knudsen, Eva C.; Scholz, Hanne; Yndestad, Arne; Sahraoui, Afaf; Smith, Camilla; Lekva, Tove; Otterdal, Kari; Halvorsen, Bente; Seljeflot, Ingebjørg; Aukrust, Pål

    2011-01-01

    OBJECTIVE On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells. RESULTS 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73–15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-?. CONCLUSIONS We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress. PMID:21464440

  4. Fabrication and optical nonlinearities of composite films derived from the water-soluble Keplerate-type polyoxometalate and chloroform-soluble porphyrin.

    PubMed

    Shi, Zonghai; Zhou, Yunshan; Zhang, Lijuan; Yang, Di; Mu, Cuncun; Ren, Haizhou; Shehzad, Farooq Khurum; Li, Jiaqi

    2015-02-17

    Composite films derived from the water-soluble Keplerate-type polyoxometalate (NH4)42[Mo132O372(CH3COO)30(H2O)72]·ca. 300H2O·ca. 10CH3COONH4 (denoted (NH4)42{Mo132}) and chloroform-soluble tetraphenylporphyrin perchlorate [H2TPP](ClO4)2 are successfully fabricated by a layer-by-layer self-assembly method and characterized by UV-vis spectroscopy and X-ray photoelectron spectroscopy (XPS). The structure of the {Mo132} and [H2TPP](2+) in the films remain intact in light of the results of UV-vis spectroscopy and XPS. UV-vis spectra measurements reveal that the amounts of deposition of {Mo132} and [H2TPP](2+) remain constant in every adsorption cycle in the composite films assembly process. Nonlinear optical properties of the composite films have been investigated by using the Z-scan technique at a wavelength of 532 nm and pulse width of 7 ns. The results show that the composite films have notable nonlinear saturated absorption and self-defocusing effects. The combination of {Mo132} with [H2TPP](2+) can result in composite films with remarkably enhanced optical nonlinearities. The interfacial charge transfer induced by laser from porphyrin to POM in the films is thought to play a key role in the enhancement of NLO response. The third-order NLO susceptibility ?((3)) of the composite films increases with the increase of film thickness. PMID:25623964

  5. 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.

  6. Extremely Variable Conservation of ?-Type Small, Acid-Soluble Proteins from Spores of Some Species in the Bacterial Order Bacillales ?

    PubMed Central

    Vyas, Jay; Cox, Jesse; Setlow, Barbara; Coleman, William H.; Setlow, Peter

    2011-01-01

    ?-Type small, acid-soluble spore proteins (SASP) are the most abundant proteins in spores of at least some members of the bacterial order Bacillales, yet they remain an enigma from both functional and phylogenetic perspectives. Current work has shown that the ?-type SASP or their coding genes (sspE genes) are present in most spore-forming members of Bacillales, including at least some members of the Paenibacillus genus, although they are apparently absent from Clostridiales species. We have applied a new method of searching for sspE genes, which now appear to also be absent from a clade of Bacillales species that includes Alicyclobacillus acidocaldarius and Bacillus tusciae. In addition, no ?-type SASP were found in A. acidocaldarius spores, although several of the DNA-binding ?/?-type SASP were present. These findings have elucidated the phylogenetic origin of the sspE gene, and this may help in determining the precise function of ?-type SASP. PMID:21317325

  7. A Two-Site Chemiluminescent Assay for Activin-Free Follistatin Reveals That Most Follistatin Circulating in Men and Normal Cycling Women Is in an Activin-Bound State

    Microsoft Academic Search

    DANIEL S. MCCONNELL; QIFA WANG; PATRICK M. SLUSS; NICOLA BOLF; RITA H. KHOURY; ALAN L. SCHNEYER; A. REES MIDGLEY; NANCY E. REAME; WILLIAM F. CROWLEY; VASANTHA PADMANABHAN

    Follistatin (FS) is a monomeric protein that binds and regulates the bioavailability of activin. Previously, we found circulating levels of total FS to be similar in men and cycling women. Because relative amounts of activin-bound and free FS are important considerations in determining activin bioavailability, we asked here whether the relative proportions of these two changed during different physiologic states.

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

    PubMed Central

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

    2014-01-01

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

  9. Identification of a New Member of Transforming Growth Factor-Beta Superfamily in Drosophila:The First Invertebrate Activin Gene

    Microsoft Academic Search

    Geetha Kutty; R. Krishnan Kutty; William Samuel; Todd Duncan; Cynthia Jaworski; Barbara Wiggert

    1998-01-01

    Activins, a subgroup of the transforming growth factor-? (TGF-?) superfamily, have been extensively studied in vertebrates for their roles in growth and development. However, activins are not thought to be expressed in invertebrates. The identification of the first invertebrate activin gene is reported here. A genomic clone representing 102 F region of theDrosophilachromosome 4 is found to encode a putative

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

    PubMed Central

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

    2013-01-01

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

  11. P44. Activin A is novel circulating biomarker in lung cancer

    PubMed Central

    Rozsas, Anita; Hoda, Mir Alireza; Klikovits, Thomas; Schlech, Karin; Laszlo, Viktoria; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedus, Balazs; Dome, Balazs

    2014-01-01

    Background Therapeutic decision making for the treatment of lung cancer is often a complex and challenging task. Biomarkers are urgently needed that can facilitate the early detection of these malignant diseases and can predict which therapeutic modality can significantly contribute to tumor control in a given patient. Methods In a large cohort of lung cancer patients we collected blood samples and measured the circulating levels of activin A by ELISA. The protein level in cell supernatant and the cellular mRNA level of activin A were also analyzed in lung cancer cell lines. Results We found increased plasma activin A levels in certain patients with lung adenocarcinoma, squamous cell lung cancer and small cell lung cancer (SCLC) as well. Interestingly, activin A levels were increased in a TNM stage-dependent manner in SCLC. Furthermore, in the group of extensive SCLC disease patients, Kaplan-Meier analysis revealed that the high activin A levels were associated with significantly shorter overall survival. Secretion of activin A by lung cancer cell lines was also detected in vitro and the highest activin A level was found in a cell line isolated from a brain metastasis of a SCLC tumor. Conclusions Our findings suggest that measurement of circulating activin A can support the diagnosis, staging and prognosis in small cell lung cancer.

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

    E-print Network

    Mellon, Pamela L.

    Activin Regulation of the Follicle-Stimulating Hormone -Subunit Gene Involves Smads and the TALE, a member of the TGF family of growth factors, is an important reg- ulator of FSH expression, but little) of the ovine FSH -subunit gene that are required for full activin response. All three regions contain homol

  13. NMR characterisation of inulin-type fructooligosaccharides as the major water-soluble carbohydrates from Matricaria maritima (L.).

    PubMed

    Cérantola, Stéphane; Kervarec, Nelly; Pichon, Roger; Magné, Christian; Bessieres, Marie-Anne; Deslandes, Eric

    2004-10-01

    By use of 1H and 13C NMR spectroscopy including 2D 1H,1H DQF-COSY/TOCSY and 1H,13C HMQC/HMBC experiments, the main water-soluble carbohydrate components extracted from leaves of Matricaria maritima were identified as oligofructans composed of a linear chain of (2-->1)-linked beta-D-fructofuranosyl residues specifying an inulin-type structure. Alpha-D-Glcp-(1-->2)-[beta-D-Fruf-(2-->1)-beta-D-Frucf]n-(2-->1)-beta-D-Fruf. PMID:15388360

  14. Activin A stimulates AKR1C3 expression and growth in human prostate cancer.

    PubMed

    Hofland, Johannes; van Weerden, Wytske M; Steenbergen, Jacobie; Dits, Natasja F J; Jenster, Guido; de Jong, Frank H

    2012-12-01

    Local androgen synthesis in prostate cancer (PC) may contribute to the development of castration-resistant PC (CRPC), but pathways controlling intratumoral steroidogenic enzyme expression in PC are unknown. We investigated the effects of activin, a factor involved in the regulation of PC growth and steroidogenic enzyme expression in other steroidogenic tissues, on intratumoral steroidogenesis in PC. Activin A effects and regulation of the activin-signaling pathway molecules were studied in the PC cell lines LNCaP, VCaP, and PC-3 and in 13 individual PC xenograft models. Also, expression levels of inhibin ?A- and ?B-subunits (INHBA and INHBB) and of the activin antagonist follistatin were quantitated in patient PC tissues. Activin A induced the expression and enzyme activity of 17?-hydroxysteroid dehydrogenase enzyme AKR1C3 in LNCaP and VCaP cells. Inhibition of endogenous activin A action in the PC-3 cell line decreased AKR1C3 levels and consequently testosterone synthesis. In return, androgens suppressed INHBA expression in both VCaP cells and the PC xenograft models. The antiproliferative effects of activin A were opposed by physiological concentrations of androstenedione in LNCaP cells. In patient PC tissues, expression levels of INHBA were increased in CRPC samples and correlated with AKR1C3 levels. Moreover, a high ratio of activin subunits to follistatin was associated with a worse metastasis-free survival in patients. In conclusion, activin A is controlled by androgens in PC models and regulates local androgen production. Activin A thus seems to mediate (residual) intratumoral androgen levels and could form a novel therapeutic target in CRPC. PMID:23024260

  15. P36. The prognostic potential of circulating and tissue activin A level in malignant pleural mesothelioma

    PubMed Central

    Dong, Yawen; Hoda, Mir Alireza; Schelch, Karin; Rozsas, Anita; Laszlo, Viktoria; Dome, Balazs; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedus, Balazs

    2014-01-01

    Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by poor outcome and there is a lack of prognostic biomarkers to estimate prognosis. Previously we have shown that suppression of activin A can interfere with MPM tumor growth. In the current study, we compare the circulating and tissue expression level of activin A as a prognostic biomarker in MPM. Methods In a cohort of 53 MPM patients, plasma samples were collected between 2010 and 2014. Controls consisted of age-matched healthy individuals (n=46) and patients with pleuritis or pleural fibrosis (n=16). Circulating activin A was measured by ELISA and correlated to clinicopathological data. Furthermore, activin A expression in the tumor tissue was semiquantitatively measured by immunohistochemistry in 24 patients. Results Plasma activin A level was significantly elevated in MPM patients (n=53, 843±122 pg/mL) when compared to healthy controls (452±144 pg/mL, P=0.0039). Non-malignant pleuritis or pleural fibrosis patients only showed a modest, non-significant increase (625±95 pg/mL, P=0.093). Circulating activin A levels were slightly increased in cases with non-epitheloid morphology (n=16, 1101±183) when compared to epithelioid (n=37, 732±153 pg/mL, P=0.13). MPM patients with below median activin A concentrations had a modestly and non-significantly longer overall survival when compared to the high activin A level patients (469 vs. 271 days, P=0.4751). Interestingly, there was no correlation between circulating and tissue expression level of activin A in 17 patients where both parameters could have been analyzed. Conclusions Our findings suggest that the measurement of circulating activin A may support the diagnosis and prognosis of MPM but additional patient cohorts need to be analyzed to establish the diagnostic and prognostic value of this non-invasive biomarker.

  16. The inhibin/activin signalling pathway in human gonadal and adrenal cancers.

    PubMed

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

    2014-12-01

    The biological function of the inhibin-? subunit (INHA) in gonadal tumorigenesis is different in humans compared with mouse. The INHA subunit is up-regulated in most human ovarian and testicular cancers but knock-out studies in mice showed the INHA subunit is a tumour suppressor with gonadal and adrenal specificity. The INHA subunit is a component of the inhibin/activin signalling pathway, which includes activin receptors ActRIIA/IIB and intracellular Smads-2/3. To resolve the incongruity in function in humans versus mouse, we re-evaluated the inhibin/activin pathway in human gonadal and adrenal cancers using contemporary protein and mRNA expression data for multiple pathway components rather than INHA alone. We used an INHA antibody raised against the N-terminal domain to compare immunoreactivity with the more commonly used antibody raised against the C-terminal domain. This study also described, for the first time, a comprehensive protein expression profile of activin-?C in reproductive and adrenal cancers, and its effect on a human granulosa cell line, providing evidence for a role in ovarian, testis and adrenal tumour biology. Our data show reduced INHA expression at both protein and mRNA levels, and increased activin signalling in human testicular, ovarian and malignant versus benign forms of adrenal cancer. We also found that activin-C acts as an activin-A antagonist by binding to activin receptor subunits IIA and IIB and modulating the canonical Smad pathway. In conclusion, analysis of the inhibin/activin signalling pathway helps to explain discrepancies arising from studies of only one hormone or subunit and suggests that altered expression of the inhibin and activin subunits is associated with reproductive and adrenal cancer biology. PMID:25180271

  17. Maternal Circulating Levels of Activin A, Inhibin A, sFlt-1 and Endoglin at Parturition in Normal Pregnancy and Pre-Eclampsia

    PubMed Central

    Reddy, Aparna; Suri, Sangeeta; Sargent, Ian L.; Redman, Christopher W. G.; Muttukrishna, Shanthi

    2009-01-01

    Background Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), endoglin (sEng) and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies. Methodology To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively. Results The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase. Conclusion Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum. PMID:19412349

  18. Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation

    PubMed Central

    Chen, Alice E.; Borowiak, Malgorzata; Sherwood, Richard I.; Kweudjeu, Anastasie; Melton, Douglas A.

    2013-01-01

    Embryonic stem (ES) cells hold great promise with respect to their potential to be differentiated into desired cell types. Of interest are organs derived from the definitive endoderm, such as the pancreas and liver, and animal studies have revealed an essential role for Nodal in development of the definitive endoderm. Activin A is a related TGF? member that acts through many of the same downstream signaling effectors as Nodal and is thought to mimic Nodal activity. Detailed characterization of ES cell-derived endodermal cell types by gene expression analysis in vitro and functional analysis in vivo reveal that, despite their similarity in gene expression, Nodal and Activin-derived endodermal cells exhibit a distinct difference in functional competence following transplantation into the developing mouse embryo. Pdx1-expressing cells arising from the respective endoderm populations exhibit extended differences in their competence to mature into insulin/c-peptide-expressing cells in vivo. Our findings underscore the importance of functional cell-type evaluation during stepwise differentiation of stem cells. PMID:23293299

  19. Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer.

    PubMed

    Togashi, Yosuke; Kogita, Akihiro; Sakamoto, Hiroki; Hayashi, Hidetoshi; Terashima, Masato; de Velasco, Marco A; Sakai, Kazuko; Fujita, Yoshihiko; Tomida, Shuta; Kitano, Masayuki; Okuno, Kiyotaka; Kudo, Masatoshi; Nishio, Kazuto

    2015-01-28

    We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P?=?0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC. PMID:25449777

  20. 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

  1. Effects of Activin A on the phenotypic properties of human periodontal ligament cells.

    PubMed

    Sugii, Hideki; Maeda, Hidefumi; Tomokiyo, Atsushi; Yamamoto, Naohide; Wada, Naohisa; Koori, Katsuaki; Hasegawa, Daigaku; Hamano, Sayuri; Yuda, Asuka; Monnouchi, Satoshi; Akamine, Akifumi

    2014-09-01

    Periodontal ligament (PDL) tissue plays an important role in tooth preservation by structurally maintaining the connection between the tooth root and the bone. The mechanisms involved in the healing and regeneration of damaged PDL tissue, caused by bacterial infection, caries and trauma, have been explored. Accumulating evidence suggests that Activin A, a member of the transforming growth factor-? (TGF-?) superfamily and a dimer of inhibin?a, contributes to tissue healing through cell proliferation, migration, and differentiation of various target cells. In bone, Activin A has been shown to exert an inhibitory effect on osteoblast maturation and mineralization. However, there have been no reports examining the expression and function of Activin A in human PDL cells (HPDLCs). Thus, we aimed to investigate the biological effects of Activin A on HPDLCs. Activin A was observed to be localized in HPDLCs and rat PDL tissue. When PDL tissue was surgically damaged, Activin A and IL-1? expression increased and the two proteins were shown to be co-localized around the lesion. HPDLCs treated with IL-1? or TNF-? also up-regulated the expression of the gene encoding inhibin?a. Activin A promoted chemotaxis, migration and proliferation of HPDLCs, and caused an increase in fibroblastic differentiation of these cells while down-regulating their osteoblastic differentiation. These osteoblastic inhibitory effects of Activin A, however, were only noted during the early phase of HPDLC osteoblastic differentiation, with later exposures having no effect on differentiation. Collectively, our results suggest that Activin A could be used as a therapeutic agent for healing and regenerating PDL tissue in response to disease, trauma or surgical reconstruction. PMID:24928494

  2. Activin stimulation of inhibin secretion and messenger RNA levels in cultured granulosa cells.

    PubMed

    LaPolt, P S; Soto, D; Su, J G; Campen, C A; Vaughan, J; Vale, W; Hsueh, A J

    1989-10-01

    Recent reports suggest that activin (the dimer of inhibin beta subunits with FSH-releasing activity) has specific receptors on ovarian granulosa cells. The present study examined the effects of purified porcine activin on inhibin secretion and mRNA levels in granulosa cells obtained from immature, estrogen-treated rats. Cells were cultured for 48 h in culture media, or media containing FSH (10 ng/ml) and/or activin (30 ng/ml). Western blot analyses performed with affinity-purified antisera to inhibin alpha- and beta A-subunits revealed that treatment with either FSH or activin increased the secretion of inhibin alpha beta dimer (Mr 30,000), with a further increase after cotreatment. These results were confirmed by an inhibin alpha-subunit RIA, which revealed 7-, 14-, and 71-fold increases in the secretion of immunoreactive inhibin-alpha by activin, FSH, and activin plus FSH, respectively. TGF beta, a structural homolog of activin, also stimulated inhibin release, whereas follistatin was ineffective. Total RNA from cultured cells was hybridized with 32P-labeled inhibin alpha-subunit cRNA or beta-actin cDNA probes, and inhibin-alpha message levels were normalized with beta-actin mRNA levels. Northern blot analysis revealed that treatment with FSH and activin increased hybridization of a 1.5 kilobase (kb) message, corresponding to the inhibin alpha-subunit mRNA. Slot blot analyses indicated a 6- and 8-fold stimulation of inhibin alpha-subunit mRNA levels by FSH and activin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2558301

  3. Soluble N-Type organic thin-film transistors with enhanced electrical characteristics

    NASA Astrophysics Data System (ADS)

    Lee, Ho Won; Lee, Seok Jae; Koo, Ja Ryong; Cho, Eou Sik; Kwon, Sang Jik; Kim, Woo Young; Park, Jaehoon; Kim, Young Kwan

    2013-11-01

    We fabricated and investigated soluble, organic, thin-film transistors (OTFTs) containing `[6, 6]-phenyl-C61-butyric acid methyl ester (PCBM)' as a semiconducting layer, and an organic dielectric buffer (cross-linked poly-4-vinylphenol) as a dielectric buffer-layer to improve electrical characteristics. The semiconducting layer of the devices was fabricated by the drop-casting method where PCBM was dissolved in three different solvents (odichlorobenzene, chloroform, and chlorobenzene). From the transfer and output characteristics of the PCBM OTFTs, a threshold voltage of 10 V, sub-threshold slope of 10 V/dec, on/off current ratio of 7.305 × 103, and field-effect mobility of 1.53 × 10-2 cm2/Vs were obtained; for PCBM using o-dichlorobenzene solvent and an organic dielectric buffer layer. It was also found that the hysteresis for the same device was improved conspicuously compared to the other devices, by the above-mentioned condition.

  4. Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

    PubMed Central

    2013-01-01

    Background Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. Materials and methods Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45?days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. Results NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin. PMID:23497378

  5. Prediction of Dumbbell-Type Soluble Proteins and Their Center Helices

    E-print Network

    Shun-Ya Takahashi Shigeki; Shigeki Mitaku

    Introduction Dumbbell-type proteins have two domains linked by a long helical segment. Typical examples of dumbbell-type proteins are calmodulin and troponin C, which have regulating function of other proteins [1, 2]. The function seems to be closely related to the dumbbell shape of this protein. Upon binding of calcium, calmodulin changes its structure and strongly interacts with other protein, modulating the function of the bound protein. Troponin C also binds with other proteins, tropomyosin, and regulates the muscle contraction. Therefore, if proteins of dumbbell-type proteins can be predicted from amino acid sequences of total proteome, the method will be useful for inferring the protein-protein interaction and the regulating function of the proteins. In this work, we first analyzed the 3D-structures of proteins in protein data bank (PDB), selecting all dumbbell-type proteins in PDB. Then, we tested various physical parameters of amino acid sequences that may stabilize th

  6. Effects of stabilized rice bran, its soluble and fiber fractions on blood glucose levels and serum lipid parameters in humans with diabetes mellitus Types I and II

    Microsoft Academic Search

    Asaf A Qureshi; Saeed A Sami; Farooq A Khan

    2002-01-01

    Stabilized rice bran (SRB), a source of complex carbohydrates, tocols, ?-oryzanols, and polyphenols, was treated with carbohydrases and heat to yield two fractions, rice bran water solubles (RBWS), and rice bran fiber concentrates (RBFC). Stabilized rice bran and its fractions were fed for 60 days to insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM = Type I and NIDDM = Type II)

  7. Inhibin removes the inhibitory effects of activin on steroid enzyme expression and androgen production by normal ovarian thecal cells

    PubMed Central

    Young, J M; McNeilly, A S

    2012-01-01

    Activin and inhibin are important local modulators of theca cell steroidogenesis in the ovary. Using a serum-free primary theca cell culture system, this study investigated the effects of inhibin on theca cell androgen production and expression of steroidogenic enzymes. Androstenedione secretion from theca cells cultured in media containing activin, inhibin and follistatin was assessed by RIA over 144?h. Activin (1–100?ng/ml) suppressed androstenedione production. Inhibin (1–100?ng/ml) blocked the suppressive effects of added activin, but increased androstenedione production when added alone, suggesting it was blocking endogenous activin produced by theca cells. Addition of SB-431542 (activin receptor inhibitor) and follistatin (500?ng/ml) increased androstenedione production, supporting this concept. Infection of theca cells with adenoviruses expressing inhibitory Smad6 or 7 increased androstenedione secretion, confirming that the suppressive effects of activin required activation of the Smad2/3 pathway. Activin decreased the expression levels of steroidogenic acute regulatory protein (STAR), whereas STAR expression was increased by inhibin and SB-431542, alone and in combination. CYP11A was unaffected. The expression of CYP17 encoding 17?-hydroxylase was unaffected by activin but increased by inhibin and SB-431542, and when added in combination the effect was further enhanced. The expression of 3?-hydroxysteroid dehydrogenase (3?-HSD) was significantly decreased by activin, while inhibin alone and in combination with SB-431542 both potently increased the expression of 3?-HSD. In conclusion, activin suppressed theca cell androstenedione production by decreasing the expression of STAR and 3?-HSD. Inhibin and other blockers of activin action reversed this effect, supporting the concept that endogenous thecal activin modulates androgen production in theca cells. PMID:22082494

  8. Activin A binds to perlecan through its pro-region that has heparin/heparan sulfate binding activity.

    PubMed

    Li, Shaoliang; Shimono, Chisei; Norioka, Naoko; Nakano, Itsuko; Okubo, Tetsuo; Yagi, Yoshiko; Hayashi, Maria; Sato, Yuya; Fujisaki, Hitomi; Hattori, Shunji; Sugiura, Nobuo; Kimata, Koji; Sekiguchi, Kiyotoshi

    2010-11-19

    Activin A, a member of the transforming growth factor-? family, plays important roles in hormonal homeostasis and embryogenesis. In this study, we produced recombinant human activin A and examined its abilities to bind to extracellular matrix proteins. Recombinant activin A expressed in 293-F cells was purified as complexes of mature dimeric activin A with its pro-region. Among a panel of extracellular matrix proteins tested, recombinant activin A bound to perlecan and agrin, but not to laminins, nidogens, collagens I and IV, fibronectin, and nephronectin. The binding of recombinant activin A to perlecan was inhibited by heparin and high concentrations of NaCl and abolished by heparitinase treatment of perlecan, suggesting that activin A binds to the heparan sulfate chains of perlecan. In support of this possibility, recombinant activin A was capable of directly binding to heparin and heparan sulfate chains. Site-directed mutagenesis of recombinant activin A revealed that clusters of basic amino acid residues, Lys(259)-Lys(263) and Lys(270)-Lys(272), in the pro-region were required for binding to perlecan. Interestingly, deletion of the peptide segment Lys(259)-Gly(277) containing both basic amino acid clusters from the pro-region did not impair the activity of activin A to stimulate Smad-dependent gene expressions, although it completely ablated the perlecan-binding activity. The binding of activin A to basement membrane heparan sulfate proteoglycans through the basic residues in the pro-region was further confirmed by in situ activin A overlay assays using frozen tissue sections. Taken together, the present results indicate that activin A binds to heparan sulfate proteoglycans through its pro-region and thereby regulates its localization within tissues. PMID:20843788

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

    PubMed Central

    Pacheco-Tovar, Deyanira; Bollain-y-Goytia, Juan José; Torres del Muro, Felipe; Ramírez-Sandoval, Roxana; Pacheco-Tovar, María Guadalupe; Castañeda-Ureña, María; Avalos-Díaz, Esperanza

    2013-01-01

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

  10. BMP-3 is a novel inhibitor of both activin and BMP-4 signaling in Xenopus embryos

    E-print Network

    Levin, Michael

    with activin and BMPs through a shared receptor, we show that overexpression of BMP-3 can only be rescued by co-injection, while at the same time BMPs suppress dorsal and trunk mesoderm and neural fates (Harland and Gerhart

  11. In Vitro Control of Organogenesis by ActivinA Treatment of Amphibian and Mouse Stem Cells

    Microsoft Academic Search

    Makoto Asashima; Akira Kurisaki; Tatsuo Michiue

    After identification of “organizer region” in amphibian embryos by Spemann-Mangold in 1930s, presence of limited number of\\u000a factors had been proposed for fundamental embryonic patterning with mesoderm formation. However, these factors had remained\\u000a unknown for a long time. In 1998, we have identified activin as the mesoderm-inducing factor. In this chapter, with various\\u000a conditions of activin A treatment, we demonstrated

  12. 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

  13. Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants

    PubMed Central

    Musso, Tiziana; Scutera, Sara; Vermi, William; Daniele, Roberta; Fornaro, Michele; Castagnoli, Carlotta; Alotto, Daniela; Ravanini, Maria; Cambieri, Irene; Salogni, Laura; Elia, Angela Rita; Giovarelli, Mirella; Facchetti, Fabio; Girolomoni, Giampiero; Sozzani, Silvano

    2008-01-01

    Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGF?. ?n vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGF?. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGF? family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGF?. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGF?, responsible for LC differentiation during inflammatory/autoimmune conditions. PMID:18813341

  14. Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line

    Microsoft Academic Search

    Akira Shimizu; Mitsuyasu Kato; Atsuhito Nakao; Takeshi Imamura; Peter ten Dijke; Carl-Henrik Heldin; Masahiro Kawabata; Shinji Shimada; Kohei Miyazono

    1998-01-01

    Background: Activin A is a multifunctional protein, which is a member of the transforming growth factor-b (TGF-b) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-b superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos. Results: We identified the receptors and Smad proteins activated by activin A in a human epider- mal

  15. Evidence for the participation of endogenous activin A/erythroid differentiation factor in the regulation of erythropoiesis.

    PubMed Central

    Shiozaki, M; Sakai, R; Tabuchi, M; Nakamura, T; Sugino, K; Sugino, H; Eto, Y

    1992-01-01

    Activin A/erythroid differentiation factor (EDF) is a human protein that induces differentiation of a murine erythroleukemia cell (the Friend cell). In this study, we demonstrate that endogenous activin A/EDF activity is present in murine bone marrow and spleen. In addition, this activity is secreted by bone marrow and spleen cells in primary culture. Administration of follistatin (a specific binding protein for activin A/EDF) to mice results in a decrease of erythroid progenitors in the bone marrow and spleen. These findings support the concept that activin A/EDF and follistatin have opposing actions in the regulation of erythropoiesis. PMID:1542647

  16. Solubility of HFC-134a refrigerant in glycol-type compounds: Effects of glycol structure. [1,1,1,2-tetrafluoroethane

    SciTech Connect

    Tseregounis, S.I.; Riley, M.J. (General Motors Research and Development Center, Warren, MI (United States). Fuels and Lubricants Dept.)

    1994-04-01

    Environmental concerns have dictated the replacement of CFC-12 refrigerant with HFC-134a in air-conditioning (A/C) systems. Since polyglycols are synthetic compounds compatible with HFC-134a and considered as lubricants for the A/C compressor, interactions of HFC-134a with glycol-type compounds and thermodynamic properties of the solutions are important in designing an A/C system. In this work, the solubility of HFC-134a in four glycol-type compounds was measured at [minus]5 to 80 C and 90 to 960 kPa. HFC-134a had the greatest solubility in tetraethylene glycol dimethyl ether. HFC-134a was less soluble in hexylene glycol and tetraethylene glycol and least soluble in triethylene glycol. Mixtures of HFC-134a with TRIG or TGDE showed phase separation. Solubility data were used to calculate the activity coefficient of HFC-134a in glycol solutions. An equation of the form, ln[gamma][sub r] = (1 [minus] x[sub r])[A + Bx[sub r

  17. 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

  18. Activin promotes follicular integrity and oogenesis in cultured pre-antral bovine follicles.

    PubMed

    McLaughlin, M; Bromfield, J J; Albertini, D F; Telfer, E E

    2010-09-01

    The aim of this study was to determine the individual and combined effect of activin and follicle stimulating hormone (FSH) on somatic and germ cell development in cultured pre-antral follicles. Pre-antral bovine follicles (mean diameter 157 +/- 3, range 132-199 microm) were cultured for 8 days in serum-free medium in the presence of either 100 ng/ml of recombinant human activin A (rhAct A), 100 ng/ml rhAct A combined with a high (100 ng/ml) or low (50 ng/ml) concentration of recombinant FSH (rFSH) or 50 ng/ml rFSH alone. Intrafollicular connexin 43 expression and actin-based cell adhesion were assessed on Day 2 and 4 of culture. Steroidogenesis was evaluated after Day 4 and 8. Follicles exposed to 100 ng/ml activin maintained expression of connexin 43 at the follicular periphery. In the presence of activin, with or without 100 ng/ml or 50 ng/ml FSH, follicles were steroidogenic undergoing significant growth (P < 0.01), granulosa cell proliferation (P < 0.01) and antral cavity formation (P < 0.05) compared with cultured controls. Maximum oocyte growth occurred in the presence of 100 ng/ml activin alone with a significant percentage of these oocytes maintaining normal morphology over controls (P < 0.05). These results are consistent with a role for activin in maintaining oocyte granulosa cell interactions due to increased peripheral granulosa cell adhesion to the basement membrane and retention of adhesion at the surface of the zona pellucida. Thus, the polarized expression of cell contact interactions promoted by activin supports ongoing folliculogenesis. PMID:20203128

  19. 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?

  20. 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

  1. Clinical value of soluble IgG Fc receptor type III in plasma from patients with chronic idiopathic neutropenia.

    PubMed

    Koene, H R; de Haas, M; Kleijer, M; Huizinga, T W; Roos, D; von dem Borne, A E

    1998-05-15

    Previous studies have shown that the plasma level of soluble IgG Fc receptor type III (sFcgammaRIII) is a measure of the total body neutrophil mass. The aim of this study was to determine whether the plasma level sFcgammaRIII is associated with the risk of contracting bacterial infections in patients with neutropenia. We collected blood from 66 patients suffering from acquired idiopathic neutropenia, whose blood was sent to our laboratory for diagnostic evaluation of neutropenia (neutrophil count <1,500 cells/microL). Soluble FcgammaRIII levels were measured in plasma. Genotype distibutions of FcgammaR polymorphisms were determined. Clinical data were obtained from the patient files. Patients were assessed as to whether or not they had suffered from a bacterial infection 3 months before to 3 months after a single sFcgammaRIII measurement. In addition, longitudinal data were obtained from 21 patients. Of the 66 neutropenic patients who were included, 15 had suffered from a bacterial infection in the period 3 months before to 3 months after sFcgammaRIII measurement. The age and sex distribution was equal among the groups with and without infections, as were the genotype frequencies of neutrophil FcgammaR polymorphisms. Both neutrophil count and plasma level sFcgammaRIII were significantly lower in the patient group with infections, compared with the noninfected group (P = .03 and P < .0001, respectively). No infections were reported for patients who had plasma sFcgammaRIII levels above 100 arbitrary units (AU; normal value, 30 to 200). After matching each infected patient with two noninfected patients having the same neutrophil count, sFcgammaRIII plasma levels remained significantly lower in the group with infections (P = . 0001). For the patients who were followed in time, no infections were reported when sFcgammaRIII levels were above 100 AU. In conclusion, our population of patients with chronic idiopathic neutropenia with plasma sFcgammaRIII levels above 100 AU did not show an increased risk of contracting bacterial infections. PMID:9573035

  2. Water-soluble LYNX1 residues important for interaction with muscle-type and/or neuronal nicotinic receptors.

    PubMed

    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

    2013-05-31

    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

  3. Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.

    PubMed

    DePaolo, L V; Mercado, M; Guo, Y; Ling, N

    1993-05-01

    For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin. Recent data have demonstrated a role for pituitary activin-B in mediating FSH hypersecretion after ovariectomy (OVX) and during the secondary FSH surge on estrus. Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats. At the termination of all in vivo investigations, rats were killed, trunk blood was collected for determination of serum LH and FSH levels by RIA, and pituitary tissue was collected, pooled (two or three glands per pool), and processed for determination of follistatin messenger RNA (mRNA) levels by a solution-hybridization RNase protection assay. In the first experiment, pituitary follistatin mRNA levels were significantly (P < 0.01) increased 3 weeks after OVX. Treatment of long-term ovariectomized rats with a Nal-Glu LHRH antagonist restored serum LH levels to precastration levels and suppressed serum FSH concentrations by 70%, but follistatin message levels were not altered. In contrast, treatment of castrated rats with recombinant human follistatin-288 selectively suppressed serum FSH levels (50%) and completely abolished OVX-induced increases in follistatin mRNA levels. Subsequent experiments revealed that OVX-induced increases in follistatin gene expression could be observed in pituitary tissue grafted underneath the kidney capsule of hypophysectomized rats. Furthermore, follistatin mRNA levels were significantly (P < 0.05) higher in pituitary glands taken from estrous rats during the secondary FSH surge (0200 h) than in glands obtained from rats on proestrous morning when serum FSH levels were basal. Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin. Using cultures of dispersed pituitary cells, addition of recombinant human activin-A for 72 h increased follistatin mRNA levels 3-fold while enhancing only FSH secretion. Collectively, the present results demonstrate a coupling of follistatin gene expression in the anterior pituitary gland with changes in pituitary FSH secretion under conditions where LH secretion is unaltered. Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling. PMID:8477666

  4. 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

  5. Activin signalling and pre-eclampsia: from genetic risk to pre-symptomatic biomarker.

    PubMed

    Williamson, Rachel D; O'Keeffe, Gerard W; Kenny, Louise C

    2015-02-01

    Pre-eclampsia is a multi-system condition in pregnancy that is characterised by the onset of hypertension and proteinuria in women after the 20th week and it remains a leading cause of maternal and fetal mortality. Despite this the causative molecular basis of pre-eclampsia remains poorly understood. As a result, an intensive research effort has focused on understanding the molecular mechanisms involved in pre-eclampsia and using this information to identify new pre-symptomatic bio-markers of the condition. Activin A and its receptor, ACVR2A, have been extensively studied in this regard. Activin A is a member of the transforming growth factor (TGF)-? superfamily that has a wide range of biological functions depending on the cellular context. Recent work has shown that polymorphisms in ACVR2A may be a genetic risk factor for pre-eclampsia. Furthermore, both placenta and serum levels of Activin A are significantly increased in pre-eclampsia suggesting that Activin A may be a possible biomarker for the condition. Here we review the latest advances in this field and link these with new molecular data that suggest that the oxidative stress and pro-inflammatory cytokine production seen in pre-eclampsia may result in increased placental Activin A secretion in an attempt to maintain placental function. PMID:25510903

  6. FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.

    PubMed

    Sagara, N; Kirikoshi, H; Terasaki, H; Yasuhiko, Y; Toda, G; Shiokawa, K; Katoh, M

    2001-04-01

    Frizzled-1 (FZD1)-FZD10 are seven-transmembrane-type WNT receptors, and SFRP1-SFRP5 are soluble-type WNT antagonists. These molecules are encoded by mutually distinct genes. We have previously isolated and characterized the 7.7-kb FZD4 mRNA, encoding a seven-transmembrane receptor with the extracellular cysteine-rich domain (CRD). Here, we have cloned and characterized FZD4S, a splicing variant of the FZD4 gene. FZD4S, corresponding to the 10.0-kb FZD4 mRNA, consisted of exon 1, intron 1, and exon 2 of the FZD4 gene. FZD4S encoded a soluble-type polypeptide with the N-terminal part of CRD, and was expressed in human fetal kidney. Injection of synthetic FZD4S mRNA into the ventral marginal zone of Xenopus embryos at the 4-cell stage did not induce axis duplication by itself, but augmented the axis duplication potential of coinjected Xwnt-8 mRNA. These results indicate that the FZD4 gene gives rise to soluble-type FZD4S as well as seven-transmembrane-type FZD4 due to alternative splicing, and strongly suggest that FZD4S plays a role as a positive regulator of the WNT signaling pathway. PMID:11401527

  7. Small, Acid-Soluble Spore Proteins of the ?/? Type Do Not Protect the DNA in Bacillus subtilis Spores against Base Alkylation

    PubMed Central

    Setlow, Barbara; Tautvydas, Kes J.; Setlow, Peter

    1998-01-01

    Ethyl methanesulfonate (EMS) killed wild-type Bacillus subtilis spores as rapidly as spores lacking small, acid-soluble proteins (SASP) of the ?/? type (???? spores), and 20% of the survivors had obvious mutations. A recA mutation increased the EMS sensitivity of wild-type and ???? spores similarly but reduced their mutagenesis; EMS treatment of dormant spores also resulted in the induction of RecA synthesis during spore germination. EMS generated similar levels of alkylated bases in wild-type and ???? spore DNAs, in purified DNA, or in DNA saturated with ?/?-type SASP. Ethylene oxide (EtO) also generated similar levels of base alkylation in wild-type and ???? spore DNAs. These data indicate that EMS and EtO kill spores at least in part by DNA damage but that ?/?-type SASP, which protect DNA against many types of damage, do not protect spore DNA from base alkylation. PMID:9572981

  8. Purification and Characterization of the Soluble Methane Monooxygenase of the Type II Methanotrophic Bacterium Methylocystis sp. Strain WI 14

    PubMed Central

    Grosse, Stephan; Laramee, Louise; Wendlandt, Karin-Dagmar; McDonald, Ian R.; Miguez, Carlos B.; Kleber, Hans-Peter

    1999-01-01

    Methane monooxygenase (MMO) catalyzes the oxidation of methane to methanol as the first step of methane degradation. A soluble NAD(P)H-dependent methane monooxygenase (sMMO) from the type II methanotrophic bacterium WI 14 was purified to homogeneity. Sequencing of the 16S rDNA and comparison with that of other known methanotrophic bacteria confirmed that strain WI 14 is very close to the genus Methylocystis. The sMMO is expressed only during growth under copper limitation (<0.1 ?M) and with ammonium or nitrate ions as the nitrogen source. The enzyme exhibits a low substrate specificity and is able to oxidize several alkanes and alkenes, cyclic hydrocarbons, aromatics, and halogenic aromatics. It has three components, hydroxylase, reductase and protein B, which is involved in enzyme regulation and increases sMMO activity about 10-fold. The relative molecular masses of the native components were estimated to be 229, 41, and 18 kDa, respectively. The hydroxylase contains three subunits with relative molecular masses of 57, 43, and 23 kDa, which are present in stoichiometric amounts, suggesting that the native protein has an ?2?2?2 structure. We detected 3.6 mol of iron per mol of hydroxylase by atomic absorption spectrometry. sMMO is strongly inhibited by Hg2+ ions (with a total loss of enzyme activity at 0.01 mM Hg2+) and Cu2+, Zn2+, and Ni2+ ions (95, 80, and 40% loss of activity at 1 mM ions). The complete sMMO gene sequence has been determined. sMMO genes from strain WI 14 are clustered on the chromosome and show a high degree of homology (at both the nucleotide and amino acid levels) to the corresponding genes from Methylosinus trichosporium OB3b, Methylocystis sp. strain M, and Methylococcus capsulatus (Bath). PMID:10473397

  9. Plasma Levels of Soluble Urokinase-Type Plasminogen Activator Receptor Associate with the Clinical Severity of Acute Puumala Hantavirus Infection

    PubMed Central

    Outinen, Tuula K.; Tervo, Laura; Mäkelä, Satu; Huttunen, Reetta; Mäenpää, Niina; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne

    2013-01-01

    Objectives Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to ?3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease. Design A single-centre prospective cohort study. Subjects and Methods Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA). Results The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0–18.2 ng/ml vs. median 4.7 ng/ml, range 2.4–12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r?=?0.475, p<0.001), maximum plasma creatinine concentration (r?=?0.378, p<0.001), change in weight during the hospitalization (r?=?0.406, p<0.001) and the length of hospitalization (r?=?0.325, p?=?0.001), and an inverse correlation with minimum platelet count (r?=??0.325, p?=?0.001) and minimum hematocrit (r?=??0.369, p<0.001). Conclusion Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates ?3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease. PMID:23990945

  10. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children: A Single-Center Report

    PubMed Central

    Price, Heather E.; Gallon, Lorenzo; Langman, Craig B.

    2013-01-01

    Summary Background and objectives FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children. Design, setting, participants, & measurements This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases. Results This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1–21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P>0.05). However, suPAR levels (median [25%–75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml [2695–4392]) versus FSGS (2487 pg/ml [2191–3351]; P<0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr >2) had lower suPAR levels than those without proteinuria (2380 pg/ml [2116–2571] versus 3125 pg/ml [2516–4198], respectively; P<0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P>0.05). Conclusions On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS. PMID:23620441

  11. Immunolocalization of inhibin/activin subunit proteins during the breeding season in testes and scented glands of muskrats (Ondatra zibethicus).

    PubMed

    Ma, Xiaoting; Zhang, Haolin; Weng, Jiaju; Sheng, Xia; Lu, Lu; Hu, Xiao; Liu, Shuqiang; Xu, Meiyu; Weng, Qiang; Watanabe, Gen; Taya, Kazuyoshi

    2011-09-01

    The objective of this study was to investigate the cellular immunolocalization of inhibin a and inhibin/activin (?(A) and ?(B)) subunits in the muskrat testes and scented glands during the breeding season. Inhibin ? and inhibin/activin (?(A) and ?(B)) subunits were expressed in Sertoli cells and Leydig cells of testes and glandular cells of scented glands, respectively. Also, positive signals of inhibin ? and inhibin/activin (?(A) and ?(B)) subunits by Western blotting were both observed in testicular and scented glandular tissues. These results suggested that the testes and scented glands of the muskrats had the ability to synthesize inhibins and activins and that activins and inhibins might play an important role in testicular and scented glandular function in muskrats. PMID:21532261

  12. Activin-A binding and biochemical effects in osteoblast-enriched cultures from fetal-rat parietal bone.

    PubMed Central

    Centrella, M; McCarthy, T L; Canalis, E

    1991-01-01

    Activin, a disulfide-linked polypeptide dimer first isolated from gonadal tissue extracts, has amino acid sequence and structural homology with transforming growth factor beta (TGF beta). Along with other activities, TGF beta regulates replication and differentiation and interacts with a defined set of binding sites on isolated bone cells. To determine if activin shares these properties, recombinant human activin-A (A-chain homodimer) was examined in osteoblast-enriched cultures obtained from fetal-rat parietal bone. After 23 h of treatment, 60 to 6,000 pM activin-A increased the rate of [3H]thymidine incorporation into DNA 1.5- to 4.0-fold, and at 600 to 6,000 pM, it enhanced the rate of [3H]proline incorporation into collagen and noncollagen protein by up to 1.7-fold. Like earlier studies with TGF beta in primary osteoblast-enriched cultures, the stimulatory effects of activin-A on DNA and protein synthesis were opposed by parathyroid hormone, and the influence of activin-A on collagen synthesis was independent of cell replication. Binding studies with 125I-activin-A indicated approximately 8,000 high-affinity (Kd = 0.4 nM) and 300,000 low-affinity (Kd = 40 to 50 nM) binding sites per cell. Polyacrylamide gel analysis revealed 125I-activin-A-binding complexes of Mr greater than 200,000 and 73,000 which did not appear to correspond to primary TGF beta-binding sites. These results indicate that activin-A produces TGF beta-like effects in bone and that some of these effects may be mediated, at least in part, by distinct activin receptors on bone cells. Images PMID:1846021

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

    PubMed

    Papanayotou, Costis; Collignon, Jérôme

    2014-12-01

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

  14. Diagnostic accuracy of serum activin A in detection of ectopic pregnancy

    PubMed Central

    Roghaei, Mohammad Ali; Sabet, Fahimeh; Mohamadi, Keivan

    2012-01-01

    Background: Ectopic pregnancy (EP) still remains a main cause of maternal mortalities. This study is designed to evaluate the accuracy of serum Activin A in detection of ectopic pregnancy. Methods: This prospective observational study was conducted from 2009 to 2010 at two main referral university hospitals, Isfahan University of Medical Sciences, Isfahan, Iran. Two hundred subjects who were under 10 week's pregnancy with clinical presentations of abdominal pain and vaginal bleeding were enrolled. After sampling serum Activin A, patients underwent ultrasonography, titer of B-HCG and surgery (if indicated) and were divided into two groups: EP (n = 100) and intrauterine pregnancy (IUP) (n = 100). The mean of Activin A was compared between groups and by ROC curve, the optimal cut off with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined. Results: The mean age of women with IUP was 25.4 ± 4.3 years (15-40 years) compared with 25.9 ± 4.1 years in women in EP group (P = 0.448). Statistical difference was not found between EP versus IUP groups in gestational age (6.32 ± 1.03 vs. 6.85 ± 1.82 weeks, P = 0.124). The mean of serum Activin A in EP group was 0.264 ± 0.0703 ng/ml versus 0.949 ± 0.5283 ng/ml in IUP group (P < 0.05). According to ROC curve (area under the curve = 0.981, P < 0.05, confidence interval: 0.961-1.000), the optimal cut off was estimated as 0.504 ng/ml with sensitivity of 97% and specificity of 93.5%. Conclusion: This study indicated that the mean of serum Activin A is lower in EP compared with IUP. The serum Activin A has a fair accuracy in detecting EP. PMID:23267401

  15. MicroRNA-181a Suppresses Mouse Granulosa Cell Proliferation by Targeting Activin Receptor IIA

    PubMed Central

    Jiang, Yue; Ding, Lijun; Wu, Shaogen; Fang, Ting; Yan, Guijun; Hu, Yali

    2013-01-01

    Activin, a member of the transforming growth factor-? superfamily, promotes the growth of preantral follicles and the proliferation of granulosa cells. However, little is known about the role of microRNAs in activin-mediated granulosa cell proliferation. Here, we reported a dose- and time-dependent suppression of microRNA-181a (miR-181a) expression by activin A in mouse granulosa cells (mGC). Overexpression of miR-181a in mGC suppressed activin receptor IIA (acvr2a) expression by binding to its 3?-untranslated region (3?-UTR), resulting in down-regulation of cyclin D2 and proliferating cell nuclear antigen expression, leading to inhibition of the cellular proliferation, while overexpression of acvr2a attenuated the suppressive effect of miR-181a on mGC proliferation. Consistent with the inhibition of acvr2a expression, miR-181a prevented the phosphorylation of the activin intracellular signal transducer, mothers against decapentaplegic homolog 2 (Smad2), leading to the inactivation of activin signaling pathway. Interestingly, we found that miR-181a expression decreased in ovaries of mice at age of 8, 12, and 21 days, as compared with that in ovaries of 3-day old mice, and its level was reduced in preantral and antral follicles of mice compared with that in primary ones. Moreover, the level of miR-181a in the blood of patients with premature ovarian failure was significantly increased compared with that in normal females. This study identifies an interplay between miR-181a and acvr2a, and reveals an important role of miR-181a in regulating granulosa cell proliferation and ovarian follicle development. PMID:23527246

  16. Controls on iron distributions in the deep water column of the North Pacific Ocean: Iron(III) hydroxide solubility and marine humic-type dissolved organic matter

    Microsoft Academic Search

    Saori Kitayama; Kenshi Kuma; Eri Manabe; Koji Sugie; Hyoe Takata; Yutaka Isoda; Kenji Toya; Sei-ichi Saitoh; Shohgo Takagi; Yoshihiko Kamei; Keiichiro Sakaoka

    2009-01-01

    Dissolved Fe in the western and central North Pacific Ocean was characterized by surface depletion, middepth maxima and, below that, a slight decrease with depth similar to the vertical distributions of nutrients, apparent oxygen utilization, Fe(III) hydroxide solubility, and humic-type fluorescence (H-flu) intensity. Dissolved Fe concentrations ([D-Fe], <0.22-?m fraction) in the deep water column were one-half lower in the central

  17. Dengue Virus Type 1 Nonstructural Glycoprotein NS1 Is Secreted from Mammalian Cells as a Soluble Hexamer in a Glycosylation-Dependent Fashion

    Microsoft Academic Search

    MARIE FLAMAND; FRANCOISE MEGRET; MAGALI MATHIEU; JEAN LEPAULT; FELIX A. REY; VINCENT DEUBEL; Biochimie Structurales

    1999-01-01

    Nonstructural glycoprotein NS1, specified by dengue virus type 1 (Den-1), is secreted from infected green monkey kidney (Vero) cells in a major soluble form characterized by biochemical and biophysical means as a unique hexameric species. This noncovalently bound oligomer is formed by three dimeric subunits and has a molecular mass of 310 kDa and a Stokes radius of 64.4 Å.

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

    PubMed Central

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

    2011-01-01

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

  19. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor ? type II receptor: A potential new therapy for hepatic fibrosis

    PubMed Central

    George, Jacob; Roulot, Dominique; Koteliansky, Victor E.; Bissell, D. Montgomery

    1999-01-01

    Transforming growth factor ? (TGF-?) is a well characterized cytokine that appears to play a major role in directing the cellular response to injury, driving fibrogenesis, and, thus, potentially underlying the progression of chronic injury to fibrosis. In this study, we report the use of a novel TGF-? receptor antagonist to block fibrogenesis induced by ligation of the common bile duct in rats. The antagonist consisted of a chimeric IgG containing the extracellular portion of the TGF-? type II receptor. This “soluble receptor” was infused at the time of injury; in some experiments it was given at 4 days after injury, as a test of its ability to reverse fibrogenesis. The latter was assessed by expression of collagen, both as the mRNA in stellate cells isolated from control or injured liver and also by quantitative histochemistry of tissue sections. When the soluble receptor was administered at the time of injury, collagen I mRNA in stellate cells from the injured liver was 26% of that from animals receiving control IgG (P < 0.0002); when soluble receptor was given after injury induction, collagen I expression was 35% of that in control stellate cells (P < 0.0001). By quantitative histochemistry, hepatic fibrosis in treated animals was 55% of that in controls. We conclude that soluble TGF-? receptor is an effective inhibitor of experimental fibrogenesis in vivo and merits clinical evaluation as a novel agent for controlling hepatic fibrosis in chronic liver injury. PMID:10535989

  20. Synthesis and reactions of cubane-type iron-sulfur-phosphine clusters, including soluble clusters of nuclearities 8 and 16.

    PubMed

    Zhou, Hong-Cai; Holm, R H

    2003-01-13

    A family of soluble, reduced iron-sulfur clusters with nuclearities 4, 8, and 16 having tertiary phosphine ligation and based on the Fe(4)S(4) cubane-type structural motif has been synthesized. The results of this investigation substantially extend and improve the results of our original work on iron-sulfur-phosphine clusters (Goh, C.; Segal, B. M.; Huang, J.; Long, J. R.; Holm, R. H. J. Am. Chem. Soc. 1996, 118, 11844). A general property of this cluster family is facile phosphine substitution. The clusters [Fe(4)S(4)(PR(3))(4)](+) are precursors to monosubstituted [Fe(4)S(4)(PR(3))(3)X] (X = Cl-, RS-), homoleptic [Fe(4)S(4)(SR)(4)](3-), and all-ferrous monocubanes [Fe(4)S(4)(PR(3))(4)] (R = Pr(i), Cy, Bu(t); generated in solution). In turn, [Fe(4)S(4)(PPr(i)()(3))(3)(SSiPh(3))] and [Fe(4)S(4)(PPr(i)(3))(4)] can be transformed into the dicubanes [Fe(8)S(8)(PPr(i)()(3))(4)(SSiPh(3))(2)] and [Fe(8)S(8)(PPr(i)((3))(6)], respectively. Further, the tetracubanes [Fe(16)S(16)(PR(3))(8)] are also accessible from [Fe(4)S(4)(PR(3))(4)] under different conditions. X-ray structures are described for [Fe(4)S(4)(PCy(3))(3)X] (X = Cl-, PhS-), [Fe(8)S(8)(PPr(i)(3))(4)(SSiPh(3))(2)], [Fe(8)S(8)(PPr(i)()(3))(6)], and [Fe(16)S(16)(PCy(3))(8)]. The monosubstituted clusters show different distortions of the [Fe(4)S(4)](+) cores from idealized cubic symmetry. The dicubanes possess edge-bridged double cubane structures with an Fe(2)(mu(4)-S)(2) bridge rhomb and idealized C(2)(h)() symmetry. The ready cleavage of these clusters into single cubanes is considered a probable consequence of strained bond angles at the mu(4)-S atoms. Tetracubanes contain four individual cubanes, each of which is implicated in two bridge rhombs so as to generate a cyclic structure of idealized D(4) symmetry. Redox properties and Mössbauer spectroscopic parameters are reported. The species [Fe(4)S(4)(PR(3))(4)] (in solution), [Fe(8)S(8)(PR(3))(6)], and [Fe(16)S(16)(PR(3))(8)] are the only synthetic all-ferrous clusters with tetrahedral iron sites that have been isolated. Their utility as precursors to other highly reduced iron-sulfur clusters is under investigation. PMID:12513073

  1. Selective and indirect modulation of human multipotential and erythroid hematopoietic progenitor cell proliferation by recombinant human activin and inhibin.

    PubMed Central

    Broxmeyer, H E; Lu, L; Cooper, S; Schwall, R H; Mason, A J; Nikolics, K

    1988-01-01

    Activin and inhibin are biomolecules that, respectively, enhance and suppress the release of follicle-stimulating hormone from pituitary cells in vitro. Purified recombinant human (rhu) activin A and inhibin A were assessed for their effects on colony formation in vitro by human multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells. It was found that (i) rhu-activin A enhances colony formation by normal bone marrow erythroid and multipotential progenitor cells; (ii) purified rhu-inhibin A decreases activin, but not rhu-interleukin 3, rhu-granulocyte-macrophage colony-stimulating factor, or rhu-interleukin 4, enhancement of erythropoietin-stimulated colony formation by erythroid and multipotential progenitor cells; (iii) modulatory actions of rhu-activin and rhu-inhibin are mediated through monocytes and T lymphocytes within the marrow; (iv) actions are apparent in the absence or presence of serum; and (v) rhu-activin and rhu-inhibin have no effect on colony formation by granulocyte-macrophage progenitor cells. This defines an indirect mode of action and a specificity for activin and inhibin on multipotential and erythroid progenitor cells. PMID:3194407

  2. 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.

  3. Presence of activin signal transduction in normal ovarian cells and epithelial ovarian carcinoma

    PubMed Central

    Ito, I; Minegishi, T; Fukuda, J; Shinozaki, H; Auersperg, N; Leung, P C K

    2000-01-01

    In this study, we have investigated the expression of inhibin subunits and activin receptors (ActRs) in normal and malignant ovarian cells. Each product of the inhibin subunits (?, ?a, ?b) and activin receptors (ActRs) amplified by reverse transcription polymerase chain reaction were detected as a single band in human granulosa cells, surface epithelial cells (OSE), and the ovarian cancer cell lines OVCAR 3 and SKOV 3. Western blot analysis was performed using polyclonal antibodies against ActR IIa or IIb peptides based on 13 COOH-terminal amino acids; cultured human granulosa cells were used as a positive control. Using ActR IIa antibody, one major band corresponding to approximately 80 kDa and one minor band corresponding to 105 kDa were observed in the samples. One single band at approximately 60 kDa was detected in OVCAR 3 and a 50 kDa band was detected with ActR IIb antibody in cultured granulosa cell, OSE and SKOV 3. Although no detectable change was induced in Smad 4 mRNA in OVCAR 3, Smad 2 mRNA levels were increased during 48 h treatment with activin A (50 ng ml–1). These data provide a better understanding as the first step in the mechanism of action of the activin in the epithelial ovarian carcinoma. © 2000 Cancer Research Campaign PMID:10780520

  4. 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

  5. Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts.

    PubMed

    Sarkar, Prasenjit; Randall, Shan M; Collier, Timothy S; Nero, Anthony; Russell, Teal A; Muddiman, David C; Rao, Balaji M

    2015-04-01

    Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. PMID:25670856

  6. Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia

    Microsoft Academic Search

    Bethany A. Cruise; Pin Xu; Alison K. Hall

    2004-01-01

    Successful healing of skin wounds requires sensory innervation and the release of vasoactive neuropeptides that dilate blood vessels and deliver serum proteins to the wound, and that cause pain that protects from further injury. Activin has been proposed as a target-derived regulator of sensory neuropeptides during development, but its role in the mature nervous system is unknown. While adult skin

  7. Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion.

    PubMed

    Flamand, M; Megret, F; Mathieu, M; Lepault, J; Rey, F A; Deubel, V

    1999-07-01

    Nonstructural glycoprotein NS1, specified by dengue virus type 1 (Den-1), is secreted from infected green monkey kidney (Vero) cells in a major soluble form characterized by biochemical and biophysical means as a unique hexameric species. This noncovalently bound oligomer is formed by three dimeric subunits and has a molecular mass of 310 kDa and a Stokes radius of 64.4 A. During protein export, one of the two oligosaccharides of NS1 is processed into an endo-beta-N-acetylglucosaminidase F-resistant complex-type sugar while the other remains of the polymannose type, protected in the dimeric subunit from the action of maturation enzymes. Complete processing of the complex-type sugar appears to be required for efficient release of soluble NS1 into the culture fluid of infected cells, as suggested by the repressive effects of the N-glycan processing inhibitors swainsonine and deoxymannojyrimicin. These results, together with observations related to the absence of secretion of NS1 from Den-infected insect cells, suggest that maturation and secretion of hexameric NS1 depend on the glycosylation status of the host cell. PMID:10364366

  8. Controls on iron distributions in the deep water column of the North Pacific Ocean: Iron(III) hydroxide solubility and marine humic-type dissolved organic matter

    NASA Astrophysics Data System (ADS)

    Kitayama, Saori; Kuma, Kenshi; Manabe, Eri; Sugie, Koji; Takata, Hyoe; Isoda, Yutaka; Toya, Kenji; Saitoh, Sei-Ichi; Takagi, Shohgo; Kamei, Yoshihiko; Sakaoka, Keiichiro

    2009-08-01

    Dissolved Fe in the western and central North Pacific Ocean was characterized by surface depletion, middepth maxima and, below that, a slight decrease with depth similar to the vertical distributions of nutrients, apparent oxygen utilization, Fe(III) hydroxide solubility, and humic-type fluorescence (H-flu) intensity. Dissolved Fe concentrations ([D-Fe], <0.22-?m fraction) in the deep water column were one-half lower in the central region (0.3-0.6 nM) than the western region (0.5-1.2 nM) although the Fe(III) solubility ([Fe(III)sol], <0.025-?m fraction) levels and distributions in deep waters were almost the same between both regions with middepth maxima (˜0.6 nM) at 500-1500-m depth range and then a gradual decrease to ˜0.3 nM at 5000-m depth. Higher [D-Fe] than [Fe(III)sol] in the deep water column of the western region results from the higher production of dissolved Fe from the decomposition of sinking particulate organic matter in the western region than the central region because of the high atmospheric and/or lateral Fe inputs in the western region. Similarity between [D-Fe] level and [Fe(III)sol] value at each deep water depth in the central region may be attributed to [D-Fe] being nearly in the solubility equilibrium with Fe(III) hydroxide in seawater. Strong linear correlation between [D-Fe] and H-flu intensity in the central region and relatively similar linear relationships between [Fe(III)sol] and H-flu intensity in the western and central regions are the first confirmation that humic-type fluorescent dissolved organic matter may be responsible for [D-Fe] in the deep water column as natural organic ligands complexing with Fe(III).

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

    PubMed Central

    2014-01-01

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

  10. A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia.

    PubMed

    Sela, Shay; Itin, Ahuva; Natanson-Yaron, Shira; Greenfield, Caryn; Goldman-Wohl, Debra; Yagel, Simcha; Keshet, Eli

    2008-06-20

    A human-specific splicing variant of vascular endothelial growth factor (VEGF) receptor 1 (Flt1) was discovered, producing a soluble receptor (designated sFlt1-14) that is qualitatively different from the previously described soluble receptor (sFlt1) and functioning as a potent VEGF inhibitor. sFlt1-14 is generated in a cell type-specific fashion, primarily in nonendothelial cells. Notably, in vascular smooth muscle cells, all Flt1 messenger RNA is converted to sFlt1-14, whereas endothelial cells of the same human vessel express sFlt1. sFlt1-14 expression by vascular smooth muscle cells is dynamically regulated as evidenced by its upregulation on coculture with endothelial cells or by direct exposure to VEGF. Increased production of soluble VEGF receptors during pregnancy is entirely attributable to induced expression of placental sFlt1-14 starting by the end of the first trimester. Expression is dramatically elevated in the placenta of women with preeclampsia, specifically induced in abnormal clusters of degenerative syncytiotrophoblasts known as syncytial knots, where it may undergo further messenger RNA editing. sFlt1-14 is the predominant VEGF-inhibiting protein produced by the preeclamptic placenta, accumulates in the circulation, and hence is capable of neutralizing VEGF in distant organs affected in preeclampsia. Together, these findings revealed a new natural VEGF inhibitor that has evolved in humans, possibly to protect nonendothelial cells from adverse VEGF signaling. Furthermore, the study uncovered the identity of a VEGF-blocking protein implicated in preeclampsia. PMID:18515749

  11. Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra-bone marrow involvement in multiple myeloma patients.

    PubMed

    Rigolin, Gian Matteo; Tieghi, Alessia; Ciccone, Maria; Bragotti, Letizia Zenone; Cavazzini, Francesco; Della Porta, Matteo; Castagnari, Barbara; Carroccia, Rosanna; Guerra, Giovanni; Cuneo, Antonio; Castoldi, Gianluigi

    2003-03-01

    The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P < 0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM. PMID:12648064

  12. Trpc2-expressing sensory neurons in the mouse main olfactory epithelium of type B express the soluble guanylate cyclase Gucy1b2.

    PubMed

    Omura, Masayo; Mombaerts, Peter

    2015-03-01

    Chemoreception in the mouse olfactory system occurs primarily at two chemosensory epithelia in the nasal cavity: the main olfactory epithelium (MOE) and the vomeronasal epithelium. The canonical chemosensory neurons in the MOE, the olfactory sensory neurons (OSNs), express the odorant receptor (OR) gene repertoire, and depend on Adcy3 and Cnga2 for chemosensory signal transduction. The canonical chemosensory neurons in the vomeronasal epithelium, the vomeronasal sensory neurons (VSNs), express two unrelated vomeronasal receptor (VR) gene repertoires, and involve Trpc2 for chemosensory signal transduction. Recently we reported the discovery of two types of neurons in the mouse MOE that express Trcp2 in addition to Cnga2. These cell types can be distinguished at the single-cell level by expression of Adcy3: positive, type A and negative, type B. Some type A cells express OR genes. Thus far there is no specific gene or marker for type B cells, hampering further analyses such as physiological recordings. Here, we show that among MOE cells, type B cells are unique in their expression of the soluble guanylate cyclase Gucy1b2. We came across Gucy1b2 in an explorative approach based on Long Serial Analysis of Gene Expression (LongSAGE) that we applied to single red-fluorescent cells isolated from whole olfactory mucosa and vomeronasal organ of mice of a novel Trcp2-IRES-taumCherry gene-targeted strain. The generation of a novel Gucy1b2-IRES-tauGFP gene-targeted strain enabled us to visualize coalescence of axons of type B cells into glomeruli in the main olfactory bulb. Our molecular and anatomical analyses define Gucy1b2 as a marker for type B cells within the MOE. The Gucy1b2-IRES-tauGFP strain will be useful for physiological, molecular, cellular, and anatomical studies of this newly described chemosensory subsystem. PMID:25701815

  13. Trpc2-expressing sensory neurons in the mouse main olfactory epithelium of type B express the soluble guanylate cyclase Gucy1b2

    PubMed Central

    Omura, Masayo; Mombaerts, Peter

    2015-01-01

    Chemoreception in the mouse olfactory system occurs primarily at two chemosensory epithelia in the nasal cavity: the main olfactory epithelium (MOE) and the vomeronasal epithelium. The canonical chemosensory neurons in the MOE, the olfactory sensory neurons (OSNs), express the odorant receptor (OR) gene repertoire, and depend on Adcy3 and Cnga2 for chemosensory signal transduction. The canonical chemosensory neurons in the vomeronasal epithelium, the vomeronasal sensory neurons (VSNs), express two unrelated vomeronasal receptor (VR) gene repertoires, and involve Trpc2 for chemosensory signal transduction. Recently we reported the discovery of two types of neurons in the mouse MOE that express Trcp2 in addition to Cnga2. These cell types can be distinguished at the single-cell level by expression of Adcy3: positive, type A and negative, type B. Some type A cells express OR genes. Thus far there is no specific gene or marker for type B cells, hampering further analyses such as physiological recordings. Here, we show that among MOE cells, type B cells are unique in their expression of the soluble guanylate cyclase Gucy1b2. We came across Gucy1b2 in an explorative approach based on Long Serial Analysis of Gene Expression (LongSAGE) that we applied to single red-fluorescent cells isolated from whole olfactory mucosa and vomeronasal organ of mice of a novel Trcp2-IRES-taumCherry gene-targeted strain. The generation of a novel Gucy1b2-IRES-tauGFP gene-targeted strain enabled us to visualize coalescence of axons of type B cells into glomeruli in the main olfactory bulb. Our molecular and anatomical analyses define Gucy1b2 as a marker for type B cells within the MOE. The Gucy1b2-IRES-tauGFP strain will be useful for physiological, molecular, cellular, and anatomical studies of this newly described chemosensory subsystem. PMID:25701815

  14. Regulation of Germ Cell and Sertoli Cell Development by Activin, Follistatin, and FSH

    Microsoft Academic Search

    Terri Meehan; Stefan Schlatt; Moira K. O'Bryan; David M. de Kretser; Kate Lakoski Loveland

    2000-01-01

    We have demonstrated a role for activin A, follistatin, and FSH in male germ cell differentiation at the time when spermatogonial stem cells and committed spermatogonia first appear in the developing testis. Testis fragments from 3-day-old rats were cultured for 1 or 3 days with various combinations of these factors, incubated with bromodeoxyuridine (BrdU) to label proliferating cells, and then

  15. Plasma matrix metalloproteinases, low density lipoprotein oxidisability and soluble adhesion molecules after a glucose load in Type 2 diabetes

    Microsoft Academic Search

    Mike Sampson; Isabel Davies; Jelena Gavrilovic; Brendan Sussams; Jackie Brown; Sian Astley; David A Hughes

    2004-01-01

    BACKGROUND: Acute hyperglycaemia is an independent cardiovascular risk factor in Type 2 diabetes which may be mediated through increased oxidative damage to plasma low density lipoprotein, and in vitro, high glucose concentrations promote proatherogenic adhesion molecule expression and matrix metalloproteinase expression. METHODS: We examined these atherogenic risk markers in 21 subjects with Type 2 diabetes and 20 controls during an

  16. 418 Genome Informatics 11: 418–419 (2000) Prediction of Dumbbell-Type Soluble Proteins and Their Center Helices

    E-print Network

    Shun-ya Takahashi; Shigeki Mitaku

    Dumbbell-type proteins have two domains linked by a long helical segment. Typical examples of dumbbell-type proteins are calmodulin and troponin C, which have regulating function of other proteins [1, 2]. The function seems to be closely related to the dumbbell shape of this protein. Upon binding of calcium, calmodulin changes its structure and strongly interacts with other protein, modulating

  17. 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 ...

  18. 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

  19. Changes in the reproductive function and developmental phenotypes in mice following intramuscular injection of an activin betaA-expressing plasmid

    PubMed Central

    Kim, Mi-Nyeu; Park, Moon Nyeo; Jung, Hoi Kyung; Cho, Chunghee; Mayo, Kelly E; Cho, Byung-Nam

    2008-01-01

    Background The TGF-beta family protein activin has numerous reported activities with some uncertainty in the reproductive axis and development. The precise roles of activin in in vivo system were investigated using a transient gain of function model. Methods To this end, an expression plasmid, pCMV-rAct, with the activin betaA cDNA fused to the cytomegalovirus promoter, was introduced into muscle of the female adult mice by direct injection. Results Activin betaA mRNA was detected in the muscle by RT-PCR and subsequent Southern blot analysis. Activin betaA was also detected, and western blot analysis revealed a relatively high level of serum activin with correspondingly increased FSH. In the pCMV-rAct-injected female mice, estrus stage within the estrous cycle was extended. Moreover, increased numbers of corpora lutea and a thickened granulosa cell layer with a small antrum in tertiary follicles within the ovary were observed. When injected female mice were mated with males of proven fertility, a subset of embryos died in utero, and most of those that survived exhibited increased body weight. Conclusion Taken together, our data reveal that activin betaA can directly influence the estrous cycle, an integral part of the reproduction in female mice and activin betaA can also influence the embryo development as an endocrine fashion. PMID:19077325

  20. Expression patterns of activin, inhibin and follistatin variants in the adult male mouse reproductive tract suggest important roles in the epididymis and vas deferens.

    PubMed

    Winnall, Wendy R; Wu, Hui; Sarraj, Mai A; Rogers, Peter A W; de Kretser, David M; Girling, Jane E; Hedger, Mark P

    2013-01-01

    Activin A and its inhibitors follistatin and inhibin play key roles in development and function of the male reproductive tract. Quantitative (q) polymerase chain reaction (PCR) was used to evaluate the expression of Inhba (the gene encoding activin A subunits), Inha and Inhbb (genes encoding the inhibin B subunits), as well as the genes for follistatin (Fst) and follistatin-like 3 (Fstl3) and the activin receptor subunits, in the male mouse reproductive tract. A qPCR assay that discriminated between the two follistatin variants of Fst288 (tissue-bound form) and Fst315 (circulating) was established. Activin A protein was measured by ELISA, whereas the inhibin ?-subunit and total follistatin proteins were measured by radioimmunoassay (RIA). A screen of 22 tissues demonstrated tissue-specific regulation of the follistatin variants, with Fst288 highly expressed in the vas deferens and Fst315 most highly expressed in the skin. The expression of Fst288 and Fst315 and follistatin protein levels increased progressively from the testis through to the distal vas deferens. Inhba and the activin receptors were highly expressed in the epididymis, but activin A protein was elevated in both the epididymis and vas deferens. Inhibin ?-subunit mRNA and protein and Inhbb expression were highest in the testis. These results indicate a role for activin A within the epididymis, but also that activin A bioactivity may be increasingly inhibited by follistatin distally along the male reproductive tract. PMID:23164397

  1. Pre-meal insulin aspart compared with pre-meal soluble human insulin in type 1 diabetes

    Microsoft Academic Search

    P. D. Home; P. Hallgren; K. H. Usadel; T. Sane; J. Faber; V. Grill; H. H. Friberg

    2006-01-01

    Insulin aspart has been shown, in medium-term studies, to achieve reductions in HbA1c without increasing the risk of major hypoglycaemia compared with pre-meal human insulin. The aim of the present 3-year study was to evaluate the long-term safety and efficacy of insulin aspart in people with type 1 diabetes.This was a 30-month extension of a multinational, multicentre, open-label, parallel-group study

  2. 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.

  3. The soluble ectodomain of RetC634Y inhibits both the wild-type and the constitutively active Ret.

    PubMed Central

    Cerchia, Laura; Libri, Domenico; Carlomagno, Maria Stella; de Franciscis, Vittorio

    2003-01-01

    Substitution of Cys-634 in the extracellular domain of the Ret tyrosine kinase receptor causes its dimerization and activation of its transforming potential. To gain further insight into the molecular basis leading to Ret activation we purified a mutant protein consisting of the entire ectodomain of the Ret carrying a Cys-634-->Tyr substitution (EC-Ret(C634Y)). The protein is glycosylated, like the native one, and is biologically active. By using an in vitro cell system we show that EC-Ret(C634Y) inhibits the membrane-bound receptor Ret(C634Y), interfering with its dimerization. Furthermore, we demonstrate that EC-Ret(C634Y) competes with the wild-type Ret receptor for ligand binding. The results presented support the notion of the possible involvment of glial cell line-derived neurotrophic factor (GDNF) with multiple endocrine neoplasia type 2A (MEN2A) tumours, and describe a useful tool for generating molecular mimetics directed towards specific mutations of the ret oncogene. PMID:12630912

  4. 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.

  5. Moisture solubility for differently conditioned transformer oils

    Microsoft Academic Search

    Y. DUI; A. V. Mamishev; B. C. Lesieutre; M. Zahn; S. H. Kang

    2001-01-01

    It is important to monitor the moisture content of transformer oil in a transformer. One parameter of particular interest is the moisture solubility of transformer oil. It has been reported that transformer oils under different conditions have different solubility. Measurements of solubility for four different types of conditioned oil are presented in this paper: fresh Shell Diala AX oil, lab-aged

  6. Interleukin 1beta and progesterone stimulate activin a expression and secretion from cultured human endometrial stromal cells.

    PubMed

    Florio, Pasquale; Rossi, Marco; Viganò, Paola; Luisi, Stefano; Torricelli, Michela; Torres, Paulo B; Di Blasio, Anna Maria; Petraglia, Felice

    2007-01-01

    Steroid hormones, cytokines, and growth factors have a major role in evoking local endometrial changes needed for trophoblast implantation. In the present study, the effect of interleukin-1beta (IL-1beta), 17-beta estradiol (E2), and progesterone (Pr) on activin A and follistatin (FS) secretion from cultured human endometrial stromal cells (HESCs) is evaluated. HESCs were obtained from healthy human endometrial samples (n = 8) collected from healthy women. The cells were cultured and stimulated with E2 (10(-7) M, 10(-6)M), Pr (10(-7)M, 10(-6)M), IL-1beta (500 pg/mL), IL-1beta (500 pg/mL) + E2 (10(-6)M), and IL-1beta (500 pg/mL) + Pr (10(-6)M). Activin A and FS secretion and mRNA expression were assayed by enzyme-linked immunosorbent assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. Pr (10(-7) M, 10(-6) M) significantly increased activin A secretion and mRNA expression from HESCs, but E2 did not show remarkable effects. The addition of IL-1beta (P< .001), IL- 1beta + E2 (P < .01), and IL-1beta + Pr (P< .001). significantly stimulated activin A secretion and mRNA expression, compared to untreated cells. Activin A expression and secretion after the coincubation of IL-1beta+ Pr were significantly higher than after IL-1betaand IL-1beta+ E2 stimuli ( P< .01 and P< .001, respectively). Neither Pr nor E2 and IL-1beta had a significant effect on FS secretion and expression. IL-1betaand Pr stimulated activin A but not FS secretion from cultured HESCs, and the effect of IL-1betawas augmented by Pr. These findings, together with the evidence that activin A is involved in trophoblast implantation, suggest the existence of a complex cross-talk by which the ovary, through Pr secretion, and the embryo, through IL-1beta production, may trigger the endometrial induction of activin A and consequently timing implantation. PMID:17636213

  7. Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers.

    PubMed

    Lengil, Tamar; Gancz, Dana; Gilboa, Lilach

    2015-03-01

    How the numbers of niches and resident stem cells within a particular organ are determined during development and how they may be modulated or corrected is a question with significant medical implications. In the larval ovary of Drosophila melanogaster, somatic precursors for niches, and germ cells that will become germline stem cells, co-develop. Somatic precursors proliferate during the first 3 days of larval development. By mid-third instar, adult terminal filament (TF) (part of the germline stem cell niche) cells first appear, and differentiation terminates 24?h later when 16-20 TFs fully form. The developmental sequence responsible for TF cell determination and final TF numbers is only partially understood. We show that TF formation proceeds through several, hitherto uncharacterized stages, which include an early exit from the cell cycle to form TF precursors and two steps of cell shape change to form the mature TF cells. The Activin receptor Baboon (Babo) is required for somatic precursor cell proliferation and therefore determines the pool of TF precursors available for TF differentiation. During the final differentiation stage, Babo facilitates TF and germ cell differentiation, and promotes the accumulation of Broad-Z1, which is also a target of the steroid hormone ecdysone. Epistasis analysis shows that Activin controls cell proliferation in an ecdysone-independent manner and TF differentiation by affecting ecdysone targets. We propose that this mode of function allows Activin to balance proliferation and differentiation, and to equilibrate niche numbers. These results suggest a novel model for how niche numbers are corrected during development. PMID:25633355

  8. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis

    PubMed Central

    Pancera, Marie; Lebowitz, Jacob; Schön, Arne; Zhu, Ping; Freire, Ernesto; Kwong, Peter D.; Roux, Kenneth H.; Sodroski, Joseph; Wyatt, Richard

    2005-01-01

    The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, mediates binding to the viral receptors and, along with the transmembrane glycoprotein gp41, is a major target for neutralizing antibodies. We asked whether replacing the gp41 fusion/trimerization domain with a stable trimerization motif might lead to a more stable gp120 trimer that would be amenable to structural and immunologic analysis. To obtain stable gp120 trimers, a heterologous trimerization motif, GCN4, was appended to the C terminus of YU2gp120. Biochemical analysis indicated that the gp120-GCN4 trimers were superior to gp140 molecules in their initial homogeneity, and trilobed structures were observable by electron microscopy. Biophysical analysis of gp120-GCN4 trimers by isothermal titration calorimetry (ITC) and ultracentrifugation analyses indicated that most likely two molecules of soluble CD4 could bind to one gp120-GCN4 trimer. To further examine restricted CD4 stoichiometric binding to the gp120-GCN4 trimers, we generated a low-affinity CD4 binding trimer by introducing a D457V change in the CD4 binding site of each gp120 monomeric subunit. The mutant trimers could definitively bind only one soluble CD4 molecule, as determined by ITC and sedimentation equilibrium centrifugation. These data indicate that there are weak interactions between the gp120 monomeric subunits of the GCN4-stabilized trimers that can be detected by low-affinity ligand sensing. By similar analysis, we also determined that removal of the variable loops V1, V2, and V3 in the context of the gp120-GCN4 proteins allowed the binding of three CD4 molecules per trimer. Interestingly, both the gp120-GCN4 variants displayed a restricted stoichiometry for the CD4-induced antibody 17b of one antibody molecule binding per trimer. This restriction was not evident upon removal of the variable loops V1 and V2 loops, consistent with conformational constraints in the wild-type gp120 trimers and similar to those inherent in the functional Env spike. Thus, the gp120-GCN4 trimers demonstrate several properties that are consistent with some of those anticipated for gp120 in the context of the viral spike. PMID:16014956

  9. 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

  10. Novel Protein Interactions with Endoglin and Activin Receptor-like Kinase 1: Potential Role in Vascular Networks*

    PubMed Central

    Xu, Guoxiong; Barrios-Rodiles, Miriam; Jerkic, Mirjana; Turinsky, Andrei L.; Nadon, Robert; Vera, Sonia; Voulgaraki, Despina; Wrana, Jeffrey L.; Toporsian, Mourad; Letarte, Michelle

    2014-01-01

    Endoglin and activin receptor-like kinase 1 are specialized transforming growth factor-beta (TGF-?) superfamily receptors, primarily expressed in endothelial cells. Mutations in the corresponding ENG or ACVRL1 genes lead to hereditary hemorrhagic telangiectasia (HHT1 and HHT2 respectively). To discover proteins interacting with endoglin, ACVRL1 and TGF-? receptor type 2 and involved in TGF-? signaling, we applied LUMIER, a high-throughput mammalian interactome mapping technology. Using stringent criteria, we identified 181 novel unique and shared interactions with ACVRL1, TGF-? receptor type 2, and endoglin, defining potential novel important vascular networks. In particular, the regulatory subunit B-beta of the protein phosphatase PP2A (PPP2R2B) interacted with all three receptors. Interestingly, the PPP2R2B gene lies in an interval in linkage disequilibrium with HHT3, for which the gene remains unidentified. We show that PPP2R2B protein interacts with the ACVRL1/TGFBR2/endoglin complex and recruits PP2A to nitric oxide synthase 3 (NOS3). Endoglin overexpression in endothelial cells inhibits the association of PPP2R2B with NOS3, whereas endoglin-deficient cells show enhanced PP2A-NOS3 interaction and lower levels of endogenous NOS3 Serine 1177 phosphorylation. Our data suggest that endoglin regulates NOS3 activation status by regulating PPP2R2B access to NOS3, and that PPP2R2B might be the HHT3 gene. Furthermore, endoglin and ACVRL1 contribute to several novel networks, including TGF-? dependent and independent ones, critical for vascular function and potentially defective in HHT. PMID:24319055

  11. Delayed Activin A administration attenuates tissue death after transient focal cerebral ischemia and is associated with decreased stress-responsive kinase activation

    PubMed Central

    Mukerji, Shibani S.; Rainey, Riley N.; Rhodes, Jamie L.; Hall, Alison K.

    2009-01-01

    Focal cerebral ischemia and reperfusion initiates complex cellular and molecular interactions that lead to either cell repair or destruction. In earlier work, we found that Activin A is an early gene response to cerebral ischemia and supports cortical neuron survival in vitro. In this study, the ability of exogenous activin A to attenuate injury from transient middle cerebral artery occlusion (MCAO) was tested in adult mice. Intracerebroventricular administration of activin A prior to MCAO reduced infarct volume apparent one day after experimental stroke. A single Activin A administration at 6 hr following ischemia/reperfusion reduced lesion volumes at 1 and 3 days and led to improved neurobehavior. Moreover, activin A treatment spared neurons within the ischemic hemisphere and led to a concomitant reduction in microglial activation. Activation of the stress-responsive kinases p38 and c-Jun N-terminal kinase implicated in neuronal apoptosis after stroke was reduced following activin A treatment. Together these findings suggest that activin A promotes tissue survival after focal cerebral ischemia/reperfusion with an extended therapeutic window. PMID:19780899

  12. 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

  13. 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

  14. 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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  16. Dynamic Changes in the Intrafollicular Inhibin\\/Activin\\/ Follistatin Axis during Human Follicular Development: Relationship to Circulating Hormone Concentrations

    Microsoft Academic Search

    ALAN L. SCHNEYER; TOSHIHIRO FUJIWARA; JANIS FOX; CORRINE K. WELT; JUDITH ADAMS; GERALYN M. MESSERLIAN; ANN E. TAYLOR

    Previous studies of normal human ovaries suggest that inhibins, activins, and follistatin (FS) are produced in a stage-specific pattern indicative of intraovarian, autocrine\\/paracrine roles in regulating follicle development. However, these studies relied largely on surgical specimens and thus include little information about the menstrual cycle stage or dominant follicle status at the time follicles or ovaries were obtained. The purpose

  17. Inhibition of transforming growth factor-? via the activin receptor-like kinase-5 inhibitor attenuates pulmonary fibrosis.

    PubMed

    Koh, Rhun Yian; Lim, Chooi Ling; Uhal, Bruce David; Abdullah, Maha; Vidyadaran, Sharmili; Ho, Coy Choke; Seow, Heng Fong

    2015-05-01

    Idiopathic pulmonary fibrosis is a chronic pulmonary disease that is characterized by formation of scar tissue in lungs. Transforming growth factor-? (TGF-?) is considered an important cytokine in the pathogenesis of this disease. Hence, the antifibrotic effect of an inhibitor of the TGF-? type I receptor, namely, SB 431542, was investigated in our study. SB 431542 was used to treat TGF-?-treated IMR-90 cells; the expression of ?-smooth muscle actin (?-SMA) was detected at the protein level by using an anti-?-SMA antibody, and at the gene level by reverse transcription-quantitative PCR. The effect of the inhibitor on cell proliferation was determined by a cell growth assay. The inhibitor was also administered into bleomycin-treated mice. Histopathological assessment and determination of total collagen levels were carried out to evaluate the severity of lung fibrosis in these mice. Our results demonstrated that treatment with SB 431542 inhi-bits TGF-??induced ?-SMA expression in lung fibroblasts, at both the protein and the mRNA levels (P<0.05). However, the inhibitor did not significantly reduce lung fibroblast proliferation. In the bleomycin-induced pulmonary fibrosis mouse model, bleomycin treatment caused important morphological changes, accompanied by an increase in the collagen level of the lungs. Early treatment with SB 431542 prevented the manifestation of histopathological alterations, whereas delayed treatment significantly decreased the collagen level (P<0.05). These results suggest that inhibition of TGF-? signaling, via inhibition of the activin receptor-like kinase-5 (ALK-5) by SB 431542, may attenuate pulmonary fibrosis. PMID:25585520

  18. 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 ...

  19. Androgen Regulates Follicle-Stimulating Hormone ? Gene Expression in an Activin-Dependent Manner in Immortalized Gonadotropes

    PubMed Central

    SPADY, THOMAS J.; SHAYYA, RANA; THACKRAY, VARYKINA G.; EHRENSBERGER, LISA; BAILEY, JANICE S.; MELLON, PAMELA L.

    2010-01-01

    Little is known about the molecular mechanisms of androgen regulation of the FSH? gene; however, studies suggest that it consists of a complex feedback loop that involves multiple mechanisms acting at both the level of the hypothalamus and the pituitary. In the present study, we address androgen regulation of the FSH? gene in immortalized gonadotrope cells and investigate the roles of activin and GnRH in androgen action. Using transient transfection assays in the FSH?-expressing mouse gonadotrope cell line, L?T2, we demonstrate that androgens stimulate expression of an ovine FSH? reporter gene in a dose-dependent manner. Mutation of either of two conserved androgen response elements at ?245/?231 and ?153/?139 within the proximal region of the ovine FSH? gene promoter abolishes this stimulation, and androgen receptor binds directly to the ?244 ARE in vitro. Androgen induction of the FSH? reporter gene is also dependent upon the activin autocrine loop present in the L?T2 cells, as well as an activin-response element at ?138/?124 of the FSH? gene. However, activin regulation of other genes remains unaffected by androgens. In addition, androgens stimulate expression of a mouse GnRH receptor reporter gene, and thus may indirectly augment the response of the FSH? gene to GnRH. Taken together, these data demonstrate that, in mouse gonadotropes, androgens act directly on the ovine FSH? gene to stimulate expression by a mechanism that is dependent upon activin, as well as acting indirectly, potentially through a second mechanism that may be dependent upon induction of GnRH receptor. PMID:14701939

  20. Soluble vs. insoluble fiber

    MedlinePLUS

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

  1. 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

  2. Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals with Mycobacterium avium Complex Disease

    PubMed Central

    Havlir, Diane V.; Torriani, Francesca J.; Schrier, Rachel D.; Huang, Jimmy Y.; Lederman, Michael M.; Chervenak, Keith A.; Boom, W. Henry

    2001-01-01

    To characterize changes in serum cytokine levels in human immunodeficiency virus type 1 (HIV-1)-infected persons with Mycobacterium avium complex (MAC) bacteremia, the levels of IL-1? (interleukin-1?), IL-6, IL-10, tumor necrosis factor alpha (TNF-?), soluble type II TNF receptor (sTNF-RII), and transforming growth factor ? (TGF-?) in serum were measured in two cohorts of HIV-1-infected persons with MAC bacteremia. The first cohort was part of a MAC prophylaxis study. Patients with bacteremia were matched with controls without bacteremia. Elevated IL-6, IL-10, TNF-?, sTNF-RII, and TGF-? levels were noted at baseline for all subjects, a result consistent with advanced HIV-1 disease. IL-1? was not detected. No differences in cytokine levels in serum were noted at baseline and at the time of bacteremia between patients with MAC and controls. In the second cohort, subjects had serum samples collected at the time of MAC bacteremia and thereafter while on macrolide therapy. Serum samples at time of bacteremia were collected from HIV-1-infected persons at a time when neither highly active antiretroviral therapy (HAART) nor MAC prophylaxis was used routinely. MAC treatment resulted in decreased levels of IL-6 and TNF-? in serum, which were evident for IL-6 by 4 to 6 weeks and for TNF-? by 8 to 16 weeks. Thus, antibiotic treatment for MAC results in decreased levels of IL-6 and TNF-? in serum in HIV-1-infected persons who are not on HAART. PMID:11136787

  3. Macrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile.

    PubMed

    Soler Palacios, Blanca; Estrada-Capetillo, Lizbeth; Izquierdo, Elena; Criado, Gabriel; Nieto, Concha; Municio, Cristina; González-Alvaro, Isidoro; Sánchez-Mateos, Paloma; Pablos, Jose Luis; Corbí, Angel L; Puig-Kröger, Amaya

    2015-02-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease whose pathogenesis and severity correlates with the presence of macrophage-derived pro-inflammatory cytokines within the inflamed synovium. Macrophage-derived cytokines fuel the pathological processes in RA and are targets of clinically successful therapies. However, although macrophage polarization determines cytokine production, the polarization state of macrophages in RA joints remains poorly defined. To dissect the molecular basis for the tissue-damaging effects of macrophages in RA joints, we undertook the phenotypic and transcriptomic characterization of ex vivo isolated CD14(+) RA synovial fluid (RA-SF) macrophages. Flow cytometry and gene profiling indicated that RA-SF macrophages express pro-inflammatory polarization markers (MMP12, EGLN3, CCR2), lack expression of markers associated with homeostatic and anti-inflammatory polarization (IGF1, HTR2B) and exhibit a transcriptomic profile that resembles the activin A-dependent gene signature of pro-inflammatory in vitro-generated macrophages. In fact, high levels of Smad-activating activin A were found in RA-SF and, accordingly, the Smad signalling pathway was activated in ex vivo-isolated RA-SF macrophages. In vitro experiments on monocytes and macrophages indicated that RA-SF promoted the acquisition of pro-inflammatory markers (INHBA, MMP12, EGLN3, CCR2) but led to a significant reduction in the expression of genes associated with homeostasis and inflammation resolution (FOLR2, SERPINB2, IGF1, CD36), thus confirming the pro-inflammatory polarization ability of RA-SF. Importantly, the macrophage-polarizing ability of RA-SF was inhibited by an anti-activin A-neutralizing antibody, thus demonstrating that activin A mediates the pro-inflammatory macrophage-polarizing ability of RA-SF. Moreover, and in line with these findings, multicolour immunofluorescence evidenced that macrophages within RA synovial membranes (RA-SM) also express pro-inflammatory polarization markers whose expression is activin A-dependent. Altogether, our results demonstrate that macrophages from RA synovial fluids and membranes exhibit an MMP12(+) EGLN3(+) CCR2(+) pro-inflammatory polarization state whose acquisition is partly dependent on activin A from the synovial fluid. PMID:25319955

  4. Activin A is essential for Feeder-free culture of human induced pluripotent stem cells.

    PubMed

    Tomizawa, Minoru; Shinozaki, Fuminobu; Sugiyama, Takao; Yamamoto, Shigenori; Sueishi, Makoto; Yoshida, Takanobu

    2013-03-01

    Feeder-free culture of human induced pluripotent stem (hiPS) cells is necessary for their clinical application to avoid adverse effects of foreign proteins. hiPS cells were cultured with combinations of activin (A), CHIR99021 (C), basic fibroblast growth factor (F), and leukemia inhibitory factor (L) under feeder-free conditions. Culture was terminated after 12 passages or when the cell morphology changed from pluripotency. Pluripotency was analyzed by alkaline phosphatase (ALP) staining and immunostaining with antibodies to Oct3/4, Nanog, SSEA4, and TRA-1-60. SB431542 (SB), an activin inhibitor, was added to the culture, and the morphology of the cells was observed. hiPS cells cultured with A, AC, and ACL after 12 passages were positive for ALP staining. Oct3/4 was positive in hiPS cells cultured with A, AC, and ACL. hiPS cells were positive for Nanog when cultured with A and AC; however, Nanog signal was weaker in cells cultured with ACL. SSEA4 was positive in hiPS cells cultured with A and AC but almost negative in those cultured with ACL. hiPS cells were positive for TRA-1-60 when cultured with A, AC, and ACL. hiPS cells lose their undifferentiated morphology at six passages when cultured with A + SB, five passages with AC + SB, and nine passages with ACL. We conclude that feeder-free culture of hiPS cells requires A or AC to maintain pluripotency. PMID:22991093

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

    E-print Network

    Mayo, Kelly E.

    of the anterior pituitary gland. Here, we identified the gene encoding the steroidogenic enzyme, 17b by primary pituitary cell cultures (Ling et al. 1986a,b, Vale et al. 1986). The ligands were subsequently to the pituitary as they play important pleiotropic roles in a variety of tissues during development

  6. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

    PubMed Central

    Yu, Y; Hanssen, KF; Kalyanaraman, V; Chirindel, A; Jenkins, AJ; Nankervis, AJ; Torjesen, PA; Scholz, H; Henriksen, T; Lorentzen, B; Garg, SK; Menard, MK; Hammad, SM; Scardo, JA; Stanley, JR; Wu, M; Basu, A; Aston, CE; Lyons, TJ

    2014-01-01

    Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), N?-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE : hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE : AGE and sRAGE : CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. PMID:22900949

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

    Microsoft Academic Search

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

    2001-01-01

    OBJECTIVEPeripheral 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.METHODSHeparinised blood was

  8. The activin binding proteins follistatin and follistatin-related protein are differentially regulated in vitro and during cutaneous wound repair.

    PubMed

    Wankell, M; Kaesler, S; Zhang, Y Q; Florence, C; Werner, S; Duan, R

    2001-12-01

    Follistatin is a secreted protein that binds activin in vitro and in vivo and thereby inhibits its biological functions. Recently, related human and murine genes, designated follistatin-related gene (FLRG), were identified, and their products were shown to bind activin with high affinity. In this study we further characterized the murine FLRG protein, and we analyzed its tissue-specific expression and regulation in comparison with those of follistatin. Transient expression of the mouse FLRG protein in COS-1 cells revealed that the FLRG cDNA encodes a secreted glycoprotein. FLRG mRNA was expressed at high levels in the lung, the testis, the uterus and, particularly, the skin. Immunohistochemistry revealed the presence of FLRG in the basement membrane between the dermis and the epidermis and around blood vessels. FLRG mRNA expression was induced in keratinocytes by keratinocyte growth factor, epidermal growth factor and transforming growth factor-beta 1, and in fibroblasts by platelet-derived growth factor and epidermal growth factor. The induction was more rapid, but weaker, than that of follistatin. Most interestingly, both follistatin and FLRG were expressed during the wound healing process, but their distribution within the wound was different. The different expression pattern of FLRG and follistatin and their differential regulation suggest different functions of these activin-binding proteins in vivo. PMID:11739004

  9. 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

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

    PubMed Central

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

    2015-01-01

    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

  12. Antisense-Oligonucleotide Mediated Exon Skipping in Activin-Receptor-Like Kinase 2: Inhibiting the Receptor That Is Overactive in Fibrodysplasia Ossificans Progressiva

    PubMed Central

    de Gorter, David J. J.; Sanchez-Duffhues, Gonzalo; Kemaladewi, Dwi U.; Hoogaars, Willem M. H.; Aartsma-Rus, Annemieke; ’t Hoen, Peter A. C.; ten Dijke, Peter

    2013-01-01

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

  13. Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells

    PubMed Central

    McTavish, Kirsten J.; Nonis, David; Hoang, Yvonne D.; Shimasaki, Shunichi

    2013-01-01

    A single somatic FOXL2 mutation (FOXL2C134W) was identified in almost all granulosa cell tumor (GCT) patients. In the pituitary, FOXL2 and Smad3 coordinately regulate activin stimulation of follistatin transcription. We explored whether a similar regulation occurs in the ovary, and whether FOXL2C134W has altered activity. We show that in primary granulosa cells, GDF-9 and activin increase Smad3-mediated follistatin transcription. In contrast to findings in the pituitary, FOXL2 negatively regulates GDF-9 and activin-stimulated follistatin transcription in the ovary. Knockdown of endogenous FOXL2 confirmed this inhibitory role. FOXL2C134W displayed enhanced inhibitory activity, completely ablating GDF-9 and activin-induced follistatin transcription. GDF-9 and activin activity was lost when either the smad binding element or the forkhead binding element were mutated, indicating that both sites are required for Smad3 actions. This study highlights that FOXL2 negatively regulates follistatin expression within the ovary, and that the pathogenesis of FOXL2C134W may involve an altered interaction with Smad3. PMID:23567549

  14. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    PubMed Central

    Silva, R.N.; Bueno, P.G.; Avó, L.R.S.; Nonaka, K.O.; Selistre-Araújo, H.S.; Leal, A.M.O.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-? superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin ?A subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved. PMID:25075578

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

    SciTech Connect

    Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org; Tewari, Shruti, E-mail: stewari@tcmedc.org; Atamna, Wafa, E-mail: watamna@tcmedc.org; Lazarova, Darina L., E-mail: dlazarova@tcmedc.org

    2011-06-10

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

  16. APPLICATIONS OF SOLUBLE DIETARY FIBERS IN BEVERAGES APLICACIONES DE LA FIBRA DIETETICA SOLUBLE EN BEBIDAS

    Microsoft Academic Search

    C. I. Beristain; F. Cruz-Sosa; C. Lobato-Calleros; R. Pedroza-Islas; M. E. Rodríguez; J. R. Verde-Calvo

    In this work the importance of soluble dietary fibers in the human diet is discussed. Traditional and new sources of soluble dietary fiber are mentioned, and a description of how to apply them in different types of beverages such as energy drinks, sport drinks, carbonated beverages and protein-based beverages in order to achieve enhanced functional properties is given.

  17. The structure-activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels.

    PubMed

    Yamamoto, Takashi; Niwa, Seiji; Ohno, Seiji; Tokumasu, Munetaka; Masuzawa, Yoko; Nakanishi, Chika; Nakajo, Akira; Onishi, Tomoyuki; Koganei, Hajime; Fujita, Shin-Ichi; Takeda, Tomoko; Kito, Morikazu; Ono, Yukitsugu; Saitou, Yuki; Takahara, Akira; Iwata, Seinosuke; Shoji, Masataka

    2008-09-01

    In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708. PMID:18684623

  18. Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration.

    PubMed

    Tsugawa, Daisuke; Oya, Yuki; Masuzaki, Ryota; Ray, Kevin; Engers, Darren W; Dib, Martin; Do, Nhue; Kuramitsu, Kaori; Ho, Karen; Frist, Audrey; Yu, Paul B; Bloch, Kenneth D; Lindsley, Craig W; Hopkins, Corey R; Hong, Charles C; Karp, Seth J

    2014-12-01

    Pharmacologic agents to enhance liver regeneration after injury would have wide therapeutic application. Based on previous work suggesting inhibition of bone morphogenetic protein (BMP) signaling stimulates liver regeneration, we tested known and novel BMP inhibitors for their ability to accelerate regeneration in a partial hepatectomy (PH) model. Compounds were produced based on the 3,6-disubstituted pyrazolo[1,5-a] pyrimidine core of the BMP antagonist dorsomorphin and evaluated for their ability to inhibit BMP signaling and enhance liver regeneration. Antagonists of the BMP receptor activin receptor-like kinase 3 (ALK3), including LDN-193189 (LDN; 4-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline), DMH2 (4-(2-(4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine; VU0364849), and the novel compound VU0465350 (7-(4-isopropoxyphenyl)-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine; VU5350), blocked SMAD phosphorylation in vitro and in vivo, and enhanced liver regeneration after PH. In contrast, an antagonist of the BMP receptor ALK2, VU0469381 (5-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinolone; 1LWY), did not affect liver regeneration. LDN did not affect liver synthetic or metabolic function. Mechanistically, LDN increased serum interleukin-6 levels and signal transducer and activator of transcription 3 phosphorylation in the liver, and modulated other factors known to be important for liver regeneration, including suppressor of cytokine signaling 3 and p53. These findings suggest that inhibition of ALK3 may be part of a therapeutic strategy for treating human liver disease. PMID:25271257

  19. Circulating levels of urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR) in patients with atopic eczema/dermatitis syndrome.

    PubMed

    Kasperska-Zajac, Alicja; Rogala, Barbara

    2005-04-01

    Accumulating evidence has indicated that different immune and inflammatory processes may be accompanied by up-regulation of the uPA/uPAR system. Moreover, it has been suggested that the fibrinolytic system participates actively in immune-mediated skin disorders, including atopic eczema/dermatitis syndrome (AEDS). To study a possible role of such uPA/uPAR system in AEDS, we investigated circulating levels of uPA and suPAR in patients at different clinical stages of AEDS. Levels of u-PA and suPAR were measured by enzyme-linked immunoassay in plasma from 13 patients (five females and eight males; median age 27 years) with moderate AEDS, eight patients (three females and five males; median age 25.5 years) with severe AEDS, and 18 age- and sex-matched healthy subjects. Plasma levels of uPA and suPAR in AEDS patients did not differ significantly when compared with those in healthy subjects. Moreover, we failed to observe any significant differences in levels of these components between patients with moderate and severe AEDS and the controls. It seems that plasma levels of uPA and suPAR are similar in patients at the different stages of AEDS and the healthy subjects. Moreover, these data suggest that the release of uPA and its soluble receptor into the bloodstream is not increased in the course of complex immune-mediated processes associated with AEDS. PMID:16858643

  20. Bone morphogenetic protein 2 stimulates noncanonical SMAD2/3 signaling via the BMP type 1A receptor in gonadotrope-like cells: implications for FSH synthesis.

    PubMed

    Wang, Ying; Ho, Catherine C; Bang, EunJin; Rejon, Carlis A; Libasci, Vanessa; Pertchenko, Pavel; Hébert, Terence E; Bernard, Daniel J

    2014-05-01

    FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGF? superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its ?-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like L?T2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells. PMID:24601881

  1. 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…

  2. Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development.

    PubMed Central

    Johansson, B M; Wiles, M V

    1995-01-01

    Xenopus in vitro studies have implicated both transforming growth factor beta (TGF-beta) and fibroblast growth factor (FGF) families in mesoderm induction. Although members of both families are present during mouse mesoderm formation, there is little evidence for their functional role in mesoderm induction. We show that mouse embryonic stem cells, which resemble primitive ectoderm, can differentiate to mesoderm in vitro in a chemically defined medium (CDM) in the absence of fetal bovine serum. In CDM, this differentiation is responsive to TGF-beta family members in a concentration-dependent manner, with activin A mediating the formation of dorsoanterior-like mesoderm and bone morphogenetic protein 4 mediating the formation of ventral mesoderm, including hematopoietic precursors. These effects are not observed in CDM alone or when TGF-beta 1, -beta 2, or -beta 3, acid FGF, or basic FGF is added individually to CDM. In vivo, at day 6.5 of mouse development, activin beta A RNA is detectable in the decidua and bone morphogenetic protein 4 RNA is detectable in the egg cylinder. Together, our data strongly implicate the TGF-beta family in mammalian mesoderm development and hematopoietic cell formation. PMID:7799920

  3. Assessment of Biomarkers of Cardiovascular Risk Among HIV Type 1-Infected Adolescents: Role of Soluble Vascular Cell Adhesion Molecule As an Early Indicator of Endothelial Inflammation

    PubMed Central

    Syed, Salma S.; Balluz, Rula S.; Kabagambe, Edmond K.; Meyer, William A.; Lukas, Susan; Wilson, Craig M.; Kapogiannis, Bill G.; Nachman, Sharon A.

    2013-01-01

    Abstract Cardiovascular disease (CVD) biomarkers were examined in a cohort of HIV-infected and HIV-uninfected adolescents who participated in Adolescent Trials Network study 083 utilizing samples from the Reaching for Excellence in Adolescent Care cohort, a longitudinal study of youth infected through adult risk behavior. Nonfasting blood samples from 97 HIV-infected and 81 HIV-uninfected adolescents infected by adult risk behaviors were analyzed for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglycerides, apolipoprotein A-I, high-sensitivity C-reactive protein (hsCRP), soluble vascular adhesion molecule-1 (sVCAM-1), myeloperoxidase, and neopterin at baseline and 18 months later. Results were analyzed using ANOVA, Wilcoxon signed-rank, and paired t tests. Among infected subjects 67 received antiretroviral therapy and 30 were treatment naive. The HIV-infected and HIV-uninfected subjects were similar in gender, ethnicity, and cardiovascular risk factors such as smoking and obesity. In all groups lipid parameters were within accepted guidelines for cardiovascular risk. Among HIV-infected youth on antiretroviral therapy (ART), HDL and apoprotein A-I were significantly lower when compared to uninfected youth. hsCRP was not elevated and thus not predictive for risk in any group. sVCAM-1 levels were significantly elevated in both HIV-infected groups: 1,435?ng/ml and 1,492?ng/ml in untreated and treated subjects, respectively, and 1,064?ng/ml in the uninfected group (p<0.0001). Across all groups neopterin correlated with sVCAM at 18 months (Spearman correlation coefficient 0.58, p<0.0001). Only 9% of ART-treated subjects fully suppressed virus. Lipid profiles and hsCRP, traditional markers of cardiovascular disease, are not abnormal among HIV-infected youth but elevated sVCAM may be an early marker of atherosclerosis. PMID:23062187

  4. 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.

  5. 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

    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

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

    EPA Science Inventory

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

  7. 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

  8. 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

  9. Effect of the interaction of heat-processing style and fat type on the micellarization of lipid-soluble pigments from green and red pungent peppers (Capsicum annuum).

    PubMed

    Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús; Yahia, Elhadi M; Failla, Mark L

    2013-04-17

    The high diversity of carotenoids and chlorophylls in foods contrasts with the reduced number of pigments that typically are investigated in micellarization studies. In this study, pepper samples (raw and heat-treated) contained 68 individual pigments, but only 38 of them were micellarized after in vitro digestion. The micellarization of pigments was majorly determined by the interaction effect of processing style (food matrix effect) and fat type (saturated and unsaturated). The highest micellarization was observed with raw peppers. Unsaturated fat increased the micellarization of carotenoid esters, while the impact of fat on the micellarization of free carotenoids seemed to be dependent on pigment structure. The micellarization efficiency was diminished as the esterification level of carotenoids increased. The type of fatty acid moiety and the polarity of the carotenoids modulated their micellarization. Chlorophylls were transformed into pheophytins by heat-processing and digestion, with the pheophytins being stable under gastrointestinal conditions. Micellarization of pheophytins was improved by fat. PMID:23517119

  10. Impaired Angiogenesis Following Hindlimb Ischemia in Type 2 Diabetes Mellitus Differential Regulation of Vascular Endothelial Growth Factor Receptor 1 and Soluble VEGFR-1

    Microsoft Academic Search

    Surovi Hazarika; Ayotunde O. Dokun; Yongjun Li; Aleksander S. Popel; Christopher D. Kontos; Brian H. Annex

    Deficient angiogenesis following ischemia may contribute to worse outcomes of peripheral arterial disease in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) and its receptors promote angiogenesis. We hypothesized that in peripheral arterial disease, maladaptive changes in VEGF ligand\\/receptor expression could account for impaired angiogenesis in DM. Skeletal muscle from diet-induced, type 2 diabetic (DM) and age-matched normal

  11. Impaired Angiogenesis After Hindlimb Ischemia in Type 2 Diabetes Mellitus Differential Regulation of Vascular Endothelial Growth Factor Receptor 1 and Soluble Vascular Endothelial Growth Factor Receptor 1

    Microsoft Academic Search

    Surovi Hazarika; Ayotunde O. Dokun; Yongjun Li; Aleksander S. Popel; Christopher D. Kontos; Brian H. Annex

    Deficient angiogenesis after ischemia may contribute to worse outcomes of peripheral arterial disease in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) and its receptors promote angiogenesis. We hypothesized that in peripheral arterial disease, maladaptive changes in VEGF ligand\\/receptor expression could account for impaired angiogenesis in DM. Skeletal muscle from diet-induced, type 2 diabetic (DM) and age-matched normal

  12. Learning about solubility.

    PubMed

    Salinas, Dino G; Reyes, Juan G

    2015-01-01

    Qualitative questions are proposed to assess the understanding of solubility and some of its applications. To improve those results, a simple quantitative problem on the precipitation of proteins is proposed. PMID:25395353

  13. Solubility of Organic Compounds

    ERIC Educational Resources Information Center

    James, K. C.

    1972-01-01

    Outlines factors to be considered in choosing suitable solvents for non-electrolytes and salts of weak acids and bases. Describes how, in some simple situation, the degree of solubility can be estimated. (Author/DF)

  14. Protein solubility modeling.

    PubMed

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

    1999-07-20

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

  15. Learning about Solubility

    ERIC Educational Resources Information Center

    Salinas, Dino G.; Reyes, Juan G.

    2015-01-01

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

  16. Protein solubility modeling

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  17. Detection of a latent soluble form of membrane type 1 matrix metalloprotease bound with tissue inhibitor of matrix metalloproteinases-2 in periprosthetic tissues and fluids from loose arthroplasty endoprostheses.

    PubMed

    Niarakis, Anna; Giannopoulou, Eleftheria; Ravazoula, Panagiota; Panagiotopoulos, Elias; Zarkadis, Ioannis K; Aletras, Alexios J

    2013-12-01

    Membrane type 1 matrix metalloproteinase (MT1-MMP) is implicated in pericellular proteolysis, and, together with tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), in the activation of pro-matrix metalloproteinase-2 on the cell surface. It is expressed on the cell surface either activated or as a proenzyme. A soluble form of MT1-MMP (sMT1-MMP) has been previously identified in periprosthetic tissues and fluid of patients with loose arthroplasty endoprostheses. The aim of this study was to examine periprosthetic tissues and fluids from patients with loose arthroplasty endoprostheses, as well as tissues and fluids from patients with other disorders, for the presence of sMT1-MMP, and to investigate its activation state and possible role. With antibody against MT1-MMP, a protein with molecular mass of ~ 57 kDa was detected by western blotting in all samples tested, representing a soluble form of MT1-MMP, which cannot be ascribed to alternative splicing, as northern blotting showed only one transcript. With various biochemical methods, it was shown that this species occurs in a latent form bearing the N-terminal prodomain, and, additionally, it is bound to TIMP-2, which appeared to be bound via its C-terminal domain to a site different from the active site. Cell ELISA and immunohistochemical analysis revealed that, besides fibroblasts, all other cells, such as inflammatory, epithelial, endothelial, giant and cancer cells, express MT1-MMP on their plasma membrane as a proenzyme. Taking into account the proteolytic abilities of MT1-MMP, the latent sMT1-MMP-TIMP-2 complex could be considered as a new interstitial collagenase. However, the exact role, the production mechanism and the cell origin of this complex remain to be elucidated. PMID:24112707

  18. The basic residues of placenta growth factor type 2 retrieve sequestered angiogenic factors into a soluble form: implications for tumor angiogenesis.

    PubMed Central

    Barillari, G.; Albonici, L.; Franzese, O.; Modesti, A.; Liberati, F.; Barillari, P.; Ensoli, B.; Manzari, V.; Santeusanio, G.

    1998-01-01

    Placenta growth factor type 1 (PIGF-1) can be synthesized by neoplastic cells in an alternative form (PIGF-2) by the addition of basic amino acids to its classic sequence. Here we show that the basic residues of PIGF-2 compete for the binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to heparan sulfate proteoglycans of the cell surface and extracellular matrix. In doing so, PIGF-2 basic sequences inhibit the sequestering of VEGF and bFGF and maintain them in a highly diffusible form, thus enhancing their angiogenic effect. In agreement with these in vitro data, the presence of PIGF-2 transcripts in tumors correlates with their blood vessel number. These results suggest a mechanism by which growth factor isoforms produced by neoplastic cells enhance the formation of new blood vessels supporting tumor growth and progression. Images Figure 1 Figure 3 PMID:9588884

  19. Efficient Derivation of Alveolar Type II Cells from Embryonic Stem Cells for In Vivo Application

    PubMed Central

    Roszell, Blair; Mondrinos, Mark J.; Seaton, Ariel; Simons, Donald M.; Koutzaki, Sirma H.; Fong, Guo-Hua

    2009-01-01

    In the present study, mouse embryonic stem cells (ESCs) were differentiated into alveolar epithelial type II (AEII) cells for endotracheal injection. These enriched lung-like populations expressed lung epithelial markers SP-A, SP-B, SP-C, and CC10. First we show that rapid differentiation of ESCs requires a dissociated seeding method instead of an embryoid body culture method. We then investigated a two-step differentiation of ESCs into definitive endoderm by activin or A549-conditioned medium as a precursor to lung epithelial cells. When conditioned medium from A549 cells was used to derive endoderm, yield was increased above that of activin alone. Further studies showed that Wnt3a may be one of the secreted factors produced by A549 cells and promotes definitive endoderm differentiation, in part, through suppression of primitive endoderm. Activin and Wnt3a together at appropriate doses with dissociated cell seeding promoted greater endoderm yield than activin alone. Next, fibroblast growth factor 2 was shown to induce a dose-dependent expression of SPC, and these cells contained lamellar bodies characteristic of mature AEII cells from ESC-derived endoderm. Finally, ES-derived lung cells were endotracheally injected into preterm mice with evidence of AEII distribution within the lung parenchyma. This study concludes that a recapitulation of development may enhance derivation of an enriched population of lung-like cells for use in cell-based therapy. PMID:19388834

  20. Hydrothermal solubility of uraninite

    NASA Astrophysics Data System (ADS)

    Parks, George A.; Pohl, Demetrius C.

    1988-04-01

    The solubility of UO 2 has been measured at temperatures from 100° to 300°C under 50 MPa H 2 in water solutions of HCl, NaOH, or LiOH at calculated pH values from 1 to 10. Fluoride contamination invalidated results in the pH range 2 to 4 and is probably responsible for a solubility maximum observed near pH = 3. At pH < 2, solubilities at 200°C and below agree, within combined experimental error, with measurements by NIKOLAEVA and PIROZKHOV (1978) and BRUNOet al. (1986a), and fall well within the range selected for amorphous and crystalline UO 2 by WOLER (1983). pH dependence suggests predominance of UOH 3+. Solubilities in alkaline media are much lower than measured or estimated by previous investigators at all temperatures, suggesting that the U(OH) -5 complex is very weak or non-existent and does not contribute to solubility significantly at any pH < 10. There are no published measurements of the solubility of UO 2 in the neutral pH range at subcritical temperatures. Existing thermodynamic data for the expected hydroxo complexes, U(OH) 4-nn ( n = 2, 3, 4), are estimated ( WOLER, 1983; LEMIRE and TREMAINE, 1980; LANGMUIR, 1978). When pH = 4 to 8, our measured solubilities are up to three orders of magnitude lower than calculated on the basis of the estimated thermodynamic data for temperatures exceeding 200°C, and up to two orders higher than predicted at lower temperatures. Temperature and pH dependence are statistically insignificant in the experimental results for all pH4, suggesting predominance of the single species U(OH) 4(aq), and the dissolution reaction. UO2 + 2 H2O = U( OH) 4( aq) for which, at all temperatures from 100° to 300°C, log ( Ks4 ) = -9.47 ± 0.3.

  1. Cyclic changes in messenger RNAs encoding inhibin/activin subunits in the ovary of the golden hamster (Mesocricetus auratus).

    PubMed

    Arai, Koji Y; Kishi, Hisashi; Onodera, Satoshi; Jin, Wanzhu; Watanabe, Gen; Suzuki, Akira K; Takahashi, Shinji; Kamada, Toshihiko; Nishiyama, Toshio; Taya, Kazuyoshi

    2005-06-01

    To elucidate changing patterns of inhibin/activin subunit mRNAs in the ovary of the golden hamster (Mesocricetus auratus) during the oestrous cycle, inhibin/activin subunit cDNAs of this species were cloned and ribonuclease protection assay and in situ hybridization were carried out. Inhibin alpha-subunit mRNA was localized in granulosa cells of primary, secondary, tertiary and atretic follicles throughout the 4-day oestrous cycle. It was also expressed in luteal cells on days 1 (oestrus), 2 (metoestrus) and 3 (dioestrus). betaA-subunit mRNA was localized in granulosa cells of large secondary (>200 microm) and tertiary follicles throughout the oestrous cycle. betaB-subunit mRNA was confined to granulosa cells of large secondary and tertiary follicles. Both alpha- and betaA-subunit mRNAs were also found in ovarian interstitial cells and theca interna cells of tertiary and atretic follicles in the evening of day 4 (pro-oestrus). A striking increase in betaA-subunit mRNA levels was also observed during the preovulatory period. The expression pattern of betaA-subunit mRNA during the preovulatory period is unique and not found in other species. An i.v. injection of anti-luteinizing hormone-releasing hormone (LHRH) serum before the LH surge abolished the expression of alpha- and betaA-subunit mRNAs in ovarian interstitial cells and theca interna cells. The treatment also abolished the preovulatory increase in betaA-subunit mRNA. Furthermore, administration of human chorionic gonadotrophin (hCG), which followed the injection of anti-LHRH serum, restored the expression patterns of alpha- and betaA-subunit mRNAs. The present study revealed that the golden hamster showed a unique expression pattern of betaA-subunit mRNA in response to the LH surge. PMID:15930182

  2. Water solubility in aluminosilicate melts

    Microsoft Academic Search

    Paul F. McMillan; John R. Holloway

    1987-01-01

    We have compiled water solubility data for a wide range of natural and synthetic aluminosilicate melts in a search for correlations between melt composition and solubility. The published data reveal some interesting systematics. For example, molar water solubility increases with decreasing silica content in binary and pseudobinary silicates, and much higher solubilities are associated with alkali systems compared to alkaline

  3. Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor.

    PubMed Central

    Fernandez-Catalan, C; Bode, W; Huber, R; Turk, D; Calvete, J J; Lichte, A; Tschesche, H; Maskos, K

    1998-01-01

    The proteolytic activity of matrix metalloproteinases (MMPs) towards extracellular matrix components is held in check by the tissue inhibitors of metalloproteinases (TIMPs). The binary complex of TIMP-2 and membrane-type-1 MMP (MT1-MMP) forms a cell surface located 'receptor' involved in pro-MMP-2 activation. We have solved the 2.75 A crystal structure of the complex between the catalytic domain of human MT1-MMP (cdMT1-MMP) and bovine TIMP-2. In comparison with our previously determined MMP-3-TIMP-1 complex, both proteins are considerably tilted to one another and show new features. CdMT1-MMP, apart from exhibiting the classical MMP fold, displays two large insertions remote from the active-site cleft that might be important for interaction with macromolecular substrates. The TIMP-2 polypeptide chain, as in TIMP-1, folds into a continuous wedge; the A-B edge loop is much more elongated and tilted, however, wrapping around the S-loop and the beta-sheet rim of the MT1-MMP. In addition, both C-terminal edge loops make more interactions with the target enzyme. The C-terminal acidic tail of TIMP-2 is disordered but might adopt a defined structure upon binding to pro-MMP-2; the Ser2 side-chain of TIMP-2 extends into the voluminous S1' specificity pocket of cdMT1-MMP, with its Ogamma pointing towards the carboxylate of the catalytic Glu240. The lower affinity of TIMP-1 for MT1-MMP compared with TIMP-2 might be explained by a reduced number of favourable interactions. PMID:9724659

  4. Enhancing Dopant Solubility via Epitaxial Surfactant Growth

    SciTech Connect

    Zhang, L.; Yan, Y.; Wei, S.-H.

    2009-01-01

    A general concept for enhancing dopant solubility via epitaxial surfactant growth is proposed. The key of the concept is to find the appropriate surfactants that generate high (low) levels that can transfer electrons (holes) to dopant acceptor (donor) levels in p-type (n-type) doping, thus significantly lowering the formation energy of dopants. Using first-principles density-functional calculations, our concept explains excellently the recently discovered dual-surfactant effect of Sb and H on enhancing Zn doping in epitaxially grown GaP(100) thin film and suggests that sole surfactant Te can also induce enhancement of N solubility in ZnSe(100) film. We also proposed the surfactants for enhancing p-type doing of ZnO with epitaxial growth with (000{bar 1}) surface. General rules for selecting surfactants for enhancing both p-type and n-type dopings are provided.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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…

  10. Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures.

    PubMed

    Fowler, Tristan W; Kamalakar, Archana; Akel, Nisreen S; Kurten, Richard C; Suva, Larry J; Gaddy, Dana

    2015-02-15

    The process of osteoclastic bone resorption is complex and regulated at multiple levels. The role of osteoclast (OCL) fusion and motility in bone resorption are unclear, with the movement of OCL on bone largely unexplored. RANKL (also known as TNFSF11) is a potent stimulator of murine osteoclastogenesis, and activin A (ActA) enhances that stimulation in whole bone marrow. ActA treatment does not induce osteoclastogenesis in stroma-free murine bone marrow macrophage cultures (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized that ActA and RANKL differentially regulate osteoclastogenesis by modulating OCL precursors and mature OCL migration. Time-lapse video microscopy measured ActA and RANKL effects on BMM and OCL motility and function. ActA completely inhibited RANKL-stimulated OCL motility, differentiation and bone resorption, through a mechanism mediated by ActA-dependent changes in SMAD2, AKT1 and inhibitor of nuclear factor ?B (I?B) signaling. The potent and dominant inhibitory effect of ActA was associated with decreased OCL lifespan because ActA significantly increased activated caspase-3 in mature OCL and OCL precursors. Collectively, these data demonstrate a dual action for ActA on murine OCLs. PMID:25609708

  11. Differential effect of Activin A and WNT3a on definitive endoderm differentiation on electrospun nanofibrous PCL scaffold.

    PubMed

    Hoveizi, Elham; Massumi, Mohammad; Ebrahimi-Barough, Somayeh; Tavakol, Shima; Ai, Jafar

    2015-05-01

    The first step in the formation of hepatocytes and beta cells is the generation of definitive endoderm (DE) which involves a central issue in developmental biology. Human induced pluripotent stem cells (hiPSCs) have the pluripotency to differentiate into all three germ layers in vitro and have been considered potent candidates for regenerative medicine as an unlimited source of cells for therapeutic applications. In this study, we investigated the differentiating potential of hiPSCs on poly (?-caprolactone) (PCL) nanofibrous scaffold into DE cells. Here, we demonstrate directed differentiation of hiPSCs by factors such as Activin A and Wnt3a. The differentiation was determined by immunofluoresence staining with Sox17, FoxA2 and Goosecoid (Gsc) and also by qRT-PCR analysis. The results of this study showed that hiPSCs, as a new cell source, have the ability to differentiate into DE cells with a high capacity and also demonstrate that three dimension (3D) culture provides a suitable nanoenviroment for growth, proliferation and differentiation of hiPSCs. PCL nanofibrous scaffold with essential supplements, stimulating factors and EB-derived cells is able to provide a novel method for enhancing functional differentiation of hiPSCs into DE cells. PMID:25640312

  12. Thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery.

    PubMed

    Sutariya, Vijaykumar; Miladore, Nicholas; Geldenhuys, Werner; Bhatia, Deepak; Wehrung, Daniel; Nakamura, Hiroshi

    2013-01-01

    The purpose of this study is to investigate a thermoreversible gel using Pluronic F-127 to deliver an activin receptor-like kinase 5 (ALK-5) inhibitor SB-505124 in glaucoma filtration surgery (GFS). The gel was characterized for in vitro drug release and viscosity studies. Cytotoxicity of Pluronic F-127 was examined by MTT assay using cultured rabbit subconjunctival fibroblasts. In addition, Pluronic F-127 gel (18% w/v) containing 5 mg of SB-505124 was applied at the surgical site in an in vivo rabbit GFS model. In the in vitro viscosity study, the gel showed a change in viscosity (from 1000 cps to 45,000 cps) from low temperature (10°C) to body temperature (37°C). The in vitro drug release study demonstrated 100% drug release within 12 h. The gel did not show cytotoxicity to the cultured rabbit subconjunctival cells by MTT assay. In the in vivo rabbit GFS model, the drug was successfully delivered by injection and no severe post-surgical complications were observed. A thermoreversible gel system with SB-505124 was successfully prepared and delivered for the rabbit GFS model, and it may provide a novel delivery system in GFS. PMID:22206499

  13. An experimental study on gold solubility in amino acid solution and its geological significance

    Microsoft Academic Search

    Zhang Jingrong; Lu Jianjun; Yang Fan; Wu Jingwei; Zhu Fahua

    1996-01-01

    The experiments on gold solubility in amino acid solution indicate that gold is very intensively soluble in amino acid (or\\u000a other organic acids), which is extensively present in geological bodies, and is most soluble in histidine. The temperature\\u000a and concentration, acidity and type of amino acid in the solution are important factors affecting gold-amino acid complexing.\\u000a The solubility of gold

  14. 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

    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

  15. 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

  16. Hydrogen adsorption on and solubility in graphites

    Microsoft Academic Search

    S. L. Kanashenko; A. E. Gorodetsky; V. N. Chernikov; A. V. Markin; A. P. Zakharov

    1995-01-01

    The experimental data on sorption and solubility of hydrogen isotopes in graphite in a wide ranges of temperature and pressure are reviewed. The Langmuir type adsorption is proposed for the hydrogen -- graphites interaction with taking into account dangling sp²-bonds relaxation. Three kinds of traps are proposed: Carbon interstitial loops with the adsorption enthalpy of -4.4 eV\\/Hâ (Traps l); carbon

  17. 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.

  18. 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.

  19. 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

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

    E-print Network

    Mayo, Kelly E.

    of estrogen action in the early mouse ovary. (Endocrinology 148: 1968­1976, 2007) OVARIAN FOLLICLE DEVELOPMENT involves interactions be- tween multiple cell types within the ovary. Factors produced by ovarian granulosa cells (10, 11). The importance of estrogen in ovarian follicle development and maturation has been

  1. Computer Simulations of Salt Solubility

    NSDL National Science Digital Library

    Computer Simulations of Salt Solubility provides an animated, visual interpretation of the different solubilities of related salts based on simple entropy changes associated with dissolution: configurational disorder and thermal disorder. This animation can also help improve students conceptual understanding of chemical equilibrium before any quantitative interpretation of equilibrium constants is attempted.

  2. The Ksp-Solubility Conundrum.

    ERIC Educational Resources Information Center

    Clark, Roy W.; Bonicamp, Judith M.

    1998-01-01

    Argues that there are only a few cases in which solubility and Ksp are related in a simple way. States that illustrations of the solubility product principle for one-to-one salts are adequate for students. Contains 23 references. (DDR)

  3. Recombinant soluble adenovirus receptor

    DOEpatents

    Freimuth, Paul I. (East Setauket, NY)

    2002-01-01

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

  4. 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...

  5. Discovery of 7-methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole (TASP0382088): a potent and selective transforming growth factor-? type I receptor inhibitor as a topical drug for alopecia.

    PubMed

    Amada, Hideaki; Asanuma, Hajime; Koami, Takeshi; Okada, Atsushi; Endo, Mayumi; Ueda, Yasuji; Naruse, Takumi; Ikeda, Akiko

    2013-01-01

    7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-? (TGF-?) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitor. Compound 11, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50=4.8?nM) as well as inhibitory activity against TGF-?-induced Smad2/3 phosphorylation at a cellular level (IC50=17?nM). The introduction of a methoxy group to the benzothiazole ring in 1 and the break up of the planarity between the imidazole ring and the thiazole ring improved the solubility in the lotion base of 11. Furthermore, the topical application of 3% 11 lotion significantly inhibited Smad2 phosphorylation in mouse skin at 8?h after application (71% inhibition, compared with vehicle-treated animals). PMID:23449197

  6. 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%.

  7. 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%.

  8. 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%.

  9. 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.

  10. Thermodynamics of chromium in UO2 fuel: A solubility model

    NASA Astrophysics Data System (ADS)

    Riglet-Martial, Ch.; Martin, Ph.; Testemale, D.; Sabathier-Devals, C.; Carlot, G.; Matheron, P.; Iltis, X.; Pasquet, U.; Valot, C.; Delafoy, C.; Largenton, R.

    2014-04-01

    The solubility and speciation of chromium in doped uranium oxide are measured in carefully controlled temperature and oxygen potential conditions using electron probe microanalysis (EPMA) and scanning electron spectroscopy (SEM). The examination of the samples by X-ray Absorption Spectroscopy (XAS) provides evidence that (i) chromium is soluble in the UO2 matrix under the +3 oxidation state only regardless of the sintering conditions which is in accordance with a soluble species of type CrO3/2 and (ii) soluble chromium exhibits octahedral symmetry with 6 atoms of oxygen forming CrO6 patterns in the UO2 structure. In consistency with all available experimental information including previously published data, the solubility of chromium in UO2 corresponding to each two-phase field with either Cr, CrO and Cr2O3 may be described in the ranges 1500 °C < T < 2000 °C and -460 < ?O2 < -360 kJ/mol using the standard thermodynamic equations governing solubility equilibria. The characteristic parameters of the solubility laws in UO2 for the three chromium phases are derived.

  11. 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.

  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. Tough, Soluble, Aromatic, Thermoplastic Copolyimides

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    1998-01-01

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

  14. Method for enhancing the solubility of dopants in silicon

    DOEpatents

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

    2003-09-30

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

  15. Isolation of an Arabidopsis thaliana Mutant, mto1, That Overaccumulates Soluble Methionine (Temporal and Spatial Patterns of Soluble Methionine Accumulation).

    PubMed Central

    Inaba, K.; Fujiwara, T.; Hayashi, H.; Chino, M.; Komeda, Y.; Naito, S.

    1994-01-01

    We isolated Arabidopsis thaliana mutants that are resistant to ethionine, a toxic analog of methionine (Met). One of the mutants was analyzed further, and it accumulated 10- to 40-fold more soluble Met than the wild type in the aerial parts during the vegetative growth period. When the mutant plants started to flower, however, the soluble Met content in the rosette region decreased to the wild-type level, whereas that in the inflorescence apex region and in immature fruits was 5- to 8-fold higher than the wild type. These results indicate that the concentration of soluble Met is temporally and spatially regulated and suggest that soluble Met is translocated to sink organs after the onset of reproductive growth. The causal mutation, designated mto1, was a single, nuclear, semidominant mutation and mapped to chromosome 3. Accumulation profiles of soluble amino acids suggested that the mutation affects a later step(s) in the Met biosynthesis pathway. Ethylene production of the mutants was only 40% higher than the wild-type plants, indicating that ethylene production is tightly regulated at a step after Met synthesis. This mutant will be useful in studying the translocation of amino acids, as well as regulation of Met biosynthesis and other metabolic pathways related to Met. PMID:12232133

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

    NASA Astrophysics Data System (ADS)

    Buck, C. S.; Paytan, A.

    2009-12-01

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

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

    Microsoft Academic Search

    Hui Yin; Bao-jun Huang; Heng Yang; Ya-fei Huang; Ping Xiong; Fang Zheng; Xiao-ping Chen; Yi-fa Chen; Fei-li Gong

    2006-01-01

    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

  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. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy

    PubMed Central

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

    2015-01-01

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

  20. Preliminary considerations concerning actinide solubilities

    SciTech Connect

    Newton, T.W.; Bayhurst, B.P.; Daniels, W.R.; Erdal, B.R.; Ogard, A.E.

    1980-01-01

    Work at the Los Alamos Scientific Laboratory on the fundamental solution chemistry of the actinides has thus far been confined to preliminary considerations of the problems involved in developing an understanding of the precipitation and dissolution behavior of actinide compounds under environmental conditions. Attempts have been made to calculate solubility as a function of Eh and pH using the appropriate thermodynamic data; results have been presented in terms of contour maps showing lines of constant solubility as a function of Eh and pH. Possible methods of control of the redox potential of rock-groundwater systems by the use of Eh buffers (redox couples) is presented.

  1. Thorium oxalate solubility and morphology

    SciTech Connect

    Monson, P.R. Jr.; Hall, R.

    1981-10-01

    Thorium was used as a stand-in for studying the solubility and precipitation of neptunium and plutonium oxalates. Thorium oxalate solubility was determined over a range of 0.001 to 10.0 in the concentration parameter (H/sub 2/C/sub 2/O/sub 4/)/(HNO/sub 3/)/sup 2/. Morphology of thorium oxide made from the oxalate precipitates was characterized by scanning electron microscopy. The different morphologies found for oxalate-lean and oxalate-rich precipitations were in agreement with predictions based on precipitation theory.

  2. 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-

  3. RESEARCH PAPER Soluble epoxide hydrolase

    E-print Network

    Hammock, Bruce D.

    -induced cardiac hypertrophy Hassan N Althurwi1 , Mandy MY Tse1 , Ghada Abdelhamid1 , Beshay NM Zordoky1 , Bruce D@ualberta.ca ---------------------------------------------------------------- Keywords Isoprenaline (isoproterenol); cardiac hypertrophy; cytochrome P450; soluble epoxide hydrolase that isoprenaline-induced cardiac hypertrophy causes significant changes in the expression of cytochromes P450 (CYP

  4. Soluble NSF-attachment proteins

    Microsoft Academic Search

    Gudrun Stenbeck

    1998-01-01

    Soluble NSF-attachement proteins (SNAPs) are highly conserved proteins that participate in intracellular membrane fusion and vesicular trafficking. In mammals, there are three different isoforms of SNAPs, ?-, ?- and ?-SNAP. ?- and ?-SNAP are ubiquitously expressed, whereas ?-SNAP is the brain-specific isoform. SNAPs recruit NSF to the membrane after being bound to specific membrane receptors termed SNAREs. NSF, SNAPs and

  5. [Molecular cloning of the DNA sequence of activin beta A subunit gene mature peptides from panda and related species and its application in the research of phylogeny and taxonomy].

    PubMed

    Wang, Xiao-Jing; Wang, Xiao-Xing; Wang, Ya-Jun; Wang, Xi-Zhong; He, Guang-Xin; Chen, Hong-Wei; Fei, Li-Song

    2002-09-01

    Activin, which is included in the transforming growth factor-beta (TGF beta) superfamily of proteins and receptors, is known to have broad-ranging effects in the creatures. The mature peptide of beta A subunit of this gene, one of the most highly conserved sequence, can elevate the basal secretion of follicle-stimulating hormone (FSH) in the pituitary and FSH is pivotal to organism's reproduction. Reproduction block is one of the main reasons which cause giant panda to extinct. The sequence of Activin beta A subunit gene mature peptides has been successfully amplified from giant panda, red panda and malayan sun bear's genomic DNA by using polymerase chain reaction (PCR) with a pair of degenerate primers. The PCR products were cloned into the vector pBlueScript+ of Esherichia coli. Sequence analysis of Activin beta A subunit gene mature peptides shows that the length of this gene segment is the same (359 bp) and there is no intron in all three species. The sequence encodes a peptide of 119 amino acid residues. The homology comparison demonstrates 93.9% DNA homology and 99% homology in amino acid among these three species. Both GenBank blast search result and restriction enzyme map reveal that the sequences of Activin beta A subunit gene mature peptides of different species are highly conserved during the evolution process. Phylogeny analysis is performed with PHYLIP software package. A consistent phylogeny tree has been drawn with three different methods. The software analysis outcome accords with the academic view that giant panda has a closer relationship to the malayan sun bear than the red panda. Giant panda should be grouped into the bear family (Uersidae) with the malayan sun bear. As to the red panda, it would be better that this animal be grouped into the unique family (red panda family) because of great difference between the red panda and the bears (Uersidae). PMID:12561224

  6. Protection from Fas-Mediated Apoptosis by a Soluble Form of the Fas Molecule

    Microsoft Academic Search

    Jianhua Cheng; Tong Zhou; Changdan Liu; John P. Shapiro; Matthew J. Brauer; Michael C. Kiefer; Philip J. Barr; John D. Mountz

    1994-01-01

    Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. Molecular cloning and nucleotide sequence analysis revealed a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain because of the deletion of an exon encoding this region. The expression of soluble Fas was confirmed by flow cytometry and

  7. Pinpoint-fluorinated phenacenes: new synthesis and solubility enhancement strategies.

    PubMed

    Fuchibe, Kohei; Morikawa, Toshiyuki; Shigeno, Kento; Fujita, Takeshi; Ichikawa, Junji

    2015-03-01

    The Pd(II)-catalyzed cyclizations of 2,2-difluorovinylated biaryls, following a Friedel-Crafts-type mechanism, provide a new route to pinpoint-fluorinated phenacenes. The single fluorine substituent stabilized the synthesized fluoropicenes (fluoro[5]phenacenes) toward aerial oxidation and contributed to their solubility in organic solvents. For example, 6- and 13-fluoropicenes were 25- and 15-fold more soluble in THF than nonfluorinated picene. X-ray crystal structure analysis revealed that the fluorine substituent did not alter molecular planarity. PMID:25686405

  8. Soluble adenylyl cyclase of sea urchin spermatozoa.

    PubMed

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

    2014-12-01

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

  9. A "SOLUBLE SPECIFIC SUBSTANCE" DERIVED FROM GUM ARABIC

    PubMed Central

    Heidelberger, Michael; Avery, Oswald T.; Goebel, Walther F.

    1929-01-01

    1. By partial acid hydrolysis a specific carbohydrate may be isolated from gum arabic (gum acacia). This carbohydrate is comparable in its precipitating activity for Type II (and Type III) antipneumococcus serum with the bacterial soluble specific substances themselves. 2. On hydrolysis this fraction yields galactose and two or more complex sugar acids, one of which appears to be a disaccharide add comparable with those isolated from the specific polysaccharides of the Type III pneumococcus and the Type A Friedländer bacillus. 3. The significance of these findings is discussed. PMID:19869586

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

    E-print Network

    Lecara, Grace

    1980-01-01

    COCCIOIOIDES IMMITIS VACCINE: POTENTIAL OF AN ALKALI-SOLUBLE, WATER-SOLUBLE CEI. L WALL ANTIGEN A Thesis by GRACE LECARA Aporoved as to style and content by: (Chairman of Committee) (Member) (Member) (Member) (Head of Department) August l...930 ABSTRACT Coccidioides immitis Vaccine: Potential of an Alkali- Soluble, Water-Soluble Cell Wall Antigen. (August 1980) Grace Lecara, B. A. , M. T. , Trinity University Chairman of Advisory Committee: Dr. R. B. Simpson An alkali-soluble, water...

  11. GATA6 Promotes Angiogenic Function and Survival in Endothelial Cells by Suppression of Autocrine Transforming Growth Factor ?/Activin Receptor-like Kinase 5 Signaling*

    PubMed Central

    Froese, Natali; Kattih, Badder; Breitbart, Astrid; Grund, Andrea; Geffers, Robert; Molkentin, Jeffery D.; Kispert, Andreas; Wollert, Kai C.; Drexler, Helmut; Heineke, Joerg

    2011-01-01

    Understanding the transcriptional regulation of angiogenesis could lead to the identification of novel therapeutic targets. We showed here that the transcription factor GATA6 is expressed in different human primary endothelial cells as well as in vascular endothelial cells of mice in vivo. Activation of endothelial cells was associated with GATA6 nuclear translocation, chromatin binding, and enhanced GATA6-dependent transcriptional activation. siRNA-mediated down-regulation of GATA6 after growth factor stimulation led to a dramatically reduced capacity of macro- and microvascular endothelial cells to proliferate, migrate, or form capillary-like structures on Matrigel. Adenoviral overexpression of GATA6 in turn enhanced angiogenic function, especially in cardiac endothelial microvascular cells. Furthermore, GATA6 protected endothelial cells from undergoing apoptosis during growth factor deprivation. Mechanistically, down-regulation of GATA6 in endothelial cells led to increased expression of transforming growth factor (TGF) ?1 and TGF?2, whereas enhanced GATA6 expression, accordingly, suppressed Tgfb1 promoter activity. High TGF?1/?2 expression in GATA6-depleted endothelial cells increased the activation of the activin receptor-like kinase 5 (ALK5) and SMAD2, and suppression of this signaling axis by TGF? neutralizing antibody or ALK5 inhibition restored angiogenic function and survival in endothelial cells with reduced GATA6 expression. Together, these findings indicate that GATA6 plays a crucial role for endothelial cell function and survival, at least in part, by suppressing autocrine TGF? expression and ALK5-dependent signaling. PMID:21127043

  12. Incomplete solubility in nitride alloys

    SciTech Connect

    Ho, I.H.; Stringfellow, G.B. [Univ. of Utah, Salt Lake City, UT (United States). Dept. of Materials Science and Engineering

    1997-12-31

    A model based on the valence-force-field (VFF) model has been developed specifically for the calculation of the miscibility gaps in III-V nitride alloys. In the dilute limit, this model allows the relaxation of the atoms on both sublattices. It was found that the energy due to bond stretching and bond bending was lowered and the solubility limit was increased substantially when both sublattices were allowed to relax to distances as large as the sixth nearest neighbor positions. Using this model, the equilibrium mole fraction of N in GaP was calculated to be 6 {times} 10{sup {minus}7} at 700 C. This is slightly higher than the calculated results from the semi-empirical delta lattice parameter (DLP) model. Both the temperature dependence and the absolute values of the calculated solubility agree closely with the experimental data. The solubility is more than three orders of magnitude larger than the result obtained using the VFF model with the group V atom positions given by the virtual crystal approximation, i.e., with relaxation of only the first neighbor bonds. Other nitride systems, such as GaAsN, AlPN, AlAsN, InPN, and InAsN were investigated as well. The equilibrium mole fractions of nitrogen in InP and InAs are the highest, which agrees well with recent experimental data where high N concentrations have been produced in InAsN alloys. Calculations were also performed for the alloy systems with mixing on the group III sublattice that are so important for device applications. Allowing relaxation to the 3rd nearest neighbor gives an In solubility in GaN at 800 C of less than 6%. Again, this is in agreement with the results of the DLP model calculation. This result may partially explain the difficulties experienced with the growth of these alloys. Indeed, evidence of solid immiscibility has recently been reported. A significant miscibility gap was also calculated for the AlInN system, but the AlGaN system is completely miscible.

  13. 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

  14. Fusogenic activity of various water-soluble polymers

    Microsoft Academic Search

    Naoki Nakajima; Yoshito Ikada

    1995-01-01

    The fusogenic activity of seven water-soluble polymers was investigated using L929 cells in a monolayer state. Among these polymers, only two, poly(ethylene glycol) (PEG) and EPAN 680 were capable of inducing the membrane fusion of L929 cells. EPAN 680 is an ABA type block copolymer composed of 80% ethylene oxide(A) and 20% propylene oxide(B) sequences with a total molecular weight

  15. 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.

  16. Crosslinking of water-soluble polymers

    NASA Astrophysics Data System (ADS)

    Lei, Cuiyue

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

  17. 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

  18. 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

  19. 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)

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

    E-print Network

    Magee, Joseph W.

    IUPAC-NIST Solubility Data Series 70. Solubility of Gases in Glassy Polymers Volume Editors Russell Synthesis, Moscow, Russia Received December 11, 1998 Solubility of gases in polymers is an important in polymers is a fun- damental concern in such areas as food packaging, beverage storage, and polymer pro

  1. Soluble graphene derived from graphite fluoride

    Microsoft Academic Search

    Kimberly A. Worsley; Palanisamy Ramesh; Swadhin K. Mandal; Sandip Niyogi; Mikhail E. Itkis; Robert C. Haddon

    2007-01-01

    Soluble graphene layers were formed by reacting graphite fluoride with alkyl lithium reagents. IR spectral studies confirmed the covalent attachment of alkyl chains to the graphene layers. Raman scattering and XRD studies of the starting materials and products revealed that the chemical process partially restores the sp2 carbon network. The solubility and extinction coefficient were determined by UV–vis-near infrared spectroscopy.

  2. 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...

  3. Soluble guanylate cyclase: the forgotten sibling

    Microsoft Academic Search

    A. J. Hobbs

    1997-01-01

    Despite widespread distribution in most mammalian cells, the role of soluble guanylate cyclase has, until recently, been poorly defined, especially when compared with its more illustrious sibling, adenylate cylase. In this review Adrian Hobbs outlines some of the reasons why the soluble guanylate cyclase–cGMP pathway has remained outside the signalling spotlight for much of the past 30 years. He goes

  4. Water sorption and solubility of resin-based materials following inadequate polymerization by a visible-light curing system.

    PubMed

    Pearson, G J; Longman, C M

    1989-01-01

    The water sorption and solubility of three hybrid and one microfine composite are reported. The values obtained are dependent on composite type and resin system. Incomplete polymerization of the two materials resulted in increased solubility and sorption due to incomplete conversion of the monomer. The marked increased in both parameters will have clinical significance on the durability of the material. PMID:2526208

  5. Solubilities of Oligomer Mixtures Produced by the Hydrolysis of Xylans and Corn Stover in Water at 180 C

    E-print Network

    California at Riverside, University of

    that have greater solubility and dissolve as the chains decrease in length with reaction.5 However dissolution: reaction time, solids loading, and initial substrate type. Because long-chain oligomers predominate at short reaction times and solubility is expected to decrease with increasing chain length

  6. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum

    Microsoft Academic Search

    Seong-Kug Eo; Young-So Kim; Chong-Kil Lee; Seong-Sun Han

    1999-01-01

    In order to find antiviral substances from basidiomycetes, two water soluble substances, GLhw and GLlw, and eight methanol soluble substances, GLMe-1–8, were prepared from carpophores of Ganoderma lucidum. These substances were examined for their activities against five strains of pathogenic viruses such as herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), influenza A virus (Flu A) and vesicular stomatitis

  7. Solubilities of benzoin, propyl 4-hydroxybenzoate and mandelic acid in supercritical carbon dioxide

    Microsoft Academic Search

    Kong-Wei Cheng; Muoi Tang; Yan-Ping Chen

    2002-01-01

    A semi-flow type apparatus was used to measure the equilibrium solubilities of benzoin , propyl 4-hydroxybenzoate, and mandelic acid in supercritical carbon dioxide at 308.15, 318.15, and 328.15K over the pressure range from 9 to 24MPa. New equilibrium data of solid solubility in supercritical carbon dioxide are presented. The approach to solid–fluid phase equilibrium is examined based on a plug

  8. Soluble Thrombomodulin Protects Ischemic Kidneys

    PubMed Central

    Sharfuddin, Asif A.; Sandoval, Ruben M.; Berg, David T.; McDougal, Grant E.; Campos, Silvia B.; Phillips, Carrie L.; Jones, Bryan E.; Gupta, Akanksha; Grinnell, Brian W.; Molitoris, Bruce A.

    2009-01-01

    Altered coagulation and inflammation contribute to the pathogenesis of ischemic renal injury. Thrombomodulin is a necessary factor in the anticoagulant protein C pathway and has inherent anti-inflammatory properties. We studied the effect of soluble thrombomodulin (sTM) in a hypoperfusion model of ischemic kidney injury. To markedly reduce infrarenal aortic blood flow and femoral arterial pressures, we clamped the suprarenal aorta of rats, occluding them 90%, for 60 min. Reversible acute kidney injury (AKI) occurred at 24 h in rats subjected to hypoperfusion. Histologic analysis at 24 h revealed acute tubular necrosis (ATN), and intravital two-photon microscopy showed flow abnormalities in the microvasculature and defects of endothelial permeability. Pretreatment with rat sTM markedly reduced both I-R-induced renal dysfunction and tubular histologic injury scores. sTM also significantly improved microvascular erythrocyte flow rates, reduced microvascular endothelial leukocyte rolling and attachment, and minimized endothelial permeability to infused fluorescence dextrans, assessed by intravital quantitative multiphoton microscopy. Furthermore, sTM administered 2 h after reperfusion protected against ischemia-induced renal dysfunction at 24 h and improved survival. By using an sTM variant, we also determined that the protective effects of sTM were independent of its ability to generate activated protein C. These data suggest that sTM may have therapeutic potential for ischemic AKI. PMID:19176699

  9. Water-soluble conductive polymers

    DOEpatents

    Aldissi, M.

    1988-02-12

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

  10. Water-soluble conductive polymers

    DOEpatents

    Aldissi, Mahmoud (Sante Fe, NM)

    1990-01-01

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

  11. Water-soluble conductive polymers

    DOEpatents

    Aldissi, Mahmoud (Sante Fe, NM)

    1989-01-01

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

  12. Inverse correlation between baseline inhibin B and FSH after stimulation with GnRH: a study of serum levels of inhibin A and B, pro alpha-C and activin A in women with ovulatory disturbances before and after stimulation with GnRH

    Microsoft Academic Search

    Fritz W Casper; Rudolf J Seufert; Kunhard Pollow

    2000-01-01

    Objective: Interest has focused recently on the influences of the polypeptide factors inhibin and activin on the selective regulation of the pituitary secretion of gonadotropins. Design: Measurement of the concentrations of inhibin-related proteins in relation to the changes in pituitary gonadotropin (FSH, LH) parameters, after GnRH stimulation with a bolus injection of 100 mg gonadorelin, in 19 women with ovulatory

  13. Dengue and Soluble Mediators of the Innate Immune System

    PubMed Central

    Espada-Murao, Lyre Anni; Morita, Kouichi

    2011-01-01

    Huge emphasis has been placed on the role of the adaptive immune system in dengue pathogenesis. Yet there is increasing evidence for the importance of the innate immune system in regulating dengue infection and possibly influencing the disease. This review focuses on the interplay between the innate immune system and dengue and highlights the role of soluble immunological mediators. Type I and type II interferons of the innate immune system demonstrate non-overlapping roles in dengue infection. Furthermore, while some IFN responses to dengue are protective, others may exert disease-related effects on the host. But aside from interferons, a number of cytokines have also been implicated in dengue pathogenesis. Our expanding knowledge of cytokines indicates that these soluble mediators act upon a complicated network of events to provoke the disease. This cytokine storm is generally attributed to massive T cell activation as an outcome of secondary infection. However, there is reason to believe that innate immune response-derived cytokines also have contributory effects, especially in the context of severe cases of primary dengue infection. Another less popular but interesting perspective on dengue pathogenesis is the effect of mosquito feeding on host immune responses and viral infection. Various studies have shown that soluble factors from vector saliva have the capacity to alter immune reactions and thereby influence pathogen transmission and establishment. Hence, modulation of the innate immune system at various levels of infection is a critical component of dengue disease. In the absence of an approved drug or vaccine for dengue, soluble mediators of the innate immune system could be a strategic foothold for developing anti-viral therapeutics and improving clinical management. PMID:22500137

  14. Isolation, Screening and Characterization of Soluble Exopolymer-Producing Bacteria For Enhanced Oil Recovery

    Microsoft Academic Search

    Munirah Tharek; Zaharah Ibrahim; S. Hasila Hamzah; Noraha Markum; Aslizah Mohd Aris; Fareh Nunizawati Daud; Adibah Yahya; Liew Chong Wai; Nozieana Khairuddin; Rosli Illias; Mohamad Ismail Omar; Khor Siak Foo; Ezrin Johanna Elias

    Various types of bacteria isolated from samples of water-oil and palm oil mill effluents (POME) were screened for soluble exopolymers which has potential use in microbial enhanced oil recovery (MEOR) applications. The samples were collected from several Malaysian oil reservoirs and Sedenak palm oil mill. Based on the chemical analyses of the water-oil samples, 6 types of media (HAA, HAG,

  15. Solubility-Excipient Classification Gradient Maps

    Microsoft Academic Search

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

    2007-01-01

    Abstract  This study assessed the effect of excipients (sodium taurocholate, 2-hydroxypropyl-?-cyclodextrin, potassium chloride, propylene\\u000a glycol, 1-methyl-2-pyrrolidone, and polyethylene glycol 400) on the apparent intrinsic solubility properties of eight sparingly\\u000a soluble drugs (four bases, two neutrals, and two acids): astemizole, butacaine, clotrimazole, dipyridamole, griseofulvin,\\u000a progesterone, glibenclamide, and mefenemic acid. Over 1,200 UV-based solubility measurements (pH 3–10) were made with a high-throughput\\u000a instrument. New

  16. Water-soluble extracts from defatted sesame seed flour show antioxidant activity in vitro.

    PubMed

    Ben Othman, Sana; Katsuno, Nakako; Kanamaru, Yoshihiro; Yabe, Tomio

    2015-05-15

    Defatted white and gold sesame seed flour, recovered as a byproduct after sesame oil extraction, was extracted with 70% ethanol to obtain polar-soluble crude extracts. The in vitro antioxidant activity of the extract was evaluated by DPPH free radical scavenging activity and oxygen radical absorbing capacity (ORAC). The polar-soluble crude extracts of both sesame seed types exhibited good antioxidant capacity, especially by the ORAC method with 34,720 and 21,700 ?mol Trolox equivalent/100g of white and gold sesame seed extract, respectively. HPLC, butanol extraction, and UPLC-MS analyses showed that different compounds contributed to the antioxidant activity of the polar-soluble crude extracts. Sesaminol glycosides were identified in the butanol-soluble fractions; whereas, purified water-soluble fraction contained ferulic and vanillic acids. This study shows that hydrophilic antioxidants in the purified water-soluble fraction contributed to the antioxidant activity of white and gold sesame seed polar-soluble crude extracts. PMID:25577085

  17. 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)

    1991-09-09

    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. Heteropolyanions (HPAs) offer the opportunity to develop soluble forms of surface confined catalysts. HPAs are multi-functional catalysts that could be used to promote both hydroliquefaction and hydrotreating. In theory, these functions could be employed sequentially or simultaneously and could permit exceptional control of liquefaction reactions and reaction conditions. Thus, the current research program involves efforts to evaluate HPAs as soluble liquefaction nd hydrotreating catalysts, with the goal of developing soluble analogs of surface confined catalysts.

  18. ANALYSIS OF WATER-SOLUBLE ORGANICS

    EPA Science Inventory

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

  19. Acid soluble, pepsin resistant platelet aggregating material

    SciTech Connect

    Schneider, M.D.

    1982-08-31

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

  20. 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)

  1. The Solubility of Phenylborate Compounds in Benzene

    SciTech Connect

    Eibling, R.E. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1998-04-01

    The original goal of this scoping study was to determine if the solubility of sodium and potassium tetraphenylborates in benzene was sufficiently large to justify designing and performing kinetic studies on a benzene-phase catalytic reaction.

  2. Soluble high molecular weight polyimide resins

    NASA Technical Reports Server (NTRS)

    Jones, R. J.; Lubowitz, H. R.

    1970-01-01

    High molecular weight polyimide resins have greater than 20 percent /by weight/ solubility in polar organic solvents. They permit fabrication into films, fibers, coatings, reinforced composite, and adhesive product forms. Characterization properties for one typical polyimide resin are given.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  4. 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.

  5. Dihydroartemisinin-cyclodextrin complexation: Solubility and stability

    Microsoft Academic Search

    Muhammad Tayyab Ansari; Ijaz Iqbal; Vivian Bruce Sunderland

    2009-01-01

    Dihydroartemisinin (DHA) is a major metabolite of artemisinin and its derivatives, including arteether, artemether, and artesunate.\\u000a To improve the solubility and stability of poorly soluble DHA, we prepared inclusion complexes with hydroxypropyl-?-cyclodextrin\\u000a (HP?CD) and recrystalized DHA to study its thermal stability. The complexes were characterized by differential scanning calorimetery\\u000a (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), thermal

  6. GADOLINIUM SOLUBILITY AND VOLATILITY DURING DWPF PROCESSING

    SciTech Connect

    Reboul, S

    2008-01-30

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

  7. Solubility of Carbon in Silicon and Germanium

    Microsoft Academic Search

    R. I. Scace; G. A. Slack

    1959-01-01

    The solubility of carbon in silicon has been measured over the temperature range 1560 to 2900°C. The enthalpy of solution is 59±3 kcal\\/mole. A phase diagram for the system Si&sngbnd;C is presented, embodying these solubility data as well as the results of other high-temperature experiments with silicon carbide. It is found that SiC possesses a peritectic point at 2830±40°C. These

  8. 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

  9. Nanoemulsion: a promising tool for solubility and dissolution enhancement of celecoxib.

    PubMed

    Shakeel, Faiyaz; Faisal, Mohammed S

    2010-01-01

    The solubility and dissolution of the poorly soluble drug celecoxib (CXB) was enhanced using many techniques like nanoemulsion, solid lipid nanoparticle and solid dispersion in the present investigation. The solubility of CXB in each formulation was determined using the reported HPLC method at the wavelength of 250 nm. Dissolution studies of pure CXB and its formulations were performed using USP dissolution apparatus in distilled water. The highest solubility (228. 24 mg/mL) as well as % dissolution (99.9) of CXB was obtained with nanoemulsion technique. The results of solubility and dissolution were highly significant using the nanoemulsion technique as compared to other techniques (P < 0.01). All three formulations showed a sustained type of drug release. The best sustained type drug release was obtained with nanoemulsion. This indicated that nanoemulsion can be successfully used for sustained and controlled drug delivery of CXB. Overall these findings suggested that nanoemulsion is a promising vehicle for solubility and dissolution enhancement of CXB. PMID:19552546

  10. Influence of excipients on solubility and dissolution of pharmaceuticals.

    PubMed

    Paus, Raphael; Prudic, Anke; Ji, Yuanhui

    2015-05-15

    In this work, solubilities and dissolution profiles of the active pharmaceutical ingredients (APIs) indomethacin and naproxen were measured in water in the presence of one excipient out of polyethylene glycol (PEG) 2000, 6000 and 12000, polyvinylpyrrolidone (PVP) K 25 and mannitol. It was found that the solubility of indomethacin and naproxen was increased with an addition of the selected excipients, which was also predicted by the perturbed-chain statistical associating fluid theory (PC-SAFT). The two-step chemical-potential-gradient model was applied to investigate the dissolution mechanism of indomethacin and naproxen in water in the presence of the excipient. It was found that the dissolution mechanisms of indomethacin and naproxen were changed by the presence of excipients. Although the solubility of the API was increased by the addition of excipients, the dissolution rate of the API was decreased in some cases. This was mainly due to the combination of the molecular interactions between the API and the polymer with the influence of the excipients on the kinetic part (rate constant of the surface reaction or diffusion of the API or both) of API dissolution as function of PEG molar mass as well as of the API type. Based upon the determined rate constants, the dissolution profiles were modeled with a high accuracy compared with the experimental data. PMID:25749073

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

    PubMed Central

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

    2014-01-01

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

  12. Ammonia Solubility in High Concentration Salt Solutions

    SciTech Connect

    HEDENGREN, D.C.

    2000-02-01

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

  13. Sibutramine characterization and solubility, a theoretical study

    NASA Astrophysics Data System (ADS)

    Aceves-Hernández, Juan M.; Nicolás Vázquez, Inés; Hinojosa-Torres, Jaime; Penieres Carrillo, Guillermo; Arroyo Razo, Gabriel; Miranda Ruvalcaba, René

    2013-04-01

    Solubility data from sibutramine (SBA) in a family of alcohols were obtained at different temperatures. Sibutramine was characterized by using thermal analysis and X-ray diffraction technique. Solubility data were obtained by the saturation method. The van't Hoff equation was used to obtain the theoretical solubility values and the ideal solvent activity coefficient. No polymorphic phenomena were found from the X-ray diffraction analysis, even though this compound is a racemic mixture of (+) and (-) enantiomers. Theoretical calculations showed that the polarisable continuum model was able to reproduce the solubility and stability of sibutramine molecule in gas phase, water and a family of alcohols at B3LYP/6-311++G (d,p) level of theory. Dielectric constant, dipolar moment and solubility in water values as physical parameters were used in those theoretical calculations for explaining that behavior. Experimental and theoretical results were compared and good agreement was obtained. Sibutramine solubility increased from methanol to 1-octanol in theoretical and experimental results.

  14. Solubility of uranium in alkaline salt solutions

    SciTech Connect

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

    1994-03-29

    The solubility of uranium in alkaline salt solutions was investigated to screen for significant factors and interactions among the major salt components and temperature. The components included in the study were the sodium salts of hydroxide, nitrate, nitrite, aluminate, sulfate, and carbonate. General findings from the study included: (1) uranium solubilities are very low (1-20 mg/L) for all solution compositions at hydroxide concentrations from 0.1 to 17 molar (2) carbonate, sulfate, and aluminate are not effective complexants for uranium at high hydroxide concentration, (3) uranium solubility decreases with increasing temperature for most alkaline salt solutions, and (4) uranium solubility increases with changes in solution chemistry that reflect aging of high level waste (increase in nitrite and carbonate concentrations, decrease in nitrate and hydroxide concentrations). A predictive model for the concentration of uranium as a function of component concentrations and temperature was fitted to the data. All of the solution components and temperature were found to be significant. There is a significant lack of fit for the model, which suggests that the dependence on the uranium solubility over the wide range of solution compositions is non-linear and/or that there are other uncontrolled parameters which are important to the uranium solubility.

  15. Biological activities of water-soluble fullerene derivatives

    NASA Astrophysics Data System (ADS)

    Nakamura, S.; Mashino, T.

    2009-04-01

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

  16. Evaluation of Water Soluble and No-Clean Solder Pastes with Palladium Plated and Solder Plated SMT Devices Understanding what factors influence performance of these new technology pastes in reflow processes

    Microsoft Academic Search

    Douglas Romm; Neil McLellan

    In response to increasing environmental concern over the use of chlorofluorocarbons (CFC's) to clean printed circuit assemblies, many surface mount operations are converting to water soluble or no-clean type solder pastes. Current trends indicate that this conversion will progress rapidly until water soluble and no-clean pastes constitute the majority of the product mix. With the introduction of water soluble and

  17. 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.

  18. 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.

  19. 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, the level of Casol and Psol, as mmol·kg-1 , increased and the pH decreased as the milk concentration as the milk concentration was increased. At any given milk concentration, the level of Casol, Psol and milk pH

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

    PubMed Central

    Sareen, Swati; Mathew, George; Joseph, Lincy

    2012-01-01

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

  1. 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.

  2. Diffusion and solubility of oxygen in silver

    NASA Technical Reports Server (NTRS)

    Eichenauer, W.; Miller, G.

    1985-01-01

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

  3. Respiratory carcinogenicity assessment of soluble nickel compounds.

    PubMed Central

    Oller, Adriana R

    2002-01-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided. PMID:12426143

  4. Chemical characterization of extractable water soluble matter associated with PM10 from Mexico City during 2000.

    PubMed

    Gutiérrez-Castillo, M E; Olivos-Ortiz, M; De Vizcaya-Ruiz, A; Cebrián, M E

    2005-11-01

    We report the chemical composition of PM10-associated water-soluble species in Mexico City during the second semester of 2000. PM10 samples were collected at four ambient air quality monitoring sites in Mexico City. We determined soluble ions (chloride, nitrate, sulfate, ammonium, sodium, potassium), ionizable transition metals (Zn, Fe, Ti, Pb, Mn, V, Ni, Cr, Cu) and soluble protein. The higher PM(10) levels were observed in Xalostoc (45-174 microg m(-3)) and the lowest in Pedregal (19-54 microg m(-3)). The highest SO2 average concentrations were observed in Tlalnepantla, NO2 in Merced and O3 and NO(x) in Pedregal. The concentration range of soluble sulfate was 6.7-7.9 and 19-25.5 microg m(-3) for ammonium, and 14.8-29.19 for soluble V and 3.2-7.7 ng m(-3) for Ni, suggesting a higher contribution of combustion sources. PM-associated soluble protein levels varied between 0.038 and 0.169 mg m(-3), representing a readily inhalable constituent that could contribute to adverse outcomes. The higher levels for most parameters studied were observed during the cold dry season, particularly in December. A richer content of soluble metals was observed when they were expressed by mass/mass units rather than by air volume units. Significant correlations between Ni-V, Ni-SO4(-2), V-SO4(-2), V-SO2, Ni-SO2 suggest the same type of emission source. The variable soluble metal and ion concentrations were strongly influenced by the seasonal meteoclimatic conditions and the differential contribution of emission sources. Our data support the idea that PM10 mass concentration by itself does not provide a clear understanding of a local PM air pollution problem. PMID:15893788

  5. Nitrogen solubility in upper mantle minerals

    NASA Astrophysics Data System (ADS)

    Li, Yuan; Wiedenbeck, Michael; Shcheka, Svyatoslav; Keppler, Hans

    2013-09-01

    Nitrogen solubility in the upper mantle minerals forsterite, diopside, enstatite and pyrope has been quantified by SIMS measurements of nitrogen-saturated, synthetic samples. The crystals were grown in a 15N-H-O fluid buffered by Ni-NiO, Co-CoO, and Fe-FeO, at 1000-1300?°C and 15-35 kbar in a piston cylinder apparatus. Nitrogen solubility in minerals is significantly affected by temperature, pressure, mineral composition and, in particular, by oxygen fugacity. Nitrogen in all crystals buffered by Ni-NiO or Co-CoO is below detection limit or at most a few ?g/g at very high pressures. Concentrations of 5-24 ?g/g nitrogen have been quantified in diopside, enstatite and pyrope buffered by Fe-FeO at 1100?°C/15 kbar. Very high nitrogen solubility up to 100 ?g/g is observed at the Fe-FeO buffer in enstatite at high-temperature or in Al-bearing enstatite and diopside. The nitrogen solubility in forsterite at the Fe-FeO buffer also clearly increases with temperature and pressure; a maximum solubility of 10 ppm is obtained at 1300?°C/35 kbar. The strong enhancement of nitrogen solubility under reducing conditions may be related to nitrogen dissolution as either NH+4 or as N3- directly replacing O2-. Both mechanisms require some charge compensation, consistent with the enhancement of nitrogen solubility with Al content in enstatite. Our results demonstrate that the reduced lower part of the upper mantle has a large nitrogen storage capacity, and may store ˜20-50 times more nitrogen than the present atmosphere. Therefore, some 'missing' nitrogen may still be retained in the Earth's deep, reduced mantle. The calculated nitrogen partition coefficients between upper mantle minerals and silicate melt reveal that an oxidized mantle source would lose almost its entire nitrogen during partial melting, whereas under reducing conditions a considerable fraction of nitrogen could be retained in the residual solids. The high nitrogen solubility in upper mantle minerals at reducing conditions also suggests that solidification of the magma ocean on the early Earth should have retained significant nitrogen, yielding higher N/Ar and N/C ratios in the young upper mantle as compared to the young atmosphere.

  6. Three solutions of the protein solubility problem.

    PubMed Central

    Jenkins, W. T.

    1998-01-01

    Three simple equations are presented, which describe the variation of protein solubility (S) with changes in salt concentration, in terms of either the salt molality (M), the salt activity (ax), or the water activity (aw). Each equation yields, essentially independent, estimates of the numbers of salt ions (delta vx) and water molecules (delta vw) involved in the dissolution of a mol of the protein. The equations can be used to elucidate the physical significance of the parameters in other empirical equations for protein solubility. PMID:9521114

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Barney, G.S.

    1996-09-30

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

  9. How does aqueous solubility of organic reactant affect a water-promoted reaction?

    PubMed

    Zuo, Yi-Jie; Qu, Jin

    2014-08-01

    It was widely reported that under the "on water" condition, various water-promoted organic reactions can proceed with very high speed. Thus, it is considered that the aqueous solubility of reactant is not an important issue in these reactions. Three types of water-promoted organic reactions were investigated in the current study to distinguish whether the reaction rate of an aqueous reaction was affected by the aqueous solubilities of the reactants. The results showed that, for a Diels-Alder reaction which was fast under the neat conditions, the aqueous solubilities of reactants had little influence on the reaction. However, for the reactions which proceeded slowly under the neat conditions, such as [2?+2?+2?] cycloaddition reactions and epoxide aminolysis reactions, the reactants with good aqueous solubilities proceeded fast in water. Poorly aqueous soluble reactants reacted slowly or did not react under the "on water" condition, and an appropriate amount of organic cosolvent was needed to make the reaction become efficient. This evidence suggested that for these two types of reactions, the dissolution of the reactants in water was required. PMID:25000435

  10. 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.

  11. 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...

  12. Factors controlling the solubility of aerosol trace metals in the atmosphere and on mixing into seawater

    Microsoft Academic Search

    Lucinda J. Spokes; Tim D. Jickells

    1995-01-01

    Previous work has shown that the type and pH history of an aerosol governs trace metal solubility in rainwater. This study concentrates on the crustal elements Al, Fe and Mn and identifies additional processes which affect dissolution not only in the atmosphere but also on mixing into seawater. Aerosol dissolution experiments (at aerosol concentrations of about 30 mg 1-1) show

  13. Effect of Cooking on Soluble and Insoluble Oxalate Contents in Selected Pakistani Vegetables and Beans

    Microsoft Academic Search

    Muhammad Shoaib Akhtar; Beenish Israr; Nighat Bhatty; Amanat Ali

    2011-01-01

    The present study evaluated the effects of cooking on the total, soluble and insoluble oxalate contents in six different types of locally consumed vegetables and beans (spinach, carrots, beet root, white bean, red bean and soybean). The foods were cooked in water until they reached the soft consistency (12–15 min for vegetable and 2 h for beans). The raw and

  14. Inhibitive properties of amphoteric, water-soluble cellulosic polymers on bentonite swelling

    Microsoft Academic Search

    L.-M. Zhang

    1999-01-01

    Amphoteric, water-soluble cellulose derivatives were prepared by the quaternization of anionic carboxymethylcellulose (CMC)\\u000a with 3-chloro-2-hydroxypropyltrimethyl-ammonium chloride. These polymers suppress the swelling of bentonite more effectively\\u000a than CMC and their inhibitive effect depends on the degree of quaternization, the molecular conformation and the type of counterions.

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

    DOEpatents

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

    2014-07-22

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

  16. Soluble antigen of bovine viral diarrhea virus

    Microsoft Academic Search

    Donald E. Gutekunst; Winston A. Malmquist

    1965-01-01

    Summary Complement-fixing (CF) soluble antigen (SA) was detectable intra-cellularly prior to the appearance of infectious NADL-MD bovine viral diarrhea (BVD) virus during synthesis in roller flask cultures of bovine embryonic kidney cells. The release of infective virus into the extracellular fluid was concomitant with the release of SA.

  17. 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...

  18. A condition on finitely generated soluble groups

    Microsoft Academic Search

    Alireza Abdollahi; Bijan Taeri

    1999-01-01

    In this note we show that if Gis a finitely generated soluble group, then every infinite subset of Gcontains two elements generating a nilpotent group of class at most kif and only if Gis finite by a group in which every two generator subgroup is nilpotent of class at most k.

  19. 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.

  20. RESEARCH PAPER Pharmacokinetic optimization of four soluble

    E-print Network

    Hammock, Bruce D.

    -inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility parameters (higher Cmax, longer t1/2 and greater AUC) were obtained from the tested inhibitors, compared are vasodilators in various animal models (Carroll et al., 1987a,b; Imig et al., 1995; Pomposiello et al., 2003

  1. 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.

  2. Water-soluble polymers and compositions thereof

    DOEpatents

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

    2002-01-01

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

  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. Surface shear inviscidity of soluble surfactants

    PubMed Central

    Zell, Zachary A.; Nowbahar, Arash; Mansard, Vincent; Leal, L. Gary; Deshmukh, Suraj S.; Mecca, Jodi M.; Tucker, Christopher J.; Squires, Todd M.

    2014-01-01

    Foam and emulsion stability has long been believed to correlate with the surface shear viscosity of the surfactant used to stabilize them. Many subtleties arise in interpreting surface shear viscosity measurements, however, and correlations do not necessarily indicate causation. Using a sensitive technique designed to excite purely surface shear deformations, we make the most sensitive and precise measurements to date of the surface shear viscosity of a variety of soluble surfactants, focusing on SDS in particular. Our measurements reveal the surface shear viscosity of SDS to be below the sensitivity limit of our technique, giving an upper bound of order 0.01 ?N·s/m. This conflicts directly with almost all previous studies, which reported values up to 103–104 times higher. Multiple control and complementary measurements confirm this result, including direct visualization of monolayer deformation, for SDS and a wide variety of soluble polymeric, ionic, and nonionic surfactants of high- and low-foaming character. No soluble, small-molecule surfactant was found to have a measurable surface shear viscosity, which seriously undermines most support for any correlation between foam stability and surface shear rheology of soluble surfactants. PMID:24563383

  5. 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.

  6. Solubilities of stearic acid, stearyl alcohol, and arachidyl alcohol in supercritical carbon dioxide at 35[degree]C

    SciTech Connect

    Iwai, Yoshio; Koga, Yoshio; Maruyama, Hironori; Arai, Yasuhiko (Kyushu Univ., Fukuoka (Japan). Dept. of Chemical Engineering)

    1993-10-01

    The solubilities of stearic acid (octadecanoic acid), stearyl alcohol (1-octadecanol), and arachidyl alcohol (1-eicosanol) in supercritical carbon dioxide were measured by using a flow-type apparatus at 35 C up to 23.7 MPa. The solubilities of those substances and other fatty acids and higher alcohols in supercritical carbon dioxide at 35 C were correlated by a solution model based on the regular solution model coupled with the Flory-Huggins theory.

  7. Soluble Intercellular Adhesion Molecules, Soluble Vascular Cell Adhesion Molecules, and Risk of Coronary Heart Disease

    Microsoft Academic Search

    Iris Shai; Tobias Pischon; Frank B. Hu; Alberto Ascherio; Nader Rifai; Eric B. Rimm

    2006-01-01

    Objective: We examined the association of circulating levels of soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecules (sVCAM-1) with coronary heart disease (CHD) risk factors and whether the adhesion molecules alone, and in combination, can serve as predictors of coronary CHD.Research Methods and Procedures: Among 18,225 men from the Health Professional Follow-up Study who provided blood in

  8. 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

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

    PubMed

    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

  10. ATTENUATION OF WATER-SOLUBLE POLYCHLORINATED BIPHENYLS BY EARTH MATERIALS

    EPA Science Inventory

    The aqueous solubility, adsorption, mobility, microbial degradation, and volatility of polychlorinated biphenyls (PCBs) were studied under laboratory conditions. The dissolution of Aroclor 1242 in water required five months to reach equilibrium. Generally, the water-soluble fract...

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

    SciTech Connect

    De Visscher, Alex; Vanderdeelen, Jan [Department of Chemical and Petroleum Engineering, and Centre for Environmental Engineering Research and Education (CEERE), Schulich School of Engineering, University of Calgary, Calgary, Alberta, T2N 1N4 (Canada); Department of Applied Analytical and Physical Chemistry, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent (Belgium)

    2012-06-15

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

  12. 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.

  13. Solubility properties and diffusional extraction behavior of natamycin from Streptomyces gilvosporeus biomass.

    PubMed

    Zeng, Xianhai; Danquah, Michael K; Jing, Keju; Woo, Meng Wai; Chen, Xiao Dong; Xie, Youping; Lu, Yinghua

    2013-01-01

    Natamycin is a type of polyene macrolide antibiotic and has been produced in submerged microbial cultures of some natural Streptomyces strains. Natamycin extraction from cellular biomass is greatly affected by the molecular and solubilization characteristics of the extraction solvent, and this is a major reason for the routine attainment of low volumetric titers, resulting from sparing natamycin solubility. In this work, a series of experiments were conducted to investigate the solubility of natamycin in some selected organic solvents in order to assess the influence on natamycin extraction yield. Natamycin showed the highest solubility in 75% aqueous methanol under the conditions of pH 2, 30°C and 1 atm. Furthermore, the extraction of natamycin using 75% aqueous methanol was performed and the highest extraction yield of 45.7% was obtained under pH 2. A mathematical model derived from Fick's law of the biomolecular diffusion process was developed to fit the experimental kinetic data of natamycin extraction. PMID:23125192

  14. 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.

  15. Solubility approach for modeling waste glass liquidus

    SciTech Connect

    Plodinec, M.J.

    1999-07-01

    The liquidus temperature of a waste glass (the temperature at which the system glass + crystalline material is in equilibrium with the amorphous glass of the same composition) often is a measure of the solubility of a specific component in the waste in the base glass. A new approach toward predicting the liquidus temperatures of waste glasses has been developed based on solubility. The approach predicts liquidus temperature as well as more complicated expressions developed by other researchers. At the same time, simple process control limits can be easily derived from this model, which is difficult to do with other approaches. While the approach is not applicable to all waste glass components, it can be used for important species such as nickel-iron spinel, chromium oxide, and probably plutonium dioxide. The approach also has led to two new techniques for determining liquidus of waste glass systems.

  16. Role of soluble adenylyl cyclase in mitochondria.

    PubMed

    Valsecchi, Federica; Konrad, Csaba; Manfredi, Giovanni

    2014-12-01

    The soluble adenylyl cyclase (sAC) catalyzes the conversion of ATP into cyclic AMP (cAMP). Recent studies have shed new light on the role of sAC localized in mitochondria and its product cAMP, which drives mitochondrial protein phosphorylation and regulation of the oxidative phosphorylation system and other metabolic enzymes, presumably through the activation of intra-mitochondrial PKA. In this review article, we summarize recent findings on mitochondrial sAC activation by bicarbonate (HCO(3)(-)) and calcium (Ca²?) and the effects on mitochondrial metabolism. We also discuss putative mechanisms whereby sAC-mediated mitochondrial protein phosphorylation regulates mitochondrial metabolism. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. PMID:24907564

  17. 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

  18. Soluble Guanylate Cyclase Modulators in Heart Failure

    Microsoft Academic Search

    Veselin Mitrovic; Ana Jovanovic; Stefan Lehinant

    2011-01-01

    This review summarizes the role of soluble guanylate cyclase (sGC)-cyclic guanosine 3?, 5?-monophosphate pathways in heart\\u000a failure and several new drugs that modify guanylate cyclase. The sGC activators and stimulators as modulators of sGC are promising\\u000a drugs in the therapy for decompensated heart failure and pulmonary hypertension. Cinaciguat is a nitric oxide (NO)–independent\\u000a direct activator of sGC, which also may

  19. Solubility and structure of calcium silicate hydrate

    Microsoft Academic Search

    Jeffrey J. Chen; Jeffrey J. Thomas; Hal F. W. Taylor; Hamlin M. Jennings

    2004-01-01

    The poorly crystalline calcium silicate hydrate (C-S-H) phases that form near room temperature, which include the technically important C-S-H gel phase formed during the hydration of Portland cement, have a broad similarity to the crystalline minerals tobermorite and jennite, but are characterized by extensive atomic imperfections and structural variations at the nanometer scale. Relationships between the aqueous solubility and chemical

  20. Improved Radiolabeled Substrates for Soluble Epoxide Hydrolase

    Microsoft Academic Search

    B. Borhan; T. Mebrahtu; S. Nazarian; M. J. Kurth; B. D. Hammock

    1995-01-01

    Two rapid assays for the soluble epoxide hydrolase (sEH) are described. First, a sensitive radiometric assay based on thin-layer chromatography of [14C]-cis-9,10-epoxystearic acid and its corresponding diol ([14C]-9,10-dihydroxystearic acid) is described. The cis fatty acid oxide exhibits higher specific activity of hydration with sEH from mouse, rat, human, and potato compared to trans-stilbene oxide (TSO). The Km and Vmax obtained

  1. Cure study of soluble aromatic polyimide films

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  2. Apparent oxygen solubility in refractory carbides

    Microsoft Academic Search

    D. Gozzi; M. Montozzi; P. L. Cignini

    1999-01-01

    The occurrence of an apparent solubility of oxygen in polycrystalline NbC, TiC, VC and ZrC is discussed. This is shown by experiments in which the oxygen consumed by the sample is directly measured as a function of temperature in an argon stream at 1.6 bar (rel) where the oxygen partial pressure was as low as 0.8 Pa. The parameter ?,

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. Solubility data are compiled for metals in liquid zinc

    NASA Technical Reports Server (NTRS)

    Dillon, I. G.; Johnson, I.

    1967-01-01

    Available data is compiled on the solubilities of various metals in liquid zinc. The temperature dependence of the solubility data is expressed using the empirical straight line relationship existing between the logarithm of the solubility and the reciprocal of the absolute temperature.

  10. Aluminum Solubility in Complex Electrolytes - 13011

    SciTech Connect

    Agnew, S.F. [Columbia Energy and Environmental Services, Inc., 1806 Terminal Dr., Richland, WA 99354 (United States)] [Columbia Energy and Environmental Services, Inc., 1806 Terminal Dr., Richland, WA 99354 (United States); Johnston, C.T. [Dept. of Crop, Soil, and Environmental Sciences, Purdue University, West Lafayette, IN 47907 (United States)] [Dept. of Crop, Soil, and Environmental Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2013-07-01

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

  11. 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

  12. 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.

  13. Reversibly soluble biocatalyst: optimization of trypsin coupling to Eudragit S-100 and biocatalyst activity in soluble and precipitated forms

    Microsoft Academic Search

    V. Arasaratnam; I. Yu. Galaev; B. Mattiasson

    2000-01-01

    Eudragit S-100, a copolymer of methacrylic acid and methyl methacrylate is soluble at pH above 5 and insoluble at pH below 4.5. pH-dependent solubility of the polymer is used for the development of reversibly soluble biocatalyst, which combines the advantages of both soluble and immobilized biocatalysts. Activity of trypsin, covalently coupled to Eudragit S-100, was improved by protecting the active

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

    SciTech Connect

    Barney, G.S.

    1997-09-16

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

  15. 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.

  16. Assessment of the combined approach of N-alkylation and salt formation to enhance aqueous solubility of tertiary amines using bupivacaine as a model drug.

    PubMed

    Nielsen, Anders Bach; Frydenvang, Karla; Liljefors, Tommy; Buur, Anders; Larsen, Claus

    2005-01-01

    Quaternary prodrug types of poorly water-soluble tertiary amines have been shown to exhibit significantly enhanced solubilities as compared to the parent amine. In the present study the combined effect of N-alkylation and salt formation to enhance aqueous solubility of tertiary amines have been investigated using bupivacaine as a model compound. X-ray structure analyses of selected salts were included to investigate the potential existence of correlations between salt solubility and crystal packing modes. Alkyl groups were methyl, ethyl, propyl, and butyl and the derivatives were isolated as their iodide salts. Chloride, mesylate, formate, acetate, glycolate, and tosylate salts were obtained by anion exchange of the N-methyl-bupivacaine derivative. N-Alkylation and salt formation afforded quaternary ammonium salts possessing pH-independent aqueous solubilities far exceeding that of the parent tertiary amine (up to a factor of 3200 at pH 8). A moderate reduction in solubility with increasing length of the alkyl chain was observed for the iodide salts of the N-alkylated bupivacaine derivatives. In case of the N-methyl-bupivacaine derivative variation of the counterion had a significant impact on the solubility with the iodide salt being 200 times less soluble than the chloride salt. X-ray analysis revealed that both the alkyl substituent and the anionic counterion influenced salt packing modes, however, in an unpredictable manner making establishment of quantitative correlations between crystal packing and solubility difficult even for a series of closely related derivatives. PMID:15626581

  17. 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

  18. 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.

  19. 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 (OC6H6N)2Ti(OC6H2(CH2N(CH3)2)3-2,4,6)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.

  20. 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.

  1. Levels of soluble Fc?RIII correlate with disease severity in sepsis

    PubMed Central

    Muller Kobold, A C; Zijlstra, J G; Koene, H R; DE Haas, M; Kallenberg, C G M; Cohen Tervaert, J W

    1998-01-01

    Neutrophil activation is thought to play a crucial role in the pathogenesis of sepsis. During activation, neutrophils adhere to and migrate through the endothelium. Therefore, the amount of circulating neutrophils does not adequately reflect the total amount of neutrophils that are involved in the pathophysiologic process of this condition. In this study we test the hypothesis that the severity of sepsis is associated with the total body mass of neutrophils as reflected in the plasma concentration of soluble Fc? receptor type III (sFc?RIII). Nineteen patients with sepsis (12 male, seven female, median age of 69 years, range 29–87 years) were included in this study. Ten healthy volunteers served as controls. Plasma sFc?RIII concentrations were measured by ELISA. Other parameters that were studied were leucocyte count, plasma concentrations of lactoferrin and soluble l-selectin, and surface expression of CD11b and CD66b on circulating neutrophils. Disease activity was measured using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Soluble Fc?RIII levels were elevated in sepsis patients whereas soluble l-selectin levels were moderately decreased compared with healthy controls. Markers of cell activation were significantly increased in sepsis patients. Soluble Fc?RIII correlated with disease severity as measured by the APACHE score (P < 0.05, r = 0.53), whereas the other parameters did not correlate with the APACHE score. In conclusion, this study demonstrates that soluble Fc?RIII is a useful marker for disease severity in patients with sepsis. PMID:9822280

  2. Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro.

    PubMed

    McNeilly, Jane D; Heal, Mathew R; Beverland, Iain J; Howe, Alan; Gibson, Mark D; Hibbs, Leon R; MacNee, William; Donaldson, Ken

    2004-04-01

    Epidemiological studies have consistently reported a higher incidence of respiratory illnesses such as bronchitis, metal fume fever (MFF), and chronic pneumonitis among welders exposed to high concentrations of metal-enriched welding fumes. Here, we studied the molecular toxicology of three different metal-rich welding fumes: NIMROD 182, NIMROD c276, and COBSTEL 6. Fume toxicity in vitro was determined by exposing human type II alveolar epithelial cell line (A549) to whole welding fume, a soluble extract of fume or the "washed" particulate. All whole fumes were significantly toxic to A549 cells at doses >63 microg ml(-1) (TD 50; 42, 25, and 12 microg ml(-1), respectively). NIMROD c276 and COBSTEL 6 fumes increased levels of IL-8 mRNA and protein at 6 h and protein at 24 h, as did the soluble fraction alone, whereas metal chelation of the soluble fraction using chelex beads attenuated the effect. The soluble fraction of all three fumes caused a rapid depletion in intracellular glutathione following 2-h exposure with a rebound increase by 24 h. In addition, both nickel based fumes, NIMROD 182 and NIMROD c276, induced significant reactive oxygen species (ROS) production in A549 cells after 2 h as determined by DCFH fluorescence. ICP analysis confirmed that transition metal concentrations were similar in the whole and soluble fractions of each fume (dominated by Cr), but significantly less in both the washed particles and chelated fractions. These results support the hypothesis that the enhanced pro-inflammatory responses of welding fume particulates are mediated by soluble transition metal components via an oxidative stress mechanism. PMID:15050411

  3. Studies on the Preparation, Characterization, and Solubility of 2-HP-?-Cyclodextrin-Meclizine HCl Inclusion Complexes

    PubMed Central

    George, SJ; Vasudevan, DT

    2012-01-01

    Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-?-cyclodextrins and ?-cyclodextrins on its aqueous solubility and dissolution rate was investigated. The phase solubility profile indicated that the solubility of Meclizine HCl was significantly increased in the presence of both 2-hydroxypropyl-?-cyclodextrin and ?- cyclodextrin; an extend of increase being more for 2-hydroxypropyl-?-cyclodextrin. It was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. The complexes formed were quite stable. The solid complexes prepared by physical mixtures, kneading methods, and co-precipitation methods were characterized using differential scanning calorimetry and FTIR. An in vitro study showed that the solubility and dissolution rate of Meclizine HCl were significantly improved by complexation with 2-hydroxypropyl-?-cyclodextrin. Tablet formulation using 1:1 kneading complex of Meclizine HCl and 2-hydroxypropyl-?-cyclodextrin with drug equivalent to 25 mg was prepared by a direct compression method. A dissolution study of prepared tablets was performed in 0.5% SLS in water (pH 7.0). Almost 96% drug was released from the formulation at the end of 30min. A comparison study of prepared tablets was done with marketed a Meclizine HCl 25 mg conventional tablet. From the results of dissolution study, it was found that the prepared formulation was showing better release, which was statistically significant P < 0.01 than a marketed tablet (paired t-test). Only 54% drug release was observed from the marketed tablet at the end of 30 min. Hence this study concludes that the solubility enhancement of Meclizine HCl could be successfully achieved using the inclusion complexation technique. PMID:23493156

  4. Water soluble fraction of Asian dust particles

    NASA Astrophysics Data System (ADS)

    Osada, Kazuo

    2013-04-01

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

  5. Soluble adenylyl cyclase in the eye.

    PubMed

    Lee, Yong S; Marmorstein, Lihua Y; Marmorstein, Alan D

    2014-12-01

    Adenylyl cyclases (ACs) are a family of enzymes which convert ATP to cAMP, an essential intermediate in many signal transduction pathways. Of the 10 AC genes in man, 9 fall into the category of transmembrane ACs (tmACs), which associate with G-protein coupled receptors (GPCRs) and are activated by forskolin. The 10th AC, termed soluble AC (sAC) is neither activated by forskolin nor does it interact with GPCRs. Rather, sAC can be found in many compartments within the cell and is activated by bicarbonate. As such, sAC is considered a major sensor of bicarbonate in many tissues. The pathways involving sAC vary in different tissues and organ systems, and are as diverse as facilitating sperm capacitation and regulating pressure in the eye. The role of sAC in the eye has only recently begun to receive significant attention. Here we summarize what is known about the roles of sAC in the eye. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. PMID:25108282

  6. 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%.

  7. 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

  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. Soluble proteins in chemosensory organs of phasmids.

    PubMed

    Mameli, M; Tuccini, A; Mazza, M; Petacchi, R; Pelosi, P

    1996-01-01

    Soluble proteins of low molecular weight have been purified from chemosensory organs of five species of Phasmids. On the basis of their N-terminal amino acid sequences, two classes can be identified. Polypeptides of 14 and 15 kDa, expressed in the antennae and legs of Eurycantha calcarata and Extatosoma tiaratum, as well as in the antennae of Carausius morosus, bear a close similarity (around 45% identity) with a soluble protein associated with the sensilla coeloconica of Drosophila melanogaster. Two proteins of 19 and 18 kDa, isolated from the antennae and the maxillary palpi, respectively, of Acrophylla wuelfingi, are 59 and 75% identical, in their N-terminal region, to a 19 kDa antennal protein of Carausius morosus. Similarity between members of the two classes is not significant, being limited to two to three identical amino acids in the most favorable cases. Finally, a 17 kDa protein, specifically expressed in the antennae of Sipyloidea sipylus, did not show any homology with other proteins. The expression in sensory organs and the characteristics of these proteins may suggest a function in chemosensory transduction. PMID:9014332

  10. 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

  11. Studies on the effect of water-soluble polymers on drug-cyclodextrin complex solubility.

    PubMed

    Hirlekar, Rajashree S; Sonawane, Suneeta N; Kadam, Vilasrao J

    2009-01-01

    The effect of complexation of irbesartan (IRB), a practically water-insoluble drug, with cyclodextrins in presence of different concentrations of water-soluble polymers (PEG 4000 and PVP K-90) on the dissolution rate of the drug has been investigated. Phase solubility studies were carried out to evaluate the solubilizing power of betaCD in association with water-soluble polymers towards IRB and to determine the apparent stability constant (K (S)) of the complexes. Improvement in K(S) value for ternary complexes (IRB-betaCD-polymers) clearly proved the benefit on the addition of water-soluble polymer to increase complexation efficiency. The dissolution rate of the drug from ternary systems containing PEG 4000 and PVP K-90 was higher as compared to the binary system. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% w/w for PVP K-90 and 10% w/w for PEG 4000. DSC, FTIR, SEM, and XRD studies were carried out to characterize the complexes. PMID:19562489

  12. Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid.

    PubMed

    Yuvaraja, K; Khanam, Jasmina

    2014-08-01

    Aim of the present work is to enhance aqueous solubility of carvedilol (CV) by solid dispersion technique using wide variety of carriers such as: ?-cyclodextrin (?CD), hydroxypropyl-?-cyclodextrin (HP?CD), tartaric acid (TA), polyvinyl pyrrolidone K-30 (PVP K-30) and poloxamer-407 (PLX-407). Various products of 'CV-solid dispersion' had been studied extensively in various pH conditions to check enhancement of solubility and dissolution characteristics of carvedilol. Any physical change upon interaction between CV and carriers was confirmed by instrumental analysis: XRD, DSC, FTIR and SEM. Negative change of Gibb's free energy and complexation constants (Kc, 75-240M(-1), for cyclodextrins and 1111-20,365M(-1), for PVP K-30 and PLX-407) were the evidence of stable nature of the binding between CV and carriers. 'Solubility enhancement factor' of ionized-CV was found high enough (340 times) with HP?CD in presence of TA. TA increases the binding efficiency of cyclodextrin and changing the pH of microenvironment in dissolution medium. In addition, ionization process was used to increase the apparent intrinsic solubility of drug. In vitro, dissolution time of CV was remarkably reduced in the solid dispersion system compared to that of pure drug. This may be attributed to increased wettability, dispersing ability and transformation of crystalline state of drug to amorphous one. PMID:24705456

  13. Oxireductases in the Enzymatic Synthesis of Water-Soluble Conducting Polymers

    Microsoft Academic Search

    Estibalitz Ochoteco; David Mecerreyes

    2011-01-01

    \\u000a This chapter reviews recent advances in the field of biocatalytic synthesis of water-soluble conducting polymers. Biocatalysis\\u000a is proposed as a versatile tool for synthesis of conducting polymers. First, the enzymatic synthesis of conducting polymers\\u000a and its mechanism is discussed as well as the use of different type of enzymes. Next, we describe the use of a new bifunctional\\u000a template (sodium

  14. Synthesis of a novel water-soluble polymeric UV-absorber for cotton

    Microsoft Academic Search

    Wei Ma; Xue Jiang; Yong Liu; Bing Tao Tang; Shu Fen Zhang

    2011-01-01

    A water-soluble polymeric UV-absorber with polyvinylamine as backbone and benzotriazole type UV absorber as anti-UV functional group was synthesized by grafting brominated (2?-acetoxy-5?-methylphenyl)-2H-benzotriazole onto polyvinylamine. The intermediates and synthesized polymeric UV absorber were characterized by 1H NMR, MS, IR and UV spectroscopy. The finishing properties of the polymeric UV absorber on cotton were investigated to show good UV protection property

  15. The carbon dioxide solubility in alkali basalts: an experimental study

    Microsoft Academic Search

    Priscille Lesne; Bruno Scaillet; Michel Pichavant; Jean-Michel Beny

    2011-01-01

    Experiments were conducted to determine CO2 solubilities in alkali basalts from Vesuvius, Etna and Stromboli volcanoes. The basaltic melts were equilibrated with nearly\\u000a pure CO2 at 1,200°C under oxidizing conditions and at pressures ranging from 269 to 2,060 bars. CO2 solubility was determined by FTIR measurements. The results show that alkalis have a strong effect on the CO2 solubility and confirm

  16. Effects of solid dispersions on the solubility of antibiotics

    Microsoft Academic Search

    I. I. Krasnyuk Jr

    2009-01-01

    The effects of solid dispersions (SD) on the solubility of antibiotics were studied. Rifampicin, amoxycillin trihydrate and\\u000a their SD with polyethylene glycol 1500, polyvinylpyrrolidone 10,000, and ?-cyclodextrin were investigated. Preparation of\\u000a SD increased the solubility and rate of dissolution of antibiotics. The solubility of rifampicin from SD increased by a factor\\u000a of 2 – 2.7. The rate of dissolution from

  17. Increases in the solubility of Mezapam by forming solid dispersions

    Microsoft Academic Search

    I. I. Krasnyuk Jr; A. S. Lapshova; R. U. Khabriev; V. A. Popkov; V. Yu. Reshetnyak; S. O. Zvereva; O. I. Krasnyuk

    2011-01-01

    The effects of solid dispersions (SD) on the solubility of Mezapam were investigated. Mezapam and its SD with polyethylene\\u000a glycol 1500, polyvinylpyrrolidone 10,000, and ?-cyclodextrin were studied. These SD increased the solubility and rate of dissolution\\u000a of Mezapam. The solubility of Mezapam from SD increased by factors of 2 – 8. The rate of dissolution of Mezapam form SD increased

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

    PubMed

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

    2014-04-15

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

  19. Soluble Neuregulin and Schwann Cell Myelination: a Therapeutic Potential for Improving Remyelination of Adult Axons

    PubMed Central

    Syed, Neeraja; Kim, Haesun A.

    2011-01-01

    Myelination in the peripheral nervous system (PNS) is induced by close contact signaling between axons and Schwann cells. Previous studies have identified membrane-bound neuregulin-1 (Nrg1) type III, expressed on the axons, as the key instructive signal that regulates Schwann cell myelination. In our recent study, we show that recombinant soluble Nrg1 elicits a similar pro-myelinating effect on Schwann cells, albeit in a dosage-dependent manner: Nrg1 promotes myelination at low concentrations but inhibits it at high concentrations. The inhibitory effect of Nrg1 is mediated through its activation of the Ras/Raf/Erk pathway in Schwann cells, and inhibition of the pathway using a pharmacologic inhibitor restores myelination. We also show that soluble Nrg1 enhances myelination on axons that do not express sufficient amount of Nrg1 type III needed for robust myelination. These findings are significant as they suggest that combined therapies aimed at enhancing Nrg1 signaling and blocking the Ras/Raf/Erk activation may be an effective strategy for improving remyelination on adult axons, which, as shown in our recent data, express low levels of Nrg1 type III. In this report we provide an overview of our recent findings and discuss the therapeutic potential of soluble Nrg1. PMID:21274416

  20. 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.

  1. Method of increasing biodegradation of sparingly soluble vapors

    DOEpatents

    Cherry, Robert S. (Idaho Falls, ID)

    2000-01-01

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

  2. SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer.

    PubMed

    Vangara, Kiran Kumar; Ali, Hamed Ismail; Lu, Dai; Liu, Jingbo Louise; Kolluru, Srikanth; Palakurthi, Srinath

    2014-04-01

    SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether ?-cyclodextrin (SBE?CD), hydroxypropyl ?-cyclodextrin, randomly methylated ?-cyclodextrin, and methyl ?-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-?CD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBE?CD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an AP-type system. Aqueous solubility of SN-38 was enhanced by about 30-1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBE?CD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBE?CD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBE?CD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications. PMID:24477982

  3. Phenol-soluble modulins and staphylococcal infection.

    PubMed

    Peschel, Andreas; Otto, Michael

    2013-10-01

    Staphylococcus aureus is an important human pathogen and a leading cause of death worldwide. Phenol-soluble modulins (PSMs) have recently emerged as a novel toxin family defining the virulence potential of highly aggressive S. aureus isolates. PSMs have multiple roles in staphylococcal pathogenesis, causing lysis of red and white blood cells, stimulating inflammatory responses and contributing to biofilm development and the dissemination of biofilm-associated infections. Moreover, the pronounced capacity of PSMs to kill human neutrophils after phagocytosis might explain failures in the development of anti-staphylococcal vaccines. Here, we discuss recent progress made in our understanding of the biochemical and genetic properties of PSMs and their role in S. aureus pathogenesis, and suggest potential avenues to target PSMs for the development of anti-staphylococcal drugs. PMID:24018382

  4. Soluble guanylate cyclase modulators in heart failure.

    PubMed

    Mitrovic, Veselin; Jovanovic, Ana; Lehinant, Stefan

    2011-03-01

    This review summarizes the role of soluble guanylate cyclase (sGC)-cyclic guanosine 3', 5'-monophosphate pathways in heart failure and several new drugs that modify guanylate cyclase. The sGC activators and stimulators as modulators of sGC are promising drugs in the therapy for decompensated heart failure and pulmonary hypertension. Cinaciguat is a nitric oxide (NO)-independent direct activator of sGC, which also may be effective under oxidative stress conditions resulting in oxidized or heme-free sGC refractory to organic nitrates. Riociguat is an NO-independent direct stimulator of sGC with beneficial effects in patients with decompensated heart failure and pulmonary hypertension. The sGC modulators play an important role in patients with heart failure and pulmonary hypertension. PMID:21207207

  5. Polymerized soluble venom--human serum albumin

    SciTech Connect

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

    1985-03-01

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

  6. Solubility of magnesium carbonate in natural waters

    USGS Publications Warehouse

    Wells, R.C.

    1915-01-01

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

  7. Benzene solubility in water: A reassessment

    NASA Astrophysics Data System (ADS)

    Graziano, Giuseppe

    2006-09-01

    It is shown that the results of molecular dynamics simulations on the hydration thermodynamics of benzene at room temperature [Schravendijk and van der Vegt, J. Chem. Theory Comput. 1 (2005) 643] are in line with a former theoretical analysis [Graziano and Lee, J. Phys. Chem. B 105 (2001) 10367]. In fact: (a) the benzene-water van der Waals interaction energy proves to be larger in magnitude than the work of cavity creation and is able to account for the experimental finding that the hydration of benzene is a spontaneous process under the Ben-Naim standard conditions around room temperature; (b) the weak benzene-water H-bonds do not provide a significant contribution to benzene solubility in water because the favorable enthalpic component is almost entirely compensated for by an unfavorable entropic component. This enthalpy-entropy compensation occurs because the H-bonding potential of benzene is not strong.

  8. 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

  9. Communication: Epistructural thermodynamics of soluble proteins

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    2012-03-01

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

  10. IUPAC-NIST Solubility Data Series. 76. Solubility of Ethyne in Liquids

    NASA Astrophysics Data System (ADS)

    Fogg, Peter G. T.; Bligh, Sim-wan Annie; Derrick, M. Elizabeth; Yampol'skii, Yuri P.; Clever, H. Lawrence; Skrzecz, Adam; Young, Colin L.; Fogg, Peter G. T.

    2001-11-01

    Ethyne was probably first made in the laboratory by Edmund Davy in 1836. It was rediscovered nearly a quarter of a century later by Berthelot who gave it the name acetylene. Since that time ethyne has become a cheap raw material for the synthesis of organic materials and an important industrial fuel. A summary of the available solubility data for ethyne was published by Miller in 1965 [S. A Miller, Acetylene—Its Properties, Manufacture, and Uses (Academic, New York, 1965), Vol. I]. Many more data are now available in a wide range of research papers and patent applications. These data vary in their reliability. In the current work the data for systems included in Miller's book have been reassessed and complemented by data published more recently. Literature has been surveyed to 1999. Data for a system may be unreliable unless two or more groups of workers have published values in close agreement. Where possible values of the mole fraction solubility at a partial pressure of 101.3 kPa have been tabulated. Equations have been given for the variation of mole fraction with temperature in cases in which values over a temperature range are available. The greater the number of independent sources of the data the more the reliance which can be placed on the utility of the resulting equation. Extrapolation of such equations beyond the temperature range of experimental measurements can lead to errors. In many of the systems it may be assumed that approximate values of the mole fraction solubility, x1, at a partial pressure of 101.3 kPa may be obtained by linear extrapolation of values for lower partial pressures, p1, on the assumption that x1/p1 is approximately constant. However a similar linear extrapolation of solubilities at pressures appreciably higher that 101.3 kPa to give mole fraction solubilities at 101.3 kPa can lead to gross errors. For the purpose of evaluation of data use has been made of the Krichevsky-Il'inskaya equation to obtain approximate values of solubilities at 101.3 kPa from measurements at higher pressures. These values were then compared with measurements made at or near to 101.3 kPa.

  11. 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

  12. Solubility Enhanced Oxidation of Hydrophobic Organic Contaminants

    NASA Astrophysics Data System (ADS)

    Boving, T. B.; Eberle, D. E.; Ball, R.

    2012-12-01

    In-situ chemical oxidation (ISCO) is a remediation technique considered to be effective at overcoming some of the limitations of conventional subsurface treatment processes for volatile and semi-volatile organic contaminants (VOC, SVOC). ISCO reactions occur predominately in the aqueous phase and as a result, contaminant availability is a major limiting factor, i.e. contaminants with higher aqueous solubility's are typically more accessible for oxidation than more hydrophobic, sorbed compounds. The purpose of this study was to determine the feasibility of a new integrated desorption-oxidation process for the remediation of contaminated waters and sediments. Specifically, this study examined the potential of using hydroxypropyl-?-cyclodextrin (HPCD), a modified cyclic sugar, and a blend of oxidants commercially known as OxyZone® (U.S. patent No. 7,667,087) for the remediation of polycyclic aromatic hydrocarbons (PAH). Laboratory scale batch experiments confirmed prior studies that HPCD increases the aqueous concentration of these contaminants, making a greater mass of contaminant available for subsequent oxidation. When exposed to the same amount of oxidant, the mass of PAH destroyed increased linearly with increasing HPCD concentration. Relative to PAH saturated solutions without HPCD, 11 times more PAH mass was destroyed when a PAH saturated 15 g/L HPCD solution was treated with the same mass of oxidant. Destruction of the aqueous phase contaminants followed first order exponential decay kinetics in both deionized water and HPCD solutions. However, the destruction of complexed PAH was slower than for uncomplexed PAH. The cause of this is likely due to the preferential destruction of the HPCD molecule by the oxidant, followed by the subsequent oxidation of the PAH. The destruction of the cyclodextrin was minimized by modifying the oxidant formulation. Overall, these findings establish the potential of utilizing HPCD and OxyZone® as an integrated desorption-oxidation process for the remediation of low solubility organic contaminants at the field scale.

  13. Connecting the solubility and CCN activation of complex organic aerosols: a theoretical study using the Solubility Basis Set (SBS)

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    We present a theoretical study investigating the cloud condensation nucleus (CCN) activation of multicomponent organic mixtures. We modeled these complex mixtures using the solubility basis set (SBS, analogous to the volatility basis set VBS), describing the mixture as a set of surrogate compounds with varying water-solubilities in a given range. We conducted Köhler theory calculations for 144 different mixtures with varying solubility range, number of components, assumption about the organic mixture thermodynamics and the shape of the solubility distribution, yielding approximately 6000 unique CCN-activation points. The results from these comprehensive calculations were compared to three simplifying assumptions about organic aerosol solubility: (1) complete dissolution at the point of activation, (2) combining the aerosol solubility with the molar mass and density into a single hygroscopicity parameter ?, (3) assuming a fixed water-soluble fraction ϵeff. While the complete dissolution was able to reproduce the activation points with a reasonable accuracy only when the majority (70-80%) of the material was dissolved at the point of activation, the single parameter representations of complex mixture solubility were confirmed to be powerful semi-empirical tools for representing the CCN activation of organic aerosol. Depending on the condensed-phase interactions between the organic molecules, material with solubilities larger than about 1-10 g L-1 could be treated as completely soluble in the CCN activation process over particle dry diameters between 20 and 500 nm and supersaturations between 0.03 and 8%. Our results indicate that understanding the details of the solubility distribution in the range of 0.1 to 100 g L-1 is critical for capturing the CCN activation, while resolution outside this solubility range will probably not add much information except in some special cases. The connection of these results to the previous observations of the CCN activation of complex organic mixture aerosols is discussed.

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

    PubMed

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

    2015-01-25

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

  15. 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

  16. Nanoemulsion-based delivery systems for poorly water-soluble bioactive compounds: Influence of formulation parameters on polymethoxyflavone crystallization

    Microsoft Academic Search

    Yan Li; Jinkai Zheng; Hang Xiao; David Julian McClements

    Polymethoxyflavones (PMFs) extracted from citrus peel exhibit potent anti-cancer activity, but are highly hydrophobic molecules with poor solubility in both water and oil at ambient and body temperature, which limits their bioavailability. The possibility of encapsulating PMFs within nanoemulsion-based delivery systems to facilitate their application in nutraceutical and pharmaceutical products was investigated. The influence of oil type (corn oil, MCT,

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. Solubility of selected esters in supercritical carbon dioxide

    Microsoft Academic Search

    S. Ismadji; S. K. Bhatia

    2003-01-01

    The solubility of ethyl propionate, ethyl butyrate, and ethyl isovalerate in supercritical carbon dioxide was measured at temperature ranging from 308.15 to 333.15 K and pressure ranging from 85 to 195 bar. At the same temperature, the solubility of these compounds increases with pressure. The crossover pressure region was also observed in this study. The experimental data were correlated by

  2. The synthesis of water soluble prodrugs analogs of echinocandin B.

    PubMed

    Rodriguez, M J; Vasudevan, V; Jamison, J A; Borromeo, P S; Turner, W W

    1999-07-01

    A facile synthesis of phosphonate and phosphate ester prodrugs on the phenolic hydroxy of two echinocandin semisynthetic derivatives is reported. The water solubility and stability profiles of the ECB compounds varied with the choice of alkyl group used. In some cases, the ester prodrugs with small aliphatic side chains retained antifungal activity while enhancing water solubility. PMID:10406656

  3. 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.

  4. Genetic Analyses of Soluble Carbohydrate Concentrations in Onion Bulbs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fructans are the primary soluble carbohydrate in onion (Allium cepa L.) bulbs and show significant correlations with dry weights and pungency. In this research, we estimated the genetic effects and interactions between two chromosome regions associated with higher amounts of soluble carbohydrates i...

  5. Properties of soluble protein powders from Alaska pollock (Theragra chalcogramma)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soluble protein powders were produced from pollock by-products and evaluated for their functional, nutritional and rheological properties. Soluble protein powders were made from pollock viscera (PVSP), viscer without liver (PVWLSP), heads (PHSP), frames (PFSP), trimmings (PTSP), and liver (PLSP) and...

  6. Phase selectively soluble polymer supports to facilitate homogeneous catalysis

    E-print Network

    Ortiz-Acosta, Denisse

    2009-05-15

    ............................................. 11 4 Liquid-liquid separation technique for soluble polymer supports separation ................................................................................................... 14 5 The SHOP production of ?-olefins... ................................................................................................. 61 4 Phase selective solubility of poly(N-octadecylacrylamide-co-N-n-butyl- acrylamide) copolymers ............................................................................. 63 5 Molecular weights, polydispersity indeces, and degrees...

  7. 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.

  8. 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

  9. 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

  10. Facilitating protein solubility by use of peptide extensions

    DOEpatents

    Freimuth, Paul I; Zhang, Yian-Biao; Howitt, Jason

    2013-09-17

    Expression vectors for expression of a protein or polypeptide of interest as a fusion product composed of the protein or polypeptide of interest fused at one terminus to a solubility enhancing peptide extension are provided. Sequences encoding the peptide extensions are provided. The invention further comprises antibodies which bind specifically to one or more of the solubility enhancing peptide extensions.

  11. 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

  12. A Lab Experiment to Introduce Gas/Liquid Solubility

    ERIC Educational Resources Information Center

    Fonsecaa, I. M. A.; Almeida, J. P. B.; Fachada, H. C.

    2008-01-01

    A simplified version of a volumetric apparatus for gas/liquid solubility measurements is proposed. The procedure familiarizes undergraduate students with the experimental study of the solubility of a gas in a liquid and contributes to the understanding of this important phase equilibrium concept. The experimental results report the determination…

  13. Solubility and crystallization of xylose isomerase from Streptomyces rubiginosus

    NASA Astrophysics Data System (ADS)

    Vuolanto, Antti; Uotila, Sinikka; Leisola, Matti; Visuri, Kalevi

    2003-10-01

    We have studied the crystallization and crystal solubility of xylose isomerase (XI) from Streptomyces rubiginosus. In this paper, we show a rational approach for developing a large-scale crystallization process for XI. Firstly, we measured the crystal solubility in salt solutions with respect to salt concentration, temperature and pH. In ammonium sulfate the solubility of XI decreased logarithmically when increasing the salt concentration. Surprisingly, the XI crystals had a solubility minimum at low concentration of magnesium sulfate. The solubility of XI in 0.17 M magnesium sulfate was less than 0.5 g l -1. The solubility of XI increased logarithmically when increasing the temperature. We also found a solubility minimum around pH 7. This is far from the isoelectric point of XI (pH 3.95). Secondly, based on the solubility study, we developed a large-scale crystallization process for XI. In a simple and economical cooling crystallization of XI from 0.17 M magnesium sulfate solution, the recovery of crystalline active enzyme was over 95%. Moreover, we developed a process for production of uniform crystals and produced homogenous crystals with average crystal sizes between 12 and 360 ?m.

  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. 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

  16. Development of soluble inulin microparticles as a potent and safe vaccine adjuvant and delivery system.

    PubMed

    Kumar, Sunny; Tummala, Hemachand

    2013-05-01

    The goal of the present study is to develop a potent and safe vaccine adjuvant that can also stabilize vaccine formulations during lyophilization and storage. Inulin is a safe plant polysaccharide, and in its water soluble isoform, it is known to stabilize protein formulations during storage. However, soluble inulins have never been shown to stimulate the immune system. In this study, for the first time, we showed that water soluble inulins could be developed into vaccine adjuvants by formulating as antigen encapsulated microparticles. A method was developed to prepare soluble inulin microparticles (sIMs) with high encapsulation efficiency (?75%) and loading (?75 ?g/mg) of the antigen. When immunized in mice, sIMs have generated robust Th2-type antibody titers (IgG1: 500,000) compared to unadjuvanted antigens (IgG1: 17,500) or alum adjuvanted antigens (IgG1: 80,000). In vitro assays showed that a higher proportion of antigen presenting cells (APC's) have taken up the antigen when presented in sIMs versus in solution (99 % vs 22 %). In addition, the amount of antigen taken up per cell has also been enhanced by more than 25 times when antigen was presented in sIMs. Efficient uptake of the antigen by APCs through sIMS was attributed to the observed enhancement in the immune response by antigen loaded sIMs. The sIMs neither caused any granuloma/tissue damage at the injection site in mice nor were they toxic to the APC's in cell culture. In conclusion, the current study has developed a safe, soluble inulin based vaccine adjuvant and delivery system. PMID:23506468

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

    PubMed Central

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

    2015-01-01

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

  18. Soluble organic compounds in the Tagish Lake meteorite

    NASA Astrophysics Data System (ADS)

    Hilts, Robert W.; Herd, Christopher D. K.; Simkus, Danielle N.; Slater, Greg F.

    2014-04-01

    The C2 ungrouped Tagish Lake meteorite preserves a range of lithologies, reflecting variable degrees of parent-body aqueous alteration. Here, we report on soluble organic compounds, including aliphatic and aromatic hydrocarbons, monocarboxylic acids, and amino acids, found within specimens representative of the range of aqueous alteration. We find that differences in soluble organic compounds among the lithologies may be explained by oxidative, fluid-assisted alteration, primarily involving the derivation of soluble organic compounds from macromolecular material. In contrast, amino acids probably evolved from precursor molecules, albeit in parallel with other soluble organic compounds. Our results demonstrate the role of parent-body alteration in the modification of organic matter and generation of prebiotic compounds in the early solar system, and have implications for interpretation of the complement of soluble organic compounds in carbonaceous chondrites.

  19. Synergism between Soluble and Dietary Fiber Bound Antioxidants.

    PubMed

    Çelik, Ecem Evrim; Gökmen, Vural; Skibsted, Leif H

    2015-03-01

    This study investigates the synergism between antioxidants bound to dietary fibers (DF) of grains and soluble antioxidants of highly consumed beverages or their pure antioxidants. The interaction between insoluble fractions of grains containing bound antioxidants and soluble antioxidants was investigated using (i) a liposome-based system by measuring the lag phase before the onset of oxidation and (ii) an ESR-based system by measuring the reduction percentage of Fremy's salt radical. In both procedures, antioxidant capacities of DF-bound and soluble antioxidants were measured as well as their combinations, which were prepared at different ratios. The simple addition effects of DF-bound and soluble antioxidants were compared with measured values. The results revealed a clear synergism for almost all combinations in both liposome- and ESR-based systems. The synergism observed in DF-bound-soluble antioxidant system paints a promising picture considering the role of fiber in human gastrointestinal (GI) tract health. PMID:25690181

  20. Various Solvent Systems for Solubility Enhancement of Enrofloxacin

    PubMed Central

    Seedher, Neelam; Agarwal, Pooja

    2009-01-01

    Solubility enhancement of antimicrobial drug enrofloxacin has been studied using a series of co-solvents and surfactants. Aqueous solubility of enrofloxacin could be increased up to 26 times. Co-solvents alone produced only small increase in solubility. However, the combined effect of co-solvents and buffer was synergistic and a large increase in solubility could be attained. Ionic surfactants were found to be much better solubilizing agents than non-ionic surfactant. Amongst ionic surfactants, solubility was found to be very high in anionic surfactant, sodium dodecylsulphate as compared to the cationic surfactant, cetyltrimethylammonium bromide. Up to 3.8 mg/ml of enrofloxacin could be dissolved in sodium dodecylsulphate. Mechanism of solubilization has been proposed and surfactant solubilization parameters have been calculated. PMID:20177468

  1. 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.

  2. 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.

  3. Biological significance of soluble IL-2 receptor

    PubMed Central

    Candore, Giuseppina; Cigna, Diego; Colucci, Antonio Tobia; Modica, Maria Assunta

    1993-01-01

    A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC) activation and interleukin-2 receptor (IL-2R) expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R) is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting findings are discussed in the light of the data showing that sIL-2R production correlates with IL-2 production. PMID:18475497

  4. Soluble Interleukin2 Receptor (sIL2R), Tumor Necrosis Factor Alpha (TNF-a) and Its Receptor as Prognostic Markers in \\

    Microsoft Academic Search

    Elham Abdel Samie; Sherif H Abdel Wahab; Amal E Khalifa

    This study aimed at assessing whether pretreatment levels of interleukin-6 (IL6), interleukin-10 (IL- lo), tumor necrosis factor-a (TNF-a), soluble TNF type 1 receptor (p55-R-TNF) and soluble interleukin-2 receptor (sIL-2R) are related to known clinical and biological prognostic factors of lymphoma. Thirty-five patients diagnosed to have non-Hodgkin's lymphoma (NHL) were studied. Patients were treated by 6 cycles of multiagent chemotherapy regimen

  5. 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.

  6. Release of soluble peptidoglycan from growing gonococci: hexaminidase and amidase activities.

    PubMed Central

    Rosenthal, R S

    1979-01-01

    Peptidoglycan (PG) turnover in exponentially growing Neisseria gonorrhoeae RD5 type 4 was accompanied by release of soluble PG fragments into the medium. Turnover of the D-[14C]glucosamine-labeled glycan moiety and of the meso-[3H]diaminopimelic acid (DAP)-labeled peptide region occurred at similar rates (ca. 35% per generation). Turnover of D-[14C]alanine-labeled sites within the peptide side chain of PG occurred at roughly twice this rate; no turnover of L-[3H]proline-labeled protein was detected. Gel filtration of supernatants of cultures grown in the presence of labeled DAP, glucosamine, and D-alanine as described above and paper chromatography of hydrolyzed peak fractions revealed four major types of soluble PG. Two of these contained both peptide and glycan moieties and appeared to represent forms of disaccharide peptide monomers and dimers. The other two were (i) a 3H-labeled product lacking 14C and (ii) a 14C-containing product lacking 3H, which were similar in size to that expected for free tetrapeptides and free disaccharides, respectively. Together the appearance of these PG fragments and the concurrent turnover of glycan and peptide regions indicate that both glycan splitting and amidase PG hydrolase activities are involved in the turnover of PG in growing gonococci. If released during gonococcal infections, similar soluble PG fragments might influence the consequences of host-gonococcus interactions. PMID:112060

  7. Accuracy of calculated pH-dependent aqueous drug solubility.

    PubMed

    Bergström, Christel A S; Luthman, Kristina; Artursson, Per

    2004-08-01

    The aim of the present study was to investigate the extent to which the Henderson-Hasselbalch (HH) relationship can be used to predict the pH-dependent aqueous solubility of cationic drugs. The pH-dependent solubility for 25 amines, carrying a single positive charge, was determined with a small-scale shake flask method. Each sample was prepared as a suspension in 150 mM phosphate buffer. The pH-dependent solubility curves were obtained using at least 10 different pH values. The intrinsic solubility, the solubility at the pKa and the solubility at pH values reflecting the pH of the bulk and acid microclimate in the human small intestine (pH 7.4 and 6.5, respectively) were determined for all compounds. The experimental study revealed a large diversity in slope, from -0.5 (celiprolol) to -8.6 (hydralazine) in the linear pH-dependent solubility interval, which is in sharp contrast to the slope of -1 assumed by the HH equation. In addition, a large variation in the range of solubility between the completely uncharged and completely charged drug species was observed. The range for disopyramide was only 1.1 log units, whereas that for amiodarone was greater than 6.3 log units, pointing at the compound specific response to counter-ion effects. In conclusion, the investigated cationic drugs displayed compound specific pH-dependent solubility profiles, indicating that that the HH equation in many cases will only give rough estimations of the pH-dependent solubility of drugs in divalent buffer systems. PMID:15265508

  8. Influence of Slightly Soluble Organics on Aerosol Activation

    SciTech Connect

    Abdul-Razzak, Hayder; Ghan, Steven J.

    2005-03-22

    This paper examines the effects of slightly soluble organics on aerosol activation in a parcel of air rising adiabatically. Slightly soluble organics can affect aerosol activation by three mechanisms: lowering surface tension, altering the bulk hygroscopicity, and delaying the growth of particles due to their lower solubilities. Here, we address the third mechanism by simulating the activation process of aerosol particles modeled using a single lognormal size distribution and consisting of an internal uniform chemical mixture of adipic acid (representing slightly soluble organics having extremely low solubility) and ammonium sulfate. The simulations were carried out using measured solubility of adipic acid spanning a wide range of physical and dynamical parameters. The same conditions were re-simulated but assuming fully soluble aerosols. Results of the simulations show that although that the low solubility of the adipic acid alters Köhler curves and increases critical supersaturation of the smaller particles (Köhler curves of the larger particles are not effected since these particles are completely dissolved at the initial supersaturation of zero), it has minimal to no effect on the parcel’s supersaturation except for particles consisting of more than 95% adipic acid. Accordingly, since aerosols in realistic atmospheric conditions do not contain more than 90% organics, we conclude that it is not necessary to retune the parameterization of aerosol activation previously developed and modified to address the other two mechanisms. The slightly soluble organics can thus be assumed to be fully soluble for the purpose of predicting the fraction of activation and the maximum supersaturation with negligible error.

  9. 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

  10. 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…

  11. 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…

  12. Solubility profiles of poly(ethylene glycol)\\/solvent systems, I: Qualitative comparison of solubility parameter approaches

    Microsoft Academic Search

    C. Özdemir; A. Güner

    2007-01-01

    Solubility of systems involving four different molecular weights of poly(ethylene glycol) (PEG) in tetrahydrofuran (THF), chloroform, dimethylsulfoxide (DMSO), methanol and water have been investigated by different algorithmic approaches as the mathematical application of the “like dissolves like” principle. In this study, the solubility parameters and their components for PEG and solvents have been evaluated by using of atomic group contribution

  13. Soluble CD4 enhances simian immunodeficiency virus SIVagm infection.

    PubMed Central

    Werner, A; Winskowsky, G; Kurth, R

    1990-01-01

    The CD4 molecule is expressed on T-helper cells and serves as the cellular receptor for the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for the simian immunodeficiency viruses SIVmac and SIVagm. HIV-1, HIV-2, and SIVmac infectivity can be blocked by monoclonal antibodies (MAbs) directed against the CD4 molecule and by soluble CD4 proteins (sCD4). In the present study, we demonstrated not only lack of inhibition, but 10- to 100-fold sCD4-dependent enhancement of SIVagm infectivity of human T-cell lymphoma lines, although SIVagm infection was blocked by MAbs OKT4a and Leu3a. SIVagm enhancement with sCD4 was suppressed by MAbs OKT4a and Leu3a to levels observed without addition of sCD4. The infectivity of all four tested SIVagm variants was enhanced by sCD4 on all tested lymphoma cell lines. These results suggest a second step (second or secondary receptor) required for enhancing virus entry into the cell and may have serious implications for approaches to the treatment of acquired immunodeficiency syndrome on the basis of modified sCD4 molecules. PMID:1700834

  14. Isolation and characterization of Xenopus soluble epoxide hydrolase.

    PubMed

    Purba, Endang R; Oguro, Ami; Imaoka, Susumu

    2014-07-01

    Soluble epoxide hydrolase (sEH) contributes to cell growth, but the contribution of sEH to embryonic development is not well understood. In this study, Xenopus sEH cDNA was isolated from embryos of Xenopus laevis. The Xenopus sEH was expressed in Escherichia coli and was purified. The epoxide hydrolase and phosphatase activities of purified sEH were investigated. The Xenopus sEH did not show phosphatase activity toward 4-methylumbelliferyl phosphate or several lysophosphatidic acids although it had EH activity. The amino acid sequence of Xenopus sEH was compared with that reported previously. We found amino acid substitutions of the 29th Thr to Asn and the 146th Arg to His and prepared a sEH mutant (N29T/H146R), designed as mutant 1. Neither wild-type sEH nor mutant 1 had phosphatase activity. Additional substitution of the 11th Gly with Asp was found by comparison with human sEH which has phosphatase activity, but the Xenopus sEH mutant G11D prepared as mutant 2 did not have phosphatase activity. The epoxide hydrolase activity of sEH seemed to be similar to that of human sEH, while Xenopus sEH did not have phosphatase activity toward several substrates that human sEH metabolizes. PMID:24681163

  15. 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

  16. Soluble guanylyl cyclase: more secrets revealed.

    PubMed

    Pyriochou, Anastasia; Papapetropoulos, Andreas

    2005-04-01

    Guanylyl cyclases (GCs) are enzymes that convert guanosine-5'-triphosphate (GTP) to cyclic guanosine-3',5'-monophosphate (cGMP). The second messenger cGMP participates in signaling by (1) stimulating the activity of kinases that belong to the protein kinase G family, (2) altering the conductance of cGMP-gated ion channels and (3) changing the activity of cGMP-regulated phosphodiesterases. In contrast to adenylyl cyclases which exist as membrane-bound molecules, guanylyl cyclases (GC) occur in both membrane-bound and cytosolic forms. The particulate GC (pGC) isoforms serve as receptors for natriuretic peptides, while soluble GC (sGC) is the "receptor" for nitric oxide (NO). In addition to the difference in ligands and subcellular organization, the two forms of GC also differ in that pGC exists in homodimeric form, while typically sGC occurs as a heterodimer. Herein, we will review the literature on sGC subunit structure and discuss the regulation of the enzyme at the transcriptional and post-translational level. PMID:15601619

  17. Substrate radical intermediates in soluble methane monooxygenase

    SciTech Connect

    Liu Aimin [Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455 (United States); Jin Yi [Department of Chemistry, University of Minnesota, Minneapolis, MN 55455 (United States); Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455 (United States); Zhang Jingyan [Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455 (United States); Brazeau, Brian J. [Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455 (United States); Lipscomb, John D. [Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States) and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455 (United States)]. E-mail: lipsc001@umn.edu

    2005-12-09

    EPR spin-trapping experiments were carried out using the three-component soluble methane monooxygenase (MMO). Spin-traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO), {alpha}-4-pyridyl-1-oxide N-tert-butylnitrone (POBN), and nitrosobenzene (NOB) were used to investigate the possible formation of substrate radical intermediates during catalysis. In contrast to a previous report, the NADH-coupled oxidations of various substrates did not produce any trapped radical species when DMPO or POBN was present. However, radicals were detected by these traps when only the MMO reductase component and NADH were present. DMPO and POBN were found to be weak inhibitors of the MMO reaction. In contrast, NOB is a strong inhibitor for the MMO-catalyzed nitrobenzene oxidation reaction. When NOB was used as a spin-trap in the complete MMO system with or without substrate, EPR signals from an NOB radical were detected. We propose that a molecule of NOB acts simultaneously as a substrate and a spin-trap for MMO, yielding the long-lived radical and supporting a stepwise mechanism for MMO.

  18. Developmental Changes in Soluble CD40 Ligand

    PubMed Central

    Cholette, Jill M.; Blumberg, Neil; Phipps, Richard P.; McDermott, Michael P.; Gettings, Kelly F.; Lerner, Norma B.

    2008-01-01

    Objectives To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations. Study design sCD40L was measured in 25 neonates, 74 children (3 months –15 years) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were performed. Correlation coefficients assessed relationships between plasma and serum sCD40L. Results Plasma sCD40L levels were higher in neonates than in all other age groups, (p<0.001). All grouped pediatric plasma levels were significantly higher than in adults (p<0.0001). There were no significant differences in plasma sCD40L between pediatric age groups. Serum levels were significantly higher in neonates than in any other age group (p <0.0001). Pediatric and adult serum sCD40L levels were not significantly different. Conclusions Plasma sCD40L levels are highest at birth and remain higher than those in adults throughout childhood. Reasons for such developmental changes remain to be investigated. Age appropriate reference ranges should be used when sCD40L is being evaluated in pediatric disorders. PMID:18154898

  19. On the efficiency of water soluble antioxidants.

    PubMed

    Elia, Paz; Azoulay, Amnon; Zeiri, Yehuda

    2012-03-01

    The wide use of high intensity ultrasound (HIU) in modern medicine raises the question of bio-safety. It has been shown that the effect of HIU in biological media may have similarity to the effects of ionizing radiation. Exposure of biological media to HIU field may lead to cavitation phenomenon followed by formation of free radicals such as hydroxyl radical (OH(·)) and the super-oxide ion (O(2)(·-)). These are highly reactive species that may cause harmful effects and induce oxidative stress. In the present study we employed electron spin resonance (ESR) spectroscopy together with spin traps to quantify the dynamics of hydroxyl radical formation during exposure to HIU field in the presence of different amounts of six antioxidants. Thus, the efficiency of water-soluble antioxidants, namely Allicin, Melatonin, Deoxyribose, Trolox, Nuphlutine and Hermidin, to suppress accumulation of OH radicals was examined. The results show that among the six, Trolox and Allicin reduce hydroxyl concentration with the highest efficiency. PMID:21798788

  20. 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

  1. Apoptosis induced by islet amyloid polypeptide soluble oligomers is neutralized by diabetes-associated specific antibodies

    PubMed Central

    Bram, Yaron; Frydman-Marom, Anat; Yanai, Inbal; Gilead, Sharon; Shaltiel-Karyo, Ronit; Amdursky, Nadav; Gazit, Ehud

    2014-01-01

    Soluble oligomeric assemblies of amyloidal proteins appear to act as major pathological agents in several degenerative disorders. Isolation and characterization of these oligomers is a pivotal step towards determination of their pathological relevance. Here we describe the isolation of Type 2 diabetes-associated islet amyloid polypeptide soluble cytotoxic oligomers; these oligomers induced apoptosis in cultured pancreatic cells, permeated model lipid vesicles and interacted with cell membranes following complete internalization. Moreover, antibodies which specifically recognized these assemblies, but not monomers or amyloid fibrils, were exclusively identified in diabetic patients and were shown to neutralize the apoptotic effect induced by these oligomers. Our findings support the notion that human IAPP peptide can form highly toxic oligomers. The presence of antibodies identified in the serum of diabetic patients confirms the pathological relevance of the oligomers. In addition, the newly identified structural epitopes may also provide new mechanistic insights and a molecular target for future therapy. PMID:24589570

  2. 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

  3. Complexation of capsaicin with ?-cyclodextrins to improve pesticide formulations: effect on aqueous solubility, dissolution rate, stability and soil adsorption

    Microsoft Academic Search

    Changyun ShenXinghao; Xinghao Yang; Yan Wang; Jinwen Zhou; Chen Chen

    The binary systems of capsaicin (CP) and ?-cyclodextrin (?CD) or hydroxypropyl-?-cyclodextrin (HP?CD) were investigated in\\u000a an attempt to improve formulations of this pesticide. UV spectral shift methods indicated guest–host complex formation between\\u000a CP and the two cyclodextrins (CDs). Phase solubility analysis showed Bs type diagrams with ?CD, AL type with HP?CD indicating the formation of an inclusion complex at 1:1

  4. Solubility of Lysozyme in Polyethylene Glycol-Electrolyte Mixtures: The Depletion Interaction and Ion-Specific Effects

    PubMed Central

    Bon?ina, Matjaž; Reš?i?, Jurij; Vlachy, Vojko

    2008-01-01

    The solubility of aqueous solutions of lysozyme in the presence of polyethylene glycol and various alkaline salts was studied experimentally. The protein-electrolyte mixture was titrated with polyethylene glycol, and when precipitation of the protein occurred, a strong increase of the absorbance at 340 nm was observed. The solubility data were obtained as a function of experimental variables such as protein and electrolyte concentrations, electrolyte type, degree of polymerization of polyethylene glycol, and pH of the solution; the last defines the net charge of the lysozyme. The results indicate that the solubility of lysozyme decreases with the addition of polyethylene glycol; the solubility is lower for a polyethylene glycol with a higher degree of polymerization. Further, the logarithm of the protein solubility is a linear function of the polyethylene glycol concentration. The process is reversible and the protein remains in its native form. An increase of the electrolyte (NaCl) concentration decreases the solubility of lysozyme in the presence and absence of polyethylene glycol. The effect can be explained by the screening of the charged amino residues of the protein. The solubility experiments were performed at two different pH values (pH = 4.0 and 6.0), where the lysozyme net charge was +11 and +8, respectively. Ion-specific effects were systematically investigated. Anions such as Br?, Cl?, F?, and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{H}}_{2}{\\mathrm{PO}}_{4}^{-}\\end{equation*}\\end{document} (all in combination with Na+), when acting as counterions to a protein with positive net charge, exhibit a strong effect on the lysozyme solubility. The differences in protein solubility for chloride solutions with different cations Cs+, K+, and Na+ (coions) were much smaller. The results at pH = 4.0 show that anions decrease the lysozyme solubility in the order \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{F}}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{H}}_{2}{\\mathrm{PO}}_{4}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{Cl}}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{Br}}^{-}\\end{equation*}\\end{document} (the inverse Hofmeister series), whereas cations follow the direct Hofmeister series (Cs+ < K+ < Na+) in this situation. PMID:18441020

  5. Design, Synthesis, and Biological Activity of 1,3-Disubstituted Ureas as Potent Inhibitors of the Soluble Epoxide Hydrolase of Increased Water Solubility

    E-print Network

    Hammock, Bruce D.

    of the Soluble Epoxide Hydrolase of Increased Water Solubility In-Hae Kim, Christophe Morisseau, Takaho WatanabeEH that are active both in vitro and in vivo. However, their poor solubility in either water or lipid reduces, water solubility, octanol/water partition coefficients (log P), and melting points. No loss

  6. Tat Peptide-Mediated Soluble Expression of the Membrane Protein LSECtin-CRD in Escherichia coli

    PubMed Central

    Dong, Guofu; Wang, Changzhen; Wu, Yonghong; Cong, Jianbo; Cheng, Li; Wang, Mingqun; Zhao, Pengkai; Tang, Li; Zhang, Chenggang; Wu, Ke

    2013-01-01

    The human liver and lymph node sinusoidal endothelial cell C-type lectin (hLSECtin), a type II integral membrane protein, containing a Ca2+-dependent carbohydrate recognition domain (CRD), has a well-established biological activity, yet its three-dimensional structure is unknown due to low expression yields and aggregation into inclusion bodies. Previous study has demonstrated that the HIV-1 virus-encoded Tat peptide (‘YGRKKRRQRRR’) can increase the yields and the solubility of heterologous proteins. However, whether the Tat peptide could promote the high-yield and soluble expression of membrane proteins in Escherichia coli is not known. Therefore, the prokaryotic expression vector pET28b-Tat-hLSECtin-CRD (using pET28b and pET28b-hLSECtin-CRD as controls) was constructed, and transformed into E. coli BL21 (DE3) cells and induced with isopropyl-?-d-thiogalactoside (IPTG) followed with identifying by SDS-PAGE and Western blot. Subsequently, the bacterial subcellular structure, in which overexpressed the heterologous proteins Tat-hLSECtin-CRD and Tat-free hLSECtin-CRD, was analyzed by transmission electron microscope (TEM) respectively, and the mannose-binding activity of Tat-hLSECtin-CRD was also determined. Expectedly, the solubility of Tat-LSECtin-CRD significantly increased compared to Tat-free LSECtin-CRD (**p < 0.01) with prolonged time, and the Tat-LSECtin-CRD had a significant mannose-binding activity. The subcellular structure analysis indicated that the bacterial cells overexpressed Tat-hLSECtin-CRD exhibited denser region compared with controls, while dot denser region aggregated in the two ends of bacterial cells overexpressed Tat-free hLSECtin-CRD. This study provided a novel method for improving the soluble expression of membrane proteins in prokaryotic systems by fusion with the Tat peptide, which may be potentially expanded to the expression of other membrane proteins. PMID:24358298

  7. Expression of Betaglycan, an Inhibin Coreceptor, in Normal Human Ovaries and Ovarian Sex Cord-Stromal Tumors and Its Regulation in Cultured Human Granulosa-Luteal Cells

    Microsoft Academic Search

    JIANQI LIU; TIINA KUULASMAA; VELI-MATTI KOSMA; RALF BUTZOW; TEEMU VANTTINEN; CHRISTEL HYDEN-GRANSKOG; RAIMO VOUTILAINEN

    Activins and inhibins are often antagonistic in the regulation of ovarian function. TGF type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we char- acterized the expression and regulation pattern of betaglycan gene in

  8. Soluble ST2 Testing in the General Population.

    PubMed

    Ho, Jennifer E; Sritara, Piyamitr; deFilippi, Christopher R; Wang, Thomas J

    2015-04-01

    ST2 is a member of the interleukin (IL)-1 receptor family biomarker, and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in community-based populations free of cardiovascular disease. This report reviews the role of soluble ST2 in relation to cardiovascular risk factors and clinical outcomes in the general population. Furthermore, the recommendations regarding the role of soluble ST2 in general population-based testing, as formulated by the International ST2 Consensus Panel, are presented. There may be a role for soluble ST2 in improving current risk-stratification strategies for the prediction of cardiovascular outcomes, potentially in combination with other biomarkers in a multimarker strategy. However, the role of soluble ST2 testing in the general population has not yet been conclusively established. Future studies investigating the clinical utility of soluble ST2 screening in the general population are warranted. PMID:25665763

  9. 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.

  10. 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.

  11. CCN activation of fumed silica aerosols mixed with soluble pollutants

    NASA Astrophysics Data System (ADS)

    Dalirian, M.; Keskinen, H.; Ahlm, L.; Ylisirniö, A.; Romakkaniemi, S.; Laaksonen, A.; Virtanen, A.; Riipinen, I.

    2014-09-01

    Particle-water interactions of completely soluble or insoluble particles are fairly well understood but less is known of aerosols consisting of mixtures of soluble and insoluble components. In this study, laboratory measurements were performed to investigate cloud condensation nuclei (CCN) activity of silica particles coated with ammonium sulphate (a salt), sucrose (a sugar) and bovine serum albumin known as BSA (a protein). In addition, the agglomerated structure of the silica particles was investigated by estimating the surface equivalent diameter based on measurements with a Differential Mobility Analyzer (DMA) and an Aerosol Particle Mass Analyzer (APM). By using the surface equivalent diameter the non-sphericity of the particles containing silica was accounted for when estimating CCN activation. Furthermore, characterizing critical supersaturations of particles consisting of pure soluble on insoluble compounds using existing frameworks showed that the CCN activation of single component particles was in good agreement with Köhler and adsorption theory based models when the agglomerated structure was accounted for. For mixed particles the CCN activation was governed by the soluble components, and the soluble fraction varied considerably with particle size for our wet-generated aerosols. Our results confirm the hypothesis that knowing the soluble fraction is the key parameter needed for describing the CCN activation of mixed aerosols, and highlight the importance of controlled coating techniques for acquiring a detailed understanding of the CCN activation of atmospheric insoluble particles mixed with soluble pollutants.

  12. Generation of a vector suite for protein solubility screening

    PubMed Central

    Correa, Agustín; Ortega, Claudia; Obal, Gonzalo; Alzari, Pedro; Vincentelli, Renaud; Oppezzo, Pablo

    2014-01-01

    Recombinant protein expression has become an invaluable tool for academic and biotechnological projects. With the use of high-throughput screening technologies for soluble protein production, uncountable target proteins have been produced in a soluble and homogeneous state enabling the realization of further studies. Evaluation of hundreds conditions requires the use of high-throughput cloning and screening methods. Here we describe a new versatile vector suite dedicated to the expression improvement of recombinant proteins (RP) with solubility problems. This vector suite allows the parallel cloning of the same PCR product into the 12 different expression vectors evaluating protein expression under different promoter strength, different fusion tags as well as different solubility enhancer proteins. Additionally, we propose the use of a new fusion protein which appears to be a useful solubility enhancer. Above all we propose in this work an economic and useful vector suite to fast track the solubility of different RP. We also propose a new solubility enhancer protein that can be included in the evaluation of the expression of RP that are insoluble in classical expression conditions. PMID:24616717

  13. Hydrogen Solubility in Al-bearing Perovskite

    NASA Astrophysics Data System (ADS)

    Watson, H. C.; Krawczynski, M. J.; Fei, Y.

    2005-12-01

    It is generally accepted that silicate perovskite is the dominant mineral in the Earth's lower mantle. Previous studies have been completed to determine the physical and chemical characteristics of the pure end-member MgSiO3. Recent studies have shown that the addition of Al to MgSiO3 can have a significant effect on the material properties of the mineral, such as compressibility, and defect structure, as well as a great potential to dissolve water. We have synthesized Al-bearing perovskite samples under hydrous conditions in a multi-anvil apparatus at pressures ranging from 23-26 GPa and 1800oC. The starting materials consisted of brucite and silica powders mixed together and finely ground in a 1:1 molar ratio, with subsequent addition of Al2O3 powder at 2wt% intervals from 0%-6%. The mixed powders were tightly packed in Au capsules, housed in BN sleeves, and loaded into standard 8/3 multi-anvil assemblies. The experiments were brought to the appropriate pressure conditions for solubility of the different Al2O3 contents. The resulting perovskite crystals range in size from <20 microns to >100 microns in size. Their major element chemistry has been characterized by EPMA, and the H content of some samples has been measured by secondary ion mass spectrometry using a 6f Cameca ion microprobe and is substantial (>1200ppm in some samples). In this study, we correlate H content in the perovskites with Al concentration, and discussion follows on what effects this may have on potential substitution mechanisms, and correlated formation of oxygen vacancies, as well as water storage in the mantle, oxygen diffusion, and the potential of an oxygen ionic diffusion contribution to electrical conductivity in the mantle.

  14. Effect of dry heat processing of sorghum on nitrogen solubility and utilization in the ruminant

    E-print Network

    Connelly, Jon Christie

    1979-01-01

    must be evaluated along with its solubility. Mangan (1972) demonstrated that proteins of different solubilities are degraded in the rumen at their own respective rates even when fed together. Therefore, to reliably formulate rations by soluble...

  15. Organic-inorganic nanocomposite membranes from highly ordered mesoporous thin films for solubility-based separations

    E-print Network

    Yoo, Suk Joon

    2009-05-15

    Solubility-based membrane separation, in which the more soluble species preferentially permeates across the membrane, has attracted considerable recent attention due to both economic and environmental concerns. This solubility-selective mode...

  16. 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...

  17. 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...

  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. Soluble aromatic polyimides for film and coating applications

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

    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.

  20. 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.

  1. The solubility of hydrogen in rhodium, ruthenium, iridium and nickel.

    NASA Technical Reports Server (NTRS)

    Mclellan, R. B.; Oates, W. A.

    1973-01-01

    The temperature variation of the solubility of hydrogen in rhodium, ruthenium, iridium, and nickel in equilibrium with H2 gas at 1 atm pressure has been measured by a technique involving saturating the solvent metal with hydrogen, quenching, and analyzing in resultant solid solutions. The solubilities determined are small (atom fraction of H is in the range from 0.0005 to 0.00001, and the results are consistent with the simple quasi-regular model for dilute interstitial solid solutions. The relative partial enthalpy and excess entropy of the dissolved hydrogen atoms have been calculated from the solubility data and compared with well-known correlations between these quantities.

  2. Predicting the solubility of recombinant proteins in Escherichia coli.

    PubMed

    Harrison, Roger G; Bagajewicz, Miguel J

    2015-01-01

    We describe a statistical model that uses binomial logistic regression for predicting the solubility of heterologous proteins expressed in E. coli. The model is based on a set of proteins reported to have been expressed in E. coli in either soluble or insoluble form. The 22 parameters used in the final model based on proteins' amino acid composition are discussed. The overall accuracy of the model developed is 94%. The way to use this model on the website http://www.ou.edu/ for the prediction of protein solubility is explained. PMID:25447878

  3. 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.

  4. Structural Characterization of Minor Ampullate Spidroin Domains and Their Distinct Roles in Fibroin Solubility and Fiber Formation

    PubMed Central

    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-CTDMi, the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTDMi 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-CTDMi 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

  5. 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

  6. 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 ...

  7. Water-soluble dopamine-based polymers for photoacoustic imaging.

    PubMed

    Repenko, Tatjana; Fokong, Stanley; De Laporte, Laura; Go, Dennis; Kiessling, Fabian; Lammers, Twan; Kuehne, Alexander J C

    2015-03-24

    Here we present a facile synthetic method yielding a linear form of polydopamine via Kumada-coupling, which can be converted into water-soluble melanin, generating high contrast in photoacoustic imaging. PMID:25670068

  8. Acid soluble platelet aggregating material isolated from human umbilical cord

    SciTech Connect

    Schneider, M.D.

    1983-12-27

    An acid soluble, pepsin sensitive platelet aggregating material is isolated from human umbilical cord tissue by extraction with dilute aqueous acid. The method of isolation is disclosed and its use to control bleeding is described. 2 figs.

  9. 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...

  10. Which Starch Fraction is Water-Soluble, Amylose or Amylopectin?

    ERIC Educational Resources Information Center

    Green, Mark M.; And Others

    1975-01-01

    A survey of 22 popular organic chemistry textbooks showed that only four correctly stated that of the two components of starch, amylopectin is the water-soluble, and amylose is the water-insoluble. (MLH)

  11. Anomalous solubility behavior of mixed monolayer protected metal nanoparticles

    E-print Network

    Myerson, Jacob W

    2005-01-01

    The solubility of mixed monolayer protected gold nanoparticles was studied. Monolayer protected metal nanoparticles are attractive materials because of the optical and electronic properties of their metal cores and because ...

  12. 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.

  13. The solubility of Fish Produced High Magnesium Calcite in Seawater

    NASA Astrophysics Data System (ADS)

    Woosley, R. J.; Millero, F. J.; Grosell, M.

    2011-12-01

    Fish have been shown to produce high 10 to 30% magnesium calcite as part of the physiological mechanisms responsible for maintaining salt and water balance. The importance of this source to the marine carbon cycle is only now being considered. In this paper we report the first measurements of the solubility of this CaCO3 in seawater. The resulting solubility (pKsp = 5.85 ± 0.07) is more than two times higher than aragonite and similar to the high magnesium calcite generated on the Bahamas Banks (pKsp = 5.90). This high solubility of fish produced CaCO3 renders it soluble in near surface (<2000 m) waters contributing to the input of carbonate to surface ocean waters, and at least partially explaining the increase in total alkalinity above the aragonite saturation horizon.

  14. 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.

  15. Soluble guanylate cyclase stimulators in pulmonary hypertension.

    PubMed

    Stasch, Johannes-Peter; Evgenov, Oleg V

    2013-01-01

    Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating pulmonary vascular tone is demonstrated by the dysregulation of NO production, sGC activity and cGMP degradation in pulmonary hypertension (PH). The sGC stimulators are novel pharmacological agents that directly stimulate sGC, both independently of NO and in synergy with NO. Optimisation of the first sGC stimulator, YC-1, led to the development of the more potent and more specific sGC stimulators, BAY 41-2272, BAY 41-8543 and riociguat (BAY 63-2521). Other sGC stimulators include CFM-1571, BAY 60-4552, vericiguat (BAY 1021189), the acrylamide analogue A-350619 and the aminopyrimidine analogues. BAY 41-2272, BAY 41-8543 and riociguat induced marked dose-dependent reductions in mean pulmonary arterial pressure and vascular resistance with a concomitant increase in cardiac output, and they also reversed vascular remodelling and right heart hypertrophy in several experimental models of PH. Riociguat is the first sGC stimulator that has entered clinical development. Clinical trials have shown that it significantly improves pulmonary vascular haemodynamics and increases exercise ability in patients with pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH associated with interstitial lung disease. Furthermore, riociguat reduces mean pulmonary arterial pressure in patients with PH associated with chronic obstructive pulmonary disease and improves cardiac index and pulmonary vascular resistance in patients with PH associated with left ventricular systolic dysfunction. These promising results suggest that sGC stimulators may constitute a valuable new therapy for PH. Other trials of riociguat are in progress, including a study of the haemodynamic effects and safety of riociguat in patients with PH associated with left ventricular diastolic dysfunction, and long-term extensions of the phase 3 trials investigating the efficacy and safety of riociguat in patients with PAH and chronic thromboembolic PH. Finally, sGC stimulators may also have potential therapeutic applications in other diseases, including heart failure, lung fibrosis, scleroderma and sickle cell disease. PMID:24092345

  16. 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

  17. In vitro analysis of zinc solubility in breakfast cereals

    SciTech Connect

    Woodhouse, L.R.; Carlson, M.S.; King, J.C. (Univ. of California, Berkeley (United States))

    1991-03-15

    Breakfast cereals are often fortified with zinc (Zn), as well as other minerals. The purpose of this study was to determine to what extent the grain matrix of the cereal affects the solubility of the Zn. Ten whole or mixed-grain cereals were analyzed for Zn content by AAS, and Zn solubility was assessed by an in vitro digestion method. Cereals used were fortified with Zn to 100% US RDA, 25% US RDA, and non-fortified . An in vitro digestion method was developed using pepsin and pancreatin, followed by a filtration step, in order to determine the percent of Zn released from the matrix, defined as Zn solubility. The 100% fortified cereals yielded 19-35% soluble Zn, the 25% fortified cereals yielded 6-25% soluble Zn, and the non-fortified cereals yielded 0-17% soluble Zn. Those fortified cereals containing corn, rice, oat, or wheat as the primary ingredient showed decreasing Zn solubility values of 31-35%, 25%, 23%, and 6-20%, respectively. Theoretically, only the soluble Zn would be available for absorption, suggesting that these results may give a rough estimation of Zn bioavailability. In general, a 100% Zn-may give a rough estimation of Zn bioavailability. In general, a 100% Zn-fortified cereal will provide more available Zn than a 25% or non-fortified cereal, and the extent of availability depends in part on the grain matrix of the cereal. Those Zn-fortified cereals containing grains other than wheat may provide a more absorbable Zn source.

  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. Diffusion and solubility of HCl in ice: Preliminary results

    SciTech Connect

    Domine, F.; Thibert, E.; Van Landeghem, F.; Silvente, E.; Wagnon, P. [CNRS, St. Martin (France)] [CNRS, St. Martin (France)

    1994-04-01

    The authors have measured the diffusion and solubility of gaseous HCl into ice in the temperature range from {minus}5 to {minus}15{degree}C. This information is of relevance since the question of the incorporation of HCl into the nucleation crystals which grow during the formation of polar stratospheric clouds is important due to the impact on this active chlorine compound in the atmosphere. The solubility and diffusion coefficient are both found to be quite small.

  20. Cytoprotective activities of water-soluble fullerenes in zebrafish models

    Microsoft Academic Search

    Florian Beuerle; Patrick Witte; Uwe Hartnagel; Russell Lebovitz; Chuenlei Parng; Andreas Hirsch

    2007-01-01

    Using zebrafish (Danio rerio) embryos as a model system, we compared the antioxidant and cytoprotective effects of a series of new water-soluble fullerenes 1–12. Since zebrafish embryos are transparent during the first week of life, the effects of fullerenes on multiple organ systems, including CNS, PNS, and heart, could be assessed in situ. Both positively charged and negatively charged water-soluble

  1. Solubilities of bone mineral from archaeological sites: the recrystallization window

    Microsoft Academic Search

    Francesco Berna; Alan Matthews; Stephen Weiner

    2004-01-01

    Bone mineral solubility is an important parameter for understanding the preservation of bones in the archaeological and palaeontological records. In this study we have measured the solubility of the carbonated hydroxyl apatite of sub-recent and fossil bones, as well as synthetic hydroxyl apatite in deionized water and in pH-buffered solutions. The solutions were open to the atmosphere and the pH

  2. Characterization of the water soluble component of inedible residue from candidate CELSS crops

    NASA Technical Reports Server (NTRS)

    Garland, Jay

    1992-01-01

    Recycling of inorganic nutrients required for plant growth will be a necessary component of a fully closed, bioregenerative life support system. This research characterized the recovery of plant nutrients from the inedible fraction of three crop types (wheat, potato, and soybean) by soaking, or leaching, in water. A considerable portion of the dry weight of the inedible biomass was readily soluble (29 percent for soybean, 43 percent for wheat, and 52 percent for potato). Greater weight loss from potato was a result of higher tissue concentrations of potassium, nitrate, and phosphate. Approximately 25 percent of the organic content of the biomass was water soluble, while the majority of most inorganic nutrients, except for calcium and iron, were recovered in the leachate. Direct use of the leachates in hydroponic media could provide between 40-90 percent of plant nutrient demands for wheat, and 20-50 percent of demand for soybean and potato. Further evaluation of leaching as a component of resource recovery scheme in a bioregenerative system requires study of (1) utilization of plant leachates in hydroponic plant culture; and (2) conversion of organic material (both soluble and insoluble) into edible, or other useful, products.

  3. 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.

  4. Oxireductases in the Enzymatic Synthesis of Water-Soluble Conducting Polymers

    NASA Astrophysics Data System (ADS)

    Ochoteco, Estibalitz; Mecerreyes, David

    This chapter reviews recent advances in the field of biocatalytic synthesis of water-soluble conducting polymers. Biocatalysis is proposed as a versatile tool for synthesis of conducting polymers. First, the enzymatic synthesis of conducting polymers and its mechanism is discussed as well as the use of different type of enzymes. Next, we describe the use of a new bifunctional template (sodium dodecyl diphenyloxide disulfonate) in the synthesis of polyaniline as a strategy to improve the water solubility and electrical conductivity in the obtained polymer. The recent development of enzyme-catalyzed polymerization of 3,4-ethylenedioxythiophene (EDOT) in the presence of polystyrenesulfonate is discussed. This method results in PEDOT materials that show an electrical conductivity of 2 × 1{0}^{-3} {S cm}^{-1} and posses excellent film formation ability, as confirmed by atomic force microscopy images. Finally, a simple method for immobilizing horseradish peroxidases in the biocatalytic synthesis of water-soluble conducting polymers is presented. This method is based on a biphasic catalytic system in which the enzyme is encapsulated inside the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, while other components remain in the aqueous phase. The enzyme is easily recovered after reaction and can be reused several times.

  5. 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

  6. 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.

  7. 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.

  8. Process optimization of developer soluble organic BARC and its characteristics in CMOS devices

    NASA Astrophysics Data System (ADS)

    Lim, Yeon Hwa; Kim, Young Keun; Choi, Jae Sung; Lee, Jeong Gun

    2005-05-01

    As the IC industry is moving toward 90nm node or below, the critical dimension size of implant layers has shrunk to 250nm or smaller. To achieve better CD uniformity, dyed KrF resist and top anti-reflective coating (TARC) are commonly used in advanced photo process of implant layers, while typical organic BARC are not used because it requires dry etch process that damages the substrate and needs additional process steps. In order to overcome those shortcomings, developable BARC is introduced. It is a new type of BARC which is soluble to developer, TMAH solution, in the resist development step. This developer-soluble KrF BARC consists of polyamic acid and its solubility to alkaline could be adjusted by changing bake condition. In this experiment, we evaluated the margin of developable BARC process. Developable BARC reduces the standing wave of photoresist and improves the ID bias and CD uniformity as applied to implant feature printing. However, Developable BARC has a narrow thermal process margin. It is the profile of developable BARC that easily changes according to the coating thickness or thermal process conditions. Even in the same bake conditions, developable BARC profile changes according to the pattern densities. To observe the effects of developable BARC on the device performance, we compare electrical data of devices produced with and without developable BARC. They have the differences in the threshold voltage, leakage current and saturation current. Probably, the residues of the developable BARC after the development bring about the differences.

  9. 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

  10. THE EFFECT OF FLUORIDE ON LEAD SOLUBILITY

    EPA Science Inventory

    Difficulties in predicting and controlling lead corrosion are encountered by hundreds of water systems across the country. Inorganic carbonate, sulfate, silicate, orthophosphate, pH, total organic carbon, temperature and the type/amount of chlorine residual are all known factors ...

  11. Development of meloxicam formulations utilizing ternary complexation for solubility enhancement.

    PubMed

    Awasthi, Saraf Shubhini; Kumar, Tripathi Girish; Manisha, Pandey; Preeti, Yadav; Kumar, Saraf Shailendra

    2011-10-01

    Meloxicam (an oxicam derivative), a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water (8µg/ml), which directly influences the C(max), T(max), as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using ?-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC (methocel IH), methylcellulose (400cps), PVP K30, HPMC (K(4)M), HPMC (50cps). It is reported that when small amount of water soluble polymer is added to ?-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of ?-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility (90 µg/ml) of the drug and results in superior formulations of the drug by using ?-cyclodextrin blended with 0.12% w/w HPMC (Methocel IH). Ternary complexation is a valuable tool for solubility enhancement of drugs. PMID:21959817

  12. Solubility and speciation studies for nuclear repository performance assessment

    SciTech Connect

    Nitsche, H.

    1990-10-01

    Solubility and speciation data are important in understanding aqueous radionuclide transport through the geosphere. They define the source term for transport retardation processes such as sorption and colloid formation. Solubility and speciation data are useful in verifying the validity of geochemical codes that are part of the predictive transport models. Radionuclide solubility studies in groundwaters from a repository region will provide limits on radionuclide concentrations in these waters. Meaningful thermodynamically defined solubility studies must satisfy four criteria: (1) solution equilibrium conditions, (2) effective and complete phase separation, (3) a well-defined solid phase, and (4) knowledge of the speciation/oxidation state of the soluble species at equilibrium. Results from solubility and speciation experiments of {sup 237}NpO{sub 2}{sup +}, {sup 239}Pu{sup 4+}, and {sup 241}Am{sup 3+}/Nd{sup 3+} in J-13 groundwater (from the Yucca Mountain region, Nevada, which is being investigated as a potential high-level nuclear waste disposal site) at three different temperatures (25{degrees}, 60{degrees}, and 90{degrees}C) and pH values (6, 7, and 8.5) are presented.

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

    PubMed Central

    Guglielmi, Laurence; Denis, Vincent; Vezzio-Vié, Nadia; Bec, Nicole; Dariavach, Piona; Larroque, Christian; Martineau, Pierre

    2011-01-01

    Single-chain antibody fragments (scFv) expressed in the cytoplasm of mammalian cells, also called intrabodies, have many applications in functional proteomics. These applications are however limited by the aggregation-prone behaviour of many intrabodies. We show here that two scFv with highly homologous sequences and comparable soluble expression levels in E. coli cytoplasm, have different behaviours in mammalian cells. When over-expressed, one of the scFv aggregates in the cytoplasm whereas the second one is soluble and active. When expressed at low levels, using a retroviral vector, as a fusion with the green fluorescent protein (GFP) the former does not form aggregates and is degraded, resulting in weakly fluorescent cells, whereas the latter is expressed as soluble protein, resulting in strongly fluorescent cells. These data suggest that the GFP signal can be used to evaluate the soluble expression of intrabodies in mammalian cells. When applied to a subset of an E. coli optimised intrabody library, we showed that the population of GFP+ cells contains indeed soluble mammalian intrabodies. Altogether, our data demonstrate that the requirements for soluble intrabody expression are different in E. coli and mammalian cells, and that intrabody libraries can be directly optimised in human cells using a simple GFP-based assay. PMID:21997307

  14. Sensitivity analysis of uranium solubility under strongly oxidizing conditions

    SciTech Connect

    Liu, L.; Neretnieks, I.

    1999-07-01

    To evaluate the effect of geochemical conditions in the repository on the solubility of uranium under strongly oxidizing conditions, a mathematical model has been developed to determine the solubility, by utilizing a set of nonlinear algebraic equations to describe the chemical equilibria in the groundwater environment. The model takes into account the predominant precipitation-dissolution reactions, hydrolysis reactions and complexation reactions that may occur under strongly oxidizing conditions. The model also includes the solubility-limiting solids induced by the presence of carbonate, phosphate, silicate, calcium, and sodium in the groundwater. The thermodynamic equilibrium constants used in the solubility calculations are essentially taken from the NEA Thermochemical Data Base of Uranium, with some modification and some uranium minerals added, such as soddyite, rutherfordite, uranophane, uranyl orthophosphate, and becquerelite. By applying this model, the sensitivities of uranium solubility to variations in the concentrations of various groundwater component species are systematically investigated. The results show that the total analytical concentrations of carbonate, phosphate, silicate, and calcium in deep groundwater play the most important role in determining the solubility of uranium under strongly oxidizing conditions.

  15. The Effects of Acetate Buffer Concentration on Lysozyme Solubility

    NASA Technical Reports Server (NTRS)

    Forsythe, Elizabeth L.; Pusey, Marc L.

    1996-01-01

    The micro-solubility column technique was employed to systematically investigate the effects of buffer concentration on tetragonal lysozyme solubility. While keeping the NaCl concentrations constant at 2%, 3%, 4%, 5% and 7%, and the pH at 4.0, we have studied the solubility of tetragonal lysozyme over an acetate buffer concentration range of 0.01M to 0.5M as a function of temperature. The lysozyme solubility decreased with increasing acetate concentration from 0.01M to 0.1M. This decrease may simply be due to the net increase in solvent ionic strength. Increasing the acetate concentration beyond 0.1M resulted in an increase in the lysozyme solubility, which reached a peak at - 0.3M acetate concentration. This increase was believed to be due to the increased binding of acetate to the anionic binding sites of lysozyme, preventing their occupation by chloride. In keeping with the previously observed reversal of the Hoffmeister series for effectiveness of anions in crystallizing lysozyme, acetate would be a less effective precipitant than chloride. Further increasing the acetate concentration beyond 0.3M resulted in a subsequent gradual decrease in the lysozyme solubility at all NaCl concentrations.

  16. 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

  17. 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

  18. 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

  19. 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

  20. Withaferin A Effectively Targets Soluble Vimentin in the Glaucoma Filtration Surgical Model of Fibrosis

    PubMed Central

    Bargagna-Mohan, Paola; Deokule, Sunil P.; Thompson, Kyle; Wizeman, John; Srinivasan, Cidambi; Vooturi, Sunil; Kompella, Uday B.; Mohan, Royce

    2013-01-01

    Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G0/G1 cell cycle inhibition (IC50 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27Kip1 expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked potently by downregulating soluble vimentin and ?-smooth muscle actin (SMA) expression. In the pilot proof-of-concept study using the GFS model, subconjunctival injections of a low WFA dose reduced skp2 expression in Tenon's capsule and increased p27Kip1 expression without significant alteration to vimentin-IFs. This treatment maintains significant nanomolar WFA concentrations in anterior segment tissues that correspond to WFA's cell cycle targeting activity. A ten-fold higher WFA dose caused potent downregulation of soluble vimentin and skp2 expression, but as found in cell cultures, no further increase in p27Kip1 expression was observed. Instead, this high WFA dose potently induced vimentin-IF disruption and downregulated ?-SMA expression that mimicked WFA activity in TGF-ß-treated RbTCFs that blocked cell contractile activity at submicromolar concentrations. These findings illuminate that localized WFA injection to ocular tissues exerts pharmacological control over the skp2-p27Kip1 pathway by targeting of soluble vimentin in a model of surgical fibrosis. PMID:23667686