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A soluble activin type IIA receptor induces bone formation and improves skeletal integrity  

PubMed Central

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-? superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-? signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility. PMID:18460605

Pearsall, R. Scott; Canalis, Ernesto; Cornwall-Brady, Milton; Underwood, Kathryn W.; Haigis, Brendan; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Werner, Eric D.; Glatt, Vaida; Stadmeyer, Lisa; Smith, Deanna; Seehra, Jasbir; Bouxsein, Mary L.



A Soluble Activin Receptor Type IIB Does Not Improve Blood Glucose in Streptozotocin-Treated Mice  

PubMed Central

Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of MSTN signaling has been shown to increase muscle mass and prevent the development of obesity, insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also elevated serum levels of the glucocorticoid corticosterone. These results suggest that although MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving health in patients with T1DM. PMID:25561902

Wang, Qian; Guo, Tingqing; Portas, Jennifer; McPherron, Alexandra C.



The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity  

PubMed Central

Myostatin, also known as Growth and Differentiation Factor 8, is a secreted protein that inhibits muscle growth. Disruption of myostatin signaling increases muscle mass and decreases glucose, but it is unclear whether these changes are related. We treated mice on chow and high-fat diets with a soluble activin receptor type IIB (ActRIIB.Fc) which is a putative endogenous signaling receptor for myostatin and other ligands of the TGF-? superfamily. After 4 weeks, RAP-031 increased lean and muscle mass, grip strength, and contractile force. RAP-031 enhanced the ability of insulin to suppress glucose production under clamp conditions in high-fat fed mice, but did not significantly change insulin-mediated glucose disposal. The hepatic insulin sensitizing effect of RAP-031 treatment was associated with increased adiponectin levels. RAP-031 treatment for 10 weeks further increased muscle mass and drastically reduced fat content in mice on either chow or high-fat diet. RAP-031 suppressed hepatic glucose production and increased peripheral glucose uptake in chow fed mice. In contrast, RAP-031 suppressed glucose production with no apparent change in glucose disposal in high-fat diet mice. Our findings demonstrate that disruption of ActRIIB signaling is a viable pharmacological approach for treating obesity and diabetes. PMID:19668253

Akpan, Imo; Goncalves, Marcus D.; Dhir, Ravindra; Yin, Xiaoyan; Pistilli, Emidio; Bogdanovich, Sasha; Khurana, Tejvir; Ucran, Jeffrey; Lachey, Jennifer; Ahima, Rexford S.



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

PubMed Central

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



Regulation of body mass growth through activin type IIB receptor in teleost fish.  


Myostatin is a TGF-beta family member that plays a key role in regulating skeletal muscle growth. Previous studies in mammals have demonstrated that myostatin is capable of binding the two activin type II receptors. Additionally, activin type II receptors have been shown to be capable of binding a number of other TGF-beta family members besides myostatin. An injection of a soluble form of activin type IIB receptor obtained from CHO cells into wild-type mice generated up to a 60% increase in muscle mass in 2 weeks. The knowledge on the role of activin receptors in fish is limited. In the present study, we examined the growth effect of administering a recombinant, soluble form of goldfish activin type IIB receptor extracellular domain to juvenile and larval goldfish (Carassius auratus), African catfish (Clarias gariepinus) larvae and tilapia (Oreochromis aureus) larvae. We have expressed the goldfish activin type IIB receptor extracellular domain in the yeast Pichia pastoris and we have demonstrated for the first time that this recombinant molecule stimulates growth in teleost fish in a dose-dependent manner. We provide evidence that this body weight increase is achieved by an increase in muscle mass and protein content. Histological analysis of the goldfish muscle revealed that treated fish exhibited hyperplasia as compared to controls. These findings contribute to the understanding of the mechanisms that regulate growth in non-mammalian vertebrates and suggest a powerful biotechnology approach to improving fish growth in aquaculture. PMID:19056390

Carpio, Yamila; Acosta, Jannel; Morales, Reynold; Santisteban, Yaimín; Sanchéz, Aniel; Estrada, Mario Pablo



An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy  

PubMed Central

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

Minetti, Giulia C.; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N.; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji



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


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

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



Impaired male sexual behavior in activin receptor type II knockout mice.  


Integration of multiple hormonal and neuronal signaling pathways in the medial preoptic area (mPOA) is required for elicitation of male sexual behavior in most vertebrates. Perturbation of nitric oxide synthase (NOS) activity in the mPOA causes significant defects in male sexual behavior. Although activins and their signaling components are highly expressed throughout the brain, including the mPOA, their functional significance in the central nervous system (CNS) is unknown. Here, we demonstrate a neurophysiologic role for activin signaling in male reproductive behavior. Adult activin receptor type II null (Acvr2-/-) male mice display multiple reproductive behavioral deficits, including delayed initiation of copulation, reduced mount, and intromission frequencies, and increased mount, intromission, and ejaculation latencies. These behavioral defects in the adult mice are independent of gonadotropin-releasing hormone (GnRH) homeostasis or mating-induced changes in luteinizing hormone (LH) and testosterone levels. The impairment in behavior can be correlated to the nitric oxide content in the CNS because Acvr2-/- males have decreased NOS activity in the mPOA but not the rest of the hypothalamus or cortex. Olfactory acuity tests confirmed that Acvr2-/- mice have no defects in general odor or pheromone recognition. In addition, motor functions are not impaired and the mutants demonstrate normal neuromuscular coordination and balance. Furthermore, the penile histology in mutant mice appears normal, with no significant differences in the expression of penile differentiation marker genes compared with controls, suggesting the observed behavioral phenotypes are not due to structural defects in the penis. Our studies identify a previously unrecognized role of activin signaling in male sexual behavior and suggest that activins and/or related family members are upstream regulators of NOS activity within the mPOA of the forebrain. PMID:16093358

Ma, Xiaoping; Reyna, Andrea; Mani, Shailaja K; Matzuk, Martin M; Kumar, T Rajendra



Cloning of the bovine activin receptor type II gene (ACVR2) and mapping to chromosome 2 (BTA2)  

Microsoft Academic Search

The cDNA for the bovine activin receptor type II (ACVR2) gene has been cloned and sequenced. It encodes a protein of 513 amino acids which is highly homologous (?98 % identity) to the human, mouse, and rat proteins. Using PCR analysis of bovine × hamster somatic cell lines, the ACVR2 gene was mapped to syntenic group U17, which has been

N. Flavin; A. Heriz; L. V. Monteagudo; S. Ennis; F. Martin; W. Barendse; M. V. Arruga; M. Rogers



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


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

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



Molecular Characterization of a Type I Serine-Threonine Kinase Receptor for TGF-? and Activin in the Rat Pituitary Tumor Cell Line GH3  

Microsoft Academic Search

GH3 pituitary tumor cells have surface receptors for transforming growth factors-? (TGF-?s) anti activins\\/inhibins. GH3 cell mRNA was screened by a novel reverse transcriptase-polymerase chain reaction technique with primers for receptor serine-threonine kinases. We isolated rat homologs of previously identified clones for type I (ALK-2 and ALK-5) and type II (ActRH, TGF-?RII) activin and TGF-? receptors, together with a novel

Toru Takumi; Aristidis Moustakas; Herbert Y. Lin; Harvey F. Lodish



Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning.  


Vertebral bodies are segmented along the anteroposterior (AP) body axis, and the segmental identity of the vertebrae is determined by the unique expression pattern of multiple Hox genes. Recent studies have demonstrated that a transforming growth factor beta (TGF-beta) family protein, Gdf11 (growth and differentiation factor 11), and the activin type II receptor, ActRIIB, are involved in controlling the spatiotemporal expression of multiple Hox genes along the AP axis, and that the disruption of each of these genes causes anterior transformation of the vertebrae. Skeletal defects are more severe in Gdf11-null mice than in ActRIIB-null mice, however, leaving it uncertain whether Gdf11 signals via ActRIIB. Here we demonstrate using genetic and biochemical studies that ActRIIB and its subfamily receptor, ActRIIA, cooperatively mediate the Gdf11 signal in patterning the axial vertebrae, and that Gdf11 binds to both ActRIIA and ActRIIB, and induces phosphorylation of Smad2. In addition, we also show that these two receptors can functionally compensate for one another to mediate signaling of another TGF-beta ligand, nodal, during left-right patterning and the development of anterior head structure. PMID:12414726

Oh, S Paul; Yeo, Chang-Yeol; Lee, Youngjae; Schrewe, Heindrich; Whitman, Malcolm; Li, En



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

SciTech Connect

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.

Nomura, Masatoshi, E-mail: [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)



Inhibition of Activin Receptor Type IIB Increases Strength and Lifespan in Myotubularin-Deficient Mice  

PubMed Central

X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells. It was postulated that therapeutically increasing muscle fiber size would cause symptomatic improvement in myotubularin deficiency. Recent studies have elucidated an important role for the activin-receptor type IIB (ActRIIB) in regulation of muscle growth and have demonstrated that ActRIIB inhibition results in significant muscle hypertrophy. To evaluate whether promoting muscle hypertrophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1?4) mice. Compared with wild-type mice, untreated Mtm1?4 mice have decreased body weight, skeletal muscle hypotrophy, and reduced survival. Treatment of Mtm1?4 mice with ActRIIB-mFC produced a 17% extension of lifespan, with transient increases in weight, forelimb grip strength, and myofiber size. Pathologic analysis of Mtm1?4 mice during treatment revealed that ActRIIB-mFC produced marked hypertrophy restricted to type 2b myofibers, which suggests that oxidative fibers in Mtm1?4 animals are incapable of a hypertrophic response in this setting. These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency. PMID:21281811

Lawlor, Michael W.; Read, Benjamin P.; Edelstein, Rachel; Yang, Nicole; Pierson, Christopher R.; Stein, Matthew J.; Wermer-Colan, Ariana; Buj-Bello, Anna; Lachey, Jennifer L.; Seehra, Jasbir S.; Beggs, Alan H.



Goat activin receptor type IIB knockdown by artificial microRNAs in vitro.  


Activin receptor type IIB (ACVR2B) has been known to negatively regulate the muscle growth through mediating the action of transforming growth factor beta superfamily ligands. Recently, the artificial microRNAs (amiRNAs) which are processed by endogenous miRNA processing machinery have been proposed as promising approach for efficient gene knockdown. We evaluated amiRNAs targeting goat ACVR2B in HEK293T and goat myoblasts cells. The amiRNAs were designed based on the miR-155 backbone and cloned in 5'- and 3'-UTR of GFP reporter gene under the CMV promoter. Although both 5'- and 3'-UTR-amiRNAs vectors showed efficient synthesis of GFP transcripts, amiRNAs in 5'-UTR drastically affected GFP protein synthesis in transfected goat myoblast cells. Among the four amiRNAs targeting ACVR2B derived from either 5'- or 3'-UTR, ami318 showed highest silencing efficiency against exogenously co-expressed ACVR2B in both 293T and goat myoblast cells whereas ami204 showed highest silencing efficiency against endogenous ACVR2B in goat myoblasts cells. The 3'-UTR-derived amiRNA exerted higher knockdown efficiency against endogenous ACVR2B at transcript level whereas 5'-UTR-derived amiRNAs exerted higher knockdown efficiency at protein level. The expression of ACVR2B showed positive correlation with the expression of MYOD (r = 0.744; p = 0.009) and MYOG (r = 0.959; p = 0.000) in the amiRNA-transfected myoblasts. Although both 5'- and 3'-UTR-amiRNA vectors led to substantial induction of interferon response, the magnitude of the response was found to be higher with the 3'-UTR-amiRNA vectors. PMID:25080379

Patel, Amrutlal K; Shah, Ravi K; Parikh, Ishan K; Joshi, Chaitanya G



Mutant Activin-Like Kinase 2 in Fibrodysplasia Ossificans Progressiva are Activated via T203 by BMP Type II Receptors.  


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

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



Endoglin-Mediated Suppression of Prostate Cancer Invasion Is Regulated by Activin and Bone Morphogenetic Protein Type II Receptors  

PubMed Central

Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor ? (TGF?) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGF? receptor, activin receptor-like kinase 2 (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGF? receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA) and bone morphogenetic protein receptor type II (BMPRII). Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII’s Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact. PMID:23967299

Breen, Michael J.; Moran, Diarmuid M.; Liu, Wenzhe; Huang, Xiaoke; Vary, Calvin P. H.; Bergan, Raymond C.



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


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

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



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

SciTech Connect

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.

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



Intertwining of Activin A and TGF? Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion.  


In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor ? (TGF?) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGF? superfamily ligands, TGF?, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGF?s and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFb and highlights how its dysregulation contributes to cancer progression and cell invasion. PMID:25560921

Loomans, Holli A; Andl, Claudia D



Activin A inhibits activities of lipopolysaccharide-activated macrophages via TLR4, not of TLR2.  


Activin A, a member of TGF-? superfamily, is involved in either pro-inflammatory or anti-inflammatory responses. Our previous studies have reported that lipopolysaccharide (LPS) can simulate activin A secretion from macrophage, and activin A can induce rest macrophage activation in mice, but inhibit the activities of the activated macrophages. However, the relationship of activin and LPS actions and their mechanism are not well characterized. In the present study, the results showed that both activin A and LPS promoted the phagocytic activities of mouse peritoneal macrophages in vivo and in vitro, but activin A inhibited the phagocytosis of LPS-activated macrophages. Simultaneously, the results revealed that activin A inhibited the Toll-like receptor 4 (TLR4) expression on LPS-activated mouse peritoneal macrophages in vivo and in vitro, whereas there was no obvious change of TLR2 expression. Moreover, the results showed that activin A obviously reduced the TLR4 mRNA and protein expressions in LPS-activated macrophage cell line RAW264.7 cells, and the inhibitory effect of activin A on the TLR4 expression was significantly attenuated in Smad3 knock-down RAW264.7 cells. Interestingly, LPS promoted the expression of activin type IIA receptor (ActRIIA) on mouse peritoneal macrophages in vivo, and also up-regulated ActRIIA and activin signal molecules Smad2, 3 mRNA expressions. These data suggest that activin A inhibits LPS action on macrophages in vivo via suppressing TLR4 expression, and LPS further augments the negative feedback action of activin A via up-regulating activin signaling transduction. PMID:23665022

Li, Nan; Cui, Xueling; Ge, Jingyan; Li, Jiru; Niu, Liman; Liu, Haiyan; Qi, Yan; Liu, Zhonghui; Wang, Yinan



Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants.  

PubMed Central

Activin, a member of the TGF-beta superfamily, regulates the growth and differentiation of a variety of cell types. Based on the expression of activin in pancreatic rudiments of rat embryos and stimulation of insulin secretion from adult rat pancreatic islets by activin, activin is implicated in the development and function of islets. To examine the significance of activin signaling in the fetal and postnatal development of islets, transgenic mice expressing a dominant negative form of activin receptor (dn-ActR) or a constitutively active form of activin receptor (ActR-T206D) in islets were generated together with the transgenic mice expressing intact activin receptor (intact ActR) as a negative control. Transgenic mice with both dn-ActR and ActR-T206D showed lower survival rates, smaller islet area, and lower insulin content in the whole pancreas with impaired glucose tolerance when compared with transgenic mice with intact ActR or littermates, but they showed the same alpha cell/beta cell ratios as their littermates. In addition to islet hypoplasia, the insulin response to glucose was severely impaired in dn-ActR transgenic mice. It is suggested that a precisely regulated intensity of activin signaling is necessary for the normal development of islets at the stage before differentiation into alpha and beta cells, and that activin plays a role in the postnatal functional maturation of islet beta cells. PMID:9664070

Yamaoka, T; Idehara, C; Yano, M; Matsushita, T; Yamada, T; Ii, S; Moritani, M; Hata, J; Sugino, H; Noji, S; Itakura, M



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


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

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



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

SciTech Connect

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.

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:; 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)



Regulation of FSH? induction in L?T2 cells by BMP2 and an Activin A/BMP2 chimera, AB215.  


Activins and bone morphogenetic proteins (BMPs) share activin type 2 signaling receptors but utilize different type 1 receptors and Smads. We designed AB215, a potent BMP2-like Activin A/BMP2 chimera incorporating the high-affinity type 2 receptor-binding epitope of Activin A. In this study, we compare the signaling properties of AB215 and BMP2 in HEK293T cells and gonadotroph L?T2 cells in which Activin A and BMP2 synergistically induce FSH?. In HEK293T cells, AB215 is more potent than BMP2 and competitively blocks Activin A signaling, while BMP2 has a partial blocking activity. Activin A signaling is insensitive to BMP pathway antagonism in HEK293T cells but is strongly inhibited by constitutively active (CA) BMP type 1 receptors. By contrast, the potencies of AB215 and BMP2 are indistinguishable in L?T2 cells and although AB215 blocks Activin A signaling, BMP2 has no inhibitory effect. Unlike HEK293T, Activin A signaling is strongly inhibited by BMP pathway antagonism in L?T2 cells but is largely unaffected by CA BMP type 1 receptors. BMP2 increases phospho-Smad3 levels in L?T2 cells, in both the absence and the presence of Activin A treatment, and augments Activin A-induced FSH?. AB215 has the opposite effect and sharply decreases basal phospho-Smad3 levels and blocks Smad2 phosphorylation and FSH? induction resulting from Activin A treatment. These findings together demonstrate that while AB215 activates the BMP pathway, it has opposing effects to those of BMP2 on FSH? induction in L?T2 cells apparently due to its ability to block Activin A signaling. PMID:25100748

Jung, Jae Woo; Ahn, Chihoon; Shim, Sun Young; Gray, Peter C; Kwiatkowski, Witek; Choe, Senyon



Activin inhibits telomerase activity in cancer  

SciTech Connect

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.

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: [Department of Immunology, Monash University, Melbourne (Australia)] [Department of Immunology, Monash University, Melbourne (Australia)



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


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

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



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

PubMed Central

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

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



Activin Receptor Signaling Regulates Prostatic Epithelial  

E-print Network

RII), as necessary, although not sufficient, for PCC proliferation. Activin A induced Smad2 phosphorylation and PCC or antisense-P de- creased mature ActRII expression, Smad2 phosphorylation, and the apparent viability of PCCs

Sheridan, Jennifer


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


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. Am. J. Hematol. 90:8-14, 2015. © 2014 Wiley Periodicals, Inc. PMID:25236856

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




NSDL National Science Digital Library

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.



Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I.  


Pain hypersensitivity is a cardinal sign of tissue damage, but how molecules from peripheral tissues affect sensory neuron physiology is incompletely understood. Previous studies have shown that activin A increases after peripheral injury and is sufficient to induce acute nociceptive behavior and increase pain peptides in sensory ganglia. This study was designed to test the possibility that the enhanced nociceptive responsiveness associated with activin involved sensitization of transient receptor potential vanilloid I (TRPV1) in primary sensory neurons. Activin receptors were found widely distributed among adult sensory neurons, including those that also express the capsaicin receptor. Whole-cell patch-clamp recording from sensory neurons showed that activin acutely sensitized capsaicin responses and depended on activin receptor kinase activity. Pharmacological studies revealed that the activin sensitization of capsaicin responses required PKCepsilon signaling, but not PI3K (phosphoinositide 3-kinase), ERK (extracellular signal-regulated protein kinase), PKA, PKCalpha/beta, or Src. Furthermore, activin administration caused acute thermal hyperalgesia in wild-type mice, but not in TRPV1-null mice. These data suggest that activin signals through its own receptor, involves PKCepsilon signaling to sensitize the TRPV1 channel, and contributes to acute thermal hyperalgesia. PMID:18077689

Zhu, Weiguo; Xu, Pin; Cuascut, Fernando X; Hall, Alison K; Oxford, Gerry S



Multifunctional Regulation of the Biological Effects of TNF-? by the Soluble Type I and Type II TNF Receptors  

Microsoft Academic Search

Two soluble receptors of tumour necrosis factor were evaluated for development as potential therapeutic agents for inflammatory disease. The recombinant human soluble Type I and Type II TNF receptors, rsTNF-RI and rsTNF-RII, were expressed at high levels in E. coli, refolded, and chromatographically purified to homogeneity. The potencies of both recombinant soluble receptors were similar to their naturally occurring soluble

Karin K. Hale; Christopher G. Smith; Susan L. Baker; Rebecca W. Vanderslice; Charles H. Squires; Thomas M. Gleason; Kathy K. Tucker; Tadahiko Kohno; Deborah A. Russell



Seasonal Changes in Immunoreactivity of Inhibin/Activin Subunits in the Epididymis of Wild Ground Squirrels (Citellus dauricus Brandt)  

PubMed Central

Abstract The inhibin/activin subunits (?, ?A and ?B) have been found in epididymal tissue of many mammals, but there have been no data available for wild seasonal breeders so far. The aim of this study was to investigate the immunoreactivities of inhibin/activin ?, ?A and ?B subunits in the epididymis of wild ground squirrels during the breeding and nonbreeding seasons. Immunohistochemistry and Western blotting were performed to detect the epididymal immunolocalizations and immunoreactivities of the three subunits. Strong immunostaining of ? subunit was present in the interstitial part of the caput epididymis and epithelial parts of the corpus epididymis and cauda epididymis during the breeding season, whereas no ? subunit was found in the nonbreeding season. ?A and ?B subunits were expressed in all cell types of the epithelium throughout the whole seasonal cycle, and immunostaining in the breeding season was likely stronger compared with that of the nonbreeding season. These results suggested that the epididymis might be a potential source of inhibin and activin in the wild male ground squirrel, and the secretion of epididymal inhibin and activin showed distinct seasonal changes. Furthermore, inhibin and activin might function as paracrine and/or autocrine factors that have an effect on the epididymis. PMID:23535148

ZHANG, Mengyuan; SHENG, Xia; SUN, Rongbo; LI, Qinglin; ZHANG, Haolin; ZHOU, Jiao; XU, Meiyu; WENG, Qiang; WATANABE, Gen; TAYA, Kazuyoshi



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

PubMed Central

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

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



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

E-print Network

to activin B in pancreatic islets and beta cells, while Smad2 showed a preference for activin A, indicating, but not Smad2, decreased GSIS in pancreatic islets. Conclusions/interpretation These results reveal a tug

Ibáñez, Carlos


Characterization of Activin/BMP2 chimera, AB204, formulated for preclinical studies.  


AB204 is an Activin/BMP2 chimera, which has been found to exhibit a higher activity than Bone Morphogenetic Protein 2 (BMP2) in osteogenic activity. To prepare AB204 for its preclinical studies, AB204 has been characterized in various formulation buffers. We observed that AB204 purified by ion-exchange chromatography has low water solubility (2.0 mg/ml), whereas it has high water solubility (higher than 10.0 mg/ml) when purified by reverse-phase chromatography. Analysis of the purification procedures reveals that the buffer composition at the lyophilization step determines the solubility. Lyophilization from sodium acetate buffer at pH 4.5 resulted in formation of sodium hydroxide, which caused low solubility of AB204 by pH increase upon reconstitution in water. However, lyophilization from buffers, containing acetic acid or trifluoroacetic acid (TFA) rendered AB204 to be highly soluble. During the course of these analyses, we found a simple procedure to further reduce residual amount of TFA in the purified AB204. PMID:24555430

Ahn, Chihoon; Maslennikov, Innokentiy; Choi, Jung Youn; Oh, Hyosun; Cheong, Chaejoon; Choe, Senyon



Activin-A in myometrium: characterization of the actions on myometrial cells.  


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

Ciarmela, Pasquapina; Wiater, Ezra; Vale, Wylie



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

SciTech Connect

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.

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



Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary*  

E-print Network

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

Mayo, Kelly E.



PubMed Central

PURPOSE Platelet-rich plasma (PRP) has recently been found to be a useful delivery system for growth factors important in oral tissue healing. However, application of PRP in a liquid form to a wound site within the oral cavity can be complicated by significant loss of the PRP into the surrounding oral space unless gelation via the clotting mechanism is accomplished. Gelation is currently accomplished using bovine thrombin; however, rare but serious complications of this method have led to the search for alternative clotting mechanisms, including the use of soluble collagen as a clotting activator. In this paper, our hypothesis was that soluble Type I collagen would be as effective as bovine thrombin in causing clotting of the PRP and of stimulating growth factor release from the platelets and granulocytes. MATERIALS AND METHODS PRP from human donors was clotted using Type I collagen or bovine thrombin. Clot retraction was determined by measuring clot diameters over time. The release of PDGF-AB, TGF-?1 and VEGF from both types of clots was measured over 10 days using ELISA. RESULTS Clots formed using Type I collagen had far less retraction than those formed with bovine thrombin. Bovine thrombin and Type I collagen stimulated similar release of PDGF-AB and VEGF between 1 and 10 days; however, thrombin activation resulted in a greater release of TGF-?1 during the first five days after activation. CONCLUSIONS The use of Type I collagen to activate clotting of PRP may be a safe and effective alternative to bovine thrombin. The use of collagen results in less clot retraction and equal release of PDGF-AB and VEGF when compared to currently available methods of clot activation. PMID:18355591

Fufa, Duretti; Shealy, Blake; Jacobson, May; Kevy, Sherwin; Murray, Martha M.



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

E-print Network

on reporter gene activity, but the combination of Smad2 and Smad4 strongly stimulated transcription. Activin signaling in- duced a rapid relocation of Smad2 to the nucleus, as determined using a green fluorescence protein-Smad2 fusion protein. In contrast, green fluorescence protein-Smad4 remained localized

Mayo, Kelly E.


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


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

Ojeda-May, P; Pu, Jingzhi



Mechanism of Protection by Soluble Epoxide Hydrolase Inhibition in Type 2 Diabetic Stroke  

PubMed Central

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

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



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

PubMed Central

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



The bright and the dark sides of activin in wound healing and cancer.  


Activin was initially described as a protein that stimulates release of follicle stimulating hormone from the pituitary, and it is well known for its important roles in different reproductive functions. In recent years, this multifunctional factor has attracted the attention of researchers in other fields, as new functions of activin in angiogenesis, inflammation, immunity, fibrosis and cancer have been discovered. Studies from our laboratory have identified activin as a crucial regulator of wound healing and skin carcinogenesis. On the one hand, it strongly accelerates the healing process of skin wounds but, on the other hand, it enhances scar formation and the susceptibility to skin tumorigenesis. Finally, results from several laboratories have revealed that activin enhances tumour formation and/or progression in some other organs, in particular through its effect on the tumour microenvironment, and that it also promotes cancer-induced bone disruption and muscle wasting. These findings provide the basis for the use of activin or its downstream targets for the improvement of impaired wound healing, and of activin antagonists for the prevention and treatment of fibrosis and of malignant tumours that overexpress activin. Here, we summarize the previously described roles of activin in wound healing and scar formation and discuss functional studies that revealed different functions of activin in the pathogenesis of cancer. The relevance of these findings for clinical applications will be highlighted. PMID:22991378

Antsiferova, Maria; Werner, Sabine



The activin A-follistatin system: potent regulator of human extracellular matrix mineralization.  


Bone quality is an important determinant of osteoporosis, and proper osteoblast differentiation plays an important role in the control and maintenance of bone quality. We investigated the impact of activin signaling on human osteoblast differentiation, extracellular matrix formation, and mineralization. Activins belong to the transforming growth factor-beta superfamily and activin A treatment strongly inhibited mineralization in osteoblast cultures, whereas the activin antagonist follistatin increased mineralization. Osteoblasts produced activin A and follistatin in a differentiation-dependent manner, leading to autocrine regulation of extracellular matrix formation and mineralization. In addition, mineralization in a vascular smooth muscle cell-based model for pathological calcification was inhibited. Comparative activin A and follistatin gene expression profiling showed that activin signaling changes the expression of a specific range of extracellular matrix proteins prior to the onset of mineralization, leading to a matrix composition with reduced or no mineralizing capacity. These findings demonstrate the regulation of osteoblast differentiation and matrix mineralization by the activin A-follistatin system, providing the possibility to control bone quality as well as pathological calcifications such as atherosclerosis by using activin A, follistatin, or analogs thereof. PMID:17449718

Eijken, Marco; Swagemakers, Sigrid; Koedam, Marijke; Steenbergen, Cobie; Derkx, Pieter; Uitterlinden, André G; van der Spek, Peter J; Visser, Jenny A; de Jong, Frank H; Pols, Huibert A P; van Leeuwen, Johannes P T M



Ferricenium complexes: a new type of water-soluble antitumor agent.  


The antitumor activity of a series of iron complexes, i.e., of ferrocene [Cp2Fe], of tetrachloroferrates(III) [R4N]+[FeCl4]-, and of ferricenium complexes [Cp2Fe]+X- (X- = [FeCl4]-, 1/2 [Cl3FeOFeCl3]2-, [H5Mo7O24]- X 2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]- X 2 CCl3COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic properties, with optimum cure rates of 100%, were found for ferricenium picrate and ferricenium trichloroacetate. The ferricenium compounds are the first iron complexes for which antineoplastic activity has now been shown. They represent a new type of antitumor agent insofar as they differ fundamentally from known inorganic and organometallic antitumor agents (a) by their ionic, salt-like character, which is responsible for their high water solubility, and (b) by the absence of a cis-dihalometal moiety; this moiety has been recognized as important for the intracellular action of other known inorganic cytostatics. PMID:6511806

Köpf-Maier, P; Köpf, H; Neuse, E W



Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)  

PubMed Central

Background Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions. Materials and methods Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45?days. At the planned sacrification time (after 45?days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation. Results NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver. Conclusion The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin. PMID:22762693



Repression of Bone Morphogenetic Protein and Activin-inducible Transcription by Evi-1*  

E-print Network

with Smad1 and Smad2, downstream targets of BMP and activin signaling, re- spectively. Evi-1 interacted with and repressed the re- ceptor-activated transcription through Smad1 and Smad2, similarly to Smad3. In addition, Evi-1 repressed BMP/Smad1- and activin/Smad2-mediated induction of endogenous Xenopus gene expression

Derynck, Rik


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


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

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



Second trimester levels of maternal serum total activin A and placental inhibin\\/activin a and bA subunit messenger ribonucleic acids in Down syndrome pregnancy  

Microsoft Academic Search

Objectives: Previous data have shown that inhibin A (a\\/bA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (bA\\/bA) was similarly increased in maternal serum from pregnancies affected with fetal Down syndrome, and to investigate whether increased expression of each inhibin\\/activin subunit occurred in placental tissue from cases of

Geralyn M Lambert-Messerlian; Stefano Luisi; Pasquale Florio; Vincenzo Mazza; Jacob A Canick; Felice Petraglia


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


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

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



Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients  

PubMed Central

Background The interaction of advanced glycation end products (AGEs) and its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy receptor for AGEs. Oxidative stress is demonstrated in pathological condition such as atherosclerosis and diabetes mellitus. It has been suggested to be involved in the pathogenesis of both macro- and microvascular complications. This study was designed to evaluate the effect of glycemic control on sRAGE and oxidative stress markers in type 2 diabetic patients. Methods Seventy patients with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using commercially available colorimetric kits, blood superoxide dismutase (SOD) activity was measured by the method of Marklund and Marklund, and plasma C-peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using competitive ELISA kits. Results Plasma sRAGE levels were significantly lower (p?



Identification of a new member of transforming growth factor-beta superfamily in Drosophila: the first invertebrate activin gene.  


Activins, a subgroup of the transforming growth factor-beta (TGF-beta) 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 the Drosophila chromosome 4 is found to encode a putative activin beta. The predicted protein sequence has a multibasic protease site that would generate a mature C-terminal peptide containing 113 amino acids showing > 60% similarity to the vertebrate activin beta B (inhibin beta B) sequences. A TGF-beta family signature as well as all 9 cysteine residues conserved in the vertebrate activins are also present in this mature peptide sequence. Northern blot and RT-PCR analyses indicated that the activin beta gene is expressed in embryo, larva and adult stages of Drosophila. PMID:9618266

Kutty, G; Kutty, R K; Samuel, W; Duncan, T; Jaworski, C; Wiggert, B



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


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

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



Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.  


The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general. PMID:24227781

Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine



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

PubMed Central

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

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



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


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.Kidney International advance online publication, 29 October 2014; doi:10.1038/ki.2014.346. PMID:25354239

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



Activin-A promotes the development of goat isolated secondary follicles in vitro.  


Summary The role of activin-A in follicular development and on the mRNA expression levels of different genes in goat secondary follicles was evaluated. Goat secondary follicles (?150 ?m) were cultured for 18 days under control conditions or with the addition of either 50 or 100 ng/ml activin-A (Experiment 1). The mRNA levels for the genes that code for activin-A, ActR-IA, ActR-IB, ActR-IIA, ActR-IIB, follicle stimulating hormone receptor (FSH-R) and P450 aromatase were measured in each condition (Experiment 2). We observed that after 6 days of culture, the antrum formation rate was higher in cultures with added activin-A than in the cultured control (P < 0.05). The addition of 50 ng/ml activin-A increased the follicular growth rate in the final third of the culture (days 12-18), resulting in a higher percentage of meiosis resumption (P < 0.05). On day 6, the addition of activin-A (50 ng/ml) increased the levels of ActR-IA mRNA compared with the cultured control (P < 0.05). After 18 days, the addition of 50 ng/ml activin-A significantly increased the levels of its own mRNA compared with the non-cultured control. Moreover, this treatment reduced the mRNA levels of P450 aromatase in comparison with the cultured control (P < 0.05). Higher levels of P450 aromatase mRNA were found for both activin-A treatments compared with the non-cultured control (P < 0.05). No difference in estradiol levels was detected among any of the tested treatments. In conclusion, the addition of activin-A to culture medium stimulated early antrum formation as well as an increase in the daily follicular growth rate and the percentage of meiosis resumption. PMID:23941689

da Silva, Cleidson Manoel Gomes; Castro, Simone Vieira; Faustino, Luciana Rocha; Rodrigues, Giovanna Quintino; Brito, Ivina Rocha; Rossetto, Rafael; Saraiva, Márcia Viviane Alves; Campello, Claudio Cabral; Lobo, Carlos Henrique; Souza, Carlos Eduardo Azevedo; de Alencar Araripe Moura, Arlindo; Donato, Mariana Aragão Matos; Peixoto, Christina Alves; de Figueiredo, José Ricardo



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

PubMed Central

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

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



A comparative study of volatile compounds in the water-soluble fraction of various types of ripened cheese  

Microsoft Academic Search

Volatile constituents present in the water-soluble fraction (WSF) of eight hard-type cheeses (Cheddar, Edam, Gouda, Gouda 20+, Proosdij, Maasdam, Gruyère and Parmesan) were isolated and identified by using a dynamic headspace technique. The compounds were isolated from the WSF of cheeses by purge-and-trap extraction and analysed by gas chromatography-mass spectrometry. Fifty-three components were identified and 25 were quantitatively determined. The

W. J. M. Engels; R. Dekker; C. de Jong; R. Neeter; S. Visser



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

NASA Technical Reports Server (NTRS)

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.



Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development  

PubMed Central

The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgf? family members has indicated that Tgf?'s are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGF?'s, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGF? signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGF? receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGF? and Activin signaling during testis formation and male germ cell development. PMID:23342175

Stringer, Jessica M.; van den Bergen, Jocelyn A.; Wilhelm, Dagmar; Sinclair, Andrew H.; Western, Patrick S.



A Complex Role of Activin A in Non-Alcoholic Fatty Liver Disease  

Microsoft Academic Search

OBJECTIVES:Recent studies suggest that activin A, a member of the transforming growth factor (TGF) superfamily, is involved in the pathogenesis of liver disorders. We sought to explore its possible role in non-alcoholic fatty liver disease (NAFLD).METHODS:Serum levels of activin A and its natural inhibitor, follistatin, were measured in patients with NAFLD (n=70) and in control subjects (n=30). Gene expression was

Arne Yndestad; John Willy Haukeland; Tuva Børresdatter Dahl; Kristian Bjøro; Ivar Prydz Gladhaug; Christ Berge; Jan Kristian Damås; Terese Haaland; Else Marit Løberg; Paul Linnestad; Kåre Birkeland; Zbigniew Konopski; Bente Halvorsen; Rolf Kristian Berge; Pål Aukrust



Extremely variable conservation of ?-type small, acid-soluble proteins from spores of some species in the bacterial order Bacillales.  


?-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

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



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

PubMed Central

?-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

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



Type and concentration of acid on solubility and molecular size of acid–methanol-treated rice starches differing in amylose content  

Microsoft Academic Search

Rice starches differing in amylose content were treated in methanol with acid at 45°C for 1h, effects of acid type and concentration on the solubility and molecular size of starch were investigated. Significant differences were found in solubility and weight-average degree of polymerization (DPw) among starches treated with different acids at the equal normality. Starch treated with HCl had lower

Yung-Ho Chang; Jheng-Hua Lin; Ciao-Ling Pan



BMP-4 increases activin A gene expression during osteogenic differentiation of mouse embryonic stem cells.  


Abstract Activin A is a growth factor released by mature osteoblasts that has a critical effect on bone formation. We investigated the effect of bone morphogenetic protein (BMP)-4 on activin A gene expression during in vitro osteogenic differentiation of mouse embryonic stem (ES) cells. Embryoid bodies were cultured in retinoic acid (RA) for three days and then without RA for two days. Seeded cells received osteogenic medium with ?-glycerophosphate, L-ascorbic acid 2-phosphate and dexamethasone during 19 days, with or without BMP-4. Six independent experiments were carried out. Real-time PCR was used to detect gene expression of activin A, Oct-4, Nanog, osteocalcin, RUNX2 and bone alkaline phosphatase. Immunofluorescence was used to co-localize activin A with the undifferentiation marker stage-specific embryonic antigen 1. Cells treated with BMP-4 had an increased gene expression of activin A, osteocalcin and bone alkaline phosphatase (p?activin A gene expression during mouse ES cell differentiation into bone precursors. PMID:25413949

Camargos, Bruno M; Tavares, Rubens L C; Del Puerto, Helen L; Andrade, Luciana O; Camargos, Aroldo F; Reis, Fernando M



Development of High Temperature Type Vacuum Insulation Panel using Soluble Polyimide and Characteristic Evaluation  

NASA Astrophysics Data System (ADS)

The utilization is expected from the high-insulated characteristic as a tool for energy saving also in the high temperature insulation fields as in vacuum insulation panels (VIP) in the future. For high temperature, the material composition and process of VIP were reviewed, the SUS foil was adopted as packaging material, and soluble polyimide was developed as the thermo compression bonding material for high temperature VIP at 150°C. To lower the glass-transition temperature (Tg) under 200°C, we elaborated the new soluble polyimide using aliphatic diamine copolymer, and controlled Tg to about 176°C. By making from trial VIP and evaluations, it was possible to be maintain high performance concerning the coefficient of thermal conductivity [?<0.008 W/(m·K) at 150°C].

Araki, Kuninari; Kamoto, Daigorou; Matsuoka, Shin-Ichi


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


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

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



Ferricenium complexes: A new type of water-soluble antitumor agent  

Microsoft Academic Search

The antitumor activity of a series of iron complexes, i.e., of ferrocene [Cp2Fe], of tetrachloroferrates(III) [R4N]+[FeCl4]-, and of ferricenium complexes [Cp2Fe]+X- (X-=[FeCl4]-, 1\\/2[Cl3FeOFeCl3]2-, [H5Mo7O24]-·2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]-·2 CCl3COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic

P. Köpf-Maier; H. Köpf; E. W. Neuse



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

PubMed Central

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

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



Follistatin antagonizes activin signaling and acts with notum to direct planarian head regeneration.  


Animals establish their body plans in embryogenesis, but only a few animals can recapitulate this signaling milieu for regeneration after injury. In planarians, a pluripotent stem cell population and perpetual signaling of polarity axes collaborate to direct a steady replacement of cells during homeostasis and to power robust regeneration after even severe injuries. Several studies have documented the roles of conserved signaling pathways in maintaining and resetting axial polarity in planarians, but it is unclear how planarians reestablish polarity signaling centers after injury and whether these centers serve to influence identity decisions of stem cell progeny during their differentiation. Here we find that a planarian Follistatin homolog directs regeneration of anterior identity by opposing an Activin/ActR-1/Smad2/3 signaling pathway. Follistatin and Notum, a Wnt inhibitor, are mutually required to reestablish an anterior signaling center that expresses both cues. Furthermore, we show that the direction of cells down particular differentiation paths requires regeneration of this anterior signaling center. Just as its amphibian counterpart in the organizer signals body plan and cell fate during embryogenesis, planarian Follistatin promotes reestablishment of anterior polarity during regeneration and influences specification of cell types in the head and beyond. PMID:23297191

Roberts-Galbraith, Rachel H; Newmark, Phillip A



Molecular pathways: can activin-like kinase pathway inhibition enhance the limited efficacy of VEGF inhibitors?  


The vascular endothelial growth factor (VEGF) pathway is critical for tumor angiogenesis. However, VEGF pathway inhibition has been limited by intrinsic and acquired resistance. Simultaneously targeting multiple steps involved in tumor angiogenesis is a potential means of overcoming this resistance. Activin like kinase 1 (ALK1) and endoglin (ENG) have effects on angiogenesis that are distinct from those of VEGF. Whereas VEGF is important for vessel initiation, ALK1 and endoglin are involved in vessel network formation. Thus, ALK1 and endoglin pathway inhibitors are attractive partners for VEGF-based combination antiangiogenic therapy. Genetic evidence supports a role for this receptor family and its ligands, bone morphogenetic proteins (BMP) 9 and 10, in vascular development. Patients with genetic alterations in ALK1 or endoglin develop hereditary hemorrhagic telangiectasia, a disorder characterized by abnormal vessel development. There are several inhibitors of the ALK1 pathway advancing in clinical development for treatment of various tumor types, including renal cell and ovarian carcinomas. Targeting of alternate angiogenic pathways, particularly in combination with VEGF pathway blockade, holds the promise of optimally inhibiting angiogenically driven tumor progression. Clin Cancer Res; 20(11); 2838-45. ©2014 AACR. PMID:24714770

Bhatt, Rupal S; Atkins, Michael B



Activin A Suppresses Osteoblast Mineralization Capacity by Altering Extracellular Matrix (ECM) Composition and Impairing Matrix Vesicle (MV) Production*  

PubMed Central

During bone formation, osteoblasts deposit an extracellular matrix (ECM) that is mineralized via a process involving production and secretion of highly specialized matrix vesicles (MVs). Activin A, a transforming growth factor-? (TGF-?) superfamily member, was previously shown to have inhibitory effects in human bone formation models through unclear mechanisms. We investigated these mechanisms elicited by activin A during in vitro osteogenic differentiation of human mesenchymal stem cells (hMSC). Activin A inhibition of ECM mineralization coincided with a strong decline in alkaline phosphatase (ALP1) activity in extracellular compartments, ECM and matrix vesicles. SILAC-based quantitative proteomics disclosed intricate protein composition alterations in the activin A ECM, including changed expression of collagen XII, osteonectin and several cytoskeleton-binding proteins. Moreover, in activin A osteoblasts matrix vesicle production was deficient containing very low expression of annexin proteins. ECM enhanced human mesenchymal stem cell osteogenic development and mineralization. This osteogenic enhancement was significantly decreased when human mesenchymal stem cells were cultured on ECM produced under activin A treatment. These findings demonstrate that activin A targets the ECM maturation phase of osteoblast differentiation resulting ultimately in the inhibition of mineralization. ECM proteins modulated by activin A are not only determinant for bone mineralization but also possess osteoinductive properties that are relevant for bone tissue regeneration. PMID:23781072

Alves, Rodrigo D. A. M.; Eijken, Marco; Bezstarosti, Karel; Demmers, Jeroen A. A.; van Leeuwen, Johannes P. T. M.



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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



Emodin prevents hypoxic-ischemic neuronal injury: Involvement of the activin A pathway?  

PubMed Central

Emodin, an extract of dried rhizomes and the root of the Rhizoma Polygoni Cuspidati, can protect neurons from hypoxic-ischemic brain damage. This study aimed to verify the underlying mechanism. After PC12 cells had differentiated into neuron-like cells under the induction of mouse nerve growth factor, cells were subjected to oxygen-glucose deprivation and treated with emodin. Results showed that the viability of neuron-like cells cultured under an ischemia-hypoxia environment decreased, while the expression of activin A and caspase-3 in cells increased. Emodin raised the survival rate of oxygen-glucose deprived neuron-like cells, increased activin A expression, and decreased caspase-3 expression. Experimental findings indicate that emodin can inhibit neuronal apoptosis and alleviate the injury of nerve cells after oxygen-glucose deprivation through the activin A pathway. PMID:25206430

Guo, Hongliang; Shen, Xiaoran; Xu, Ye; Yuan, Junliang; Zhao, Dongming; Hu, Wenli



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


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

Papanayotou, Costis; Collignon, Jérôme



Soluble murine IL-1 receptor type I induces release of constitutive IL-1 alpha.  


IL-1 alpha and IL-1 beta are proinflammatory cytokines involved in the pathogenesis of many infectious and noninfectious inflammatory diseases. To reduce IL-1 toxicity, extracellular domains of the soluble (s) IL-1R are shed from cell membranes and prevent triggering of cell-bound receptors. We investigated to what extent murine sIL-1RI can neutralize the IL-1 produced by LPS-stimulated macrophages. When mouse peritoneal macrophages were incubated with LPS, addition of sIL-1RI significantly inhibited the bioactivity of IL-1. Stimulation of cells with sIL-1RI alone induced no bioactive IL-1. When immunoreactive cytokine concentrations were measured with specific radioimmunoassays, sIL-1RI alone appeared to induce a significant release of IL-1 alpha in a concentration-dependent manner. This effect was independent of new protein synthesis. The production of IL-1 beta or TNF-alpha was not influenced by sIL-1RI. There was no interference of sIL-1RI with the IL-1 alpha radioimmunoassay. In mice, an i.v. injection of sIL-RI alone induced a rapid release of IL-1 alpha, but not of TNF-alpha or IL-1 beta. Treatment of mice with sIL-1RI improved the survival during a lethal infection with Candida albicans. In conclusion, sIL-1RI induces a rapid release of IL-1 alpha from cells, as well as into the systemic circulation. Although this IL-1 alpha may be inactivated in circulation by the same sIL-1RI, this phenomenon probably has immunostimulatory effects at local levels where the sIL-1RI-induced IL-1 alpha acts in a paracrine or autocrine manner. PMID:10202032

Netea, M G; Kullberg, B J; Boerman, O C; Verschueren, I; Dinarello, C A; Van der Meer, J W



A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength  

PubMed Central

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGF? superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A–mFc) in vivo. mBMPR1A–mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A–mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-?B ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A–mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders. PMID:22761317

Baud’huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L.; Underwood, Kathryn W.; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R. Scott; Croucher, Peter I.



Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of Type 2 diabetic model rats  

Microsoft Academic Search

The soluble dietary fibre (SDF) fraction of Trigonella foenum graecum (Tf-sdf) has previously been shown to reduce postprandial elevation in blood glucose level of Type 2 model diabetic rats by delaying the digestion of sucrose. The Tf-sdf has now been investigated for its chronic effect on serum fructosamine, insulin and lipid levels, and on platelet aggregation in Type 2 diabetic

J. M. A. Hannan; B. Rokeya; O. Faruque; N. Nahar; M. Mosihuzzaman; A. K. Azad Khan; L. Ali



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

PubMed Central

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

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



Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats.  


This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p < 0.05). Long-term administration of guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p < 0.05). On the other hand, diabetic rats treated with the ethanol extract raised the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05) only. The experiments provided evidence to support the antihyperglycemic effect of guava leaf extract and the health function of guava leaves against type 2 diabetes. PMID:18819164

Shen, Szu-Chuan; Cheng, Fang-Chi; Wu, Ning-Jung



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


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

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



Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction.  


Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of cardiac remodeling following MI. We thus aimed to inhibit TGF-beta signaling using a novel orally active TGF-beta type I receptor [activin receptor-like kinase 5 (ALK5)] inhibitor (GW788388) to attenuate left ventricular remodeling and cardiac dysfunction in a rat model of MI. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce experimental MI and then were randomized to receive GW788388 at a dosage of 50 or vehicle 1 wk after surgery. After 4 wk of treatment, echocardiography was performed before the rats were euthanized. Animals that received left anterior descending coronary artery ligation demonstrated systolic dysfunction, Smad2 activation, myofibroblasts accumulation, collagen deposition, and myocyte hypertrophy (all P < 0.05). Treatment with GW788388 significantly attenuated systolic dysfunction in the MI animals, together with the attenuation of the activated (phosphorylated) Smad2 (P < 0.01), alpha-smooth muscle actin (P < 0.001), and collagen I (P < 0.05) in the noninfarct zone of MI rats. Cardiomyocyte hypertrophy in MI hearts was also attenuated by ALK5 inhibition (P < 0.05). In brief, treatment with a novel TGF-beta type I receptor inhibitor, GW788388, significantly reduced TGF-beta activity, leading to the attenuation of systolic dysfunction and left ventricular remodeling in an experimental rat model of MI. PMID:20154262

Tan, Sih Min; Zhang, Yuan; Connelly, Kim A; Gilbert, Richard E; Kelly, Darren J



1?,25-dihydroxyvitamin D3 stimulates activin A production to fine-tune osteoblast-induced mineralization.  


In healthy bones, mineralization has to be tightly controlled to avoid pathological phenotypes. In this study, we investigated interactions between 1?,25(OH)2 D3 (1,25D3) and activin A in the regulation of osteoblast induced mineralization. In human osteoblast cultures, we demonstrated that besides stimulation of mineralization, 1,25D3 also induced activin A, a strong inhibitor of mineralization. Simultaneously, follistatin (FST), the natural antagonist of activin A, was down-regulated by1,25D3. This resulted in an increase in activin A activity during 1,25D3 treatment. We also showed that in 1,25D3-treated osteoblasts, mineralization can be further increased when activin A activity was abrogated by adding exogenous FST. This observation implies that, besides stimulation of mineralization, 1,25D3 also controls activin A-mediated inhibition of mineralization. Besides activin A, 1,25D3 also induces osteocalcin (BGLAP), another inhibitor of mineralization. Warfarin, which has been shown to inactivate osteocalcin, increased 1,25D3-induced mineralization. Interaction between these two systems became evident from the synergistic increase in BGLAP expression upon blocking activin activity in 1,25D3-treated cultures. In conclusion, we demonstrate that 1,25D3 stimulation of mineralization by human osteoblasts is suppressed by concomitant induction of inhibitors of mineralization. Mineralization induction by 1,25D3 may actually be controlled via interplay with activin A and osteocalcin. Finally, this complex regulation of mineralization substantiates the significance of tight control of mineralization to prevent excessive mineralization and consequently reduction in bone quality and strength. PMID:23589129

Woeckel, V J; van der Eerden, B C J; Schreuders-Koedam, M; Eijken, M; Van Leeuwen, J P T M



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

PubMed Central

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

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



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

E-print Network

glutathione S-transferase interaction assays, we demonstrate that Pbx1 and Prep1 interact with Smads 2 and 3 intracellular receptor-specific Smad proteins, in the case of activin, either Smad2 or 3 (5). Upon. Consensus DNA-binding sequences for Smad2/4 and Smad3/4 complexes have been identified, which contain

Mellon, Pamela L.


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

E-print Network

molecules known as receptor-associated Smads, which, in the case of activin, are Smad2 and/or Smad3 (15). Smad2 or Smad3 then associate with a common Smad, Smad4 (DPC4). The activated heteromeric Smad complex

Mellon, Pamela L.


Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling.  


Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog (Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom. DOI: PMID:24040508

Gaviño, Michael A; Wenemoser, Danielle; Wang, Irving E; Reddien, Peter W



The role of activins and follistatins in skin and hair follicle development and function  

Microsoft Academic Search

Investigations of the signalling between epithelial and mesenchymal compartments of skin during hair follicle initiation in utero and hair cycling have revealed the importance of the TGF? superfamily in ectodermal organogenesis and morphogenesis. In particular the activins, their receptors and binding proteins such as follistatin, have been shown to be important regulators of cell proliferation, differentiation and apoptosis in hair

M. McDowall; N. M. Edwards; C. A. B. Jahoda; P. I. Hynd



Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in Fibroblasts Derived from Peyronie's Plaque  

PubMed Central

Purpose Transforming growth factor-?1 (TGF-?1) is the key fibrogenic cytokine associated with Peyronie's disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-? type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. Materials and Methods Plaque tissue from a patient with PD was used for primary fibroblast culture, and we then characterized primary cultured cells. Fibroblasts were pretreated with IN-1130 (10 µM) and then stimulated with TGF-?1 protein (10 ng/ml). We determined the inhibitory effect of IN-1130 on TGF-?1-induced phosphorylation of Smad2 and Smad3 or the nuclear translocation of Smad proteins in fibroblasts. Western blot analyses for plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV were performed to evaluate effect of IN-1130 on the production of extracellular matrix proteins. Results The treatment of fibroblasts with TGF-?1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-?1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-?1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. Conclusions Overexpression of TGF-? and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-? signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD. PMID:22323974

Jang, Jin Hyuk; Ryu, Ji Kan



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

NASA Astrophysics Data System (ADS)

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

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



Type 10 Soluble Adenylyl Cyclase Is Overexpressed in Prostate Carcinoma and Controls Proliferation of Prostate Cancer Cells*  

PubMed Central

cAMP signaling plays an essential role in modulating the proliferation of different cell types, including cancer cells. Until now, the regulation of this pathway was restricted to the transmembrane class of adenylyl cyclases. In this study, significant overexpression of soluble adenylyl cyclase (sAC), an alternative source of cAMP, was found in human prostate carcinoma, and therefore, the contribution of this cyclase was investigated in the prostate carcinoma cell lines LNCaP and PC3. Suppression of sAC activity by treatment with the sAC-specific inhibitor KH7 or by sAC-specific knockdown mediated by siRNA or shRNA transfection prevented the proliferation of prostate carcinoma cells, led to lactate dehydrogenase release, and induced apoptosis. Cell cycle analysis revealed a significant rise in the G2 phase population 12 h after sAC inhibition, which was accompanied by the down-regulation of cyclin B1 and CDK1. sAC-dependent regulation of proliferation involves the EPAC/Rap1/B-Raf signaling pathway. In contrast, protein kinase A does not play a role. In conclusion, this study suggests a novel sAC-dependent signaling pathway that controls the proliferation of prostate carcinoma cells. PMID:23255611

Flacke, Jan-Paul; Flacke, Hanna; Appukuttan, Avinash; Palisaar, Rein-Jüri; Noldus, Joachim; Robinson, Brian D.; Reusch, H. Peter; Zippin, Jonathan H.; Ladilov, Yury



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

PubMed Central

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

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.



The impact of soluble dietary fibre on gastric emptying, postprandial blood glucose and insulin in patients with type 2 diabetes.  


Dietary fibre plays an important role in controlling postprandial glycemic and insulin response in diabetic patients. The intake of dietary fibre has been shown to delay the gastric emptying in healthy subjects. The relationship between gastric emptying and postprandial blood glucose in diabetic patients with fibre-load liquids needs to be investigated. To investigate the impact of soluble dietary fibre (SDF) on gastric emptying, postprandial glycemic and insulin response in patients with type 2 diabetes. 30 patients with type 2 diabetes (DM) and 10 healthy subjects (HS) matched for gender and age were randomized to receive SDF-free liquid (500 mL, 500 Kcal) and isoenergetic SDF liquid (oat ?-glucan 7.5 g, 500 mL, 500 Kcal) on two separate days based on a cross-over with 6-day wash-out period. Gastric emptying was monitored by ultrasonography at intervals of 30 min for 2 hours. Fasting and postprandial blood was collected at intervals of 30-60 min for 180 min to determine plasma glucose and insulin. Proximal gastric emptying was delayed by SDF-treatment both in DM (p=0.001) and HS (p=0.037). SDF resulted in less output volume in the distal stomach in DM (p<0.05). SDF decreased postprandial glucose (p=0.001) and insulin (p=0.001) in DM subjects. Postprandial glucose (r=-0.547, p=0.047) and insulin (r=-0.566, p=0.004) were negatively correlated with distal emptying of SDF in DM subjects. Distal gastric emptying was delayed significantly in DM subjects with HbA1c levels ?6.5% (p=0.021) or with complications (p=0.011) by SDF, respectively. SDF improved postprandial glycaemia which was related to slowing of gastric emptying. PMID:24901089

Yu, Kang; Ke, Mei-Yun; Li, Wen-Hui; Zhang, Shu-Qin; Fang, Xiu-Cai



Phosphodiesterase 5 Restricts NOS3/Soluble Guanylate Cyclase signaling to L-type Ca2+ current in Cardiac Myocytes  

PubMed Central

Endothelial nitric oxide synthase (NOS3) regulates the functional response to ?-adrenergic (?-AR) stimulation via modulation of the L-type Ca2+ current (ICa). However, the NOS3 signaling pathway modulating ICa is unknown. This study investigated the contribution of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5), a cGMP-specific PDE, in the NOS3-mediated regulation of ICa. Myocytes were isolated from NOS3 knockout (NOS3?/?) and wildtype (WT) mice. We measured ICa (whole-cell voltage-clamp), and simultaneously measured Ca2+ transients (Fluo-4 AM) and cell shortening (edge detection). Zaprinast (selective inhibitor of PDE5), decreased ?-AR stimulated (isoproterenol, ISO)-ICa, and Ca2+ transient and cell shortening amplitudes in WT myocytes. However, YC-1 (NO-independent activator of sGC) only reduced ISO-stimulated ICa, but not cardiac contraction. We further investigated the NOS3/sGC/PDE5 pathway in NOS3?/? myocytes. PDE5 is mislocalized in these myocytes and we observed dissimilar effects of PDE5 inhibition and sGC activation compared to WT. That is, zaprinast had no effect on ISO- stimulated ICa, or Ca2+ transient and cell shortening amplitudes. Conversely, YC-1 significantly decreased both ISO-stimulated ICa, and cardiac contraction. Further confirming that PDE5 localizes NOS3/cGMP signaling to ICa; YC-1, in the presence of zaprinast, now significantly decreased ISO-stimulated Ca2+ transient and cell shortening amplitudes in WT myocytes. The effects of YC-1 on ICa and cardiac contraction were blocked by KT5823 (a selective inhibitor of the cGMP-dependent protein kinase, PKG). Our data suggests a novel physiological role for PDE5 in restricting the effects of NOS3/sGC/PKG signaling pathway to modulating ?-AR stimulated ICa, while limiting effects on cardiac contraction. PMID:19345227

Wang, Honglan; Kohr, Mark J; Traynham, Christopher J; Ziolo, Mark T



Blood cell induction in Xenopus animal cap explants: Effects of fibroblast growth factor, bone morphogenetic proteins, and activin  

Microsoft Academic Search

Cultures of Xenopus blastula animal caps were used to explore the haematopoietic effects of three candidate inducers of mesoderm: basic fibroblast\\u000a growth factor (bFGF), bone morphogenetic proteins (BMPs) and activin A. In response to either bFGF or activin A, explants\\u000a expanded into egg-shaped structures, and beneath an outer layer of epidermis, a ventral mesodermal lining surrounded a fluid-filled\\u000a cavity containing

Y. Miyanaga; Robert Shiurba; Makoto Asashima



Blood cell induction in Xenopus animal cap explants: effects of fibroblast growth factor, bone morphogenetic proteins, and activin.  


Cultures of Xenopus blastula animal caps were used to explore the haematopoietic effects of three candidate inducers of mesoderm: basic fibroblast growth factor (bFGF), bone morphogenetic proteins (BMPs) and activin A. In response to either bFGF or activin A, explants expanded into egg-shaped structures, and beneath an outer layer of epidermis, a ventral mesodermal lining surrounded a fluid-filled cavity containing "blood-like cells". Immunocytochemistry identified some of these cells as early leukocytes, but erythrocytes were rare. BMP-2 or BMP-4 induced primitive erythrocytes as well as leukocytes, and a high concentration was required for these cells to differentiate in only a small proportion of explants. BMP-2 but not BMP-4 induced ventral mesoderm concomitantly. High concentrations of activin A dorsalized explants, which contained infrequent leukocytes, and an optimal combination of activin A and bFGF caused differentiation of muscle with few blood cells. By contrast, BMP-2 or BMP-4 plus activin A synergistically increased the numbers of both leukocytes and erythrocytes. Explants treated with BMPs plus activin contained a well organized cell mass in which yolk-rich cells mixed with blood cells and pigmented cells did not. BMP-2 plus bFGF also induced numerous leukocytes and fewer erythrocytes, but BMP-4 antagonized the leukopoietic effect of bFGF. The data suggest that the signalling pathways these three factors use to induce leukopoiesis overlap and that erythropoiesis may be activated when inducers are present in combination. PMID:10022950

Miyanaga, Y; Shiurba, R; Asashima, M



The study of soluble intercellular adhesion molecule-1 and ghrelin in adolescents with family history of type 2 diabetes.  


The purpose of this study was to observe both the changes of soluble intercellular adhesion molecule-1 (sICAM-1) and ghrelin in adolescents with family history of type 2 diabetes (FHD) and the relationship between sICAM-1 and ghrelin. This case-control study included 63 adolescents (boys/girls 29/34, age 14.1 ± 0.7 years) without FHD (FHD-) and 67 adolescents (boys/girls 33/34, age 14.0 ± 0.8 years) with FHD (FHD+). Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were obtained. Blood samples were collected, and fasting plasma glucose (FPG), serum lipids, true insulin, sICAM-1, and ghrelin were assayed. The results showed that the age and gender were similar in two groups (P > 0.05). Body mass index (BMI), WC, FPG, fasting insulin, HOMA-IR, and sICAM-1 were all significantly higher in the FHD+ group than in the FHD- group (P < 0.05). Ghrelin was significantly lower in the FHD+ group than in the FHD- group (P < 0.05). sICAM-1 was positively correlated with WC (r = 0.178, P = 0.043), fasting insulin (r = 0.195, P = 0.026), HOMA-IR (r = 0.197, P = 0.024), and ghrelin (r = 0.290, P = 0.001). After multivariate analysis, the ghrelin (? = 0.788, 95 % CI: 0.416-1.159, P = 0.000) and HOMA-IR (? = 0.106, 95 % CI: 0.045-0.167, P = 0.001) maintained an independent association with sICAM-1. These findings led to the conclusion that endothelial dysfunction and decline of ghrelin were found in adolescents with family history of diabetes. The decline of ghrelin maybe a protection mechanism for endothelial function in adolescents with family history of diabetes and should be examined in future studies. PMID:22588952

Liu, Bo-Wei; Lu, Qiang; Ma, Chun-Ming; Liu, Jun-Ru; Lou, Dong-Hui; Liu, Xiao-Li; Yin, Fu-Zai



Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study  

PubMed Central

Introduction 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members of the Transforming Growth Factor ? family of proteins, and their binding protein, follistatin, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. Our objectives were to evaluate whether the serum levels of activin A, B and follistatin are elevated in 518 patients with ARF from the FINNALI study compared the concentrations in 138 normal subjects that form a reference range. Methods Specific assays for activin A, B and follistatin were used and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months from the onset of the ARF. Results Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95% CI 1.28-2.12, P?=?0.00013]; both activin A and B above reference maximum: LR?+?2.78 [95% CI 1.96-3.95, P?activin A and B levels in these patients with ARF would have assisted in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate activin A and B bioactivity should be explored as potential therapeutic agents. PMID:24172607



Activin Upregulation by NF-?B Is Required to Maintain Mesenchymal Features of Cancer Stem-like Cells in Non-Small Cell Lung Cancer.  


Soluble growth factors and cytokines within the tumor microenvironment aid in the induction of the epithelial-to-mesenchymal transition (EMT). Although EMT promotes the development of cancer-initiating cells (CIC), cellular mechanisms by which cancer cells maintain mesenchymal phenotypes remain poorly understood. Work presented here indicates that induction of EMT stimulates non-small cell lung cancer (NSCLC) to secrete soluble factors that function in an autocrine fashion. Using gene expression profiling of all annotated and predicted secreted gene products, we find that NF-?B activity is required to upregulate INHBA/Activin, a morphogen in the TGF? superfamily. INHBA is capable of inducing and maintaining mesenchymal phenotypes, including the expression of EMT master-switch regulators and self-renewal factors that sustain CIC phenotypes and promote lung metastasis. Our work demonstrates that INHBA mRNA and protein expression are commonly elevated in primary human NSCLC and provide evidence that INHBA is a critical autocrine factor that maintains mesenchymal properties of CICs to promote metastasis in NSCLC. Cancer Res; 75(2); 426-35. ©2014 AACR. PMID:25432175

Wamsley, J Jacob; Kumar, Manish; Allison, David F; Clift, Sheena H; Holzknecht, Caitlyn M; Szymura, Szymon J; Hoang, Stephen A; Xu, Xiaojiang; Moskaluk, Christopher A; Jones, David R; Bekiranov, Stefan; Mayo, Marty W



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

E-print Network

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

Yang, J.


Epidermal growth factor differentially regulates activin subunits in the zebrafish ovarian follicle cells via diverse signaling pathways.  


Epidermal growth factor (EGF) promotes oocyte maturation in the zebrafish and its effect is mediated via the activin system. However, the mechanisms by which EGF regulates activin subunits in the follicle cells remain unknown. The present study demonstrated that EGF controlled expression of three activin subunits (inhbaa, inhbab and inhbb) in the follicle cells via diverse signaling pathways. The expression of inhbaa and inhbb was often co-regulated via similar pathways. Suppression of MAPK3/1, p38 MAPK, PKC and PKA each blocked or partially reduced the stimulatory effects of EGF on the expression of inhbaa and inhbb while up-regulated that of inhbab. Conversely, inhibition of PI3K did not have any effect on the expression of inhbaa and inhbb but significantly suppressed the stimulatory effect of EGF on inhbab. In summary, EGF action in the zebrafish ovary involves activin system and its regulation of activin subunits is mediated by diverse signaling pathways downstream of EGFR. PMID:22503865

Chung, Chi-Kin; Ge, Wei



Graded Nodal\\/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions  

Microsoft Academic Search

Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal\\/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of

Kian Leong Lee; Sandy Keat Lim; Yuriy Lvovich Orlov; Le Yau Yit; Henry Yang; Lay Teng Ang; Lorenz Poellinger; Bing Lim



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.


[Characteristics of aerosol water-soluble inorganic ions in three types air-pollution incidents of Nanjing City].  


In order to compare aerosol water-soluble inorganic species in different air-pollution periods, samples of PM10, PM2.1, PM1.1 and the main water-soluble ions (NH4+, Mg2+, Ca2+, Na+, K+, NO2(-), F(-), NO3(-), Cl(-), SO4(2-)) were measured, which were from 3 air-pollution incidents (continued pollution in October 16-30 of 2009, sandstorm pollution in April 27-30 of 2010, and crop burning pollution in June 14 of 2010. The results show that aerosol pollution of 3 periods is serious. The lowest PM2.1/PM10 is only 0.27, which is from sandstorm pollution period, while the largest is 0. 7 from crop burning pollution period. In continued pollution periods, NO3(-) and SO4(2-) are the dominant ions, and the total anions account for an average of 18.62%, 32.92% and 33.53% of PM10, PM2.1 and PM1.1. Total water-soluble ions only account for 13.36%, 23.72% and 28.54% of PM10, PM2.1 and PM1.1 due to the insoluble species is increased in sandstorm pollution period. The mass concentration of Ca2+ in sandstorm pollution period is higher than the other two pollution periods, and which is mainly in coarse particles with diameter larger than 1 microm. All the ten water-soluble ions are much higher in crop burning pollution especially K+ which is the tracer from crop burning. The peak mass concentrations of NO3(-), SO4(2-) and NH4+ are in 0.43-0.65 microm. PMID:22946180

Zhang, Qiu-Chen; Zhu, Bin; Su, Ji-Feng; Wang, Hong-Lei



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

PubMed Central

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



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)

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).

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



Serum Activins and Follistatin during the Treatment of Chronic Hepatitis C Genotypes 1 and 4 and Their Correlations with Viral Load and Liver Enzymes: A Preliminary Report  

PubMed Central

Aims. To measure the effect of pegylated interferon-? therapy on serum activin-A, activin-B, and follistatin and their correlation with viral load and liver fibrosis in chronic hepatitis C (CHC). Methods. This study was cross-sectional and sera were collected from 165 participants classified into 7 groups: 40 healthy negative control, 33 treatment naïve patients as positive control, 19 patients at week 4, 22 at week 12, and 19 at week 24 of treatment initiation and 21 responders and 11 nonresponders at the end of 48-week treatment protocol. Serum candidate proteins were measured using ELISA and liver fibrosis was assessed by AST platelet ratio index (APRI). Results. CHC significantly increased activins and decreased follistatin compared to negative control (P < 0.05). Activin-A and follistatin levels returned to the levels of negative control group at weeks 4, 12, and 24 following treatment initiation and were significantly different from positive control (P < 0.05). Both proteins were significantly different between responders and nonresponders. Activin-A correlated positively and significantly with the viral load and APRI. Conclusion. CHC modulates serum activin-A and follistatin and they appear to be influenced by pegylated interferon-? therapy. Further studies are needed to explore the role of activins in CHC. PMID:24799891

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



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

PubMed Central

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

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



Novel protein interactions with endoglin and activin receptor-like kinase 1: potential role in vascular networks.  


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

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



Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons.  

PubMed Central

A number of cytokines sharing limited sequence homology have been grouped as a family because of partially overlapping biological activities, receptor subunit promiscuity, and the prediction of a shared secondary structure. Since several of these cytokines regulate gene expression and cell number in the nervous and hematopoietic systems, this specific group is termed the neuropoietic cytokine family. Using a reverse transcription-polymerase chain reaction-based assay system for monitoring the expression of multiple phenotypic markers in cultured sympathetic neurons, we present further evidence that, in addition to cholinergic differentiation factor/leukemia inhibitory factor and ciliary neurotrophic factor, oncostatin M, growth promoting activity, interleukin 6, and interleukin 11 belong in this family. In addition, one member of the transforming growth factor beta superfamily, activin A, shares a selective overlap with the neuropoietic family in the spectrum of neuropeptides that it induces in sympathetic neurons. The particular neuropeptides induced by activin A, however, demonstrate that the activity of this cytokine is distinct from that of the neuropoietic family. Twenty-six other cytokines and growth factors were without detectable activity in this assay. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7904069

Fann, M J; Patterson, P H



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

ERIC Educational Resources Information Center

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…

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



Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study  

PubMed Central

Introduction Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. Methods This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers. Results A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers. Conclusion Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics. Trial registration NCT 00389337 PMID:17362525

Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte; Tvede, Michael; Petersen, Janne; Eugen-Olsen, Jesper; Larsen, Klaus



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

E-print Network

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 ...

Maier, Lisa M.


Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements.  


Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGF? superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGF? receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways. PMID:23293296

Peterson, Aidan J; O'Connor, Michael B



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


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. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25319955

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



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

SciTech Connect

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.

Sandhu, Hardip, E-mail: [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)



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

E-print Network

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

Mayo, Kelly E.


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


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

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



Impaired delayed-type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane-bound CD4  

PubMed Central

Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-? (IFN-?). IFN-? production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-? in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction. PMID:10929052

Wang, C-R; Hino, A; Yoshimoto, T; Nagase, H; Kato, T; Hirokawa, K; Matsuzawa, A; Nariuchi, H



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


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

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



An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin  

PubMed Central

Sotatercept (ACE-011), a recombinant human fusion protein containing the extracellular domain of the human Activin receptor IIA, binds to and inhibits activin and other members of the transforming growth factor -? (TGF-?) superfamily. Administration of sotatercept led to a rapid and sustained increase in red blood cell (RBC) count and haemoglobin (Hb) in healthy volunteers (phase I clinical trials), but the mechanism is not fully understood. Mice treated with RAP-011 (murine ortholog of ACE-011) respond with a rapid (within 24 h) increase in haematocrit, Hb, and RBC count. These effects are accompanied by an equally rapid stimulation of late-stage erythroid precursors in the bone marrow (BM). RAP-011 also induces a significant increase in erythroid burst-forming units and erythropoietin, which could contribute to additional, sustained effects on RBC production. Further in vitro co-culture studies demonstrate that BM accessory cells are required for RAP-011 effects. To better understand which TGF-? family ligand(s) mediate RAP-011 effects, we evaluated the impact of several of these ligands on erythroid differentiation. Our data suggest that RAP-011 may act to rescue growth differentiation factor 11/Activin A-induced inhibition of late-stage erythropoiesis. These data define the mechanism of action of a novel agent that regulates RBC differentiation and provide the rationale to develop sotatercept for the treatment of anaemia and ineffective erythropoiesis. PMID:24635723

Carrancio, Soraya; Markovics, Jennifer; Wong, Piu; Leisten, Jim; Castiglioni, Paola; Groza, Matthew C; Raymon, Heather K; Heise, Carla; Daniel, Tom; Chopra, Rajesh; Sung, Victoria



Salts & Solubility  

NSDL National Science Digital Library

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.



Moisture solubility for differently conditioned transformer oils  

Microsoft Academic Search

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

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



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

PubMed Central

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

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



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

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

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.



Comparative expression of wild-type and highly soluble mutant His103Leu of hydroxynitrile lyase from Manihot esculenta in prokaryotic and eukaryotic expression systems  

Microsoft Academic Search

Low protein solubility and inclusion body formation represent big challenges in production of recombinant proteins in Escherichia coli. We have recently reported functional expression of hydroxynitrile lyase from Manihot esculenta, MeHNL, in E. coli with high in vivo solubility and activity using directed evolution. As a part of attempts to clarify the mechanism of this phenomenon, we have described the

Mohammad Dadashipour; Yasuhisa Fukuta; Yasuhisa Asano



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

PubMed Central

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

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



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


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

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



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


A single somatic FOXL2 mutation (FOXL2(C134W)) 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 FOXL2(C134W) 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. FOXL2(C134W) 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 FOXL2(C134W) may involve an altered interaction with Smad3. PMID:23567549

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



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

SciTech Connect

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.

Bordonaro, Michael, E-mail:; Tewari, Shruti, E-mail:; Atamna, Wafa, E-mail:; Lazarova, Darina L., E-mail:



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


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

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



Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.  


Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tethering and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels of sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and diabetic subjects, we investigated an age-, sex-, and glucose-tolerance-stratified sample (n = 631) of a population-based cohort aged 50-75 years that was followed prospectively. Plasma levels of sVCAM-1 were determined in frozen -70 degrees C baseline samples. After 7.4 years (mean) of follow-up, 107 (17%) subjects had died (42 of cardiovascular causes). In the entire group, increased sVCAM-1 levels were significantly associated with increased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and glucose tolerance status). This RR was somewhat diminished by further adjustment for the presence of hypertension and cardiovascular disease; levels of total, HDL, and LDL cholesterol and homocysteine; the presence of microalbuminuria (a putative marker of endothelial dysfunction); levels of von Willebrand factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration rate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase after adjustment for age and sex, which was somewhat higher but not significantly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results. In conclusion, levels of sVCAM-1 are independently associated with the risk of cardiovascular mortality in type 2 diabetic subjects and therefore might be useful for identifying subjects at increased cardiovascular risk. Increased plasma sVCAM-1 levels may reflect progressive formation of atherosclerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sVCAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function. PMID:10868972

Jager, A; van Hinsbergh, V W; Kostense, P J; Emeis, J J; Nijpels, G; Dekker, J M; Heine, R J; Bouter, L M; Stehouwer, C D



Soluble vs. insoluble fiber  


... 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 ...


Casein kinase 2? as a novel enhancer of activin-like receptor-1 signaling  

PubMed Central

ALK-1 is a transforming growth factor ? (TGF-?) superfamily receptor that is predominantly expressed in endothelial cells and is essential for angiogenesis, as demonstrated by the embryonic lethal phentoype when targeted for deletion in mice and its mutation in the human disease hereditary hemorrhagic telangiectasia. Although ALK-1 and the endothelial-specific TGF-? superfamily coreceptor, endoglin, form a heteromeric complex and bind similar TGF-? superfamily ligands, their signaling mechanisms remain poorly characterized. Here we report the identification of CK2?, the regulatory subunit of protein kinase CK2, as a novel enhancer of ALK-1 signaling. The cytoplasmic domain of ALK-1 specifically binds to CK2? in vitro and in vivo. NAAIRS mutagenesis studies define amino acid sequences 181–199 of CK2? and 207–212 of ALK-1 as the interaction domains, respectively. The ALK-1/CK2? interaction specifically enhanced Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation in response to TGF-?1 and BMP-9 treatment. In a reciprocal manner, siRNA-mediated silencing of endogenous CK2? inhibited TGF-?1 and BMP-9-stimulated Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation. Functionally, CK2? enhanced the ability of activated or ligand-stimulated ALK-1 to inhibit endothelial cell migration. Similarly, ALK-1 and CK2? antagonized endothelial tubule formation in Matrigel. These studies support CK2? as an important regulator of ALK-1 signaling and ALK-1-mediated functions in endothelial cells.—Lee, N. Y., Haney, J. C., Sogani, J., Blobe, G. C. Casein kinase 2? as a novel enhancer of activin-like receptor-1 signaling. PMID:19592636

Lee, Nam Y.; Haney, John C.; Sogani, Julie; Blobe, Gerard C.



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


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

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



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

Microsoft Academic Search

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

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



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

SciTech Connect

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.

Sui, Lina, E-mail: [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)



Identification of Smad Response Elements in the Promoter of Goldfish FSH? Gene and Evidence for Their Mediation of Activin and GnRH Stimulation of FSH? Expression  

PubMed Central

As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH) is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSH? but suppresses LH? expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSH? in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSH? transcription, the present study was undertaken to analyze the promoter of goldfish FSH? gene (fshb) with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the L?T-2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSH? promoter-SEAP (secreted alkaline phosphatase) were co-transfected with an expression plasmid for Smads (2 or 3) followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (AGAC, ?1675/?1672) whereas the proximal site (GACCTTGA, ?212/?205) was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA) highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSH? expression by gonadotropin-releasing hormone and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSH? that are responsible for activin-induced expression of the gene. Since activin stimulation of FSH? expression is functionally conserved in fish and mammals, our findings contribute to the understanding of the fundamental mechanisms of this regulation across vertebrates. PMID:22645522

Lau, Man-Tat; Lin, Sze-Wah; Ge, Wei



Activin betaA subunit, follistatin and follistatin-like 3 are expressed in the endometrium of ovariectomized rats and regulated by estrogen replacement.  


Activin A is a growth factor expressed in the endometrium, where it modulates tissue remodeling and enhances decidualization. The effects of activin A are counteracted by two binding proteins, namely follistatin and follistatin-like 3 (FSTL3). We have evaluated the effects of estrogen and progestin on the endometrial expression of activin betaA subunit, follistatin and FSTL3 in ovariectomized rats. Adult female Wistar rats (n = 21) were ovariectomized and received one week later a single dose of estradiol benzoate (1.5 mg/kg body weight, i.m. injection), either alone (n = 7) or associated with depot medroxyprogesterone acetate (3 mg/kg body weight, i.m. injection, n = 7), or oil vehicle (control group, n = 7). One week later, activin betaA subunit mRNA levels had increased significantly in the uteri of rats treated with estradiol alone (7.4 fold increase over controls, P < 0.05) and to the same extent in rats receiving estradiol plus medroxyprogesterone (6.1 fold increase over controls, P < 0.05). This was accompanied by increase of betaA subunit immunostaining in estradiol and estroprogestin treated rats, which was noted only in the surface endometrial epithelium. Follistatin mRNA expression, conversely, showed a significant decrease in the groups treated with estrogen alone and estrogen plus progestin (P < 0.05), and follistatin immunostaining in the glandular epithelium was weaker in estradiol and estroprogestin-treated rats compared to controls. FSTL3 expression was similar in the 3 groups. In conclusion, the expression of activin betaA subunit increases and that of follistatin decreases following estrogen replacement in the endometrium of ovariectomized rats, and these effects are not further altered by the addition of progestin. PMID:18781389

Ferreira, Márcia C; Cavallo, Inês K D; Florio, Pasquale; Petraglia, Felice; Reis, Fernando M



Endoglin and activin receptor-like kinase 1 heterozygous mice have a distinct pulmonary and hepatic angiogenic profile and response to anti-VEGF treatment.  


Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia associated with dysregulated angiogenesis and arteriovascular malformations. The disease is caused by mutations in endoglin (ENG; HHT1) or activin receptor-like kinase 1 (ALK1; HHT2) genes, coding for transforming growth factor ? (TGF-?) superfamily receptors. Vascular endothelial growth factor (VEGF) has been implicated in HHT and beneficial effects of anti-VEGF treatment were recently reported in HHT patients. To investigate the systemic angiogenic phenotype of Endoglin and Alk1 mutant mice and their response to anti-VEGF therapy, we assessed microvessel density (MVD) in multiple organs after treatment with an antibody to mouse VEGF or vehicle. Lungs were the only organ showing an angiogenic defect, with reduced peripheral MVD and secondary right ventricular hypertrophy (RVH), yet distinctly associated with a fourfold increase in thrombospondin-1 (TSP-1) in Eng (+/-) versus a rise in angiopoietin-2 (Ang-2) in Alk1 (+/-) mice. Anti-VEGF treatment did reduce lung VEGF levels but interestingly, led to an increase in peripheral pulmonary MVD and attenuation of RVH; it also normalized TSP-1 and Ang-2 expression. Hepatic MVD, unaffected in mutant mice, was reduced by anti-VEGF therapy in heterozygous and wild type mice, indicating a liver-specific effect of treatment. Contrast-enhanced micro-ultrasound demonstrated a reduction in hepatic microvascular perfusion after anti-VEGF treatment only in Eng (+/-) mice. Our findings indicate that the mechanisms responsible for the angiogenic imbalance and the response to anti-VEGF therapy differ between Eng and Alk1 heterozygous mice and raise the need for systemic monitoring of anti-angiogenic therapy effects in HHT patients. PMID:24061911

Ardelean, Daniela S; Jerkic, Mirjana; Yin, Melissa; Peter, Madonna; Ngan, Bo; Kerbel, Robert S; Foster, F Stuart; Letarte, Michelle



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

PubMed Central

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



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


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

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



Hydrogen solubility in austenitic stainless steels  

SciTech Connect

The effects of thermomechanical treatment and surface condition on hydrogen solubility in Types 304L, 21-6-9, and modified A-286 austenitic stainless steels were determined. Three thermomechanical treatments were studied: annealed, 100% cold-worked, and high-energy rate forged (HERFed). Solubility in the modified Type A-286 was less in the HERFed specimens than in solution-annealed specimens. 8 refs.

Caskey, G.R. Jr.; Sisson, R.D. Jr.



Scoring function to predict solubility mutagenesis Tian et al.  

E-print Network

Scoring function to predict solubility mutagenesis Tian et al. Tian et al. Algorithms for Molecular function to predict solubility mutagenesis Ye Tian1 , Christopher Deutsch2 , Bala Krishnamoorthy1* Abstract in the wild type (WT) protein, such as increased or decreased stability, reactivity, or solubility

Krishnamoorthy, Bala


Mutations of activin-receptor-like kinase 1 ( ALK-1 ) are not found in patients with pulmonary hypertension and underlying connective tissue disease  

Microsoft Academic Search

Pulmonary arterial hypertension is a recognized clinical component of systemic autoimmune diseases, especially systemic sclerosis.\\u000a Mutations in the bone morphogenetic protein receptor 2 gene reported in sporadic and familial primary pulmonary arterial hypertension\\u000a have failed to be detected in patients with either scleroderma spectrum disease or underlying connective tissue diseases.\\u000a Activin receptor-like kinase 1 (ALK-1) gene has recently been linked

Albert Selva-O’Callaghan; Eva Balada; Silvia Serrano-Acedo; Carmen Pilar Simeon Aznar; Josep Ordi-Ros




Microsoft Academic Search

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.

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


Applications of Solubility Data  

ERIC Educational Resources Information Center

This article describes several applications of the use of solubility data. It is not meant to be exhaustive but rather to show that knowledge of solubility data is required in a variety of technical applications that assist in the design of chemical processes. (Contains 3 figures and 1 table.)

Tomkins, Reginald P. T.



What Variables Affect Solubility?  

ERIC Educational Resources Information Center

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…

Baker, William P.; Leyva, Kathryn



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


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

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



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).  


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

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



What Should We Teach Beginners about Solubility and Solubility Products?  

ERIC Educational Resources Information Center

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

Hawkes, Stephen J.



Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase.  


The heart is the most common site of congenital defects, and valvuloseptal defects are the most common of the cardiac anomalies seen in the newborn. The process of endothelial-to-mesenchymal transition (EndMT) in the cardiac cushions is a required step during early valve development, and Notch signaling is required for this process. Here we show that Notch activation induces the transcription of both subunits of the soluble guanylyl cyclase (sGC) heterodimer, GUCY1A3 and GUCY1B3, which form the nitric oxide receptor. In parallel, Notch also promotes nitric oxide (NO) production by inducing Activin A, thereby activating a PI3-kinase/Akt pathway to phosphorylate eNOS. We thus show that the activation of sGC by NO through a Notch-dependent autocrine loop is necessary to drive early EndMT in the developing atrioventricular canal (AVC). PMID:21839921

Chang, Alex C Y; Fu, YangXin; Garside, Victoria C; Niessen, Kyle; Chang, Linda; Fuller, Megan; Setiadi, Audi; Smrz, Justin; Kyle, Alastair; Minchinton, Andrew; Marra, Marco; Hoodless, Pamela A; Karsan, Aly



Lead (II) cholate solubility.  


In the framework of the research carried out on the behaviour of the salts of bile acids in aqueous solutions, the lead (II) cholate solubility was determined at 25 degrees C and in 0.100, 0.500 and 0.800 mol dm(-3) N(CH3)4Cl, as ionic medium. The change of its solubility was studied as a function of the cholate and hydrogen ion concentration. Solubility and electromotive force measurements of suitable galvanic cells were carried out and from the results lead (II) cholate solubility product could be calculated and the presence of associated species in solution in the ratio 1:3 and 1:4 between lead (II) and cholate was assumed. The relative constants were determined, as well. The results of this work allow us to obtain the free cholate concentration in equilibrium with solid lead (II) cholate. PMID:12911144

Bottari, Emilio; Festa, Maria Rosa



Protein solubility modeling  

NASA Technical Reports Server (NTRS)

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.

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



Solubility of Organic Compounds  

ERIC Educational Resources Information Center

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)

James, K. C.



Learning about Solubility  

ERIC Educational Resources Information Center

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.

Salinas, Dino G.; Reyes, Juan G.



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

SciTech Connect

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

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




SciTech Connect

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

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



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

PubMed Central

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

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



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

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

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



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

SciTech Connect

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

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



Understanding Solubility and Density  

NSDL National Science Digital Library

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.



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...


The relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients as evidenced by measurement of carotid intima-media thickness and soluble CD146 levels: a cross sectional study  

PubMed Central

Background Detection of early vascular changes prior to clinical manifestations of atherosclerosis, such as increased arterial carotid intima-media thickness (CIMT) and impaired endothelial function is of paramount importance for early identification of subjects at increased risk of accelerated atherosclerosis. The present study was designed to evaluate the relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients based on measurements of CIMT and soluble CD146 (sCD146) levels. Methods Thirty-seven patients with type 1 diabetes, 14 males (37.8%) and 23 females (62.2%), of mean (SD) age 26.2 (4.1) years admitted to the outpatient diabetes clinic at Okmeydani Training and Research Hospital, Istanbul, between January 2008 and December 2012, and 37 healthy controls, 16 males (43.2%) and 21 females (56.8%), of mean (SD) age 25.8 (3.1) years, selected from relatives of patients, were included. Anthropometric measures; fasting plasma glucose; and serum HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and creatinine concentrations were compared, as were CIMT and serum sCD146. Results Mean (SD) sCD146 levels were significantly higher in patients than in controls (314.6 (141.9) ng/ml vs. 207.8 (34.5) ng/ml, p?=?0.001), but mean (SD) CIMT did not differ (0.5 (0.1) mm vs. 0.4 (0.1) mm). ROC curves for sCD146 significantly differed in differentiating type 1 diabetics from healthy controls (p?=?0.0047) with a significantly higher percentage of patients than controls having sCD146 levels >260 ng/ml (21/37 (56.8%) vs. 2/37 (5.4%), p?=?0.00011). Conclusion Our findings emphasize that sCD146 levels may be a more sensitive marker than CIMT for earlier identification of type 1 diabetic patients at high risk for atherosclerosis. PMID:24139427



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

NASA Astrophysics Data System (ADS)

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

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



A Perspective on Solubility Rules.  

ERIC Educational Resources Information Center

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

Monroe, Manus; Abrams, Karl



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

ERIC Educational Resources Information Center

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…

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



Solubility of commercial milk protein concentrates and milk protein isolates.  


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

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



Selective deletion of leptin receptors in gonadotropes reveals activin and GnRH-binding sites as leptin targets in support of fertility.  


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

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



Soluble and colorless polyimides  

NASA Technical Reports Server (NTRS)

Results are reported in the form of reaction diagrams, graphs, and tables of research being conducted to synthesize and characterize linear aromatic polyimides which are soluble in common organic solvents and optically transparent in the 400-600 nm spectral range. These flexible and high-temperature polymeric films and coatings are needed for specific applications on space components such as antennas, solar cells, and thermal control coating systems. Several series of these polyimide films have been produced by making variations in the polymer molecular structure aimed at reducing the electronic interactions between the polymer chains.

St. Clair, Anne K.



Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy  

PubMed Central

AIM To determine the effects of laser photocoagulation on serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble angiopoietin receptor Tie-2 (Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes mellitus (T2DM) and proliferative diabetic retinopathy (PDR). We also explored the role of the Ang/Tie system in PDR. METHODS 160 patients with T2DM, including 50 patients with non-diabetic retinopathy (NDR), 58 patients with non-proliferative diabetic retinopathy (NPDR), and 52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure. RESULTS The median levels of Ang-2 and VEGF in serum were significantly higher in the NPDR group (4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group (2.67 ng/mL and 159.8 pg/mL, respectively, P<0.01), with the highest level in the PDR group (6.26 ng/mL and 531.2 pg/mL, respectively, P<0.01). The median level of Ang-1 was significantly higher in the NPDR group (10.77 ng/mL) compared to the NDR group (9.31 ng/mL) and the PDR groups (9.54 ng/mL) (P<0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups (1.49 vs 2.69 and 2.90, both P<0.01). The median level of Tie-2 was not significantly different among three groups (P>0.05). Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups (both P<0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased (both P<0.05), whereas serum Ang-1 level and Ang-1/Ang-2 ratio were weakly increased (P>0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group, however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups. CONCLUSION Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2DM patients with PDR. PMID:25161936

You, Qiao-Ying; Zhuge, Fu-Yuan; Zhu, Qi-Qian; Si, Xu-Wei



Water soluble laser dyes  


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.

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



Potential Solubility of Waste Materials  

Microsoft Academic Search

A standard solubility test can be used to assess the potential hazard associated with a wide variety of industrial wastes. This test will provide regulatory agencies with a more efficient tool with which to protect receiving waters and hence to establish environmental safeguards. Further, data generated by solubility testing will enable engineers to optimize disposal' site selection, criteria and design.

David Matchett



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.


The Ksp-Solubility Conundrum.  

ERIC Educational Resources Information Center

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)

Clark, Roy W.; Bonicamp, Judith M.



Recombinant soluble adenovirus receptor  


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.

Freimuth, Paul I. (East Setauket, NY)



Influence of soluble aluminosilicate complex formation on imogolite solubility determination  

NASA Astrophysics Data System (ADS)

In a earlier paper (Su and Harsh, 1994), we presented a free energy of formation for imogolite based on solubility studies and including a formation constant for a monomeric, soluble aluminosilicate complex (Browne and Driscoll, 1992). Farmer and Lumsdon (1994) have argued that the aluminosilicate formation constant is too high, calling into question solubility determinations utilizing this value. We have recalculated the log K value for imogolite dissolution using the new value for the aluminosilicate species. The result is a slight, but insignificant, increase in the log K for imogolite dissolution, supporting our earlier contention that the free energy of imogolite is larger than found in previous studies.

Su, Chunming; Harsh, James B.



Microemulsion formulation for enhanced absorption of poorly soluble drugs  

Microsoft Academic Search

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

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



Phenylated Polyimides With Greater Solubility  

NASA Technical Reports Server (NTRS)

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.

Harris, Frank W.




PubMed Central

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

Heidelberger, Michael; Avery, Oswald T.



Thermodynamics of chromium in UO2 fuel: A solubility model  

NASA Astrophysics Data System (ADS)

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.

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



Towards a Molecular Understanding of Protein Solubility.  

E-print Network

??Protein solubility is a problem for many protein chemists including structural biologists and those developing protein pharmaceuticals. Knowledge of how intrinsic factors influence solubility is… (more)

Kramer, Ryan 1984-



water-soluble fluorocarbon coating  

NASA Technical Reports Server (NTRS)

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.

Nanelli, P.



Method for estimating solubility parameter  

NASA Technical Reports Server (NTRS)

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.

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



Tough, Soluble, Aromatic, Thermoplastic Copolyimides  

NASA Technical Reports Server (NTRS)

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.

Bryant, Robert G. (Inventor)



Helix kinks are equally prevalent in soluble and membrane proteins  

PubMed Central

Helix kinks are a common feature of ?-helical membrane proteins, but are thought to be rare in soluble proteins. In this study we find that kinks are a feature of long ?-helices in both soluble and membrane proteins, rather than just transmembrane ?-helices. The apparent rarity of kinks in soluble proteins is due to the relative infrequency of long helices (?20 residues) in these proteins. We compare length-matched sets of soluble and membrane helices, and find that the frequency of kinks, the role of Proline, the patterns of other amino acid around kinks (allowing for the expected differences in amino acid distributions between the two types of protein), and the effects of hydrogen bonds are the same for the two types of helices. In both types of protein, helices that contain Proline in the second and subsequent turns are very frequently kinked. However, there are a sizeable proportion of kinked helices that do not contain a Proline in either their sequence or sequence homolog. Moreover, we observe that in soluble proteins, kinked helices have a structural preference in that they typically point into the solvent. PMID:24638929

Wilman, Henry R; Shi, Jiye; Deane, Charlotte M



Strategies to address low drug solubility in discovery and development.  


Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required. PMID:23383426

Williams, Hywel D; Trevaskis, Natalie L; Charman, Susan A; Shanker, Ravi M; Charman, William N; Pouton, Colin W; Porter, Christopher J H



Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate  

Microsoft Academic Search

We determined the experimental solubility of CNS marketed drugs. Of the 98 drugs measured, greater than 90% had solubility >10?M in pH 7.4 buffer. Only seven drugs had solubility <10?M. Using these data, we established a solubility criterion to support CNS discovery. The implication of poor solubility with potential safety concerns and undesirable side effects are discussed.

Yun W. Alelyunas; James R. Empfield; Dennis McCarthy; Russell C. Spreen; Khanh Bui; Luciana Pelosi-Kilby; Cindy Shen



PERSPECTIVE Overcoming the solubility limit with solubility-enhancement tags  

E-print Network

on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new), or introduction of point mutants (Huang et al. 1996; Ito and Wagner 2004; Sun et al. 1999) have been successfully uti- lized to increase the solubility of the target proteins. How- ever, these methods are often

Zhou, Pei


INVITED REVIEW The Soluble Epoxide Hydrolase as a Pharmaceutical  

E-print Network

on a previously unexplored mechanism of action. Epoxide hydrolases are enzymes that add water to three membered Words: soluble epoxide hydrolase, epoxide hydrolase, epoxide hydrolase inhibitor, inflammation (lisinopril), it was found that thiazide-type diuretics are superior in preventing one or more major forms

Hammock, Bruce D.


Soluble phenolic constituents from Cuscuta reflexa and Cuscuta platyloba  

Microsoft Academic Search

Phytochemical analysis of the phanerogamic parasites C. reflexa and C. platyloba yielded characteristic patterns of soluble phenolic constituents. Whereas C. reflexa contained mainly caffeic acid depsides, C. platyloba was characterized by the accumulation of flavonoids of the flavonol-type. The phenolic patterns proved to be stable in both Cuscuta ssp. irrespective of different host plants employed in the experiments. Segmentation of

Christiane Löffler; Antje Sahm; Victor Wray; Franz-Christian Czygan; Peter Proksch



Soluble Sugar Concentrations Associated with Tuber and Winter Bud Sprouting  

Microsoft Academic Search

Many aquatic weeds rely on vegetative structures for surviv- al and propagation, rather than seeds. American pondweed ( Potamogeton nodosus Poiret) winter buds , and hydrilla ( Hydril- la verticillata (L.f.) Royle, monoecious and dioecious types) tubers were allowed to sprout in water in the dark. At two-to- three day intervals individual propagules and dependent shoots were analyzed for soluble




Water solubility in trachytic melts  

Microsoft Academic Search

New data on water solubility in trachytic melts at pressures from 20 to 200 MPa and 850 °C are reported. Three trachytes, which differ mainly in Na\\/K ratio, were studied. The glasses obtained from water saturated experiments were analysed using both infrared spectroscopy (FTIR) and Karl Fischer Titration (KFT). The independent KFT data on total water contents were used to

V. Di Matteo; M. R. Carroll; H. Behrens; F. Vetere; R. A. Brooker



The solubility of substitutional atoms in ordered substitutional-intrestitial solid solutions  

NASA Astrophysics Data System (ADS)

The solubility of substitutional impurities in ordered bcc A-B-(C) solid solutions has been calculated in a static approximation. The effect of the energy splitting of geometrically equivalent interstitial sites into interstitial sites of two types during ordering was taken into account. The solubility has been determined as a function of temperature, alloy composition, and long-range order parameter.

Masharov, S. I.



Soluble monomeric IgG1 Fc.  


Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small size and other unique properties. However, compared with full-size antibodies, these antibody fragments lack the ability to bind the neonatal Fc receptor (FcRn) and have reduced half-lives. Fc engineered to bind antigens but preserve interactions with FcRn and Fc fused with monomeric proteins currently are being developed as candidate therapeutics with prolonged half-lives; in these and other cases, Fc is a dimer of two CH2-CH3 chains. To further reduce the size of Fc but preserve FcRn binding, we generated three human soluble monomeric IgG1 Fcs (mFcs) by using a combination of structure-based rational protein design combined with multiple screening strategies. These mFcs were highly soluble and retained binding to human FcRn comparable with that of Fc. These results provide direct experimental evidence that efficient binding to human FcRn does not require human Fc dimerization. The newly identified mFcs are promising for the development of mFc fusion proteins and for novel types of mFc-based therapeutic antibodies of small size and long half-lives. PMID:22518843

Ying, Tianlei; Chen, Weizao; Gong, Rui; Feng, Yang; Dimitrov, Dimiter S



Soluble adenylyl cyclase of sea urchin spermatozoa.  


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 HCO3(-) it is able to translate CO2/HCO3(-)/pH changes into cAMP levels. Fundamental sperm functions such as maturation, motility regulation and the acrosome reaction are influenced by cAMP; this is especially true for sperm of the sea urchin (SU), an organism that has been a model in the study of fertilization for more than 130years. 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

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



Solubilization of poorly water-soluble drugs using solid dispersions.  


Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible. PMID:23244679

Tran, Thao T-D; Tran, Phuong H-L; Khanh, Tran N; Van, Toi V; Lee, Beom-Jin



Improved solubility of replication factor C (RFC) Walker A mutants  

PubMed Central

Protein insolubility often poses a significant problem during purification protocols and in enzyme assays, especially for eukaryotic proteins expressed in a recombinant bacterial system. The limited solubility of replication factor C (RFC), the clamp loader complex from Saccharomyces cerevisiae, has been previously documented. We found that mutant forms of RFC harboring a single point mutation in the Walker A motif were even less soluble than the wild-type complex. The addition of maltose at 0.75 M to the storage and assay buffers greatly increases protein solubility and prevents the complex from falling apart. Our analysis of the clamp loading reaction is dependent on fluorescence-based assays, which are environmentally sensitive. Using wt RFC as a control, we show that the addition of maltose to the reaction buffers does not affect fluorophore responses in the assays or the enzyme activity, indicating that maltose can be used as a buffer additive for further downstream analysis of these mutants. PMID:22469630

Marzahn, Melissa R.; Bloom, Linda B.



The Solubility Parameters of Ionic Liquids  

PubMed Central

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

Marciniak, Andrzej



Tough soluble aromatic thermoplastic copolyimides  

NASA Technical Reports Server (NTRS)

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

Bryant, Robert G. (Inventor)



Presentation of Solubility Data: Units and Applications  

E-print Network

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


Developmental expression of activin/inhibin alpha- and beta(A)-subunit genes in the gonads of male and female chick embryos.  


The expression of inhibin alpha- and beta(A)-subunits was investigated in gonads of male and female chick embryos during the last week of their 21-day incubation period. Fertilized Hisex brown laying hen eggs were incubated at 37.8 +/- 0.2 degrees and 60% relative humidity in an automatic forced-draft incubator with constant lighting. Embryos were killed after 14, 18, and 21 days of incubation, sexed by macroscopical inspection of the gonadal phenotype, and further dissected to obtain the gonads. Total RNA was isolated using the ultraspec RNA method. The expression of alpha- and beta(A)-subunits was evaluated by competitive RT-PCR. Significant differences were found within and between sexes in the expression of the alpha- and beta(A)-subunits. The level of the alpha-subunit in the testis was about 23-fold higher than that in the ovary at all ages. Testicular content of inhibin alpha mRNA levels was similar at days 14 and 18 but declined significantly at day 21 of incubation, whereas no significant differences were observed between the three age groups in the ovary. Testicular and ovarian inhibin beta(A)-subunit increased significantly from day 14 to day 18 followed by a significant decline before hatch. However, inhibin beta(A) level at day 14 was significantly higher in the ovary than in the testis. At days 18 and 21, there were no differences in the levels of the inhibin beta(A) in the sexes. The expression of inhibin beta(A)-subunit in the ovary was significantly higher than that of the alpha-subunit at all ages. In the testis, however, the expression of the beta(A)-subunit was higher at days 18 and 21 than at day 14. The sex difference in gonadal inhibin subunits expression suggests differential roles of inhibin/activin in the development of the chicken gonads. The changing level of expression during incubation also suggests changing biological roles within sexes. PMID:11356042

Safi, M; Onagbesan, O M; Volckaert, G; Vanmontfort, D; Bruggeman, V; Decuypere, E



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

E-print Network

Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water

Hammock, Bruce D.


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

E-print Network

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- cessing. However, by far the main interest in the solubility of gases in polymers, and especially

Magee, Joseph W.


Solubility evaluation of murine hybridoma antibodies  

PubMed Central

The successful development of antibody therapeutics depends on the molecules having properties that are suitable for manufacturing, as well as use by patients. Because high solubility is a desirable property for antibodies, screening for solubility has become an essential step during the early candidate selection process. In considering the screening process, we formed a hypothesis that hybridoma antibodies are filtered by nature to possess high solubility and tested this hypothesis using a large number of murine hybridoma-derived antibodies. Using the cross-interaction chromatography (CIC) method, we screened the solubility of 92 murine hybridoma-derived monoclonal antibodies and found that all of these molecules exhibited CIC profiles that are indicative of high solubility (>100mg/mL). Further investigations revealed that variable region N-linked glycosylation or isoelectric parameters are unlikely to contribute to the high solubility of these antibodies. These results support the general hypothesis that hybridoma monoclonal antibodies are highly soluble. PMID:22531448

Spencer, Stacey; Bethea, Deidra; Raju, T. Shantha; Giles-Komar, Jill; Feng, Yiqing



Marangoni Flow of Soluble Amphiphiles  

NASA Astrophysics Data System (ADS)

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 these flows have a finite size that increases with a decrease of the critical micelle concentration of the surfactants. We document the universality of the surface velocity field of these finite flows and predict scaling laws based on hydrodynamics and surfactant physical chemistry that capture the flow features.

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



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.  


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

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



Determination of solubility parameters of ionic liquids and ionic liquid/solvent mixtures from intrinsic viscosity.  


The total and partial solubility parameters (dispersion, polar and hydrogen-bonding solubility parameters) of ten ionic liquids were determined. Intrinsic viscosity approaches were used that encompassed a one-dimensional method (1D-Method), and two different three-dimensional methods (3D-Method1 and 3D-Method2). The effect of solvent type, the dimethylacetamide (DMA) fraction in the ionic liquid, and dissolution temperature on solubility parameters were also investigated. For all types of effect, both the 1D-Method and 3D-Method2 present the same trend in the total solubility parameter. The partial solubility parameters are influenced by the cation and anion of the ionic liquid. Considering the effect on partial solubility parameters of the solvent type in the ionic liquid, it was observed that in both 3D methods, the dispersion and polar parameters of a 1-ethyl-3-methylimidazolium acetate/solvent (60:40 vol?%) mixture tend to increase as the total solubility parameter of the solvent increases. PMID:25145759

Weerachanchai, Piyarat; Wong, Yuewen; Lim, Kok Hwa; Tan, Timothy Thatt Yang; Lee, Jong-Min



Drug solubility: importance and enhancement techniques.  


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

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



Drug Solubility: Importance and Enhancement Techniques  

PubMed Central

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

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



Effects of cosolutes on the aqueous solubility of TNT, TNB, RDX, HMX  

SciTech Connect

Changes in the aqueous solubility of nitramine and nitroaromatic explosives in response to variations in common environmental parameters were investigated. Initial experiments focused on the cosolute effects of mixing explosive compounds together, and solubility differences produced by the presence of syringic, humic, and linolenic acids, and albumin. Aqueous solubility was determined using natural waters of different types. Effects of pH changes were also determined. Increasing humic acid concentrations increased TNT and TNB solubilities by 10--20%, compared to solubility in distilled water. Maximum increase occurred with humic acid concentrations of 96.8 and 152 mg L{sup {minus}1} for TNT and TNB, respectively. Syringic and linolenic acids, albumin, and pH changes had no apparent effect on the nitramines and nitroaromatics tested. Results were similar using natural and distilled waters.

Amos, J.C.; Simini, M. [Geo-Centers, Inc., Ft. Washington, MD (United States); Major, M.A. [Army Biomedical Research and Development Lab., Frederick, MD (United States); Checkai, R.T. [Army Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, MD (United States)



Solubility of triacylglycerols in supercritical carbon dioxide  

Microsoft Academic Search

The solubility of refined corn and sunflower seed oils, babassu (Attalea funifera) and ucuuba (Virola sebifera) fats in supercritical carbon dioxide (SC-CO2) were measured in a temperature range from 40 to 80°C and pressure between 200 and 350bar. Under working conditions, the values of solubility showed retrograde behavior. Experimental SC-CO2 solubility data were collected from the literature for the following

B. M. C. Soares; F. M. C. Gamarra; L. C. Paviani; L. A. G. Gonçalves; F. A. Cabral



Crosslinking of water-soluble polymers  

NASA Astrophysics Data System (ADS)

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.

Lei, Cuiyue


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

ERIC Educational Resources Information Center

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)

Wruck, Betty; Reinstein, Jesse




E-print Network

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



Microsoft Academic Search

Filtration experiments were conducted to investigate soluble manganese removal in granular media filtration; sand, manganese oxide coated sand (MOCS), sand + MOCS (1:1) and granular activated carbon (GAC) were used as filter media. Manganese removal, manganese oxide accumulation, turbidity removal, and regeneration of MOCS under various conditions were examined. Soluble manganese removal by the MOCS column was rapid and efficient;

J. Kim; S. Jung



Calculation of Drug Solubilities by Pharmacy Students.  

ERIC Educational Resources Information Center

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

Cates, Lindley A.



Phase Selectively Soluble Polystyrene-Supported Organocatalysts  

E-print Network

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...

Khamatnurova, Tatyana



Solubility of aceclofenac in polyamidoamine dendrimer solutions.  


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

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



Oil recovery from condensed corn distillers solubles  

Microsoft Academic Search

Condensed corn distillers solubles (CCDS) contains more oil than dried distillers grains with solubles (DDGS), 20 vs. 12% (dry weight basis). Therefore, significant amount of oil is present in the liquid fraction after fermentation and ethanol distillation. The oil removed represents a significant alternative feedstock for biodiesel production. The objectives of the present research were to study the effect of

Sandra Majoni



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

Microsoft Academic Search

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

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



Sensory evaluation of a milk formulation supplemented with n3 polyunsaturated fatty acids and soluble fibres  

Microsoft Academic Search

The hypocholesterolemic effect of some polyunsaturated fatty acids and soluble fibres has been demonstrated mostly in epidemiological studies. Two types of fatty acids (eicosapentaenoic-EPA 20:5n-3 and docosahexaenoic-DHA 22:6n-3) and soluble fibres (oat flour and guar gum), were mixed in different proportions and used in a milk formulation according to a factorial design (32) with a repetition in the central point.

Inar A. Castro; Júlio Tirapegui; Rui S. S. F. Silva; Airma J. S. Cutrim



Protein Solubility and Folding Enhancement by Interaction with RNA  

E-print Network

While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding. Studies on in vitro refolding in the presence of RNA, coexpression of RNA molecules in vivo and the mutants with impaired RNA binding ability suggests that RNA can exert chaperoning effect on their bound proteins. The results suggest that RNA binding could affect the overall kinetic network of protein folding pathway in favor of productive folding over off-pathway aggregation. In addition, the RNA binding-mediated solubility enhancement is extremely robust for increasing soluble yield of passenger proteins and could be usefully implemented for high-throughput protein expression for functional and structural genomic research initiatives. The RNA-mediated chaperone type presented

Seong Il Choi; Kyoung Sim Han; Chul Woo Kim; Ki-sun Ryu; Byung Hee Kim; Kyun-hwan Kim; Il Kim; Tae Hyun Kang; Hang-cheol Shin; Keo-heun Lim; Hyo Kyung Kim; Jeong-min Hyun; Baik L



Water-soluble conductive polymers  


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.

Aldissi, M.



Convenient access to readily soluble symmetrical dialkyl-substituted ?-oligofurans.  


An expedient approach to the synthesis of well soluble symmetrical dialkyl-substituted ?-oligofurans containing up to 8 ?-conjugated furan heterocycles is reported. An ultimate symmetry and high solubility of these ?-oligofurans were guaranteed using the 3,3'-diheptyl-2,2'-bifuran core and its symmetrical elongation through Suzuki-Miyaura or Stille cross-couplings. 3,3'-Diheptyl-2,2'-bifuran was prepared from 2,2'-bifuran-3,3'-dicarbaldehyde by the Wittig olefination and subsequent Pd/C-catalyzed transfer hydrogenation. The most appropriate access to 2,2'-bifuran-3,3'-dicarbaldehyde was achieved through a regioselective lithiation of 3-furanaldehyde acetal followed by CuCl2-induced homocoupling and deprotection. Single crystal X-ray analysis of 2,2'-bifuran-3,3'-dicarbaldehyde revealed anti-arrangement of the furan rings in planar molecules and an unexpected tight herringbone-type packing in crystals. PMID:25030451

Korshin, Edward E; Leitus, Gregory M; Bendikov, Michael



High shear treatment of concentrates and drying conditions influence the solubility of milk protein concentrate powders.  


The solubility of milk protein concentrate (MPC) powders was influenced by the method used for preparing the concentrate, drying conditions, and the type of dryer used. Increasing total solids of the ultrafiltered concentrates (23% total solids, TS) by diafiltration to 25% TS or evaporation to 31% TS decreased the solubility of MPC powders (80-83% protein, w/w dry basis), with ultrafiltration followed by evaporation to higher total solids having the greater detrimental effect on solubility. High shear treatment (homogenisation at 350/100 bar, microfluidisation at 800 bar or ultrasonication at 24 kHz, 600 watts) of ultrafiltered and diafiltered milk protein concentrates prior to spray drying increased the nitrogen solubility of MPC powders (82% protein, w/w dry basis). Of the treatments applied, microfluidisation was the most effective for increasing nitrogen solubility of MPC powders after manufacture and during storage. Manufacture of MPC powders (91% protein, w/w dry basis) prepared on two different pilot-scale dryers (single stage or two stage) from milk protein concentrates (20% TS) resulted in powders with different nitrogen solubility and an altered response to the effects of microfluidisation. Microfluidisation (400, 800 and 1200 bar) of the concentrate prior to drying resulted in increased long term solubility of MPC powders that were prepared on a single stage dryer but not those produced on a two stage spray dryer. This work demonstrates that microfluidisation can be used as a physical intervention for improving MPC powder solubility. Interactions between the method of preparation and treatment of concentrate prior to drying, the drying conditions and dryer type all influence MPC solubility characteristics. PMID:22998771

Augustin, Mary Ann; Sanguansri, Peerasak; Williams, Roderick; Andrews, Helen



Physiological function of soluble cytochrome c -552 from alkaliphilic Pseudomonas alcaliphila AL15-21 T  

Microsoft Academic Search

It has been found that the alkaliphilic Gram-negative bacterium Pseudomonas alcaliphila AL15-21T produces a larger amount of soluble c-type cytochromes at pH 10.0 under air-limited condition than at pH 7.0 under high aeration. Cytochrome c-552 was confirmed as the major c-type cytochrome among three soluble c-type cytochromes in the strain. To understand the physiological function of cytochrome c-552, a P.

Toshihede Matsuno; Kazuaki Yoshimune; Isao Yumoto


Dengue and Soluble Mediators of the Innate Immune System  

PubMed Central

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

Espada-Murao, Lyre Anni; Morita, Kouichi



Phase selectively soluble polymer supports to facilitate homogeneous catalysis  

E-print Network

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

Ortiz-Acosta, Denisse



Enhancement of Solubility and Bioavailability of -Lapachone Using  

E-print Network

Enhancement of Solubility and Bioavailability of -Lapachone Using Cyclodextrin Inclusion Complexes solubility and bio- availability problems previously noted with this drug. Methods. Inclusion complexes solubility studies, fluorescence, and 1 H-NMR spectroscopy. Biologic activity and bioavailability of -lap

Gao, Jinming



E-print Network

Norfloxacin, a Class IV (according to Biopharmaceutical Classification System) fluoroquinolone antibiotic is poorly water soluble drug. Dissolution rate is rate limiting factor for in-vivo drug absorption. Thus, an enhancement in dissolution rate is important to attain suitable blood-levels of these drugs. Different methods employed for its solubility enhancement include solid dispersions, complexation (in presence of Acidic Solubilizing additives; by EDTA and sodium caprate; and metal ion interaction), hydrotropic solubilization, crystal modification. Attempts were made to in order to obtain with better bioavailability and solubility enhancement of Norfloxacin.

Ha Varshney; Ajay Kumar Tiwari; Deepak Negi; Preti Khulbe; Peeush Singhal


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


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

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



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


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

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



Solubility Prediction of Satranidazole in Propylene Glycol-Water Mixtures Using Extended Hildebrand Solubility Approach  

PubMed Central

Extended Hildebrand solubility approach is used to estimate the solubility of satranidazole in binary solvent systems. The solubility of satranidazole in various propylene glycol-water mixtures was analyzed in terms of solute-solvent interactions using a modified version of Hildebrand-Scatchard treatment for regular solutions. The solubility equation employs term interaction energy (W) to replace the geometric mean (?1?2), where ?1 and ?2 are the cohesive energy densities for the solvent and solute, respectively. The new equation provides an accurate prediction of solubility once the interaction energy, W, is obtained. In this case, the energy term is regressed against a polynomial in ?1 of the binary mixture. A quartic expression of W in terms of solvent solubility parameter was found for predicting the solubility of satranidazole in propylene glycol-water mixtures. The expression yields an error in mole fraction solubility of ~3.74%, a value approximating that of the experimentally determined solubility. The method has potential usefulness in preformulation and formulation studies during which solubility prediction is important for drug design. PMID:23112403

Rathi, P. B.



Studies of phase separable soluble polymers  

E-print Network

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

Furyk, Steven Michael



Studies of Soluble Polymer-supported Organocatalysts  

E-print Network

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

Yang, Yun-Chin




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...


An Introduction to the Understanding of Solubility.  

ERIC Educational Resources Information Center

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)

Letcher, Trevor M.; Battino, Rubin



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

PubMed Central

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

Labute, P.



Solubility of the elements in titanium  

Microsoft Academic Search

Summary 1.The solubility of the elements in titanium follows a pattern similar to that characterizing the solubility of the elements in other metals, such as iron, nickel, and chromium.2.The formation, or non-formation, of solid solutions in binary titanium systems is associated with the relative similarity, or dissimilarity, in the properties of the elements, as indicated by Mendeleev's periodic system.3.Metals which

I. I. Kornilov



Correlation of Catalytic Rates With Solubility Parameters  

NASA Technical Reports Server (NTRS)

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

Lawson, Daniel D.; England, Christopher



Measurement of Protein Solubility in Common Feedstuffs  

Microsoft Academic Search

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

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




SciTech Connect

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.

Reboul, S



Soluble organic nitrogen in agricultural soils  

Microsoft Academic Search

The existence of soluble organic forms of N in rain and drainage waters has been known for many years, but these have not\\u000a been generally regarded as significant pools of N in agricultural soils. We review the size and function of both soluble organic\\u000a N extracted from soils (SON) and dissolved organic N present in soil solution and drainage waters

D. V. Murphy; A. J. Macdonald; E. A. Stockdale; K. W. T. Goulding; S. Fortune; J. L. Gaunt; P. R. Poulton; J. A. Wakefield; C. P. Webster; W. S. Wilmer



Soluble proteins of chemical communication: an overview across arthropods  

PubMed Central

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

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



Identification of a haem domain in human soluble adenylate cyclase  

PubMed Central

The second messengers cAMP and cGMP mediate a multitude of physiological processes. In mammals, these cyclic nucleotides are formed by related Class III nucleotidyl cyclases, and both ACs (adenylate cyclases) and GCs (guanylate cyclases) comprise transmembrane receptors as well as soluble isoforms. Whereas sGC (soluble GC) has a well-characterized regulatory HD (haem domain) that acts as a receptor for the activator NO (nitric oxide), very little is known about the regulatory domains of the ubiquitous signalling enzyme sAC (soluble AC). In the present study, we identify a unique type of HD as a regulatory domain in sAC. The sAC-HD (sAC haem domain) forms a larger oligomer and binds, non-covalently, one haem cofactor per monomer. Spectral analyses and mutagenesis reveal a 6-fold co-ordinated haem iron atom, probably with non-typical axial ligands, which can bind both NO and CO (carbon monoxide). Splice variants of sAC comprising this domain are expressed in testis and skeletal muscle, and the HD displays an activating effect on the sAC catalytic core. Our results reveal a novel mechanism for regulation of cAMP signalling and suggest a need for reanalysis of previous studies on mechanisms of haem ligand effects on cyclic nucleotide signalling, particularly in testis and skeletal muscle. PMID:22775536

Middelhaufe, Sabine; Leipelt, Martina; Levin, Lonny R.; Buck, Jochen; Steegborn, Clemens



Solubility effects in waste-glass/demineralized-water systems  

SciTech Connect

Aqueous systems involving demineralized water and four glass compositions (including standins for actinides and fission products) at temperatures of up to 150/sup 0/C were studied. Two methods were used to measure the solubility of glass components in demineralized water. One method involved approaching equilibrium from subsaturation, while the second method involved approaching equilibrium from supersaturation. The aqueous solutions were analyzed by induction-coupled plasma spectrometry (ICP). Uranium was determined using a Scintrex U-A3 uranium analyzer and zinc and cesium were determined by atomic absorption. The system that results when a waste glass is contacted with demineralized water is a complex one. The two methods used to determine the solubility limits gave very different results, with the supersaturation method yielding much higher solution concentrations than the subsaturation method for most of the elements present in the waste glasses. The results show that it is impossible to assign solubility limits to the various glass components without thoroughly describing the glass-water systems. This includes not only defining the glass type and solution temperature, but also the glass surface area-to-water volume ratio (S/V) of the system and the complete thermal history of the system. 21 figures, 22 tables. (DLC)

Fullam, H.T.



Controlled Porosity Solubility Modulated Osmotic Pump Tablets of Gliclazide.  


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

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



Ammonia Solubility in High Concentration Salt Solutions  

SciTech Connect

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.




Solubility limits of silicate melts  

Microsoft Academic Search

A statistical mechanical model of silica melt is presented in which metal oxides are incorporated into the bonding network. In this approach a Flory-type lattice model for binary silicate melts is coupled with a set of chemical reactions that determine the extent of metal oxide incorporation into the silica network and regulate the distribution of nonbridging oxygens around a central

L. Rene Corrales; Keith D. Keefer



Solubility enhancement of desloratadine by solid dispersion in poloxamers.  


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

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



Redefining solubility parameters: the partial solvation parameters.  


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

Panayiotou, Costas



1 MONAZITE SOLUBILITY EXPERIMENTS 1.1 Introduction and methods  

E-print Network

1 MONAZITE SOLUBILITY EXPERIMENTS 1.1 Introduction and methods The solubility of monazite in pure H-14 molal. Even at 1.0 GPa and 1000°C the solubility is only ~0.007 molal (Ayers 1991). At 25°C monazite solubility is known to increase as fluid acidity increases. Because REE behave as hard acids, we would expect


Cocrystals: An Approach to Solubility Enhancement Michelle Fung  

E-print Network

Cocrystals: An Approach to Solubility Enhancement Michelle Fung Aqueous solubility, and its, about 40% of drugs in the market are from the low solubility quadrants - Class II and IV are now one of the routes to enhance the dissolution rate of these low solubility drugs. Cocrystals

Thomas, David D.


Problems in determining the water solubility of organic compounds  

Microsoft Academic Search

We have been concerned for some time about the reliability of published water solubility data for organic compounds with low solubility. The problem was illustrated by the results of our studies on the solubility of the liquid trichlorobenzene (TCB). We found that the apparent solubility is strongly dependent on the method of introducing the solute into the water (Orr 1980).

A. Bharath; C. Mallard; D. Orr; G. Ozburn; A. Smith



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

E-print Network

Note Effect of milk solids concentration on the pH, soluble calcium and soluble phosphate levels of milk during heating Skelte G. ANEMA* Fonterra Research Centre, Private Bag 11029, Palmerston North, New 2009 Abstract ­ When milk is processed to dairy products, the concentration of the milk

Boyer, Edmond


Apparent Benzene Solubility in Tetraphenylborate Slurries  

SciTech Connect

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.

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



Melt extrusion with poorly soluble drugs.  


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

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



A study of the solubility of mercury in liquid hydrocarbons  

E-print Network

of the solubility of mercury in some liquid hydrocarbons was performed over a broad span of temperatures and pressures, ranging from -150 sF to 300 uF, and 14. 7 psia to 400 psia, The hydrocarbons used in the study included octane, pentane, propane, methane... Photon Excitation IV RESULTS Solubility of Mercury in Octane Solubility of Mercury in Pentane . . . . . . . . . . . . . . . . . . . . Solubility of Mercury in Toluene . . . . . . . . . . . . . . . . . . . . Solubility of Mercury in Propane...

McFarlane, David Larimer



Water soluble corrosion inhibitors help solve internal corrosion problems  

Microsoft Academic Search

The efficiency of oil-soluble, oil soluble-water dispersible, and water soluble corrosion inhibitors in protecting pipelines carrying both crude oil and water was tested for both sweet and sour crude. The tabulated results indicate that an oil soluble-water dispersible inhibitor is suitable for small diameter pipes that transport fluids at high velocities. However for large diameter pipes a water soluble inhibitor

P. L. Pettus; L. N. Strickland



Optimized expression of soluble cyclomaltodextrinase of thermophilic origin in Escherichia coli by using a soluble fusion-tag and by tuning of inducer concentration.  


Cyclomaltodextrinases are multidomain and often dimeric proteins from the alpha-amylase family (glycoside hydrolase family 13) which frequently have been very difficult to express in active form in Escherichia coli. To express the soluble form of this type of proteins in larger quantities the expression has to be optimized. We have used and combined two strategies to increase the yield of soluble recombinant cyclomaltodextrinase expressed from a gene originating from the thermophilic Gram-positive bacterium Anoxybacillus flavithermus. One strategy involved tuning of the inducer concentration while the other involved fusion of the gene encoding the target protein to the gene encoding the solubility-enhancing protein NusA. The enzyme activity could be increased 6-7 times solely by finely tuning the IPTG concentration, but the activity level was very sensitive to the amount of inducer applied. Hence, the IPTG concentration may have to be optimized for every protein under the conditions used. The fusion protein-strategy gave a slightly lower total activity but the level of soluble recombinant protein obtained was in this case significantly less sensitive to the inducer concentration applied. Moreover, the activity could be increased about 2-fold by cleaving off the solubility-tag (NusA) by enterokinase. PMID:15596360

Turner, Pernilla; Holst, Olle; Karlsson, Eva Nordberg



Miniaturized scintillation technique for protein solubility determinations  

NASA Astrophysics Data System (ADS)

We have developed a miniaturized (volume of crystallizing solution ˜100 ?l) technique for the determination of protein solubility as a function of temperature. After nucleation, crystals are detected by the light they scatter. Then the temperature at which a solution with the initial concentration is in equilibrium with the crystals is sought by stepwise, equilibrium dissolution of the crystals. The approach to solubility from the side of dissolution provides for higher accuracy of the determinations. The method was used to determine the temperature dependence of the solubility of human hemoglobin (Hb) C, for which high-resolution x-ray crystallography data are needed to understand the structural basis for the drastically different in vivo aggregation/crystallization behavior of ?6 Hb mutants.

Feeling-Taylor, Angela R.; Banish, R. Michael; Elison Hirsch, Rhoda; Vekilov, Peter G.



Diffusion and solubility of oxygen in silver  

NASA Technical Reports Server (NTRS)

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/ 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.

Eichenauer, W.; Miller, G.



Gaseous Sulfate Solubility in Glass: Experimental Method  

SciTech Connect

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.

Bliss, Mary



Recombinant soluble betaglycan is a potent and isoform-selective transforming growth factor-beta neutralizing agent.  

PubMed Central

Betaglycan is an accessory receptor of members of the transforming growth factor-beta (TGF-beta) superfamily, which regulates their actions through ligand-dependent interactions with type II receptors. A natural soluble form of betaglycan is found in serum and extracellular matrices. Soluble betaglycan, prepared as a recombinant protein using the baculoviral expression system, inhibits the actions of TGF-beta. Because of its potential use as an anti-TGF-beta therapeutic agent, we have purified and characterized baculoviral recombinant soluble betaglycan. Baculoviral soluble betaglycan is a homodimer formed by two 110 kDa monomers associated by non-covalent interactions. This protein is devoid of glycosaminoglycan chains, although it contains the serine residues, which, in vertebrate cells, are modified by these carbohydrates. On the other hand, mannose-rich carbohydrates account for approximately 20 kDa of the mass of the monomer. End-terminal sequence analysis of the soluble betaglycan showed that Gly(24) is the first residue of the mature protein. Similarly to the natural soluble betaglycan, baculoviral soluble betaglycan has an equilibrium dissociation constant (K(d)) of 3.5 nM for TGF-beta1. Ligand competition assays indicate that the relative affinities of recombinant soluble betaglycan for the TGF-beta isoforms are TGF-beta2>TGF-beta3>TGF-beta1. The anti-TGF-beta potency of recombinant soluble betaglycan in vitro is 10-fold higher for TGF-beta2 than for TGF-beta1. Compared with a commercial pan-specific anti-TGF-beta neutralizing antibody, recombinant soluble betaglycan is more potent against TGF-beta2 and similar against TGF-beta1. These results indicate that baculoviral soluble betaglycan has the biochemical and functional properties that would make it a suitable agent for the treatment of the diseases in which excess TGF-beta plays a central physiopathological role. PMID:11256966

Vilchis-Landeros, M M; Montiel, J L; Mendoza, V; Mendoza-Hernández, G; López-Casillas, F



AN-107 entrained solids - Solubility versus temperature  

SciTech Connect

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

GJ Lumetta; RC Lettau



Patterning of mouse embryonic stem cell-derived pan-mesoderm by Activin A\\/Nodal and Bmp4 signaling requires Fibroblast Growth Factor activity  

Microsoft Academic Search

Embryonic stem (ES) cells have the potential to differentiate into all cell types of the adult body, and could allow regeneration of damaged tissues. The challenge is to alter differentiation toward functional cell types or tissues by directing ES cells to a specific fate. Efforts have been made to understand the molecular mechanisms that are required for the formation of

Erik Willems; Luc Leyns



Patterning of mouse embryonic stem cell-derived pan-mesoderm by Activin A\\/Nodal and Bmp4 signaling requires fibroblast growth factor activity  

Microsoft Academic Search

Embryonic stem (ES) cells have the poten- tial to differentiate into all cell types of the adult body, and could allow regeneration of damaged tissues. The challenge is to alter differentiation toward functional cell types or tissues by directing ES cells to a specific fate. Efforts have been made to understand the molec- ular mechanisms that are required for the

Erik Willems; Luc Leyns



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

SciTech Connect

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.

Barney, G.S.



Swellable elementary osmotic pump (SEOP): An effective device for delivery of poorly water-soluble drugs  

Microsoft Academic Search

A new type of elementary osmotic pump (EOP) tablet for efficient delivery of poorly water-soluble\\/practically insoluble drugs has been designed. Drug release from the system, called swellable elementary osmotic pump (SEOP), is through a delivery orifice in the form of a very fine dispersion ready for dissolution and absorption. SEOP tablets were prepared by compressing the mixture of micronized drug

Javad Shokri; Parinaz Ahmadi; Parisa Rashidi; Mahbobeh Shahsavari; Ali Rajabi-Siahboomi; Ali Nokhodchi



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

Microsoft Academic Search

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.

L.-M. Zhang



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...


Enrichment of Artemia nauplii in PUFA, phospholipids, and water-soluble nutrients using liposomes  

Microsoft Academic Search

Different liposome formulations, includingseveral combinations of membrane composition,type of vesicle (multilamellar and largeunilamellar vesicles), preparation method, andvehiculated nutrient, have been assayed asbioencapsulation products to enrich Artemia nauplii with nutrients for feeding fish larvae.The stability of the liposome preparationsunder conditions of use as enrichment producthas been tested using water soluble fluorescentmarkers as leakage indicators. The content ofthe fatty acids and lipid

Óscar Monroig; Juan Carlos Navarro; Isabel Amat; Pedro González; Francisco Amat; Francisco Hontoria



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


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.

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



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

NASA Astrophysics Data System (ADS)

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.

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



Surface shear inviscidity of soluble surfactants.  


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 10(3)-10(4) 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

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



Towards a Molecular Understanding of Protein Solubility  

E-print Network

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...

Kramer, Ryan 1984-



Water-soluble polymers and compositions thereof  


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.

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



Water-soluble polymers and compositions thereof  


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.

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



Assessing Students' Conceptual Understanding of Solubility Equilibrium.  

ERIC Educational Resources Information Center

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

Raviolo, Andres



A new silver sulfadiazine water soluble gel  

Microsoft Academic Search

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

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



A new expanded solubility parameter approach.  


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

Stefanis, Emmanuel; Panayiotou, Costas



Biofiltration of Volatile Pollutants: Solubility Effects  

SciTech Connect

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 of obtaining these measurements, environmental models have generally used solubility constants of chemicals in pure water or, in a few rare cases, simple linear models. Our prior EMSP work has shown that the presence of biological material can increase effective solubilities by an order of magnitude for sparingly soluble organics; therefore, the previous simple approaches are not valid and are extremely poor predictors of actual bio-influenced partitioning. It is likely that environmental contaminants will partition in a similar manner into high-biomass phases (e.g. biobarriers and plants) or humic soils. Biological material in the subsurface can include lipids, fatty acids, humic materials, as well as the lumped and difficult-to-estimate 'biomass'. Our measurements include partition into these biological materials to allow better estimation. Fundamental data collected will be used in mathematical models predicting transport and sorption in subsurface environments, with the impacts on bioremediation being evaluated based on this new information. Our 2-D Win95/98/XP software program, Biofilter 1.0, developed as a part of our prior EMSP efforts for describing biofiltration processes with consideration given to both kinetic and mass transfer factors, is being extended to incorporate and use this information.

Davison, Brian H.; Barton, John W.



Biofiltration of Volatile Pollutants: Solubility Effects  

SciTech Connect

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 of obtaining these measurements, environmental models have generally used solubility constants of chemicals in pure water or, in a few rare cases, simple linear models. Our prior EMSP work has shown that the presence of biological material can increase effective solubilities by an order of magnitude for sparingly soluble organics; therefore, the previous simple approaches are not valid and are extremely poor predictors of actual bio-influenced partitioning. It is likely that environmental contaminants will partition in a similar manner into high-biomass phases (e.g. biobarriers and plants) or humic soils. Biological material in the subsurface can include lipids, fatty acids, humic materials, as well a s the lumped and difficult to estimate 'biomass'. Our measurements include partition into these biological materials to allow better estimation. Fundamental data collected will be used in mathematical models predicting transport and sorption in subsurface environments, with the impacts on bioremediation being evaluated based on this new information. Our 2-D Win95/98 software program, Biofilter 1.0, developed as a part of our prior EMSP efforts for describing biofiltration processes with consideration given to both kinetic and mass transfer factors, will be extended to incorporate and use this information.

Davison, Brian H.; Barton, John W.



Solubilities of nickel oxide in molten carbonate  

Microsoft Academic Search

Cathode dissolution is a major problem for the development of the molten carbonate fuel cell. This paper reports that in order to evaluate the stability of the cathode, the solubility of NiO has been measured for several compositions of molten alkaline carbonates in the COâ pressure range from 10{sup - 5} to 1 atm and the temperature range from 873

Ken-ichiro Ota; S. Mitsushima; S. Kato; S. Asano; H. Yoshitake; N. Kamiya



Substrate stiffness regulates solubility of cellular vimentin  

PubMed Central

The intermediate filament protein vimentin is involved in the regulation of cell behavior, morphology, and mechanical properties. Previous studies using cells cultured on glass or plastic substrates showed that vimentin is largely insoluble. Although substrate stiffness was shown to alter many aspects of cell behavior, changes in vimentin organization were not reported. Our results show for the first time that mesenchymal stem cells (hMSCs), endothelial cells, and fibroblasts cultured on different-stiffness substrates exhibit biphasic changes in vimentin detergent solubility, which increases from nearly 0 to 67% in hMSCs coincident with increases in cell spreading and membrane ruffling. When imaged, the detergent-soluble vimentin appears to consist of small fragments the length of one or several unit-length filaments. Vimentin detergent solubility decreases when these cells are subjected to serum starvation, allowed to form cell–cell contacts, after microtubule disruption, or inhibition of Rac1, Rho-activated kinase, or p21-activated kinase. Inhibiting myosin or actin assembly increases vimentin solubility on rigid substrates. These data suggest that in the mechanical environment in vivo, vimentin is more dynamic than previously reported and its assembly state is sensitive to stimuli that alter cellular tension and morphology. PMID:24173714

Murray, Maria E.; Mendez, Melissa G.; Janmey, Paul A.



Water-soluble polymers and compositions thereof  


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.

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



Zircon-xenotime solid-solubility: an experimental study  

NASA Astrophysics Data System (ADS)

The physicochemical stability of crystalline zircon depends upon minor elements in solid-solution. If solubility limits in certain parageneses could be established, the widely applied U-Th-Pb geochronometer may be directly linked with the P/T-conditions of primary zircon growth or recrystallization. The xenotime substitution Zr + Si = (Y,HREE) + P, accounting for the isostructural xenotime-type orthophosphate component in zircon, seems promising for this purpose. Knowledge of this substitution is incomplete although limited miscibility between zircon and xenotime was repeatedly suggested from coexisting natural phases. Published experimental studies succeeded in synthesizing zircon-xenotime solid-solutions by using a dry sintering technique and by the Li-Mo-flux-method [1]. However, no experimental determinations of solubility limits at the solvus between coexisting zircon and xenotime are currently availible. Using a piston cylinder apparatus, we synthesized accessory phases in fluid-saturated silicate melts (initially near albite-quartz compositions). Starting materials were prepared from admixtures of silcate glass and oxides. An explorational experimental series was done at temperatures between 800oC and 1300oC and pressures between 0.8 GPa and 2.3 GPa. Below 1000oC, results were disappointing due to sluggish reaction rates and very small crystal sizes. Higher temperature experiments, however, gave coexisting zircon and xenotime large enough for reliable electron microprobe analysis. Accordingly, the miscibility gap between zirconss and xenotimess closes with increasing temperature and pressure has the opposite effect. A comparison of our preliminary experimental data with natural zircon data from the literature suggests that xenotime solubility in xenotime-saturated zirconss lacking significant amounts of additional elements is of the order of 10 mol.% at granulite facies conditions. [1] Hanchar JM, Finch RJ, Hoskin PWO, Watson EB, Cherniak DJ &Mariano AN, Am. Min. 86, 667-680, (2001).

Tomaschek, F.; Ballhaus, C.



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


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

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



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

PubMed Central

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

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



Matrix Metalloproteinase 2 Releases Active Soluble Ectodomain of Fibroblast Growth Factor Receptor 1  

Microsoft Academic Search

Recent studies have demonstrated the existence of a soluble fibroblast growth factor (FGF) receptor type 1 (FGFR1) extracellular domain in the circulation and in vascular basement membranes. However, the process of FGFR1 ectodomain release from the plasma membrane is not known. Here we report that the 72-kDa gelatinase A (matrix metalloproteinase type 2, MMP2) can hydrolyze the Val368-Met369 peptide bond

Ehud Levi; Rafael Fridman; Hua-Quan Miao; Yong-Sheng Ma; Avner Yayon; Israel Vlodavsky



Role of soluble adenylyl cyclase in cell death and growth.  


cAMP signaling is an evolutionarily conserved intracellular communication system controlling numerous cellular functions. Until recently, transmembrane adenylyl cyclase (tmAC) was considered the major source for cAMP in the cell, and the role of cAMP signaling was therefore attributed exclusively to the activity of this family of enzymes. However, increasing evidence demonstrates the role of an alternative, intracellular source of cAMP produced by type 10 soluble adenylyl cyclase (sAC). In contrast to tmAC, sAC produces cAMP in various intracellular microdomains close to specific cAMP targets, e.g., in nucleus and mitochondria. Ongoing research demonstrates involvement of sAC in diverse physiological and pathological processes. The present review is focused on the role of cAMP signaling, particularly that of sAC, in cell death and growth. Although the contributions of sAC to the regulation of these cellular functions have only recently been discovered, current data suggest that sAC plays key roles in mitochondrial bioenergetics and the mitochondrial apoptosis pathway, as well as cell proliferation and development. Furthermore, recent reports suggest the importance of sAC in several pathologies associated with apoptosis as well as in oncogenesis. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. PMID:25010002

Ladilov, Yury; Appukuttan, Avinash



Soluble expression and purification of porcine pepsinogen from Pichia pastoris.  


This paper presents a new system for the soluble expression and characterization of porcine pepsinogen from the methylotrophic yeast Pichia pastoris. The cDNA that encodes the zymogenic form of porcine pepsin (EC was cloned into the EcoRI site of the vector pHIL-S1 downstream from the AOX1 alcohol oxidase promoter. After P. pastoris transformation, colonies were screened for expression of pepsinogen based on enzyme activity of the active form, pepsin. The recombinant enzyme was purified 138-fold by anion exchange and affinity column chromatography. Homogeneity was confirmed through SDS-PAGE, Western blot, and N-terminal sequencing. When compared to commercial pepsin, the recombinant pepsin had similar kinetic profiles, pH/temperature stability, and secondary/tertiary conformation. A glycosylated form was also isolated and found to exhibit kinetic and structural characteristics similar to those of the commercial and wild-type pepsin, but was slightly more thermal stable. The above results indicate that the P. pastoris expression system offers a convenient and efficient means to produce and purify a soluble form of pepsin(ogen). PMID:12135554

Yoshimasu, Mark A; Ahn, Jong-Kun; Tanaka, Takuji; Yada, Rickey Y



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


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

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




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...


Soluble non-cross-linked peptidoglycan polymers stimulate monocyte-macrophage inflammatory functions.  

PubMed Central

Soluble non-cross-linked peptidoglycan polymers are released by gram-positive bacteria when beta-lactam antibiotics are administered to humans. In this report, we show that this type of peptidoglycan can stimulate monocyte-macrophage functions that cause inflammation. Non-cross-linked peptidoglycan polymers from penicillin-treated Streptococcus faecium were purified and shown to stimulate the production of interleukin 1 by human monocytes and of colony-stimulating factors by a murine macrophage cell line. In addition, the release of plasminogen activator by human monocytes was inhibited by the soluble peptidoglycan. These in vitro results suggest that prolonged treatment with beta-lactam antibiotics, by causing the production of soluble peptidoglycan, may result in interleukin 1-mediated inflammatory reactions, excessive production of monocytes and granulocytes, and increased fibrin deposition. Images PMID:3875561

Gold, M R; Miller, C L; Mishell, R I



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

SciTech Connect

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.

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)



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

SciTech Connect

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.

S.E. Ziemniak



Nomenclature for mammalian soluble glutathione transferases.  


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

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



Role of soluble adenylyl cyclase in mitochondria.  


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 (HCO3(-)) and calcium (Ca(2+)) 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

Valsecchi, Federica; Konrad, Csaba; Manfredi, Giovanni



Nanoparticle Solubility in Liquid Crystalline Defects  

NASA Astrophysics Data System (ADS)

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.

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



Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury  

SciTech Connect

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.

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:; Gong Feili [Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China)]. E-mail:



Murine lung immunity to a soluble antigen  

SciTech Connect

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

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



Soluble Guanylate Cyclase Modulators in Heart Failure  

Microsoft Academic Search

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

Veselin Mitrovic; Ana Jovanovic; Stefan Lehinant



Solubilities and thermophysical properties of ionic liquids  

Microsoft Academic Search

This report presents the systematic study on the solubilities of 1-alkyl-3-methyl- imidazolium hexafluorophosphate (e, or bmim)(PF 6 ), 1-alkyl-3-methylimidazolium methylsulfate (almim)(CH 3 SO 4 ), 1-hexyloxymethyl-3-methylimidazolium ionic liquids (ILs) (C 6 H 13 OCH 2 mim)(BF 4 ), or (C 6 H 13 OCH 2 mim)((CF 3 SO 2 ) 2 N) in aliphatic hydrocar- bons (heptane, octane), cyclohydrocarbons (cyclopentane,

Urszula Domanska



Solubility data are compiled for metals in liquid zinc  

NASA Technical Reports Server (NTRS)

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.

Dillon, I. G.; Johnson, I.



Solubility of carbon in tetragonal ferrite in equilibrium with austenite  

E-print Network

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

Cambridge, University of


Selection for intrabody solubility in mammalian cells using GFP fusions  

E-print Network

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

Paris-Sud XI, Université de



E-print Network

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

Fisher, Tom


I Dependence of the Solubility of Salts George M. Bodner  

E-print Network

I Dependence of the Solubility of Salts George M. Bodner Purdue University W. Lafayette,IN 47907 in the solubility of inorganic salts with temperature. Some appreciation for the magnitude of this problem can in the table. It is worth noting that each and every one of these salts shows an increased solubility

Bodner, George M.


ACCELERATED COMMUNICATION Alterations in Detergent Solubility of Heterotrimeric G Proteins  

E-print Network

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

Vogel, Zvi


Chukwuemeka I. Okoye Carbon Dioxide Solubility and Absorption Rate in  

E-print Network

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

Rochelle, Gary T.


Improving drug solubility for oral delivery using solid dispersions  

Microsoft Academic Search

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

Christian Leuner; Jennifer Dressman




E-print Network

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

Paris-Sud XI, Université de


The Hildebrand Solubility Parameters of Ionic Liquids—Part 2  

PubMed Central

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

Marciniak, Andrzej



The Solubility of Sulphur in Hydrous Rhyolitic Melts  

E-print Network

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

Paris-Sud XI, Université de


Induction of soluble AChE expression via alternative splicing by chemical stress in Drosophila melanogaster.  


Various molecular forms of acetylcholinesterase (AChE) have been characterized in insects. Post-translational modification is known to be a major mechanism for the molecular diversity of insect AChE. However, multiple forms of Drosophila melanogaster AChE (DmAChE) were recently suggested to be generated via alternative splicing (Kim and Lee, 2013). To confirm alternative splicing as the mechanism for generating the soluble form of DmAChE, we generated a transgenic fly strain carrying the cDNA of DmAChE gene (Dm_ace) that predominantly expressed a single transcript variant encoding the membrane-anchored dimer. 3' RACE (rapid amplification of cDNA ends) and western blotting were performed to compare Dm_ace transcript variants and DmAChE forms between wild-type and transgenic strains. Various Dm_ace transcripts and DmAChE molecular forms were observed in wild-type flies, whereas the transgenic fly predominantly expressed Dm_ace transcript variant encoding the membrane-anchored dimer. This supports alternative splicing as the major determinant in the generation of multiple forms of DmAChE. In addition, treatment with DDVP as a chemical stress induced the expression of the Dm_ace splice variant without the glycosylphosphatidylinositol anchor site in a dose-dependent manner and, accordingly, the soluble form of DmAChE in wild-type flies. In contrast, little soluble DmAChE was expressed in the transgenic fly upon exposure to DDVP. DDVP bioassays revealed that transgenic flies, which were unable to express a sufficient amount of soluble monomeric DmAChE, were more sensitive to DDVP compared to wild-type flies, suggesting that the soluble monomer may exert non-neuronal functions, such as chemical defense against xenobiotics. PMID:24637386

Kim, Young Ho; Kwon, Deok Ho; Ahn, Hyo Min; Koh, Young Ho; Lee, Si Hyeock



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


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

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



On lead(II) glycocholate solubility.  


The solubility of lead(II) glycocholate was studied as a function of glycocholate ion concentration at 25 degrees C and in 0.100, 0.500 and 0.800 mol dm-3 N(CH3)4Cl as a constant ionic medium. For this purpose the total concentration of lead(II) was determined by means of atomic absorption spectrophotometry and polarography measurements in solution equilibrated with solid lead(II) glycocholate at known hydrogen ion concentration. The free concentration of lead(II) and hydrogen ions was determined by measuring the electromotive force(e.m.f.) of galvanic cells involving lead amalgam and glass electrode. The e.m.f. measurements were carried out both in clear solutions before precipitation and in the presence of the precipitate. The results of the solubility and e.m.f. measurements could be explained by assuming the presence of associated species between lead(II) and glycocholate. The solubility product and the association constants were determined for all the ionic medium concentrations. PMID:11993267

Bottari, Emilio; Festa, Maria Rosa; Franco, Magda



Determining silica solubility in bayer process liquor  

NASA Astrophysics Data System (ADS)

The efficient precipitation of dissolved silica from Bayer process liquor is essential for the production of high-quality alumina and the reduction of excessive scaling in the heat exchangers in the evaporation building of Bayer processes. The accurate prediction of silica solubility in Bayer liquor is one of the key parameters in improving the design and operation of the desilication process. Previous findings, particularly with respect to the influence of temperature and concentrations of caustic soda and alumina on the solubility of silica, are inconclusive. In this article, experimental results are presented over a wide range of temperature and alumina and caustic soda concentrations. Attempts are made to utilize artificial neural networks for identifying the process variables and modeling. The radial basis function neural network architecture was used successfully to generate a nonlinear correlation for the prediction of the solubility of silica in Bayer process liquor. The resulting correlation can predict the present data and the control data of other investigators with good accuracy.

Müller-Steinhagen, H.



Fluorite solubility equilibria in selected geothermal waters  

USGS Publications Warehouse

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

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



Solubility of nitrous oxide in amine solutions  

SciTech Connect

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

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



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

PubMed Central

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.

Patel, V. F.; Sarai, J.



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


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

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



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

NASA Astrophysics Data System (ADS)

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.

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



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

E-print Network

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

Benedek, George B.


IUPAC-NIST Solubility Data Series. 84. Solubility of Inorganic Actinide Compounds  

NASA Astrophysics Data System (ADS)

This volume presents the solubility of inorganic compounds of actinides except for carbonates, which are included in Volume 74 of this series, and nitrates, which are covered in Volume 55. Also included are solubility data of compounds such as organosulfates, phosphates, and arsenates, which are not covered in Volume 74. The predominant part of this volume covers solubility data of thorium, uranium, neptunium, and plutonium compounds. Fewer data have been published for americium compounds and very few for compounds of actinium, protactinium, and transamericium elements. The literature has been covered up to the end of 2004. Documents which remained unavailable to the editor, and could not be included in the volume are listed in the Appendix. For some compounds it was not possible to show the Chemical Abstracts registry numbers since these have not been assigned.

Miyamoto, H.




SciTech Connect

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

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



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

E-print Network

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

Decoteau, Dennis R.


Solubility of xenon in amino-acid solutions. II. Nine less-soluble amino acids  

NASA Astrophysics Data System (ADS)

Ostwald solubility (L) of xenon gas, as the radioisotope 133Xe, has been measured as a function of solute concentration, at 25.0 °C, in aqueous solutions of nine amino acids. The amino-acid concentrations investigated covered much of their solubility ranges in water, viz., asparagine monohydrate (0-0.19 M), cysteine (0-1.16 M), glutamine (0-0.22 M), histidine (0-0.26 M), isoleucine (0-0.19 M), methionine (0-0.22 M), serine (0-0.38 M), threonine (0-1.4 M), and valine (0-0.34 M). We have previously reported solubility results for aqueous solutions of six other, generally more soluble, amino acids (alanine, arginine, glycine, hydroxyproline, lysine, and proline), of sucrose and sodium chloride. In general, L decreases approximately linearly with increasing solute concentration in these solutions. If we postulate that the observed decreases in gas solubility are due to hydration, the results under some assumptions can be used to calculate hydration numbers (H), i.e., the number of H2O molecules associated with each amino-acid solute molecule. The average values of hydration number (H¯) obtained at 25.0 °C are 15.3±1.5 for asparagine, 6.8±0.3 for cysteine, 11.5±1.1 for glutamine, 7.3±0.7 for histidine, 5.9±0.4 for isoleucine, 10.6±0.8 for methionine, 11.2±1.3 for serine, 7.7± 1.0 for threonine, and 6.6±0.6 for valine. We have also measured the temperature dependence of solubility L(T) from 5-40 °C for arginine, glycine, and proline, and obtained hydration numbers H¯(T) in this range. Between 25-40 °C, arginine has an H¯ near zero. This may be evidence for an attractive interaction between xenon and arginine molecules in aqueous solution.

Kennan, Richard P.; Himm, Jeffrey F.; Pollack, Gerald L.



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

PubMed Central

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

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.



Solubility of Ketoprofen in colloidal PLGA.  


The successful design and development of pharmaceutical drug-polymer composites requires detailed information about the phase behavior of the drug-polymer binary system. This study presents an extended investigation of the phase equilibrium established between the chiral anti-inflammatory drug Ketoprofen (KET) and the bio-compatible and biodegradable polymer poly(lactic-co-glycolic) acid 5050 (PLGA). Equilibration experiments were carried out in aqueous suspensions of KET crystals together with PLGA in the form of spherical amorphous nanoparticles obtained by supercritical fluid extraction of emulsions (SFEE). The influence of temperature was studied in the range between 0°C and 50°C, while the effect of KET chirality was investigated by using two different crystalline forms of KET, namely enantiopure S-KET and a racemic compound, RS-KET, in equilibration experiments. It was found that the level of KET established in PLGA at equilibrium increases with temperature, e.g. from 6.9 wt.% at 20°C to 25.8 wt.% at 40°C for the case of S-KET. At each temperature level, the solubility of KET in PLGA was lower for equilibration with RS-KET, significantly higher for equilibration with S-KET, and the highest for simultaneous equilibration with both crystalline species. Experimental solubility data of KET in PLGA were also described in a model based on the Sanchez-Lacombe equation of state. For experiments carried out at 10°C or below, an equilibrium state could not be reached even after a prolonged equilibration period, presumably because the polymer phase had undergone a transition into the glassy state. For this temperature range, where an experimental equilibration is not any more possible, the model may be used to estimate the solubility of KET in PLGA by extrapolation. PMID:20728513

Kluge, Johannes; Mazzotti, Marco; Muhrer, Gerhard



The Marangoni flow of soluble amphiphiles  

E-print Network

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.

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



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

PubMed Central

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

George, SJ; Vasudevan, DT



miR-199a-5p inhibits monocyte/macrophage differentiation by targeting the activin A type 1B receptor gene and finally reducing C/EBP? expression.  


miRNAs are short, noncoding RNAs that regulate expression of target genes at post-transcriptional levels and function in many important cellular processes, including differentiation, proliferation, etc. In this study, we observed down-regulation of miR-199a-5p during monocyte/macrophage differentiation of HL-60 and THP-1 cells, as well as human CD34(+) HSPCs. This down-regulation of miR-199a-5p resulted from the up-regulation of PU.1 that was demonstrated to regulate transcription of the miR-199a-2 gene negatively. Overexpression of miR-199a-5p by miR-199a-5p mimic transfection or lentivirus-mediated gene transfer significantly inhibited monocyte/macrophage differentiation of the cell lines or HSPCs. The mRNA encoding an ACVR1B was identified as a direct target of miR-199a-5p. Gradually increased ACVR1B expression level was detected during monocyte/macrophage differentiation of the leukemic cell lines and HSPCs, and knockdown of ACVR1B resulted in inhibition of monocyte/macrophage differentiation of HL-60 and THP-1 cells, which suggested that ACVR1B functions as a positive regulator of monocyte/macrophage differentiation. We demonstrated that miR-199a-5p overexpression or ACVR1B knockdown promoted proliferation of THP-1 cells through increasing phosphorylation of Rb. We also demonstrated that the down-regulation of ACVR1B reduced p-Smad2/3, which resulted in decreased expression of C/EBP?, a key regulator of monocyte/macrophage differentiation, and finally, inhibited monocyte/macrophage differentiation. PMID:25258381

Lin, Hai-Shuang; Gong, Jia-Nan; Su, Rui; Chen, Ming-Tai; Song, Li; Shen, Chao; Wang, Fang; Ma, Yan-Ni; Zhao, Hua-Lu; Yu, Jia; Li, Wei-Wei; Huang, Li-Xia; Xu, Xin-Hua; Zhang, Jun-Wu



Soluble adenylyl cyclase in health and disease.  


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 HCO3(-), Ca(2+) 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

Schmid, Andreas; Meili, Dimirela; Salathe, Matthias



Soluble Mediators Regulating Immunity in Early Life  

PubMed Central

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

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



Soluble adenylyl cyclase in the eye.  


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

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



The Soluble Proteome of the Drosophila Antenna  

PubMed Central

The olfactory system of Drosophila melanogaster is one of the best characterized chemosensory systems. Identification of proteins contained in the third antennal segment, the main olfactory organ, has previously relied primarily on immunohistochemistry, and although such studies and in situ hybridization studies are informative, they focus generally on one or few gene products at a time, and quantification is difficult. In addition, purification of native proteins from the antenna is challenging because it is small and encased in a hard cuticle. Here, we describe a simple method for the large-scale detection of soluble proteins from the Drosophila antenna by chromatographic separation of tryptic peptides followed by tandem mass spectrometry with femtomole detection sensitivities. Examination of the identities of these proteins indicates that they originate both from the extracellular perilymph and from the cytoplasm of disrupted cells. We identified enzymes involved with intermediary metabolism, proteins associated with regulation of gene expression, nucleic acid metabolism and protein metabolism, proteins associated with microtubular transport, 8 odorant-binding proteins, protective enzymes associated with antibacterial defense and defense against oxidative damage, cuticular proteins, and proteins of unknown function, which represented about one-third of all soluble proteins. The procedure described here opens the way for precise quantification of any target protein in the Drosophila antenna and should be readily applicable to antennae from other insects. PMID:19917591

Williams, Taufika Islam



Water soluble fraction of Asian dust particles  

NASA Astrophysics Data System (ADS)

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.

Osada, Kazuo



Drum drying performance of condensed distillers solubles and comparison to performance of modified condensed distillers solubles  

Technology Transfer Automated Retrieval System (TEKTRAN)

Condensed distillers solubles (CDS) is a viscous, syrupy co-product of ethanol production from corn; CDS exhibits strong recalcitrance to drying due to its chemical composition, which includes a substantial amount of glycerol. The objectives of this study were to determine the drum drying performan...


Transport of soluble species in backfill and rock  

SciTech Connect

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

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



Antibacterial Activities of Peptides from the Water-Soluble Extracts of Italian Cheese Varieties  

Microsoft Academic Search

Water-soluble extracts of 9 Italian cheese varieties that differed mainly for type of cheese milk, starter, technology, and time of ripening were fractionated by reversed-phase fast protein liquid chromatography, and the antimicrobial activity of each fraction was first assayed toward Lactobacillus sakei A15 by well-diffu- sion assay. Active fractions were further analyzed by HPLC coupled to electrospray ionization-ion trap mass

C. G. Rizzello; I. Losito; M. Gobbetti; T. Carbonara; M. D. De Bari; P. G. Zambonin



Properties of Granular Cold-Water-Soluble Starches Prepared by Alcoholic-Alkaline Treatments  

Microsoft Academic Search

Cereal Chem. 71(6):623-626 Granular cold-water-soluble (GCWS) starches were prepared from no detectable degradation of starch molecules during the preparation. normal maize, Hylon V (HA5), Hylon VII (HA7), and waxy maize starches The treated GCWS starches showed V-type X-ray diffraction patterns by treating the starches with mixtures of ethanol and NaOH solutions for normal maize, HA5, and HA7 starches; the GCWS



Comparison of Disulfide Contents and Solubility at Alkaline pH of Insecticidal and Noninsecticidal Bacillus thuringiensis Protein Crystals  

PubMed Central

We compared two insecticidal and eight noninsecticidal soil isolates of Bacillus thuringiensis with regard to the solubility of their proteinaceous crystals at alkaline pH values. The protein disulfide contents of the insecticidal and noninsecticidal crystals were equivalent. However, six of the noninsecticidal crystals were soluble only at pH values of ?12. This lack of solubility contributed to their lack of toxicity. One crystal type which was soluble only at pH ?12 (strain SHP 1-12) did exhibit significant toxicity to tobacco hornworm larvae when the crystals were presolubilized. In contrast, freshly prepared crystals from the highly insecticidal strain HD-1 were solubilized at pH 9.5 to 10.5, but when these crystals were denatured, by either 8 M urea or autoclave temperatures, they became nontoxic and were soluble only at pH values of ?12. These changes in toxicity and solubility occurred even though the denatured HD-1 crystals were morphologically indistinguishable from native crystals. Our data are consistent with the view that insecticidal crystals contain distorted, destabilized disulfide bonds which allow them to be solubilized at pH values (9.5 to 10.5) characteristic of lepidopteran and dipteran larval midguts. Images PMID:16349421

Du, Cheng; Martin, Phyllis A. W.; Nickerson, Kenneth W.



Caffeine solubility in supercritical carbon dioxide\\/co-solvent mixtures  

Microsoft Academic Search

In order to assess the effect of co-solvents on the solubility of caffeine in supercritical carbon dioxide, experimental solubility of caffeine in supercritical ethanol–carbon dioxide and isopropanol–carbon dioxide mixed solvents was obtained using a high-pressure semi-continuous flow apparatus. Caffeine solubilities in 5% ethanol\\/95% CO2, 10% ethanol\\/90% CO2 and 5% isopropanol\\/95% CO2 mixed solvents were determined at 323.2 and 343.2K and

Uiram Kopcak; Rahoma Sadeg Mohamed



Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development  

Microsoft Academic Search

As the first pharmaceutical products which contain highly soluble cyclodextrin (CD) derivatives (e.g. Sporanox™=itraconazole\\/HP-?-CD by Janssen and Clorocil™=chloramphenicol\\/methyl-?-CD by Oftalder) are already on the market it seems to be timely to give an overview on the technological and commercial aspects of the chemically modified water-soluble CDs as drug carriers. This chapter deals with the chemistry and general properties of water-soluble

Lajos Szente; József Szejtli



Preparation of organo-soluble polyanilines in ionic liquid  

Microsoft Academic Search

A method for preparation of organo-soluble polyaniline (PANI) is described. Oxidative coupling polymerization of anilium chloride with ammonium persulfate in a new ionic liquid, 2-hydroxyethyl ammonium formate (HAF), gives organo-soluble polyaniline with appreciable molecular weights (Mw=86,400). Interestingly polyaniline (PANI) prepared by this method is highly soluble in many organic solvents such as acetone, tetrahydrofurane, dioxane, dimethyformamide and N-methyl, 2-pyrrolidinone. Thin

Niyazi B?çak; B. Filiz ?enkal; Esma Sezer



Solubility of carbon dioxide and hydrogen sulfide in aqueous N-methyldiethanolamine solutions  

SciTech Connect

In this work, 72 new experimental solubility data points for H{sub 2}S and CO{sub 2} mixtures in aqueous N-methyldiethanol amine (MDEA) solutions at different methane partial pressures (up to 69 bara) are presented. They are correlated using an electrolyte equation of state (E-EOS) thermodynamic model. This model has already been used to estimate the CO{sub 2} solubility in aqueous MDEA (Huttenhuis et al. Fluid Phase Equilib. 2008, 264, 99-112) and the H{sub 2}S solubility in aqueous MDEA (Huttenhuis et al. Int. J. Oil, Gas Coal Technol. 2008, 1, 399-424). Here, the model is further extended to predict the behavior of CO{sub 2} and H{sub 2}S when they are present simultaneously in aqueous MDEA. The application of an equation of state is a new development for this type of system, i.e., of acid-gas-amine systems. The molecular interactions are described by Schwarzentruber et al.'s modification of the Redlich-Kwong-Soave equation of state, with terms added to account for ionic interactions in the liquid phase. The model is used to describe acid-gas solubility data for the CO{sub 2}-H{sub 2}S-MDEA-H{sub 2}O system reported in the open literature and experimental data reported here for the CO{sub 2}-H{sub 2}S-MDEA-H{sub 2}O-CH{sub 4} system.

Huttenhuis, P.J.G.; Agrawal, N.J.; Versteeg, G.F. [Procede Group BV, Enschede (Netherlands)



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


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

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



Method of increasing biodegradation of sparingly soluble vapors  


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.

Cherry, Robert S. (Idaho Falls, ID)



Soluble Variants of Human Recombinant Glutaminyl Cyclase  

PubMed Central

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

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



Communication: Epistructural thermodynamics of soluble proteins  

NASA Astrophysics Data System (ADS)

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.

Fernández, Ariel



Solubility of magnesium carbonate in natural waters  

USGS Publications Warehouse

(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.

Wells, R.C.



Polymerized soluble venom--human serum albumin  

SciTech Connect

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.

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



A Path to Soluble Molecularly Imprinted Polymers  

PubMed Central

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

Verma, Abhilasha; Murray, George M.



U solubility in the core of Earth  

E-print Network

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

Xuezhao Bao; Richard A. Secco



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

NASA Astrophysics Data System (ADS)

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.

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



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


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

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



A nontetrameric species is the major soluble form of keratin in Xenopus oocytes and rabbit reticulocyte lysates  

PubMed Central

Inside the interphase cell, approximately 5% of the total intermediate filament protein exists in a soluble form. Past studies using velocity gradient sedimentation (VGS) indicate that soluble intermediate filament protein exists as an approximately 7 S tetrameric species. While studying intermediate filament assembly dynamics in the Xenopus oocyte, we used both VGS and size-exclusion chromatography (SEC) to analyze the soluble form of keratin. Previous studies (Coulombe, P. A., and E. Fuchs. 1990. J. Cell Biol. 111:153) report that tetrameric keratins migrate on SEC with an apparent molecular weight of approximately 150,000; the major soluble form of keratin in the oocyte, in contrast, migrates with an apparent molecular weight of approximately 750,000. During oocyte maturation, the keratin system disassembles into a soluble form (Klymkowsky, M. W., L. A. Maynell, and C. Nislow. 1991. J. Cell Biol. 114:787) and the amount of the 750-kD keratin complex increases dramatically. Immunoprecipitation analysis of soluble keratin from matured oocytes revealed the presence of type I and type II keratins, but no other stoichiometrically associated polypeptides, suggesting that the 750-kD keratin complex is composed solely of keratin. To further study the formation of the 750-kD keratin complex, we used rabbit reticulocyte lysates (RRL). The 750-kD keratin complex was formed in RRLs contranslating type I and type II Xenopus keratins, but not when lysates translated type I or type II keratin RNAs alone. The 750-kD keratin complex could be formed posttranslationally in an ATP-independent manner when type I and type II keratin translation reactions were mixed. Under conditions of prolonged incubation, such as occur during VGS analysis, the 750-kD keratin complex disassembled into a 7 S (by VGS), 150-kD (by SEC) form. In urea denaturation studies, the 7 S/150-kD form could be further disassembled into an 80-kD species that consists of cofractionating dimeric and monomeric keratin. Based on these results, the 750-kD species appears to be a supratetrameric complex of keratins and is the major, soluble form of keratin in both prophase and M-phase oocytes, and RRL reactions. PMID:8567720



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


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

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



Influence of slightly soluble organics on aerosol activation  

NASA Astrophysics Data System (ADS)

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 because of their lower solubilities. The first and second mechanisms have already been addressed in a previous paper. 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 as a worst-case scenario) 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 resimulated but assuming fully soluble aerosols. Results of the simulations show that although 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 affected because these particles are completely dissolved at the initial supersaturation of zero), low solubility has minimal to no effect on the parcel supersaturation except for particles consisting of more than 95% adipic acid. Furthermore, since aerosols in realistic atmospheric conditions do not contain more than 90% organics, we should be only interested in smaller concentrations (less than 90% by mass). Accordingly, we conclude that the slightly soluble organics can be assumed to be fully soluble for the purpose of predicting the fraction of activation and the maximum supersaturation with negligible error and it is not necessary to retune the previously developed parameterization of aerosol activation.

Abdul-Razzak, Hayder; Ghan, Steven J.



Measurement of entrainer effects of water and ethanol on solubility of caffeine in supercritical carbon dioxide by FT-IR spectroscopy  

Microsoft Academic Search

The solubilities of caffeine in supercritical CO2, supercritical CO2+water, supercritical CO2+ethanol, and supercritical CO2+water+ethanol were measured with a circulation-type apparatus combined with an on-line Fourier transform infrared (FT-IR) spectrometer at 313.2K and 15.0MPa. The solubilities of caffeine were determined with the peak absorbances of caffeine at 1190cm?1. The solubilities of caffeine increase until water is saturated in supercritical CO2. The

Yoshio Iwai; Hirotaka Nagano; Gil Sun Lee; Machiko Uno; Yasuhiko Arai



Water-Soluble Organometallic Catalysts from Carbohydrates. 1.  

E-print Network

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

RajanBabu, T. V. "Babu"


Cloud condensation nuclei activation of limited solubility organic aerosol  

NASA Astrophysics Data System (ADS)

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.

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


Is the enhanced solubility in nanocomposites an electronic effect?  

Microsoft Academic Search

In metallic nanocomposites, an enhanced solid solubility has been reported. This enhancement is suggested to result from the electric space charge in the vicinity of the interphase boundaries between two metallic crystals with different Fermi energies. The space charge modifies the electronic structure locally in such a way that the solute solubility is locally enhanced.

H Gleiter; M Fichtner



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...


Soluble Concentrate Material Safety Data Sheet 102381-0002  

E-print Network

Soluble Concentrate Material Safety Data Sheet 102381-0002 1. CHEMICAL PRODUCT & COMPANY;Soluble Concentrate Material Safety Data Sheet 102381-0002 4. EMERGENCY AND FIRST AID MEASURES Inhalation Concentrate Material Safety Data Sheet 102381-0002 7. HANDLING & STORAGE Handling Sodium hydroxide

Rollins, Andrew M.


21 CFR 520.154c - Bacitracin zinc soluble powder.  

Code of Federal Regulations, 2013 CFR

...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...



21 CFR 520.154c - Bacitracin zinc soluble powder.  

Code of Federal Regulations, 2014 CFR

...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...



21 CFR 520.154c - Bacitracin zinc soluble powder.  

Code of Federal Regulations, 2012 CFR

...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...



Water-soluble prodrugs of an Aurora kinase inhibitor  

Microsoft Academic Search

Compound 1 (SNS-314) is a potent and selective Aurora kinase inhibitor that is currently in clinical trials in patients with advanced solid tumors. This communication describes the synthesis of prodrug derivatives of 1 with improved aqueous solubility profiles. In particular, phosphonooxymethyl-derived prodrug 2g has significantly enhanced solubility and is converted to the biologically active parent (1) following iv as well

Johan D. Oslob; Stacey A. Heumann; Chul H. Yu; Darin A. Allen; Subramanian Baskaran; Minna Bui; Erlie Delarosa; Amy D. Fung; Ahmad Hashash; Jonathan Hau; Sheryl Ivy; Jeffrey W. Jacobs; Willard Lew; Jack Maung; Robert S. McDowell; Sean Ritchie; Michael J. Romanowski; Jeffrey A. Silverman; Wenjin Yang; Min Zhong; Tarra Fuchs-Knotts



Solubility of non-polar gases in electrolyte solutions  

NASA Technical Reports Server (NTRS)

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

Walker, R. L., Jr.



2 + 1 dimensional gravity as an exactly soluble system  

Microsoft Academic Search

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

Edward Witten



Assessing Junior High Students' Understanding of Density and Solubility.  

ERIC Educational Resources Information Center

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

Gennaro, Eugene D.



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

ERIC Educational Resources Information Center

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)

Treptow, Richard S.



Facilitating protein solubility by use of peptide extensions  


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.

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



Intraluminal zinc bioavailability - effect of amino acids on zinc solubility  

SciTech Connect

Human and bovine milks and simple solutions modeled after milks (milk models) have been used in the development of an intraluminal system involves subjecting a food, i.e., milk, to the pH range encountered in the digestive tract, and measuring the amount of soluble minerals at various pH's. With this system the authors have demonstrated that co-precipitation of zinc with calcium phosphate is a key factor modulating the solubility of zinc in milks and in milk models. Since a mineral must be soluble in order to be bioavailable, and since free amino acids have been suggested to increase the solubility of zinc by adding various amino acids. Of the amino acids, aspartate, glutamate, histidine, and phosphoserine, only histidine (10 mM) increased the solubility of zinc in a milk model, albeit slightly. Supplementation of bovine milk with 10 mM histidine also resulted in a slight increase in zinc solubility. No increase in zinc solubility was observed at a physiologic histidine level. Free amino acids at physiologic concentrations do not increase zinc solubility in milks, and therefore, do not seem to contribute to zinc bioavailability.

Jacobs, F.A.; Nelson, L.S. Jr.; Brushmiller, J.G.




Microsoft Academic Search

Water solubilities of solid solution forms of phenanthrene and anthracene in water between 283 K and 308 K were measured by the shake flask method. The present experimental results showed that solid composition affected the water solubility of the solid solution as follows: The saturation concentration of a solute decreased with an increase in the amount of the other in

Hidetoshi Kuramochi; Daisuke Nakajima; Sumio Goto; Katsuya Kawamoto; Kouji Maeda



What determines drug solubility in lipid vehicles: Is it predictable?  

Microsoft Academic Search

Lipid-based drug delivery systems are of increasing interest to the pharmaceutical scientist because of their potential to solubilize drug molecules that may be otherwise difficult to develop. The ability to predict lipid solubility is an important step in being able to identify the right excipients to solubilize and formulate drugs in lipid formulations. However, predicting lipid solubility is complicated by

Sagar S. Rane; Bradley D. Anderson



Effect of drug solubility on release behavior of calcium polysaccharide gel-coated pellets.  


The aim of this study was to investigate the effect of drug solubility on the release behavior from calcium polysaccharide gel (CaPG)-coated pellets. Three different drugs with similar chemical structure, but different water solubility, namely caffeine (CAF), theophylline (TPL) and theobromine (TBR), were used. Drug-loaded spherical pellets were manufactured by an extrusion-spheronization method. The CaPG was applied on the pellets loaded with different drugs by interfacial complexation coating. The encapsulation efficiency of coated pellets was found to vary from 57.6 to 84.3%, depending on the solubility of the active drug and polysaccharide type. Drug release from different uncoated pellets was relatively unaffected by pH and release media but depended mainly on drug solubility. Release behavior was significantly modified in the pellets coated with CaPG, for all of the drugs tested. Drug release from coated pellets of the different drugs showed different release kinetics. The difference in the drug release is probably due to the difference in the drug dissolution within the core, before its partition and diffusion through the CaPG coat. The CAF dissolved faster and achieved a higher concentration in solution, which drove diffusion. The release of TBR from the coated pellets was much slower than that of the CAF or TPL because of its low solubility. However, the release of all drugs was about four- to sixfold slower for coated than uncoated pellets, suggesting that the coating influenced the retardation of drug release from the coated pellets. Therefore, the CaPG coating may provide a sustained release delivery system for all drugs tested. PMID:17889515

Sriamornsak, Pornsak; Kennedy, Ross A



Tigecycline Induction of Phenol-Soluble Modulins by Invasive Methicillin-Resistant Staphylococcus aureus Strains  

PubMed Central

We examined the effects of tigecycline on three types of exoproteins, ?-type phenol-soluble modulins (PSM?1 to PSM?4), ?-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSM?s occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSM?1 to PSM?4, as protein A and ?-hemolysin production was decreased under the same conditions by all of the antibiotics used. PMID:23817369

Yamaki, Jason; Synold, Timothy



Metal solubility enhancing peptides derived from barley protein.  


Mineral supplements are required to be soluble as their bioavailability is highly correlated to their solubility in body fluids. In this study, metal binding capacity of barley protein hydrolysates and their purified fractions was investigated and expressed as increase in solubility of metal ions. Metal ions in the presence of hydrolysates exhibited a remarkable increase in solubility: 118, 32, 10, 29 and 35-fold for Fe(2+), Fe(3+), Ca(2+), Cu(2+) and Zn(2+), respectively. A mixture of low molecular weight peptides possesses a synergistic combination of both charged and hydrophobic residues and achieves the best binding metal ions. Electrostatic interactions via charged side chains and coordination binding with His and Cys, initially attract the metal ions and, afterward, hydrophobic interactions and aromatic ring stacking stabilize the positioning of metal ions in the structure of the peptide. Barley hordein hydrolysates show potential as dietary supplements that enhance both mineral solubility and bioavailability. PMID:24767088

Eckert, Ewelina; Bamdad, Fatemeh; Chen, Lingyun



Soluble organic compounds in the Tagish Lake meteorite  

NASA Astrophysics Data System (ADS)

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.

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



Solubility of multi-component biodiesel fuel systems.  


Solubility of biodiesel fuel components in fossil diesel fuel-methanol-rapeseed oil methyl ester, fossil diesel fuel-ethanol-rapeseed oil methyl ester and fossil diesel fuel-ethanol-rapeseed oil ethyl ester systems was investigated. The solubility of components in the fossil diesel fuel-ethanol-rapeseed oil methyl ester system at 20 degrees C was substantially higher than in the fossil diesel fuel-methanol-rapeseed oil methyl ester system. The solubility of components in the fossil diesel fuel-ethanol-rapeseed oil ethyl ester system was slightly lower than in the fossil diesel fuel-ethanol-rapeseed oil methyl ester mixture. The moisture content of ethanol had a great influence on mixture solubility. With decrease of temperature, the solubility of components in the fossil diesel fuel-ethanol-rapeseed oil methyl ester system decreased. PMID:15501669

Makareviciene, Violeta; Sendzikiene, Egle; Janulis, Prutenis



The removal of soluble species by warm stratiform clouds  

NASA Technical Reports Server (NTRS)

The development of a one-dimensional, time-dependent model to study the removal of soluble gases from a warm, precipitating stratiform cloud is reported. The model calculates the distributions of water vapor and condensed water, in the form of cloud drops and raindrops, as well as the in-cloud concentration of a soluble species in the gas and aqueous phases for a specified profile of pressure and temperature and an assumed updraft velocity. Highly soluble gases are found to be rapidly dissolved into cloud droplets and then slowly incorporated into raindrops as cloudwater is converted to rainwater. The rainout rate for highly soluble species is found to be ultimately limited by the rate at which new gaseous material can be transferred from the cloud-free air into the cloud. The model calculations indicate that turbulence represents an important mechanism by which highly soluble gases are transported into stratiform clouds.

Qin, YU; Chameides, W. L.



Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells.  

PubMed Central

When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain. By contrast, when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated. This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity. Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy. These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b. PMID:8690804

Vetvicka, V; Thornton, B P; Ross, G D



Biological significance of soluble IL-2 receptor  

PubMed Central

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

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



Volatile solubility in magmas at high pressure  

NASA Astrophysics Data System (ADS)

We present a new theoretical approach for the solubility of volatiles in liquid silicates, with special emphasis on the effect of pressure, aiming at better understanding vesiculation processes in ascending magmas. We use the so-called "hard sphere fluid", a reference model widely used in liquid state physics for several decades. This simple model allows describing accurately, up to pressures of several hundreds of kilobars, the equation of state of pure gases. The model also applies very well to liquid silicates under pressure, by comparison to the scarce available experimental data. We use data on the density of melts at 1 bar to constrain the cohesion of such fluids. The hard sphere model also allows studying how a noble gas atom or a CO2 molecule dissolves into a silicate melt, a process governed by the equality of the solute chemical potentials in the melt and gas phase at equilibrium at T and P. The chemical potential consists of an entropic and an energetic contribution. The model enables one to evaluate readily the entropy of cavity formation to accommodate the solute particle through the density fluctuations of the solvent melt. Correlatively, a term describing the solvation energy is added to account for the interaction between the solute and the silicate network. The latter energetic term is directly constrained by the solubilites measured at 1 bar. The hard sphere model shows that compression is important for melt, but even stronger for fluid (for P typically > 10 kbar). We thus show, for the first time, that, when pressure increases, compression of melt is counterbalanced, up to several tens of kbar, by compression of fluid. This explains very well why experiments have seen an almost linear increase of volatile concentration in melt with increasing pressure. At P > 100 kbar, compression of the melt finally dominates and the solubility in melt eventually decreases. Therefore, volatile dissolution in silicate melt at high pressure certainly does not follow Henry's law (where gas is assumed ideal). We use our model to investigate vesiculation of tholeiites at mid-ocean ridges. The until now poorly understood He/Ar elemental fractionation recorded in Mid-Ocean Ridge Basalts is well explained if a melt (with about 0.8% CO2) starts to vesiculate at about 10 kbar (35 km below sea level), and suffers, during ascent, two or three vesiculation stages followed by vesicle loss and a last vesiculation with no loss. If these successive vesiculation events occur at various depths, this explains the large variability of the He/Ar ratios observed in MORBs.

Sarda, P.; Guillot, B.



A literature review of interaction of oxidized uranium species and uranium complexes with soluble organic matter  

USGS Publications Warehouse

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.

Jennings, Joan K.; Leventhal, J.S.



Ion Association versus Ion Interaction Models in Examining Electrolyte Solutions: Application to Calcium Hydroxide Solubility Equilibrium  

ERIC Educational Resources Information Center

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…

Menéndez, M. Isabel; Borge, Javier



Illustrating the Concept of Sparingly Soluble Salts Using Various Copper Compounds: A Classroom Demonstration  

ERIC Educational Resources Information Center

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…

O'Sullivan, Daniel W.; Crouch, Collier C.



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

E-print Network

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

Krishnamoorthy, Bala


Development of supercritical fluid extraction and supercritical fluid chromatography purification methods using rapid solubility screening with multiple solubility chambers.  


Rapid solubility screening in diverse supercritical fluids (SCFs) was carried out via multiple solubility chambers with a trapping device and online ultraviolet (UV) detection. With this device, it was possible to rapidly study the solubility variations of multiple components in a mixture. Results from solubility studies have been used to develop efficient supercritical fluid extraction (SFE) and supercritical fluid chromatography (SFC) methods. After the investigation of solubilities of theophylline and caffeine in several neat organic solvents and SCFs, advantages of SFE over conventional organic solvent extraction were demonstrated with a model mixture of theophylline and caffeine. The highest solubility ratio of 1:40 (theophylline:caffeine) was observed in the SCF with 20% acetonitrile (MeCN), where a ratio of 1:11 was the highest in the neat organic solvents. A model mixture of theophylline:caffeine (85:15 w/w, caffeine as an impurity) was successfully purified by SFE by leveraging the highest solubility difference. The SCF with 20% MeCN selectively removed caffeine and left theophylline largely intact. Rapid SCF solubility screening was applied to development of SFE and SFC methods in a drug discovery environment. Two successful applications were demonstrated with proprietary Amgen compounds to either remove an achiral impurity before chiral purification or enhance chiral chromatographic throughput. PMID:21766341

Gahm, Kyung H; Huang, Ke; Barnhart, Wesley W; Goetzinger, Wolfgang



Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase  

PubMed Central

Hepoxilins are lipid signaling molecules derived from arachidonic acid through the 12-lipoxygenase pathway. These trans-epoxy hydroxy eicosanoids play a role in a variety of physiological processes, including inflammation, neurotransmission, and formation of skin barrier function. Mammalian hepoxilin hydrolase, partly purified from rat liver, has earlier been reported to degrade hepoxilins to trioxilins. Here, we report that hepoxilin hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase (sEH): i) purified mammalian sEH hydrolyses hepoxilin A3 and B3 with a Vmax of 0.4–2.5 ?mol/mg/min; ii) the highly selective sEH inhibitors N-adamantyl-N’-cyclohexyl urea and 12-(3-adamantan-1-yl-ureido) dodecanoic acid greatly reduced hepoxilin hydrolysis in mouse liver preparations; iii) hepoxilin hydrolase activity was abolished in liver preparations from sEH?/? mice; and iv) liver homogenates of sEH?/? mice show elevated basal levels of hepoxilins but lowered levels of trioxilins compared with wild-type animals. We conclude that sEH is identical to previously reported hepoxilin hydrolase. This is of particular physiological relevance because sEH is emerging as a novel drug target due to its major role in the hydrolysis of important lipid signaling molecules such as epoxyeicosatrienoic acids. sEH inhibitors might have undesired side effects on hepoxilin signaling. PMID:21217101

Cronin, Annette; Decker, Martina; Arand, Michael



[Functionally-relevant conformational dynamics of water-soluble proteins].  


A study is reported of the functional-relevant dynamics of three typical water-soluble proteins: Calmodulin, Src-tyrosine kinase as well as repressor of Trp operon. Application of the state-of-art methods of structural bioinformatics allowed to identify dynamics seen in the X-ray structures of the investigated proteins associated with their specific biological functions. In addition, Normal Mode analysis technique revealed the most probable directions of the functionally-relevant motions for all that proteins were also predicted. Importantly, overall type of the motions observed on the lowest-frequency modes was very similar to the motions seen from the analysis of the X-ray data of the examined macromolecules. Thereby it was shown that the large-scale as well as local conformational motions of the proteins might be predetermined already at the level of their tertiary structures. In particular, the determining factor might be the specific fold of the alpha-helixes. Thus functionally-relevant in vivo dynamics of the investigated proteins might be evolutionally formed by means of natural selection at the level of the spatial topology. PMID:23705506

Novikov, G V; Sivozhelezov, V S; Sha?tan, K V



Leaching Soluble Salts Increases Population Densities of Tylenchulus semipenetrans.  


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

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



Isolation and characterization of Xenopus soluble epoxide hydrolase.  


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

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



Two exactly soluble models of rigidity percolation  

PubMed Central

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

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



Soluble phthalocyanines as optical gas sensing materials  

NASA Astrophysics Data System (ADS)

A novel soluble phthalocyanine compound, i.e zinc phthalocyanine (sulfonamide) has been synthesized by chemical substitution of zinc phthalocyanine and used to produce thin solid films by means of the spin coating technique. The chemical structure of the spin coated films has been investigated by FT-IR analysis. Atomic Force Microscopy (AFM) has been used to characterize the film morphology and to measure the film thickness. The spin coated films have been tested as optical sensing materials of volatile organic compounds such as methanol, ethanol and 2-propanol. The change of optical reflectance of the films upon exposure to alcohol-vapour-containing atmospheres has been measured versus alcohol concentration and exposure time. The films exhibit a fast and reproducible response, with a complete and fast recovery in methanol and ethanol-containing atmospheres, while diffusion-driven effects appear during exposure to 2-propanol. The response and sensitivity of the films to ethanol vapour is higher than to methanol and 2-propanol.

Severova, Katerina; Maggioni, Gianluigi; Nespurek, Stanislav; Carturan, Sara; Milan, Riccardo; Tonezzer, Michele; Della Mea, Gianantonio



Two exactly soluble models of rigidity percolation.  


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 =4.41, which is above the 'mean field' value =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 =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

Thorpe, M F; Stinchcombe, R B



[Soluble brain proteins in autosomal trisomy syndromes].  


The authors examined the soluble proteins of the brain frontal lobes in the newborn with trisomias of the 13th, 18th, and 21st chromosomes (Down's, Patau's, and Edwards' syndromes). The examinations were carried out on autopsy material (the post-mortem period not exceeding 24 hours) by the method of disc electrophoresis in polyacrylamide gel. The brain tissue was taken from 17 newborn infants with Down's syndrome; 9 infants with Patau's syndrome; and 7 infants with Edwards' syndrome. For the control the brain of 21 newborn infants without defects of the CNS development (the death cause being analogous) was taken. In all the syndromes studied diversely directed but relatively specific shifts were revealed on the proteinograms. It was the albumin section which appeared to be the most sensitive to the chromosomal pathology: in cases of Down's and Patau's syndromes the protein content in it was reduced, whereas in cases of Edwards' syndrome it was increased. In the latter syndrome the relative amount of neuronines S-5 and S-6, and in Patau's syndrome the amount of neuronine S-6 were lowered, this lowering being statistically significantly. In all the trisomias a tendency to a diminution of the zone of the acidic neurospecific cerebral proteins was noted. This is, possibly, due to the lower level of the CNS functional activity in chromosomal pathologies. PMID:6458983

Mikhneva, L M; Baryshevskaia, V D



Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes  

PubMed Central

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

Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing



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


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

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



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

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

Hammock, Bruce D.


Engineered Soluble Monomeric IgG1 CH3 Domain  

PubMed Central

Most of the therapeutic antibodies approved for clinical use are full-size IgG1 molecules. The interaction of the IgG1 Fc with the neonatal Fc receptor (FcRn) plays a critical role in maintaining their long half-life. We have hypothesized that isolated Fc domains could be engineered to functionally mimic full-size IgG1 (nanoantibodies) but with decreased (10-fold) size. Here, we report for the first time the successful generation of a soluble, monomeric CH3 domain (mCH3). In contrast to the wild-type dimeric CH3, the mCH3 exhibited pH-dependent binding to FcRn similar to that of Fc. The binding free energy of mCH3 to FcRn was higher than that of isolated CH2 but lower than that of Fc. Therefore, CH3 may contribute a larger portion of the free energy of binding to FcRn than CH2. A fusion protein of mCH3 with an engineered antibody domain (m36.4) also bound to FcRn in a pH-dependent fashion and exhibited significantly higher neutralizing activity against HIV-1 than m36.4-Fc fusion proteins. The m36.4-mCH3 fusion protein was monomeric, stable, soluble, and expressed at a high level in Escherichia coli. We also found that engineering an additional disulfide bond in mCH3 remarkably increased its thermal stability, whereas the FcRn binding was not affected. These data suggest that mCH3 could not only help in the exploration of the dual mechanisms of the CH3 contribution to Fc functions (dimerization and FcRn interactions) but could also be used for the development of candidate therapeutics with optimized half-life, enhanced tissue penetration, access to sterically restricted binding sites, and increased therapeutic efficacy. PMID:23867459

Ying, Tianlei; Chen, Weizao; Feng, Yang; Wang, Yanping; Gong, Rui; Dimitrov, Dimiter S.



Solubilities of nitrogen and noble gases in basalt melt  

NASA Astrophysics Data System (ADS)

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.

Miyazaki, A.; Hiyagon, H.; Sugiura, N.


Solubilities of nitrogen and noble gases in basalt melt  

NASA Technical Reports Server (NTRS)

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.

Miyazaki, A.; Hiyagon, H.; Sugiura, N.



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


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

Jain, Shashank; Patel, Niketkumar; Lin, Senshang



CCN activation of fumed silica aerosols mixed with soluble pollutants  

NASA Astrophysics Data System (ADS)

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.

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



[The solubility of drugs in molten suppository bases].  


Solubility of 18 drugs used in rectal therapy in molten suppository base, (Massa suppositoriorum 15, Pharmacopeia of the G.D.R. Rosupol U, 37 degrees C) is determined. Separation of drug-saturated base from drug cristals is carried out in an air-heated centrifuge followed by a partition step between petroleum ether and an aqueous medium and photometrical determination of drug concentration. The procedure leads to results with relative standard deviation of 2% (medium value of 18 drugs). The investigation gave solubility values in the range between 0.002% (theobromine) and 26% (lidocaine), whereas benzoate, phenobarbital sodium and procaine hydrochloride are completely insoluble. Sodium salicylate has an unexpected high solubility (0.48%). The solubility is temperature depended and thus the solubility enthalpy can be determined. Relations between structure and solubility are discussed for pyrazolin-5-ones and purines. A correlation between solubilities in the base and in aqueous buffer (phosphate, pH 7.4) does not exist in the series studied. PMID:2381978

Pflegel, P; Schöbel, H; Klaus, T; Raguse, U



Characterizing the BMP pathway in a wild type mouse model of distraction osteogenesis.  


Distraction osteogenesis (DO) is a well established surgical technique for limb lengthening and replacement of bone loss due to trauma, infection or malignancies. Although the technique is widely used, one of its limitations is the long period of time required for the newly formed bone to consolidate. We have previously shown that exogenous application of bone morphogenetic proteins (BMPs) can increase bone formation during DO, however, exogenous BMPs have many drawbacks. An alternative method for accelerating the rate of bone formation may be to modulate the intrinsic BMP signaling pathway. The aim of the current study was to analyze the expression of various genes involved in the BMP pathway at various time periods during DO in order to identify potential targets for therapeutic manipulation. DO was applied to the right tibia of 80 adult wild type mice. Distraction began after a latency period of 5 days at a rate of 0.2 mm/12 h for 2 weeks. Mice were sacrificed in groups of 12 at the following times post surgery: day 5 (latency), days 11 and 17 (distraction) and days 34 and 51 (consolidation). Specimens were examined using radiology, microCT, histology, RT(2)PCR, immunohistochemistry and Western analysis. Genes involved in the BMP pathway including the BMP ligands, receptors, antagonists and downstream effectors were examined. A significant upregulation of BMPs 2, 4 and 6 was observed using both PCR and immunohistochemistry during the distraction phase. The expression of BMP7 remained constant throughout the distraction and consolidation process. Surprisingly, the only receptors which were upregulated significantly were the Activin Receptor Type 1 (ActR1) during distraction and Activin Receptor Type 2b (ActR2b) during consolidation. Most interestingly, simultaneously with the ligands, an increase in the expression of the antagonists, Noggin, Chordin, Inhibin and BMP3 was observed. This study provides a clearer understanding of expression patterns during DO, which is a valuable resource for finding therapeutic options to stimulate bone formation. The results suggest that blocking BMP inhibitors may be a possible method for increasing the function of intrinsic growth factors involved in bone regeneration. PMID:18372226

Haque, Tasima; Hamade, Fares; Alam, Norine; Kotsiopriftis, Maria; Lauzier, Dominique; St-Arnaud, Rene; Hamdy, Reggie C



Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q?? as naked nanocrystals.  


In this paper work, four naked nanocrystals (size range 80-700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q?? nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q?? increased as particle size decreased. The bioavailability of coenzyme Q?? after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC???? was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold. PMID:23166438

Sun, Jiao; Wang, Fan; Sui, Yue; She, Zhennan; Zhai, Wenjun; Wang, Chunling; Deng, Yihui



40 CFR 799.6786 - TSCA water solubility: Generator column method.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false TSCA water solubility: Generator column...TESTING REQUIREMENTS Product Properties Test Guidelines § 799.6786 TSCA water solubility: Generator column...1) Purpose. (i) The water solubility of a...



40 CFR 799.6786 - TSCA water solubility: Generator column method.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 false TSCA water solubility: Generator column...TESTING REQUIREMENTS Product Properties Test Guidelines § 799.6786 TSCA water solubility: Generator column...1) Purpose. (i) The water solubility of a...



40 CFR 799.6786 - TSCA water solubility: Generator column method.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false TSCA water solubility: Generator column...TESTING REQUIREMENTS Product Properties Test Guidelines § 799.6786 TSCA water solubility: Generator column...1) Purpose. (i) The water solubility of a...



40 CFR 799.6786 - TSCA water solubility: Generator column method.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false TSCA water solubility: Generator column...TESTING REQUIREMENTS Product Properties Test Guidelines § 799.6786 TSCA water solubility: Generator column...1) Purpose. (i) The water solubility of a...



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

E-print Network

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

Manning, Craig