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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.



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

PubMed Central

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

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



Activin Type 2 Receptor Restoration in MSI-H Colon Cancer Suppresses Growth and Enhances Migration With Activin  

PubMed Central

Background & Aims Colon cancers with high-frequency microsatellite instability (MSI-H) develop frameshift mutations in tumor suppressors as part of their pathogenesis. ACVR2 is mutated at its exon 10 polyadenine tract in >80% of MSI-H colon cancers, coinciding with loss of protein. ACVR2 transmits the growth effects of activin via phosphorylation of SMAD proteins to affect gene transcription. The functional effect of activin in colon cancers has not been studied. We developed and characterized a cell model in which we studied how activin signaling affects growth. Methods hMLH1 and ACVR2 mutant HCT116 cells were previously stably transferred with chromosome 2 (HCT116+chr2), restoring a single regulated copy of wild-type ACVR2 but not hMLH1. Both HCT116+chr2 and parental HCT116 cells (as well as HEC59 and ACVR2 and hMSH2 complemented HEC59+chr2 cells) were assessed for genetic complementation and biologic function. Results HCT116+chr2 cells and HEC59+chr2 cells, but not ACVR2-mutant HCT116 or HEC59 cells, acquired wild-type ACVR2 as well as expression of ACVR2 wild-type messenger RNA. Complemented ACVR2 protein complexed with ACVR1 with activin treatment, generating nuclear phosphoSMAD2 and activin-specific gene transcription. ACVR2-restored cells showed decreased growth and reduced S phase but increased cellular migration following activin treatment. ACVR2 small interfering RNA reversed these effects in complemented cells. Conclusions ACVR2-complemented MSI-H colon cancers restore activin-SMAD signaling, decrease growth, and slow their cell cycle following ligand stimulation but show increased cellular migration. Activin is growth suppressive and enhances migration similar to transforming growth factor ? in colon cancer, indicating that abrogation of the effects of activin contribute to the pathogenesis of MSI-H colon cancers. PMID:17258738




The Drosophila Activin-like ligand Dawdle signals preferentially through one isoform of the Type-I receptor Baboon  

PubMed Central

How TGF-?-type ligands achieve signaling specificity during development is only partially understood. Here we show that Dawdle, one of four Activin-type ligands in Drosophila, preferentially signals through Baboc, one of three isoforms of the Activin Type-I receptor that are expressed during development. In cell culture, Dawdle signaling is active in the presence of the Type-II receptor Punt but not Wit, demonstrating that the Type-II receptor also contributes to the specificity of the signaling complex. During development, different larval tissues express unique combinations of these receptors, and ectopic expression of Baboc in a tissue were it is not normally expressed at high levels can make that tissue sensitive to Dawdle signaling. These results reveal a mechanism by which distinct cell types can discriminate between different Activin-type signals during development as a result of differential expression of Type-I receptor isoforms. PMID:19766717

Jensen, Philip A.; Zheng, Xiaoyan; Lee, Tzumin; O'Connor, Michael B.



Activin Receptor Signaling Regulates Prostatic Epithelial  

E-print Network

proliferation, but only in the presence of fetal bovine serum (FBS). Conversely, activin A antibodies requirement in vitro for fetal serum indi- cates the necessity for a fetal serum factor(s) in cell identified the fetal serum component activin A and its signaling through the activin receptor type II (Act

Sheridan, Jennifer


The Type II Activin Receptors Are Essential for Egg Cylinder Growth, Gastrulation, and Rostral Head Development in Mice  

Microsoft Academic Search

The type II activin receptors, ActRIIA and ActRIIB, have been shown to play critical roles in axial patterning and organ development in mice. To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants. We found that embryos homozygous

Jihwan Song; Suk P. Oh; Heinrich Schrewe; Masatoshi Nomura; Hong Lei; Makiko Okano; Thomas Gridley; En Li



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)



The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse.  


Vertebrate animals exhibit segmented axial skeletons and lateral asymmetry of the visceral organs. The segment identity of individual vertebrae is believed to be determined by a combination of functionally active Hox genes that have defined expression boundaries along the anteroposterior axis (known as the axial Hox code). Disturbance of the Hox code by ectopic expression or mutation of Hox genes often leads to homeotic transformation of the vertebrae. Largely unknown, however, are the signaling molecules that provide the positional cues for the precise establishment and maintenance of the Hox code. In this study we show that disruption of the type IIB activin receptor (ActRIIB) by gene targeting results in altered expression of multiple Hox genes and abnormal patterning of the vertebrae, similar to but severer than retinoic acid (RA)-induced anterior transformation. We further show that RA and ActRIIB mutation have synergistic effects on vertebral patterning. Activin, Vg-1 and, type II activin receptors have been implicated in regulation of lateral asymmetry during chick and Xenopus development. We show here that the ActRIIB-/- mice die after birth with complicated cardiac defects including randomized heart position, malposition of the great arteries, and ventricular and atrial septal defects. In addition, the heart anomalies are associated with right pulmonary isomerism and splenic abnormalities, recapitulating the clinical symptoms of the human asplenia syndrome. These findings provide genetic evidence that the ActRIIB-mediated signaling pathway plays a critical role in patterning both anteroposterior and left-right axes in vertebrate animals. PMID:9242489

Oh, S P; Li, E



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

PubMed Central

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

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



Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice.  


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

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



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

E-print Network

by activin ligands Haiya Wu & Karima Mezghenna & Patricia Marmol & Tingqing Guo & Annalena Moliner & Shao these changes in wild-type mice. Isolated pancreatic islets from mutant mice showed enhanced GSIS, which could be rescued by exogenous activin B. Activin B negatively regulated GSIS and ATP production in wild-type islets

Ibáñez, Carlos


Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor.  


Members of the transforming growth factor-beta (TGF-beta) superfamily signal via different heteromeric complexes of two sequentially acting serine/threonine kinase receptors, i.e. type I and type II receptors. We generated two different chimeric TGF-beta superfamily receptors, i.e. TbetaR-I/BMPR-IB, containing the extracellular domain of TGF-beta type I receptor (TbetaR-I) and the intracellular domain of bone morphogenetic protein type IB receptor (BMPR-IB), and TbetaR-II/ActR-IIB, containing the extracellular domain of TGF-beta type II receptor (TbetaR-II) and the intracellular domain of activin type IIB receptor (ActR-IIB). In the presence of TGF-beta1, TbetaR-I/BMPR-IB and TbetaR-II/ActR-IIB formed heteromeric complexes with wild-type TbetaR-II and TbetaR-I, respectively, upon stable transfection in mink lung epithelial cell lines. We show that TbetaR-II/ActR-IIB restored the responsiveness upon transfection in mutant cell lines lacking functional TbetaR-II with respect to TGF-beta-mediated activation of a transcriptional signal, extracellular matrix formation, growth inhibition, and Smad phosphorylation. Moreover, TbetaR-I/BMPR-IB and TbetaR-II/ActR-IIB formed a functional complex in response to TGF-beta and induced phosphorylation of Smad1. However, complex formation is not enough for signal propagation, which is shown by the inability of TbetaR-I/BMPR-IB to restore responsiveness to TGF-beta in cell lines deficient in functional TbetaR-I. The fact that the TGF-beta1-induced complex between TbetaR-II/ActR-IIB and TbetaR-I stimulated endogenous Smad2 phosphorylation, a TGF-beta-like response, is in agreement with the current model for receptor activation in which the type I receptor determines signal specificity. PMID:9261125

Persson, U; Souchelnytskyi, S; Franzén, P; Miyazono, K; ten Dijke, P; Heldin, C H



Targeting the Activin Type IIB Receptor to Improve Muscle Mass and Function in the mdx Mouse Model of Duchenne Muscular Dystrophy  

PubMed Central

The activin receptor type IIB (ActRIIB) is a transmembrane receptor for transforming growth factor-? superfamily members, including myostatin, that are involved in the negative regulation of skeletal muscle mass. We tested the translational hypothesis that blocking ligand binding to ActRIIB for 12 weeks would stimulate skeletal muscle growth and improve muscle function in the mdx mouse. ActRIIB was targeted using a novel inhibitor comprised of the extracellular portion of the ActRIIB fused to the Fc portion of murine IgG (sActRIIB), at concentrations of 1.0 and 10.0 mg/kg?1 body weight. After 12 weeks of treatment, the 10.0 mg/kg?1 dose caused a 27% increase in body weight with a concomitant 33% increase in lean muscle mass. Absolute force production of the extensor digitorum longus muscle ex vivo was higher in mice after treatment with either dose of sActRIIB, and the specific force was significantly higher after the lower dose (1.0 mg/kg?1), indicating functional improvement in the muscle. Circulating creatine kinase levels were significantly lower in mice treated with sActRIIB, compared with control mice. These data show that targeting the ActRIIB improves skeletal muscle mass and functional strength in the mdx mouse model of DMD, providing a therapeutic rationale for use of this molecule in treating skeletal myopathies. PMID:21356379

Pistilli, Emidio E.; Bogdanovich, Sasha; Goncalves, Marcus D.; Ahima, Rexford S.; Lachey, Jennifer; Seehra, Jasbir; Khurana, Tejvir



Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle.  


Secretion of LH and FSH from the anterior pituitary is regulated primarily by hypothalamic GnRH and ovarian steroid hormones. More recent evidence indicates regulatory roles for certain members of the transforming growth factor beta (TGFbeta) superfamily including inhibin and activin. The aim of this study was to identify expression of mRNAs encoding key receptors and ligands of the inhibin/activin system in the hen pituitary gland and to monitor their expression throughout the 24-25-h ovulatory cycle. Hens maintained on long days (16 h light/8 h dark) were killed 20, 12, 6 and 2 h before predicted ovulation of a midsequence egg (n = 8 per group). Anterior pituitary glands were removed, RNA extracted and cDNA synthesized. Plasma concentrations of LH, FSH, progesterone and inhibin A were measured. Real-time quantitative PCR was used to quantify pituitary expression of mRNAs encoding betaglycan, activin receptor (ActR) subtypes (type I, IIA), GnRH receptor (GnRH-R), LH beta subunit, FSH beta subunit and GAPDH. Levels of mRNA for inhibin/activin betaA and betaB subunits, inhibin alpha subunit, follistatin and ActRIIB mRNA in pituitary were undetectable by quantitative PCR (<2 amol/reaction). Significant changes in expression (P<0.05) of ActRIIA and betaglycan mRNA were found, both peaking 6 h before ovulation just prior to the preovulatory LH surge and reaching a nadir 2 h before ovulation, just after the LH surge. There were no significant changes in expression of ActRI mRNA throughout the cycle although values were correlated with mRNA levels for both ActRIIA (r = 0.77; P<0.001) and beta-glycan (r = 0.45; P<0.01). Expression of GnRH-R mRNA was lowest 20 h before ovulation and highest (P<0.05) 6 h before ovulation; values were weakly correlated with betaglycan (r = 0.33; P = 0.06) and ActRIIA (r = 0.34; P = 0.06) mRNA levels. Expression of mRNAs encoding LH beta and FSH beta subunit were both lowest (P<0.05) after the LH surge, 2 h before ovulation. These results are consistent with an endocrine, but not a local intrapituitary, role of inhibin-related proteins in modulating gonadotroph function during the ovulatory cycle of the hen, potentially through interaction with betaglycan and ActRIIA. In contrast to mammals, intrapituitary expression of inhibin/activin subunits and follistatin appears to be extremely low or absent in the domestic fowl. PMID:16135664

Lovell, T M; Knight, P G; Gladwell, R T



Activins and Inhibins: novel regulators of thymocyte development  

PubMed Central

Activins and inhibins are members of the transforming growth factor ? superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We demonstrate that both activin A and inhibin A promote the DN3-DN4 transition in vitro, although they differentially control the transition to the DP stage. Whereas activin A induces the accumulation of a CD8+CD24hiTCR?lo intermediate subpopulation, inhibin A promotes the differentiation of DN4 to DP. In addition, both activin A and inhibin A appear to promote CD8+SP differentiation Moreover, Inhibin ? null mice have delayed in vitro T cell development, showing both a decrease in the DN-DP transition and reduced thymocyte numbers, further supporting a role for inhibins in the control of developmental signals taking place during T cell differentiation in vivo. PMID:19338778

Licona-Limón, Paula; Alemán-Muench, German; Chimal-Monroy, Jesus; Macías-Silva, Marina; García-Zepeda, Eduardo A.; Matzuk, Martin M.; Fortoul, Teresa I.; Soldevila, Gloria



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

PubMed Central

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

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



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)



Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation by Sp1  

PubMed Central

Background Activin receptor-like kinase 1 (ALK1) is a Transforming Growth Factor-? (TGF-?) receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1) give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. Results We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE) of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210) was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. Conclusions Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into the molecular mechanisms that contribute to the expression of ACVRL1 gene. Moreover, our data show that the methylation status of CpG islands markedly modulates the Sp1 regulation of ACVRL1 gene transcriptional activity. PMID:20587022



Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease  

PubMed Central

Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-? family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distal-less homeobox–5 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials. PMID:20194748

Vallet, Sonia; Mukherjee, Siddhartha; Vaghela, Nileshwari; Hideshima, Teru; Fulciniti, Mariateresa; Pozzi, Samantha; Santo, Loredana; Cirstea, Diana; Patel, Kishan; Sohani, Aliyah R.; Guimaraes, Alex; Xie, Wanling; Chauhan, Dharminder; Schoonmaker, Jesse A.; Attar, Eyal; Churchill, Michael; Weller, Edie; Munshi, Nikhil; Seehra, Jasbir S.; Weissleder, Ralph; Anderson, Kenneth C.; Scadden, David T.; Raje, Noopur



Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease.  


Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-beta family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distal-less homeobox-5 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials. PMID:20194748

Vallet, Sonia; Mukherjee, Siddhartha; Vaghela, Nileshwari; Hideshima, Teru; Fulciniti, Mariateresa; Pozzi, Samantha; Santo, Loredana; Cirstea, Diana; Patel, Kishan; Sohani, Aliyah R; Guimaraes, Alex; Xie, Wanling; Chauhan, Dharminder; Schoonmaker, Jesse A; Attar, Eyal; Churchill, Michael; Weller, Edie; Munshi, Nikhil; Seehra, Jasbir S; Weissleder, Ralph; Anderson, Kenneth C; Scadden, David T; Raje, Noopur



Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle  

Microsoft Academic Search

Secretion of LH and FSH from the anterior pituitary is regulated primarily by hypothalamic GnRH and ovarian steroid hormones. More recent evidence indicates regu- latory roles for certain members of the transforming growth factor (TGF) superfamily including inhibin and activin. The aim of this study was to identify expression of mRNAs encoding key receptors and ligands of the inhibin\\/activin system

T M Lovell; P G Knight; R T Gladwell



Differential expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and activin type-I and type-II receptors in preovulatory and prehierarchical follicles of the laying hen ovary  

Microsoft Academic Search

Ovarian follicle development is primarily regulated by an interplay between the pituitary gonadotrophins, LH and FSH, and ovary-derived steroids. Increasing evidence implicates regulatory roles of transforming growth factor- (TGF) superfamily members, including inhibins and activins. The aim of this study was to identify the expression of mRNAs encoding key receptors of the inhibin\\/activin system in ovarian follicles ranging from 4

T M Lovell; P G Knight; R T Gladwell



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 A as a mediator of NK-dendritic cell functional interactions.  


The interaction of NK cells with dendritic cells (DCs) results in reciprocal cell activation through the interaction of membrane proteins and the release of soluble factors. In this article, we report that in NK-DC cocultures, among a set of 84 cytokines investigated, activin A was the second highest induced gene, with CXCL8 being the most upregulated one. Activin A is a member of the TGF-? superfamily and was previously shown to possess both proinflammatory and anti-inflammatory activities. In NK-DC cocultures, the induction of activin A required cell contact and was dependent on the presence of proinflammatory cytokines (i.e., IFN-?, TNF-?, and GM-CSF), as well as on NK cell-mediated DC killing. CD1(+) DCs were the main activin A producer cells among myeloid blood DC subsets. In NK-DC cocultures, inhibition of activin A by follistatin, a natural inhibitory protein, or by a specific blocking Ab, resulted in the upregulation of proinflammatory cytokine release (i.e., IL-6, IL-8, TNF-?) by DCs and in the increase of DC maturation. In conclusion, our study reports that activin A, produced during NK-DC interactions, represents a relevant negative feedback mechanism that might function to prevent excessive immune activation by DCs. PMID:24395917

Seeger, Pascal; Bosisio, Daniela; Parolini, Silvia; Badolato, Raffaele; Gismondi, Angela; Santoni, Angela; Sozzani, Silvano



Activin A Inhibits Antigen-Induced Allergy in Murine Epicutaneous Sensitization  

PubMed Central

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

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



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)



R-Smad Competition Controls Activin Receptor Output in Drosophila  

PubMed Central

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

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



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


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

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




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.

Consortium, The C.



Photoreceptor-derived activin promotes dendritic termination and restricts the receptive fields of first-order interneurons in Drosophila.  


How neurons form appropriately sized dendritic fields to encounter their presynaptic partners is poorly understood. The Drosophila medulla is organized in layers and columns and innervated by medulla neuron dendrites and photoreceptor axons. Here, we show that three types of medulla projection (Tm) neurons extend their dendrites in stereotyped directions and to distinct layers within a single column for processing retinotopic information. In contrast, the Dm8 amacrine neurons form a wide dendritic field to receive ?16 R7 photoreceptor inputs. R7- and R8-derived Activin selectively restricts the dendritic fields of their respective postsynaptic partners, Dm8 and Tm20, to the size appropriate for their functions. Canonical Activin signaling promotes dendritic termination without affecting dendritic routing direction or layer. Tm20 neurons lacking Activin signaling expanded their dendritic fields and aberrantly synapsed with neighboring photoreceptors. We suggest that afferent-derived Activin regulates the dendritic field size of their postsynaptic partners to ensure appropriate synaptic partnership. PMID:24462039

Ting, Chun-Yuan; McQueen, Philip G; Pandya, Nishith; Lin, Tzu-Yang; Yang, Meiluen; Reddy, O Venkateswara; O'Connor, Michael B; McAuliffe, Matthew; Lee, Chi-Hon



Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary*  

E-print Network

demonstrated that estrogen suppresses activin gene expression, suggesting a feedback rela- tionship between activin signaling through Smad2, and small inter- fering RNAs targeting Smad2 or Smad3 suppressed ER pro- ulating gonadotropin release, activin and inhibin have been shown to play an important role in regulating

Mayo, Kelly E.


Distinct signaling of Drosophila Activin/TGF-beta family members.  


Growth factors of the TGF-beta family signal through type I/II receptor complexes that phosphorylate SMAD transcription factors. In this study, we analyzed signaling of all seven TGF-beta members to identify those that mediate growth through the Drosophila type I receptor BABO. We find that two potential ligands of BABO, Myoglianin (MYO) and Maverick (MAV), do not activate dSMAD2. Only Drosophila Activin (dACT) and the Activin-like ligand Dawdle (DAW) signal through BABO in combination with the type II receptor PUNT and activate dSMAD2. Surprisingly, we find that activation of BABO can also lead to the phosphorylation of the "BMP-specific" MAD. In wing discs, expression of an activated form of dSMAD2 promotes growth similar to dACT and activated BABO. By itself, activated dSMAD2 does not affect DPP/GBB target genes. However, coexpression of activated forms of dSMAD2 and MAD additively induces the expression of spalt. In contrast to dACT, we find that DAW does not promote growth when expressed in wings. In fact, coexpression of DAW with MAD or dSMAD2 decreases growth. daw mutants die primarily during larval stages and exhibit anal pad phenotypes reminiscent of babo mutants. The rescue of daw mutants by restricted expression in neuroendocrine cells indicates that Activin-type ligands are likely distributed through the endocrine system. The distinct signaling of dACT, DAW and MYO through BABO suggests the existence of co-receptors that modulate the canonical SMAD pathway. PMID:18820452

Gesualdi, Scott C; Haerry, Theodor E



Solubility parameter of drugs for predicting the solubility profile type within a wide polarity range in solvent mixtures.  


The solubility enhancement produced by two binary mixtures with a common cosolvent (ethanol-water and ethyl acetate-ethanol) was studied against the solubility parameter of the mixtures (delta1) to characterize different types of solubility profiles. Benzocaine, salicylic acid and acetanilide show a single peak in the least polar mixture (ethanol-ethyl acetate) at delta1=22.59, 21.70 and 20.91 MPa1/2, respectively. Phenacetin displays two solubility maxima, at delta1=25.71 (ethanol-water) and at delta1=23.30 (ethyl acetate-ethanol). Acetanilide shows an inflexion point in ethanol-water instead of a peak, and the sign of the slope does not vary when changing the cosolvent. The solubility profiles were compared to those obtained in dioxane-water, having a solubility parameter range similar to that covered with the common cosolvent system. All the drugs reach a maximum at about 90% dioxane (delta1=23 MPa1/2). A modification of the extended Hildebrand method is applicable for curves with a single maximum whereas a model including the Hildebrand solubility parameter delta1 and the acidic partial solubility parameter delta1a is required to calculate more complex solubility profiles (with inflexion point or two maxima). A single equation was able to fit the solubility curves of all drugs in the common cosolvent system. The polarity of the drug is related to the shape of the solubility profile against the solubility parameter delta1 of the solvent mixtures. The drugs with solubility parameters below 24 MPa1/2 display a single peak in ethanol-ethyl acetate. The drugs with delta2 values above 25 MPa1/2 show two maxima, one in each solvent mixture (ethanol-water and ethanol-ethyl acetate). The position of the maximum in ethanol-ethyl acetate shifts to larger polarity values (higher delta1 values) as the solubility parameter of the drug delta2 increases. PMID:16828993

Peña, M A; Reíllo, A; Escalera, B; Bustamante, P



Activin Potentiates Proliferation in Mature Avian Auditory Sensory Epithelium  

PubMed Central

Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGF? superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear. PMID:20071511

McCullar, Jennifer S.; Ty, Sidya; Campbell, Sean; Oesterle, Elizabeth C.



Activin signaling as an emerging target for therapeutic interventions  

Microsoft Academic Search

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

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



Runt-Related Transcription Factors Impair Activin Induction of the Follicle-Stimulating Hormone  

E-print Network

, suppress activin induction of FSH gene expression. Runx2 is expressed within the murine pituitary gland transcription (with or without activin) and does not interfere with GnRH induction of either gonadotropin of the five activin-responsive regions prevents activin induction and, in fact, RUNX2 suppression, instead

Mellon, Pamela L.


Oxidative stress increases placental and endothelial cell activin A secretion.  


Circulating levels of activin A are significantly increased in women with preeclampsia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin beta(A) in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preeclampsia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139.1 +/- 27.4 per mg wet weight vs 322.9 +/- 89.7 pg/ml per mg wet weight, P = 0.02) and from HUVECs (1.2 +/- 0.2 vs 3.2 +/- 1.8 ng/ml, P = 0.04). There was no effect on activin A output from monocytes. X/XO significantly increased beta(A) mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preeclampsia when compared with controls (333.8 +/- 70 vs 176.3 +/- 26.2 pg/ml, P = 0.04 and 49.5 +/- 7 vs 13.1 +/- 1.2 ng/ml, P < 0.001 respectively). In the women with preeclampsia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated (r(2) = 0.72; P < 0.001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preeclampsia. PMID:17332518

Mandang, Stephen; Manuelpillai, Ursula; Wallace, Euan M



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

PubMed Central

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

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



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



Testicular Somatic Cells, not Gonocytes, Are the Major Source of Functional Activin A during Testis Morphogenesis  

PubMed Central

Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin A, the protein product of the activin ?A (Inhba) gene, as a key regulator of murine Sertoli cell proliferation and testis cord expansion during embryogenesis. Although our genetic studies implicated fetal Leydig cells as the primary producers of testicular activin A, gonocytes are another potential source. To investigate the relative contribution of gonocyte-derived activin A to testis morphogenesis, we compared testis development in the Inhba global knockout mouse, which lacks activin A production in all cells (including the gonocytes), and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which activin A expression in testicular somatic cells is disrupted but gonocyte expression of activin A remains intact. Surprisingly, testis development was comparable in these two models of activin A insufficiency, with similar reductions in Sertoli cell proliferation and minor differences in testis histology. Thus, our findings suggest activin A from male gonocytes is insufficient to promote Sertoli cell proliferation and testis cord expansion in the absence of somatic cell-derived activin A. Evaluation of adult male mice with fetal disruption of activin A revealed reduced testis size, lowered sperm production, altered testicular histology, and elevated plasma FSH levels, defects reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia. PMID:21952240

Archambeault, Denise R.; Tomaszewski, Jessica; Childs, Andrew J.; Anderson, Richard A.



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

PubMed Central

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

Andersen, Geir ?.; Ueland, Thor; Knudsen, Eva C.; Scholz, Hanne; Yndestad, Arne; Sahraoui, Afaf; Smith, Camilla; Lekva, Tove; Otterdal, Kari; Halvorsen, Bente; Seljeflot, Ingebj?rg; Aukrust, Pal



The generation of definitive endoderm from human embryonic stem cells is initially independent from activin A but requires canonical Wnt-signaling.  


The activation of the TGF-beta pathway by activin A directs ES cells into the definitive endoderm germ layer. However, there is evidence that activin A/TGF-beta is not solely responsible for differentiation into definitive endoderm. GSK3beta inhibition has recently been shown to generate definitive endoderm-like cells from human ES cells via activation of the canonical Wnt-pathway. The GSK3beta inhibitor CHIR-99021 has been reported to generate mesoderm from human iPS cells. Thus, the specific role of the GSK3beta inhibitor CHIR-99021 was analyzed during the differentiation of human ES cells and compared against a classic endoderm differentiation protocol. At high concentrations of CHIR-99021, the cells were directed towards mesodermal cell fates, while low concentrations permitted mesodermal and endodermal differentiation. Finally, the analyses revealed that GSK3beta inhibition rapidly directed human ES cells into a primitive streak-like cell type independently from the TGF-beta pathway with mesoderm and endoderm differentiation potential. Addition of low activin A concentrations effectively differentiated these primitive streak-like cells into definitive endoderm. Thus, the in vitro differentiation of human ES cells into definitive endoderm is initially independent from the activin A/TGF-beta pathway but requires high canonical Wnt-signaling activity. PMID:24913278

Naujok, Ortwin; Diekmann, Ulf; Lenzen, Sigurd



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



Direct Evidence for a Soluble Methane Monooxygenase from Type I Methanotrophic Bacteria: Purification and Properties of a Soluble Methane Monooxygenase from Methylomonassp. GYJ3  

Microsoft Academic Search

The hydroxylase and reductase components of a soluble methane monooxygenase from type I methanotrophs—Methylomonassp. GYJ3—were purified by a multiple-step LC procedure. The hydroxylase (approximately 240 kDa, determined by an HPLC–size exclusion chromatography method) has three subunits with molecular masses of 56, 43, and 27 kDa, suggesting that the enzyme has an (???)2subunit structure. The HPLC method was developed to purify

Run-nan Shen; Chi-li Yu; Qing-quan Ma; Shu-ben Li



Wild-Type Gross Leukemia Virus: Classification of Soluble Antigens (GSA)  

PubMed Central

By inhibiting techniques using indirect immunofluorescence tests and indirect immunoelectron microscopy, the G(Gross) soluble antigens (GSA) in the body fluids of AKR and C58 mice, which have a high incidence of spontaneous leukemia, were classified according to the known specificity of G antigens in the murine Gross leukemia system. GSA existing in the plasma of nonleukemic and leukemic AKR mice and in the ascitic fluid of transplanted AKR spontaneous leukemia K36 showed the several specificities corresponding to G cell surface antigens, GCSAa, b, and c, and type-specific and group-specific viral envelope antigens, tsVEA and gsVEA, respectively. However, the plasma of nonleukemic C58 mice lacks GSAc, which can be recognized by the G-typing mouse serum. GSA corresponding to GIX antigen was not detected in the body fluids. Images PMID:4566440

Aoki, Tadao; Herberman, Ronald B.; Johnson, Patricia A.; Liu, Margaret; Sturm, Macie M.




PubMed Central

Ellner, Paul D. (University of Vermont, Burlington) and Carolyn D. Bohan. Serology of the soluble antigens of Clostridium perfringens types A–F by agar-gel diffusion. J. Bacteriol. 83:284–296. 1962.—A serological study by agar-gel diffusion of the soluble antigens of 39 strains of the Clostridium perfringens group has shown them to be extremely heterogeneous. Strain variation occurred within the six types, and common antigens shared among the six types were frequently observed. Attempts to produce type-specific sera by absorption were unsuccessful, due to incomplete removal of common antibodies. Images PMID:13890020

Ellner, Paul D.; Bohan, Carolyn D.



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


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

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



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

PubMed Central

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

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



Activin A and Follistatin-like 3 determine the susceptibility of heart to ischemic injury  

PubMed Central

Background TGF-? family cytokines have diverse actions in the maintenance of cardiac homeostasis. Activin A is a member of this family whose regulation and function in heart is not well understood at a molecular level. Follistatin-like 3 (Fstl3) is an extracellular regulator of Activin A protein, and its function in the heart is also unknown. Methods and Results We analyzed the expression of various TGF-? superfamily cytokines and their binding partners in mouse heart. Activin ?A and Follistatin-like 3 (Fstl3) were upregulated in models of myocardial injury. Overexpression of Activin A with an adenoviral vector (Ad-act?A) or treatment with recombinant Activin A protein protected cultured myocytes from hypoxia/reoxygenation- induced apoptosis. Systemic overexpression of Activin A in mice, by intravenous injection of Ad-act?A, protected hearts from ischemia/reperfusion injury. Activin A induced the expression of Bcl-2, and ablation of Bcl-2 by siRNA abrogated its protective action in myocytes. The protective effect of Activin A on cultured myocytes was abolished by treatment with Fstl3 or by a pharmacological Activin receptor-Like Kinase (ALK) inhibitor. Cardiac specific Fstl3 knock-out mice showed significantly smaller infarcts after ischemia/reperfusion injury that was accompanied by reduced apoptosis. Conclusions Activin A and Fstl3 are induced in heart by myocardial stress. Activin A protects myocytes from death and this activity is antagonized by Fstl3. Thus, the relative expression levels of these factors following injury is a determinant of cell survival in the heart. PMID:19805648

Oshima, Yuichi; Ouchi, Noriyuki; Shimano, Masayuki; Pimentel, David R.; Papanicolaou, Kyriakos N.; Panse, Kalyani D.; Tsuchida, Kunihiro; Lara-Pezzi, Enrique; Lee, Se-Jin; Walsh, Kenneth



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

SciTech Connect

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

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



Reduced Expression of Activin A in Focal Lymphoid Agglomerates Within Nasal Polyps  

Microsoft Academic Search

SUMMARY It has been previously reported that activin A, a homodimer of theA inhibin subunit, is secreted by stromal cells from mouse bone marrow and causes apoptotic death of mouse plasmacytoma tumor cells. Recent in vitro studies have also implicated this cyto- kine in the suppression of normal B-cell lymphopoiesis. In this study we examined the occurrence of activin A

Tsipi Shoham; Eitan Yaniv; Rumelia Koren; Rivka Gal; Reshmi Parameswaran; Arkadi Kravitz; Henry Geron; Dana Markovitz; Marina Lantzki; Dov Zipori



Developmentally regulated SMAD2 and SMAD3 utilization directs activin signalling outcomes  

PubMed Central

Activin is required for testis development. Activin signals via the phosphorylation and nuclear accumulation of SMAD2 and SMAD3. We present novel findings of developmentally regulated activin signalling leading to specific transcriptional outcomes in testicular Sertoli cells. In immature, proliferating, Sertoli cells, activin A induces nuclear accumulation of SMAD3, but not SMAD2, although both proteins become phosphorylated. In post-mitotic differentiating cells, both SMAD proteins accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; higher concentrations induce maximal SMAD3 nuclear accumulation and a small increase in nuclear SMAD2. Microarray analysis identified distinct transcriptional outcomes correlating with differential SMAD utilization and new activin target genes, including Gja1 and Serpina5, which are essential for Sertoli cell development and male fertility. In transgenic mice with altered activin bioactivity that display fertility phenotypes, Gja1 and Serpina5 are significantly altered. Thus, differential SMAD utilization in response to activin features during Sertoli cell maturation. PMID:19517569

Itman, Catherine; Small, Chris; Griswold, Michael; Nagaraja, Ankur K.; Matzuk, Martin M.; Brown, Chester; Jans, David A.; Loveland, Kate L.



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


High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding  

Microsoft Academic Search

BMPRII is a type II TGF-? serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-? type ligands, BMPs bind to type II receptors with

Peter D. Mace; John F. Cutfield; Sue M.. Cutfield



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

PubMed Central

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

DeAmici, Mara



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

PubMed Central

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

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



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

E-print Network

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

Swager, Timothy Manning


Activin A induction of erythroid differentiation sensitizes K562 chronic myeloid leukemia cells to a subtoxic concentration of imatinib.  


Chronic myeloid leukemia (CML) is a hematopoietic stem/progenitor cell disorder in which Bcr-Abl oncoprotein inhibits cell differentiation. Differentiation induction is considered an alternative strategy for treating CML. Activin A, a member of the transforming growth factor-? superfamily, induces erythroid differentiation of CML cells through the p38 MAPK pathway. In this study, treatment of the K562 CML stem/progenitor cell line with activin A followed by a subtoxic concentration of the Bcr-Abl inhibitor imatinib strongly induced growth inhibition and apoptosis compared with simultaneous treatment with activin A and imatinib. Imatinib-induced growth inhibition and apoptosis following activin A pretreatment were dose- and time-dependent. Imatinib-induced growth inhibition and apoptosis were also dependent on the pretreatment dose of activin A. More than 90% of the activin A-induced increases in glycophorin A-positive cells were sensitive to imatinib. However, only some of original glycophorin A-positive cells in the activin A treatment group were sensitive to imatinib. Sequential treatment with activin A and imatinib decreased Bcr-Abl, procaspase-3, Mcl-1, and Bcl-xL and also induced cleavage of procaspase-3/poly(ADP-ribose)polymerase. The reduction of erythroid differentiation in p38 MAPK dominant-negative mutants or by short hairpin RNA knockdown of p38 MAPK decreased the growth inhibition and apoptosis mediated by sequential treatment with activin A and imatinib. Furthermore, the same inhibition level of multidrug resistance 1 expression was observed in cells treated with activin A alone, treated sequentially with activin A and imatinib, or treated simultaneously with activin A and imatinib. The p38 MAPK inhibitor SB-203580 can restore activin A-inhibited multidrug resistance 1 expression. Taken together, our results suggest that a subtoxic concentration of imatinib could exhibit strong cytotoxicity against erythroid-differentiated K562 CML cells. PMID:24088895

Huang, Yu-Wen; Lee, Wei-Hwa; Tsai, Yu-Hui; Huang, Huei-Mei



Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, Activin and Inhibin  

PubMed Central

Summary There is both cellular and physiological evidence demonstrating that both Activins and Inhibins regulate osteoblastogenesis and osteoclastogenesis, and regulate bone mass in vivo. Although Activins and Inhibins were initially isolated from the gonad, Activins are also produced and stored in bone, whereas Inhibins exert their regulation on bone cell differentiation and metabolism via endocrine effects. The accumulating data provide evidence that reproductive hormones, distinct from classical sex steroids, are important regulators of bone mass and bone strength. Given the well described dominant antagonism of Inhibin over Activin, as well as over BMPs and TGF?, the gonadally-derived Inhibins are important regulators of locally produced osteotrophic factors. Thus, the cycling Inhibins in females and diurnal changes in Inhibin B in males elicit temporal shifts in Inhibin levels (tone) that de-repress the pituitary. This fundamental action has the potential to de-repress locally stimulated changes in osteoblastogenesis and osteoclastogenesis, thereby altering bone metabolism. PMID:19615428

Nicks, Kristy M.; Perrien, Daniel S.; Akel, Nisreen S.; Suva, Larry J; Gaddy, Dana



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

E-print Network

and nodals are key determinants in the establishment of left­right asymmetry and patterning of the nervous, heart, limb and skeleton (Hogan, 1996; Schier, 2003). BMPs and activin exert their effects through

Levin, Michael


Recombinant soluble CD137 prevents type one diabetes in nonobese diabetic mice.  


Nonobese diabetic (NOD) mice are genetically programmed to spontaneously develop type one diabetes (T1D). Multiple Insulin dependent diabetes (Idd) genetic loci have been identified but their functional effects are mostly poorly understood. TnfsfR9, expressing the protein product CD137, is a strong candidate gene in the Idd9.3 locus, and NOD.B10 Idd9.3 mice are significantly protected from type one diabetes (T1D). We previously showed that nonobese diabetic (NOD) mice have a deficiency in the numbers of CD137(pos) T regulatory cells, that CD137(pos) Tregs are the source of soluble CD137 (sCD137), and that NOD mice have low serum levels of sCD137. To test the hypothesis that correcting low levels of sCD137 could affect the disease, we constructed a lentiviral vector producing recombinant sCD137; this physiologic sCD137 is glycosylated and exists primarily as a dimer. NOD mice treated with the recombinant sCD137 are protected from developing T1D. Insulitis is significantly decreased, but not eliminated in the sCD137 treated mice, however insulin producing pancreatic beta cells are preserved despite residual insulitis. To begin to understand the protective immune mechanisms of sCD137, we tested sCD137 in vitro. It was previously suggested that sCD137 simply blocked the interaction between CD137 (on T cells) and CD137 ligand (on antigen presenting cells (APCs)). Here however, we use an APC independent assay and demonstrate that sCD137 can actively suppress highly purified CD4 T cells in a CD137L dependent fashion. These results support the hypothesis that sCD137 acts in a negative feedback loop to actively suppress over-zealous immune responses, and that it can be used clinically to suppress autoimmunity. sCD137 is an important Treg derived natural immunosuppressive molecule that regulates effector T cells to avert diabetes in vivo. PMID:24145149

Kachapati, Kritika; Bednar, Kyle J; Adams, David E; Wu, Yuehong; Mittler, Robert S; Jordan, Michael B; Hinerman, Jennifer M; Herr, Andrew B; Ridgway, William M



The role of maternal Activin-like signals in zebrafish embryos  

Microsoft Academic Search

Maternal Activin-like proteins, a subgroup of the TGF-? superfamily, play a key role in establishing the body axes in many vertebrates, but their role in teleosts is unclear. At least two maternal Activin-like proteins are expressed in zebrafish, including the Vg1 orthologue, zDVR-1, and the nodal-related gene, Squint. Our analysis of embryos lacking both maternal and zygotic squint function revealed

Engda G. Hagos; Xiang Fan; Scott T. Dougan



Strategies to overcome pH-dependent solubility of weakly basic drugs by using different types of alginates.  


Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading to faster drug release at lower pH. The objective of this study was to achieve pH-independent release of weakly basic drugs from extended release formulations based on the naturally occurring polymer sodium alginate. Three approaches to overcome the pH-dependent solubility of the weakly basic model drug verapamil hydrochloride were investigated. First, matrix tablets were prepared by direct compression of drug substance with different types of sodium alginate only. Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press-coated tablets consisting of an inner pH-modifier tablet core and an outer drug/sodium alginate coat were prepared. pH-Independent drug release was achieved from matrix tablets consisting of selected alginates and drug substance only. Alginates are better soluble at higher pH. Therefore, they are able to compensate the poor solubility of weakly basic drugs at higher pH as the matrix of the tablets dissolves faster. This approach was successful when using alginates that demonstrated fast hydration and erosion at higher pH. The approach failed for alginates with less-pronounced erosion at higher pH. The addition of fumaric acid to drug/alginate-based matrix systems decreased the microenvironmental pH within the tablets thus increasing the solubility of the weakly basic drug at higher pH. Therefore, pH-independent drug release was achieved irrespective of the type of alginate used. Drug release from press-coated tablets did not provide any further advantages as compound release remained pH-dependent. PMID:18720138

Gutsche, S; Krause, M; Kranz, H



Direct Effects of Activin A on the Activation of Mouse Macrophage RAW264.7 Cells  

PubMed Central

Macrophages play critical roles in innate immune and acquired immune via secreting pro-inflammatory mediators, phagocytosing microorganisms and presenting antigens. Activin A, a member of transforming growth factor ? (TGF-?) superfamily, is produced by macrophages and microglia cells. In this study, we reported a direct effect of activin A as a pro-inflammatory factor on mouse macrophage cell line RAW264.7 cells. Our data revealed that activin A could not only increase IL-1? and IL-6 production from RAW264.7 cells, but also promote pinocytic and phagocytic activities of RAW264.7 cells. In addition, activin A obviously up-regulated MHC II expression on the surface of RAW264.7 cells, whereas did not influence MHC I expression. Activin A also enhanced CD80 expression, which is a marker of activated macrophages, but did not influence RAW264.7 cell proliferation. These data suggest that activin A may regulate primary macrophage-mediated innate and acquired immune response via promoting the activation of rest macrophages. PMID:19403063

Ge, Jingyan; Wang, Yinan; Feng, Ye; Liu, Haiyan; Cui, Xueling; Chen, Fangfang; Tai, Guixiang; Liu, Zhonghui



Activin A prevents neuron-like PC12 cell apoptosis after oxygen-glucose deprivation?  

PubMed Central

In this study, PC12 cells were induced to differentiate into neuron-like cells using nerve growth factor, and were subjected to oxygen-glucose deprivation. Cells were treated with 0, 10, 20, 30, 50, 100 ng/mL exogenous Activin A. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and Hoechst 33324 staining showed that the survival percentage of PC12 cells significantly decreased and the rate of apoptosis significantly increased after oxygen-glucose deprivation. Exogenous Activin A significantly increased the survival percentage of PC12 cells in a dose-dependent manner. Reverse transcription-PCR results revealed a significant increase in Activin receptor IIA, Smad3 and Smad4 mRNA levels, which are key sites in the Activin A/Smads signaling pathway, in neuron-like cells subjected to oxygen-glucose deprivation, while mRNA expression of the apoptosis-regulation gene caspase-3 decreased. Our experimental findings indicate that exogenous Activin A plays an anti-apoptotic role and protects neurons by means of activating the Activin A/Smads signaling pathway.

Xu, Guihua; He, Jinting; Guo, Hongliang; Mei, Chunli; Wang, Jiaoqi; Li, Zhongshu; Chen, Han; Mang, Jing; Yang, Hong; Xu, Zhongxin



Activin A and Follistatin as Biomarkers for Ectopic Pregnancy and Missed Abortion  

PubMed Central

Activin A as a predictor of pregnancy failure has been the focus of heated debate, but the value of a combined activin A and follistatin (FS) measurement in serum to predict pregnancy failure has not been reported yet. We assessed whether a single serum measurement of the two physiological antagonists at 6–8 weeks gestation could differentiate ectopic pregnancies (EP) or missed abortions (MA) from healthy intrauterine pregnancies (IUP). activin A concentrations were significantly lower in women with EP (n = 30, median value of 264?pg/mL) and women with MA (n = 30, median value of 350?pg/mL) compared to IUP (n = 33, median value of 788?pg/mL); P < 0.001. At a threshold value of 505?pg/mL, activin A had 87.9% sensitivity and 100% specificity and negative predictive value of 0.974 for discriminating an ectopic pregnancy from viable pregnancies. FS was able to discriminate IUP from EP (ROC curve P < 0.001) as was their ratio (ROC curve P = 0.008), but was unable to discriminate a MA from an EP. In EP, activin A did not correlate with beta HCG levels. The present findings support the thesis that activin A or FS could be considered promising biomarkers for the discrimination between an IUP and a failed pregnancy (MA or EP). PMID:24222717

Deligeoroglou, Efthimios; Garas, Antonios; Hadjichristodoulou, Christos; Messinis, Ioannis E.



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

PubMed Central

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

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



Removal of soluble COD by a biofilm formed on a membrane in a jet loop type membrane bioreactor  

Microsoft Academic Search

The soluble chemical oxygen demand (COD) removal efficiency through a cake layer (biofilm) deposited on the surfaces of a membrane was investigated as a function of biofilm thickness in a jet loop type membrane bioreactor (JL-MBR). The mechanisms for the removal were investigated based on the microbial characteristics of the biofilm.Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) was used to

Jong-Sang Park; Chung-Hak Lee



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.



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



High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia.  

PubMed Central

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease. The highest amounts of TNFBP were seen in the sera of patients with B cell malignancies including hairy cell leukemia (HCL) and type B chronic lymphocytic leukemia. Treatment of HCL patients with recombinant human interferon-alpha was associated with decrease of circulating TNFBP. PMID:1314854

Digel, W; Porzsolt, F; Schmid, M; Herrmann, F; Lesslauer, W; Brockhaus, M



Effects of faunation and type of dietary protein on gastric solubility and liver content of copper in sheep.  


Three experiments were conducted to determine the influence of the presence of protozoa on copper (Cu) metabolism in sheep fed corn silage or corn silage supplemented with casein, fish meal or soybean meal. For each diet, eight rams were kept fauna-free; eight additional rams were faunated and housed separately from them. The faunated rams in all treatments grew faster and consumed more feed and, consequently, more Cu. However, they had a lower (P less than .01) ruminal Cu solubility and accumulated less Cu in their livers than the fauna-free rams when fed corn silage alone or in combination with soybean meal (insoluble, ruminally degraded protein). Such effects were not significant when corn silage was supplemented with fish meal (protein resistant to ruminal degradation). The presence of ciliate protozoa in the rumen had no effect on the accumulation of Cu in the liver of sheep fed corn silage supplemented with casein (soluble, ruminally degraded protein) and produced conflicting results on ruminal Cu solubility. Hence, the effect of protozoa on Cu metabolism is indirect and depends on the type of protein present in the diet. PMID:2531733

Ivan, M



Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila  

PubMed Central

Reduced insulin/IGF signaling increases lifespan in many animals. To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes. Dawdle, an Activin ligand, is bound and repressed by dFOXO when reduced insulin/IGF extends lifespan. Reduced Activin signaling improves performance and protein homeostasis in muscles of aged flies. Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a) within muscle, a factor controlling the rate of autophagy. Expression of Atg8a within muscle is sufficient to increase lifespan. These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance. While reduced Activin within muscle autonomously retards functional aging of this tissue, these effects in muscle also reduce secretion of insulin-like peptides at a distance from the brain. Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling. PMID:24244197

Bai, Hua; Kang, Ping; Hernandez, Ana Maria; Tatar, Marc



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.



Activin B Antagonizes RhoA Signaling to Stimulate Mesenchymal Morphology and Invasiveness of Clear Cell Renal Cell Carcinomas  

PubMed Central

Activin B belongs to the TGF? family of growth factors and is upregulated in clear cell renal cell carcinoma cells by hypoxia inducible factors. Expression of Activin B is required for tumor growth in vivo and tumor cell invasion in vitro. Here we show that activation of RhoA signaling counteracts Activin B mediated disassembly of actin stress fibers, mesenchymal cell morphology and invasiveness, whereas inhibition of RhoA rescues these effects in Activin B knockdown cells. Conversely, Activin B inhibits RhoA signaling suggesting that there is an antagonistic connection between both pathways. In addition we found that Rac1 plays an opposite role to RhoA, i.e. activation of Rac1 initiates loss of actin stress fibers, promotes a mesenchymal cell morphology and induces invasion in Activin B knockown cells, whereas inhibition of Rac1 abolishes these Activin B effects. Collectively, our data provide evidence that reduction of RhoA signaling by Activin B together with persistent Rac1 activity is a prerequisite for inducing an invasive phenotype in clear cell renal cell carcinoma. PMID:25343250

Wacker, Ingrid; Behrens, Jurgen



Activin A balance regulates epithelial invasiveness and tumorigenesis.  


Activin A (Act A) is a member of the TGF? superfamily. Act A and TGF? have multiple common downstream targets and have been described to merge in their intracellular signaling cascades and function. We have previously demonstrated that coordinated loss of E-cadherin and TGF? receptor II (T?RII) results in epithelial cell invasion. When grown in three-dimensional organotypic reconstruct cultures, esophageal keratinocytes expressing dominant-negative mutants of E-cadherin and T?RII showed activated Smad2 in the absence of functional T?RII. However, we could show that increased levels of Act A secretion was able to induce Smad2 phosphorylation. Growth factor secretion can activate autocrine and paracrine signaling, which affects crosstalk between the epithelial compartment and the surrounding microenvironment. We show that treatment with the Act A antagonist Follistatin or with a neutralizing Act A antibody can increase cell invasion in organotypic cultures in a fibroblast- and MMP-dependent manner. Similarly, suppression of Act A with shRNA increases cell invasion and tumorigenesis in vivo. Therefore, we conclude that maintaining a delicate balance of Act A expression is critical for homeostasis in the esophageal microenvironment. PMID:25068654

Le Bras, Grégoire F; Loomans, Holli A; Taylor, Chase J; Revetta, Frank L; Andl, Claudia D



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


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

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



Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes  

PubMed Central

Blood soluble E-selectin (sE-selectin) levels have been related to various conditions such as type 2 diabetes. We performed a genome-wide association study among women of European ancestry from the Nurses' Health Study, and identified genome-wide significant associations between a cluster of markers at the ABO locus (9q34) and plasma sE-selectin concentration. The strongest association was with rs651007, which explained ?9.71% of the variation in sE-selectin concentrations. SNP rs651007 was also nominally associated with soluble intracellular cell adhesion molecule-1 (sICAM-1) (P = 0.026) and TNF-R2 levels (P = 0.018), independent of sE-selectin. In addition, the genetic-inferred ABO blood group genotypes were associated with sE-selectin concentrations (P = 3.55 × 10?47). Moreover, we found that the genetic-inferred blood group B was associated with a decreased risk (OR = 0.44, 0.27–0.70) of type 2 diabetes compared with blood group O, adjusting for sE-selectin, sICAM-1, TNF-R2 and other covariates. Our findings indicate that the genetic variants at ABO locus affect plasma sE-selectin levels and diabetes risk. The genetic associations with diabetes risk were independent of sE-selectin levels. PMID:20147318

Qi, Lu; Cornelis, Marilyn C.; Kraft, Peter; Jensen, Majken; van Dam, Rob M.; Sun, Qi; Girman, Cynthia J.; Laurie, Cathy C.; Mirel, Daniel B.; Hunter, David J.; Rimm, Eric; Hu, Frank B.



Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells.  


The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin:follistatin ratio increased significantly (+75%) in mouse bone marrow with age, as did activin A levels (+17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice. PMID:23178301

Bowser, Matthew; Herberg, Samuel; Arounleut, Phonepasong; Shi, Xingming; Fulzele, Sadanand; Hill, William D; Isales, Carlos M; Hamrick, Mark W



Cytokines and soluble receptor changes in the transition from primary to early chronic HIV type 1 infection.  


We studied determinants of chronic inflammation and/or immune activation in plasma from patients in the transition from primary to early chronic HIV-1 infection. The following parameters were estimated in seven patients over time: plasma concentrations of soluble CD8 (sCD8), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL6R), IL-10, transforming growth factor beta1 (TGF-beta1), along with CD4- and CD8-positive T cell counts, p24 antigenemia, and clinical evaluation. Results showed that concentrations of sCD8, TNF-alpha, and sTNFRII, and peripheral CD8-positive lymphocyte counts, were significantly increased in patients, compared to HIV-negative controls, and showed a trend toward normal values over time. Levels of IL6, sIL6R, IL-10, and TGF-beta1 did not differ from those of controls and did not change over time. Heterogeneity was observed among the patients in terms of CD4-positive T cell depletion, levels of sCD8, concentrations of TNF-alpha/sTNFRII, and clinical outcome. These data indicate that in the transition phase from primary acute to chronic and asymptomatic infection the host immune activation in response to the virus is highly heterogeneous and that the sustained rise in TNF-alpha and its receptor may represent an important therapeutic target in early disease. The persistence of a state of chronic inflammation and/or immune activation could influence the progression of disease independently from CD4-positive T cell counts. PMID:8906993

Barcellini, W; Rizzardi, G P; Poli, G; Tambussi, G; Velati, C; Meroni, P L; Dalgleish, A G; Lazzarin, A



Bioinformatic analysis of pathogenic missense mutations of activin receptor like kinase 1 ectodomain.  


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 (ALK1(EC)) has been elusive so far. We here describe the building of a homology model for ALK1(EC), 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. ALK1(EC) potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1(EC) 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 ALK1(EC) 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



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

PubMed Central

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.



Detection of soluble type II receptor in the presence of its natural ligand IL-1 beta. Quantification by sandwich ELISA.  


The type II interleukin-1 receptor (IL-1R II) is a newly described 60-68 kDa protein expressed on monocytes, neutrophils, and lymphocytes. It is hypothesized that a 45 kDa soluble form of the IL-1R II attenuates the proinflammatory effects of IL-1 by preventing its binding to the type I IL-1 receptor. However, very little information exists regarding the detection of soluble IL-1R II. Specifically, there are no reports to date characterizing IL-1R II detection by enzyme-linked immunoassay in the presence of IL-1 beta or characterizing IL-1 beta detection in the presence of IL-1R II. This study addresses the detection and quantitation of IL-1R II and IL-1 beta by a number of sandwich ELISA formats and characterizes the sensitivity of detection in the presence of competitive cytokines. We generated two distinct IL-1R II sandwich ELISAs that can detect receptor down to a level of 50 pg/ml. One, M22/R2, detects only unbound IL-1R II and the other, M2/R2, detects both bound and unbound IL-1R II. In this context, a 4:1 molar ratio of IL-1 beta to IL-1R II interferes with the IL-1R II detection by the M22/R2 but not the M2/R2 ELISA. Conversely, IL-1R II at physiologically relevant concentrations interferes with the detection of IL-1 beta by three distinct IL-1 beta ELISA formats. Taken together, these studies suggest that when measuring samples that may contain both IL-1 beta and IL-1R II, careful attention must be given to assay specificity. PMID:7665893

Altenberger, E A; Pope, H A; Wewers, M D



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

E-print Network

, reduced insulin sensitivity, liver steatosis, impaired glucose tolerance, and islet enlargement the effects of activin B on Ca2 signaling. calcium insulin pancreas TGF- hyperinsulinemia The signaling the regulation of blood-glucose homeostasis. The characterization of signals regulating -cell development

Ibáñez, Carlos


Suppression of Activin-Induced Apoptosis by Novel Antisense Strategy in Human Prostate Cancer Cells  

E-print Network

but different in apoptosis induction. Because the transfection of functional apoptosin is lethal to LNCa). C-probes were delivered into activin- induced apoptotic LNCaP cells by liposome mediated transfection (10), to investigate the role of apoptosin gene expression in subsequent DNA laddering and cell

Chuong, Cheng-Ming


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


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

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



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



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

PubMed Central

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

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



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



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.



Soluble and insoluble fiber (image)  


Dietary fiber is the part of food that is not affected by the digestive process in the body. ... of the stool. There are two types of dietary fiber, soluble and insoluble. Soluble fiber retains water and ...


Soluble Human LAG3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity  

Microsoft Academic Search

The adjuvant activities of the human lymphocyte activation gene-3 (LAG-3) molecule have been evaluated in a human setting by investigating the ability of a soluble recombinant human LAG-3 protein (hLAG-3Ig) to enhance the in vitro induction of viral- and tumor-specific CTLs.We found that soluble human LAG-3 significantly sustained the generation and expansion of influenza matrix protein Melan-A\\/MART-1 and survivin-specific CD8+

Chiara Casati; Flavio Arienti; Licia Rivoltini; Frederic Triebel; Giorgio Parmiani; Chiara Castelli



Breed differences in expression of inhibin/activin subunits in porcine anterior pituitary glands.  


Chinese Meishan (MS) boars have greater plasma FSH concentrations than European White Composite boars, but this difference does not occur in females of these breeds. To understand this disparity, we studied expression of the follistatin gene and of genes for the inhibin/activin alpha-, beta A-, and beta B-subunits in porcine anterior pituitary glands using quantitative reverse transcription-PCR and ribonuclease protection techniques. We found that 1) the inhibin/activin beta A- and beta B-subunits and follistatin were expressed in porcine pituitary, 2) the alpha-subunit was not detected in the porcine pituitary, but was highly expressed in porcine follicles; and 3) the beta B-subunit gene is more abundantly expressed (2-fold greater) in MS boar pituitaries than in pituitaries of White Composite boars. We conclude that this is not due to a breed difference, because the expression levels of this gene were similar in pituitaries of females of these breeds. No breed differences were detected for other genes screened in this study. From these observations, we propose that activin B, a dimer of beta B-subunits and a stimulator of FSH secretion, may be partially responsible for the elevated plasma FSH concentrations in MS boars, and intrapituitary inhibin plays no or a very minimal role. PMID:9003006

Li, M D; MacDonald, G J; Ford, J J



The Effects of Fibroblast Co-Culture and Activin A on in vitro Growth of Mouse Preantral Follicles  

PubMed Central

Background: This study was conducted to evaluate fibroblast co-culture and Activin A on in vitro maturation and fertilization of mouse preantral follicles. Methods: The ovaries from 12-14-day-old mice were dissected, and 120-150 ?m preantral follicles were cultured individually in ?-MEM as based medium for 12 days. A total number of 456 follicles were cultured in four conditions: (i) base medium as control group (n = 113), (ii) base medium supplemented with 30 ng/ml Activin A (n = 115), (iii) base medium co-cultured with mouse embryonic fibroblast (n = 113), and (iv) base medium supplemented with 30 ng/ml Activin A and co-cultured with fibroblast (n = 115). Rate of growth, survivability, antrum formation, ovulation, embryonic development and steroid production were evaluated. Analysis of Variance and Duncan test were applied for analyzing. Results: Both co-culture and co-culture + Activin A groups showed significant difference (P<0.05) in growth (on days 4, 6, and 8 of culture period) and survival rates. However, there was no significant difference in antrum formation, ovulation rate, and embryonic development of ovulated oocytes. There were significant differences (P<0.05) in the estradiol production on days 8, 10, and 12 between co-culture + Activin A and the control group. Progesterone production also was significant (P<0.05) in co-culture + Activin A group on days 6, 8, 10, and 12 compared to control group. Conclusion: Fibroblast co-culture and Activin A promoted growth and survivability of preantral follicles. However, simultaneous use of them was more efficient. PMID:24375163

Karimpour Malekshah, Abbasali; Heidari, Mahmoud; Parivar, Kazem; Azami, Nasrin Sadat



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

PubMed Central

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

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



A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation  

Microsoft Academic Search

CD8 T lymphocytes can suppress human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8 T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. However, the mechanism by which CAF inhibits LTR activation is not understood. Here, we

Theresa Li-Yun Chang; Arevik Mosoian; Richard Pine; Mary E. Klotman; John P. Moore



Expression of soluble recombinant TGF-? type II receptor fused with the Fc portion of human IgG1 (sT?RII-Fc) in NS0 cells  

Microsoft Academic Search

We have constructed and expressed recombinant chimeric soluble TGF-? type II receptor fused with the Fc portion of human IgG1 (sT?RII-Fc) in NS0 mouse myeloma cells and isolated cell lines constitutively secreting very high levels of biologically active protein. The GS-NS0 expres- sion system takes advantage of the strong human cytomegalovirus immediate early promoter ex- pression vector and glutamine synthetase

Eliza P. Kwiatkowska; Urszula Kazimierczak; Andrzej Mackiewicz; Dariusz W. Kowalczyk



Novel Type of Prodrug Activation through a Long-Range O,N-Acyl Transfer: A Case of Water-Soluble CREB Inhibitor.  


CREB (cAMP response element binding protein) has been shown to play an important role in tumor initiation, progression, and metastasis. We discovered that naphthol AS-E, a cell-permeable CREB inhibitor, presented antiproliferative activity in a broad panel of cancer cell lines in vitro. However, it has limited aqueous solubility. In this report, we described a water-soluble inhibitor (compound 6) of CREB-mediated gene transcription with in vivo anticancer activity. Unexpectedly, compound 6 was found to be a prodrug of compound 12 necessitating an unprecedented long-range O,N-acyl transfer. The rate of this transfer was pH- and temperature-dependent. To the best of our knowledge, this is the first time to show that a long-range O,N-acyl transfer could be exploited as a prodrug activation strategy to improve aqueous solubility. This type of prodrug may be applicable to other structures with spatially arranged hydroxyl amide to improve their aqueous solubility. PMID:25313320

Li, Bingbing X; Xie, Fuchun; Fan, Qiuhua; Barnhart, Kerry M; Moore, Curtis E; Rheingold, Arnold L; Xiao, Xiangshu



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


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 possibility of expression of the highly active and soluble mutant MeHNL-His103Leu as well as wild-type enzyme in several expression systems. Methylotrophic yeast Pichia pastoris, protozoan host Leishmania tarentolae and two cell-free translations, including an E. coli lysate (WakoPURE system) and wheat germ translation system were used to compare expression profiles of the genes. Two distinguishable protein expression patterns were observed in prokaryotic and eukaryotic-based systems. The wild-type and mutant enzyme showed high activity for both genes (up to 10 U/ml) in eukaryotic hosts P. pastoris and L. tarentolae, while those of E. coli exhibited about 1 and 15 U/ml, respectively. The different activity level in prokaryotic systems but the same level among the eukaryotic hosts indicate the phenomenon is specific to the E. coli system. Both the wild-type and mutant enzymes were functionally expressed in eukaryotic systems, probably using the folding assistants such as chaperones. Properties of expression systems used in this study were precisely compared, too. PMID:21185385

Dadashipour, Mohammad; Fukuta, Yasuhisa; Asano, Yasuhisa



Treatment of neuroinflammation by soluble tumor necrosis factor receptor Type II fused to a thermally responsive carrier  

PubMed Central

Object Biochemical irritation of the dorsal root ganglion (DRG) after intervertebral disc herniation contributes to radiculopathy through tumor necrosis factor–? (TNF?)–mediated inflammation. Soluble TNF receptor Type II (sTNFRII) sequesters this cytokine, providing clinical benefit. Previous work involving conjugation of sTNFRII with thermally responsive elastin-like polypeptide (ELP) yielded a chimeric protein (ELP–sTNFRII) with in vitro anti-TNF? bioactivity. Furthermore, temperature-triggered ELP aggregation into a “depot” prolongs protein residence time following perineural injection. In this study the authors evaluated the inflammatory phenotype of DRG explants after TNF? stimulation, and assessed the abilities of sTNFRII or ELP–sTNFRII to attenuate these neuroinflammatory changes. Methods Rat lumbar DRGs (35 animals) were treated in 6 groups, as follows: control; TNF? (25 ng/ml); TNF? with low- (0.2 µg/ml) or high-dose (1 µg/ml) sTNFRII; and TNF? with low- (52.5 µg/ml) or high-dose (262.5 µg/ml) ELP–sTNFRII. After 24 hours, supernatant was evaluated for inflammatory cytokines (interleukin [IL]–1, IL-6, and IL-10); prostaglandin E2; and metabolites (glutamate, lactate, and pyruvate). Single-factor analysis of variance with post hoc Dunn analysis (? = 0.05) was used to assess treatment differences. Results Incubation of explants with TNF? caused metabolic stress reflected by an increased lactate/pyruvate ratio (1.8 ± 0.5–fold) and extracellular glutamate (79 ± 8% increase). Inflammatory activation was observed with heightened IL-6 release (5.2 ± 1.4–fold) and prostaglandin E2 production (14 ± 3–fold). An autoregulatory response occurred with an 11.8 ± 0.6–fold increase in sTNFRI shedding. Treatment with high doses of sTNFRII or ELP–sTNFRII reversed all changes. Values are expressed as the mean ± standard deviation. Conclusions These results demonstrate that TNFa stimulation of DRG explants yields a phenotype of neurotoxic metabolite release and inflammatory mediator expression. Coincubation with either sTNFRII or ELP–sTNFRII antagonizes TNFa activity to abrogate these changes, suggesting potential for therapeutic intervention to treat peripheral nerve inflammatory disease. PMID:18764758

Shamji, Mohammed F.; Jing, Liufang; Chen, Jun; Hwang, Priscilla; Ghodsizadeh, Odelia; Friedman, Allan H.; Richardson, William J.; Setton, Lori A.



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.


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.


Salts & Solubility  

NSDL National Science Digital Library

Add different salts to water, then watch them dissolve and achieve a dynamic equilibrium with solid precipitate. Compare the number of ions in solution for highly soluble NaCl to other slightly soluble salts. Relate the charges on ions to the number of ions in the formula of a salt. Calculate Ksp values.

Simulations, Phet I.; Adams, Wendy; Koch, Linda; Lemaster, Ron; Loeblein, Trish; Perkins, Kathy



Toll/Interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction  

PubMed Central

Background Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c. Methods 158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction < 50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis). Results Patients with type 2 diabetes with (p < 0.001) or without LVDD (p = 0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p = 0.213 & p = 0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p = 0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes. Conclusions Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed. PMID:22104207



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



Mapping the Determinants of the CCR5 Amino-Terminal Sulfopeptide Interaction with Soluble Human Immunodeficiency Virus Type 1 gp120-CD4 Complexes  

PubMed Central

CD4 and CCR5 mediate fusion and entry of R5 human immunodeficiency virus type 1 (HIV-1) strains. Sulfotyrosine and other negatively charged residues in the CCR5 amino-terminal domain (Nt) are crucial for gp120 binding and viral entry. We previously showed that a soluble gp120-CD4 complex specifically binds to a peptide corresponding to CCR5 Nt residues 2 to 18, with sulfotyrosines in positions 10 and 14. This sulfopeptide also inhibits soluble gp120-CD4 binding to cell surface CCR5 as well as infection by an R5 virus. Here we show that residues 10 to 18 constitute the minimal domain of the CCR5 Nt that is able to specifically interact with soluble gp120-CD4 complexes. In addition to sulfotyrosines in positions 10 and 14, negatively charged residues in positions 11 and 18 participate in this interaction. Furthermore, the CCR5 Nt binds to a CD4-induced surface on gp120 that is composed of conserved residues in the V3 loop stem and the C4 domain. Binding of gp120 to cell surface CCR5 is further influenced by residues in the crown of the V3 loop, C1, C2, and C3. Our data suggest that gp120 docking to CCR5 is a multistep process involving several independent regions of the envelope glycoprotein and the coreceptor. PMID:11356961

Cormier, Emmanuel G.; Tran, Diep N. H.; Yukhayeva, Liyana; Olson, William C.; Dragic, Tatjana



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



Soluble NCAM  

Microsoft Academic Search

\\u000a The neural cell adhesion molecule (NCAM) is a membrane-bound glycoprotein involved in homophilic interactions that facilitate\\u000a cell-cell adhesion. In addition to a number of membrane-bound isoforms, NCAM also exists in several soluble isoforms that\\u000a have been identified in cerebrospinal fluid, blood serum, brain tissue, and cell culture media. Soluble NCAM can be produced\\u000a in a number of ways, such as

Thomas Secher


Solubility Equilibria  

NSDL National Science Digital Library

This 11-page PDF document is part of an environmental geochemistry course taught by Dr. David Sherman at the University of Bristol. Topics include the formation of insoluble carbonates, sulfates, sulfides and hydroxides from +2 and +3 cations, solubility expression (congruent vs. incongruent), and the common ion effect. Also discussed are the effects of solid solution and pH dependence of hydroxide and sulfide and carbonate solubilities. Informative diagrams augment the text.

Sherman, David M.; Bristol, University O.


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



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


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

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



Activin-attenuated expression of transcripts encoding granulosa cell-derived insulin-like growth factor binding proteins 4 and 5 in the rat: a putative antiatretic effect.  


Given the suggestion that intraovarian insulin-like growth factor (IGF)-binding proteins (IGFBPs) may constitute markers of follicular atresia, we investigated the possibility that activin, a putative antiatretic principle, may modulate granulosa cell-derived IGFBPs. Untreated granulosa cells cultured for 72 h exhibited a progressive increase in the steady-state levels of transcripts corresponding to IGFBP-4 and IGFBP-5 (1.5-fold and 12-fold, respectively). Transcript levels corresponding to IGFBP-5 were consistently higher than their IGFBP-4 counterparts. Treatment with activin-A (50 ng/ml) for 72 h produced significant (p < 0.05) decrements in the steady-state levels of IGFBP-4 and IGFBP-5 transcripts (46% and 79%, respectively) as compared to controls. Thus, treatment with activin-A appears to be capable of blocking the spontaneous increase in IGFBP-4 and IGFBP-5 transcripts exhibited by untreated cultured granulosa cells. Consistent activin-A-induced decrements were also observed in the accumulation of the IGFBP-5 (but not the IGFBP-4) protein. Dose-response analysis revealed monophasic dose dependence (half maximal inhibitory doses of 16.2 and 7.8 ng/ml for IGFBP-5 and IGFBP-4 transcripts, respectively). The addition of increasing concentrations of the putative activin-binding protein, follistatin, produced dose-dependent reversal of the activin-A effect on IGFBP transcripts (IGFBP-5 > IGFBP-4). Activin-B was as effective as activin-A in reducing IGFBP-4 transcripts (31% decrement, p < 0.05) whereas it had little or no effect on IGFBP-5 transcripts (21% decrement, p > 0.1). No apparent effect was observed for the corresponding proteins. Activin-A action was specific in that treatment with transforming growth factor (TGF)-beta1, inhibin-A, or Müllerian-inhibiting substance (MIS)--all related peptides--failed to produce statistically significant alterations in the steady-state levels of IGFBP-4 and IGFBP-5 transcripts. Taken together, these observations reveal that activin-A exerts a substantial, relatively rapid, follistatin-neutralizable, dose- and time-dependent inhibitory effect on granulosa cell-derived IGFBP transcripts (IGFBP-5 > IGFBP-4). Other members of the TGFbeta superfamily (e.g., inhibin-A, TGFbeta1, and MIS) were without significant effect on the expression of IGFBP-4 and IGFBP-5. To the extent that the inhibition of IGFBP-4 and IGFBP-5 expression is associated with, and possibly causally related to, the promotion of follicular health, the present observations are in keeping with the proposition that activin may play an antiatretic role in the dynamic process of follicular selection. PMID:9116154

Choi, D; Rohan, R M; Rosenfeld, R G; Matsumoto, T; Gargosky, S E; Adashi, E Y



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  

PubMed Central

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.



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


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

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



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

NASA Astrophysics Data System (ADS)

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

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



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

PubMed Central

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

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



[Hexokinase activity in the soluble fraction of the nucleus and cytoplasm in cell cultures infected with human adenoviruses types 6 and 12].  


A study was made of the activity of hexokinase in the soluble fraction of the nucleus and cytoplasm of fibroblasts of rat embryos (primary cultures) during contact with infectious (A6) and oncogenic (A12) human adenoviruses. A high activity of the enzyme was seen in the cytoplasmic fraction in comparison with the nuclear one both in the infectious adrenovirus of type 6 this value differed from the normal and in the experimental samples. With the action of the normal but insignificantly. Marked changes in the enzyme activity were observed in case of cell contact with the oncovirus. They occurred both in the nucleus and in the cytoplasm the first days of the virus inculcation, increasing gradually with the lapse of tiay; these disturbances were much greatert in the cytoplasm than in the nucleus. It is supposed that the changes revealed possibly associated with the impossibility to regulate the cell proliferation process. PMID:779866

Ageenko, A I; Vitorgan, Iu E; Gorozhanskaia, E G; Shapot, V S



Transforming Growth Factor ?/Activin Signaling Functions as a Sugar-Sensing Feedback Loop to Regulate Digestive Enzyme Expression.  


Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, we analyzed the mechanism underlying glucose repression of digestive enzymes in the adult Drosophila midgut. We demonstrate that glucose represses the expression of many carbohydrases and lipases. Our data reveal that the consumption of nutritious sugars stimulates the secretion of the transforming growth factor ? (TGF-?) ligand, Dawdle, from the fat body. Dawdle then acts via circulation to activate TGF-?/Activin signaling in the midgut, culminating in the repression of digestive enzymes that are highly expressed during starvation. Thus, our study not only identifies a mechanism that couples sugar sensing with digestive enzyme expression but points to an important role of TGF-?/Activin signaling in sugar metabolism. PMID:25284780

Chng, Wen-Bin Alfred; Sleiman, Maroun S Bou; Schüpfer, Fanny; Lemaitre, Bruno



High Yield Production of a Soluble Human Interleukin-3 Variant from E. coli with Wild-Type Bioactivity and Improved Radiolabeling Properties  

PubMed Central

Human interleukin-3 (hIL-3) is a polypeptide growth factor that regulates the proliferation, differentiation, survival and function of hematopoietic progenitors and many mature blood cell lineages. Although recombinant hIL-3 is a widely used laboratory reagent in hematology, standard methods for its preparation, including those employed by commercial suppliers, remain arduous owing to a reliance on refolding insoluble protein expressed in E. coli. In addition, wild-type hIL-3 is a poor substrate for radio-iodination, which has been a long-standing hindrance to its use in receptor binding assays. To overcome these problems, we developed a method for expression of hIL-3 in E. coli as a soluble protein, with typical yields of >3mg of purified hIL-3 per litre of shaking microbial culture. Additionally, we introduced a non-native tyrosine residue into our hIL-3 analog, which allowed radio-iodination to high specific activities for receptor binding studies whilst not compromising bioactivity. The method presented herein provides a cost-effective and convenient route to milligram quantities of a hIL-3 analog with wild-type bioactivity that, unlike wild-type hIL?3, can be efficiently radio-iodinated for receptor binding studies. PMID:23991218

Hercus, Timothy R.; Barry, Emma F.; Dottore, Mara; McClure, Barbara J.; Webb, Andrew I.; Lopez, Angel F.; Young, Ian G.; Murphy, James M.



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

SciTech Connect

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

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



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



Splitting placodes: effects of bone morphogenetic protein and Activin on the patterning and identity of mouse incisors.  


The single large rodent incisor in each jaw quadrant is evolutionarily derived from a mammalian ancestor with many small incisors. The embryonic placode giving rise to the mouse incisor is considerably larger than the molar placode, and the question remains whether this large incisor placode is a developmental requisite to make a thick incisor. Here we used in vitro culture system to experiment with the molecular mechanism regulating tooth placode development and how mice have thick incisors. We found that large placodes are prone to disintegration and formation of two to three small incisor placodes. The balance between one large or multiple small placodes was altered through the regulation of bone morphogenetic protein (BMP) and Activin signaling. Exogenous Noggin, which inhibits BMP signaling, or exogenous Activin cause the development of two to three incisors. These incisors were more slender than normal incisors. Additionally, two inhibitor molecules, Sostdc1 and Follistatin, which regulate the effects of BMPs and Activin and have opposite expression patterns, are likely to be involved in the incisor placode regulation in vivo. Furthermore, inhibition of BMPs by recombinant Noggin has been previously suggested to cause a change in the tooth identity from the incisor to the molar. This evidence has been used to support a homeobox code in determining tooth identity. Our work provides an alternative interpretation, where the inhibition of BMP signaling can lead to splitting of the large incisor placode and the formation of partly separate incisors, thereby acquiring molar-like morphology without a change in tooth identity. PMID:20618434

Munne, Pauliina M; Felszeghy, Szabolcs; Jussila, Maria; Suomalainen, Marika; Thesleff, Irma; Jernvall, Jukka



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)



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



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


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

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



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

PubMed Central

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

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



Triiodothyronine suppresses activin-induced differentiation of erythroleukemia K562 cells under hypoxic conditions.  


Thyroid hormone stimulates erythropoietic differentiation. However, severe anemia is sometimes seen in patients with hyperthyroidism, and the mechanisms have not been fully elucidated. Bone marrow is comprised about 2-8% oxygen, and the characteristics of hematopoietic stem cells have been shown to be influenced under hypoxia. Hypoxia-inducible factor-1 is a critical mediator of cellular responses to hypoxia and an important mediator in signal transduction of thyroid hormone [triiodothyronine (T3)]. The aim of this study was to investigate the effect of T3 on erythropoiesis under hypoxia mimicking physiological conditions in the bone marrow. We maintained human erythroleukemia K562 cells under hypoxic atmosphere (2% O?) and examined their cellular characteristics. Compared to that under normal atmospheric conditions, cells under hypoxia showed a reduction in the proliferation rate and increase in the hemoglobin content or benzidine-positive rate, indicating promotion of erythroid differentiation. T3 had no effect on hypoxia-induced erythroid differentiation, but significantly inhibited activin A/erythroid differentiation factor-induced erythroid differentiation. Moreover, GATA2 mRNA expression was suppressed in association with erythroid differentiation, while T3 significantly diminished that suppression. These results suggest that T3 has a direct suppressive effect on erythroid differentiation under hypoxic conditions. PMID:24604674

Yamamoto, Yoritsuna; Shiraishi, Mieno; Fujita, Masanori; Kojima, Itaru; Tanaka, Yuji; Tachibana, Shoichi



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:



Higher Plasma Soluble Receptor for Advanced Glycation End Products (sRAGE) Levels Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes  

PubMed Central

OBJECTIVE To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, arterial stiffness, and advanced glycation end products (AGEs). RESEARCH DESIGN AND METHODS We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of sRAGE and other biomarkers were measured at baseline. The median follow-up duration was 12.3 years (7.6–12.5). RESULTS The incidence of fatal and nonfatal CVD and all-cause mortality increased with higher baseline levels of log-transformed sRAGE (Ln-sRAGE) independently of other CVD risk factors: hazard ratio (HR) 1.90 (95% CI 1.13–3.21) and 2.12 (1.26–3.57) per 1-unit increase in Ln-sRAGE, respectively. Adjustments for estimated glomerular filtration rate (eGFRMDRD), but not or to a smaller extent for markers of endothelial dysfunction, low-grade inflammation, arterial stiffness, and AGEs, attenuated these associations to HR 1.59 (95% CI 0.91–2.77) for fatal and nonfatal CVD events and to 1.90 (1.09–3.31) for all-cause mortality. In addition, in patients with nephropathy, the rate of decline of GFR was 1.38 ml/min/1.73 m2 per year greater per 1-unit increase of Ln-sRAGE at baseline (P = 0.036). CONCLUSIONS Higher levels of sRAGE are associated with incident fatal and nonfatal CVD and all-cause mortality in individuals with type 1 diabetes. sRAGE-associated renal dysfunction may partially explain this association. PMID:20522598

Nin, Johanna W.M.; Jorsal, Anders; Ferreira, Isabel; Schalkwijk, Casper G.; Prins, Martin H.; Parving, Hans-Henrik; Tarnow, Lise; Rossing, Peter; Stehouwer, Coen D.A.



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

E-print Network

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

Sharma, Ajay


Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II.  


We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors. PMID:12192538

Zhao, Wenli; Kobayashi, Masonobu; Ding, Wei; Yuan, Lan; Seth, Prem; Cornain, Santoso; Wang, Jingxin; Okada, Futoshi; Hosokawa, Masuo



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

PubMed Central

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

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



Interactions between PEG and type I soluble tumor necrosis factor receptor: Modulation by pH and by PEGylation at the N terminus  

PubMed Central

The effects of polyethylene glycol (PEG) on protein structure and the molecular details that regulate its association to polypeptides are largely unknown. These issues were addressed using type I soluble tumor necrosis factor receptor (sTNF-RI) as a model system. Changes in solution viscosity established that a truncated form of sTNF-RI bound free PEG in a pH-dependent manner. Above pH 5.3, the viscosity escalated as the pH increased, while no effect occurred below pH 5.0. Conjugation of 2 kD, 5 kD, or 20 kD PEG to the N terminus attenuated the viscosity at the higher pH values. Tryptophan phosphorescence spectroscopy correlated changes in the protein structure about Trp-107, at the C terminus, with the pH-dependent and PEGylation-dependent attenuation of the viscosity. The results indicate that specific interactions between PEG and the truncated form of sTNF-RI are elicited by an increased flexibility of the truncated protein combined perhaps with removal of steric or charge barriers. Covalently bound PEG at the N terminus reduced the protein affinity for the free polymer and induced a more rigid and polar configuration around Trp-107. Deprotonation of His-105, which is perpendicular to Trp-107, was integral to the binding mechanism producing a pH-dependent switching mechanism. These findings stress the importance of surface charge and structural plasticity in determining macromolecular binding affinities and demonstrate the ability of conjugated PEG to modify the localized surface structure in proteins away from the site of conjugation. PMID:12070334

Kerwin, Bruce A.; Chang, Byeong S.; Gegg, Colin V.; Gonnelli, Margherita; Li, Tiansheng; Strambini, Giovanni B.



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



Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster  

PubMed Central

The ability to maintain cellular and physiological metabolic homeostasis is key for the survival of multicellular organisms in changing environmental conditions. However, our understanding of extracellular signaling pathways that modulate metabolic processes remains limited. In this study we show that the Activin-like ligand Dawdle (Daw) is a major regulator of systemic metabolic homeostasis and cellular metabolism in Drosophila. We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis. Although Daw regulates sugar homeostasis by positively influencing insulin release, we find that the effect of Daw on pH balance is independent of its role in insulin signaling and is caused by accumulation of organic acids that are primarily tricarboxylic acid (TCA) cycle intermediates. RNA sequencing reveals that a number of TCA cycle enzymes and nuclear-encoded mitochondrial genes including genes involved in oxidative phosphorylation and ?-oxidation are up-regulated in the daw mutants, indicating either a direct or indirect role of Daw in regulating these genes. These findings establish Activin signaling as a major metabolic regulator and uncover a functional link between TGF-? signaling, insulin signaling, and metabolism in Drosophila. PMID:24706779

Ghosh, Arpan C.; O'Connor, Michael B.



PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGF?2.  


Mammalian proprotein convertases (PCs) play an important role in folliculogenesis, as they proteolytically activate a variety of substrates such as the transforming growth factor beta (TGF?) superfamily. PC subtilism/kexin 6 (PCSK6) is a member of the PC family and is ubiquitously expressed and implicated in many physiological and pathological processes. However, in human granulosa cells, the expression of the PC family members, their hormonal regulation, and the function of PCs are not clear. In this study, we found that PCSK6 is the most highly expressed PC family member in granulosa cells. LH increased PCSK6 mRNA level and PCSK6 played an anti-apoptosis function in KGN cells. Knockdown of PCSK6 not only increased the secretion of activin A and TGF?2 but also decreased the secretion of follistatin, estrogen, and the mRNA levels of FSH receptor (FSHR) and P450AROM (CYP19A1). We also found that, in the KGN human granulosa cell line, TGF?2 and activin A could promote the apoptosis of KGN cells and LH could regulate the follistatin level. These data indicate that PCSK6, which is regulated by LH, is highly expressed in human primary granulosa cells of pre-ovulatory follicles and plays important roles in regulating a series of downstream molecules and apoptosis of KGN cells. PMID:24860148

Wang, Ying; Wang, Xiao-Hui; Fan, Deng-Xuan; Zhang, Yuan; Li, Ming-Qing; Wu, Hai-Xia; Jin, Li-Ping



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)



Shoot-synthesized nodulation-restricting substances of wild-type soybean present in two different high-performance liquid chromatography peaks of the ethanol-soluble medium-polarity fraction  

Microsoft Academic Search

The nodule number of leguminous plants is controlled by “autoregulation”, a type of systemic regulation. Although many studies have attempted to identify key substances in this mechanism, none have been identified to date. Previously, we reported that the key substance(s) in this interaction are shoot-synthesized nodulation restricting substance(s) (SNRS), which are contained in the ethanol-soluble medium-polarity fraction of the shoot

Takashi Kenjo; Hiroko Yamaya; Yasuhiro Arima



Co-expression of Dsb proteins enables soluble expression of a single-chain variable fragment (scFv) against human type 1 insulin-like growth factor receptor (IGF-1R) in E. coli.  


Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb. PMID:25256416

Sun, Xue-Wen; Wang, Xiao-Hua; Yao, Yan-Bing



Soluble Radicals Rebecca Waldecker  

E-print Network

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

Waldecker, Rebecca


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



Stimulation of activin A expression in rat aortic smooth muscle cells by thrombin and angiotensin II correlates with neointimal formation in vivo.  

PubMed Central

Vasoactive GTP-binding protein-coupled receptor agonists (e.g., angiotensin II [AII] and alpha-thrombin) stimulate the production of mitogenic factors from vascular smooth muscle cells. In experiments to identify mitogens secreted from AII- or alpha-thrombin-stimulated rat aortic smooth muscle (RASM) cells, neutralizing antibodies directed against several growth factors (e.g., PDGF and basic fibroblast growth factor [basic FGF]) failed to inhibit the mitogenic activity of conditioned media samples derived from the cells. In this report, we found that polyclonal neutralizing antibodies directed against purified human placental basic FGF reduced the mitogenic activity of AII-stimulated RASM cell-conditioned media and in immunoblot experiments identified a 26-kD protein (14 kD under reducing conditions) that was distinct from basic FGF. After purification from RASM cell-conditioned medium, amino acid sequence analysis identified the protein as activin A, a member of the TGF-beta superfamily. Increased activin A expression was observed after treatment of the RASM cells with AII, alpha-thrombin, and the protein kinase C agonist PMA. In contrast, PDGF-BB or serum caused only a minor induction of this protein. Although activin A alone only weakly stimulated RASM cell DNA synthesis, it demonstrated a potent comitogenic effect in combination with either EGF or heparin-binding EGF-like growth factor in the RASM cells, increasing DNA synthesis by up to fourfold. Furthermore, in a rat carotid injury model, activin A mRNA was upregulated within 6 h after injury followed by increases in immunoreactive protein detected in the expanding neointima 7 and 14 d later. Taken together, these results indicate that activin A is a vascular smooth muscle cell-derived factor induced by vasoactive agonists that may, either alone or in combination with other vascular derived growth factors, have a role in neointimal formation after arterial injury. PMID:9239411

Pawlowski, J E; Taylor, D S; Valentine, M; Hail, M E; Ferrer, P; Kowala, M C; Molloy, C J



Immunosuppressor FK506 increases endoglin and activin receptor-like kinase 1 expression and modulates transforming growth factor-?1 signaling in endothelial cells.  


Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is an autosomal-dominant vascular disease. The clinical manifestations are epistaxis, mucocutaneous and gastrointestinal telangiectases, and arteriovenous malformations in internal organs. Patients show severe epistaxis, and/or gastrointestinal bleeding, both of which notably interfere with their quality of life. There are two predominant types of HHT caused by mutations in endoglin (ENG) and ACVRL1/activin receptor-like kinase 1 (ALK1) genes, named HHT1 and HHT2, respectively. ENG and ALK1 code for proteins involved in the transforming growth factor (TGF)-?1 signaling pathway, and it is widely accepted that HHT pathogenicity results from haploinsufficiency. No cure for HHT has been found, so identification of drugs able to increase the expression of these genes is essential when proposing new therapies. We report the efficacy of tacrolimus (FK506) in increasing ENG and ALK1 expression. The rationale comes from a case report of a patient with HHT who received a liver transplantation after hepatic failure due to a liver arteriovenous malformation. The liver was transplanted, and the immunosuppressor FK506 was used to prevent the rejection. After the first month of FK506 treatment, the internal and external telangiectases, epistaxes, and anemia disappeared. Here, we find that the immunosuppressor FK506 increases the protein and mRNA expression of ENG and ALK1 in cultured endothelial cells and enhances the TGF-?1/ALK1 signaling pathway and endothelial cell functions like tubulogenesis and migration. These results suggest that the mechanism of action of FK506 involves a partial correction of endoglin and ALK1 haploinsufficiency and may therefore be an interesting drug for use in patients with HHT who undergo transplantation. PMID:21310938

Albiñana, Virginia; Sanz-Rodríguez, Francisco; Recio-Poveda, Lucía; Bernabéu, Carmelo; Botella, Luisa M



Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms  

PubMed Central

Background Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers. Methods Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity (LOH) was evaluated for ACVR2 and ACVR1, and ACVR2 promoter methylation by methylation-specific PCR and bisulfite sequencing and chromosomal instability (CIN) phenotype via fluorescent LOH analysis of 3 duplicate markers. ACVR2 promoter methylation and ACVR2 expression were assessed in colon cancer cell lines via qPCR and IP-Western blots. Re-expression of ACVR2 after demethylation with 5-aza-2?-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathological criteria. Results Of 51 MSS colon tumors, 7(14%) lost ACVR2, 2 (4%) ACVR1, and 5(10%) pSMAD2 expression. No somatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (p<0.001) and ACVR2 promoter hypermethylation (p<0.05). ACVR2 LOH, but not promoter hypermethylation, correlated with CIN status. In colon cancer cell lines with fully methylated ACVR2 promoter, loss of ACVR2 mRNA and protein expression was restored with 5-Aza treatment. Loss of ACVR2 was associated with an increase in primary colon cancer volume (p<0.05). Conclusions Only a small percentage of MSS colon cancers lose expression of activin signaling members. ACVR2 loss occurs through LOH and ACVR2 promoter hypermethylation, revealing distinct mechanisms for ACVR2 inactivation in both MSI and MSS subtypes of colon cancer. PMID:20011542

Jung, Barbara; Gomez, Jessica; Chau, Eddy; Cabral, Jennifer; Lee, Jeffrey K.; Anselm, Aimee; Slowik, Przemyslaw; Ream-Robinson, Deena; Messer, Karen; Sporn, Judith; Shin, Sung K.; Boland, C. Richard; Goel, Ajay; Carethers, John M.



Structural and functional evidences for a type 1 TGF-? sensu stricto receptor in the lophotrochozoan Crassostrea gigas suggest conserved molecular mechanisms controlling mesodermal patterning across bilateria  

Microsoft Academic Search

The transforming growth factor ? (TGF?) superfamily includes bone morphogenetic proteins, activins and TGF-?sensu stricto (s.s.). These ligands have been shown to play a key role in numerous biological processes including early embryonic development and immune regulation. They transduce their signal through a hetromeric complex of type I and type II receptors. Such receptors have been identified in ecdysozoans but

A. Herpin; C. Lelong; T. Becker; F. M. Rosa; P. Favrel; C. Cunningham



The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin\\/nodal signaling  

Microsoft Academic Search

We investigated the regulation of the activin\\/nodal-inducible distal element (DE) of the Xenopus goosecoid (gsc) promoter. On the basis of its interaction with the DE, we isolated a Xenopus homolog of the human Williams-Beuren syndrome critical region 11 (XWBSCR11), and further, show that it interacts with pathway-specific Smad2 and Smad3 in a ligand-dependent manner. Interestingly, we also find that XWBSCR11

Colleen Ring; Souichi Ogata; Lauren Meek; Jihwan Song; Tatsuru Ohta; Kohei Miyazono; Ken W. Y. Cho



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

PubMed Central

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

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



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

PubMed Central

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

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



Hydrogen solubility in austenitic stainless steels  

Microsoft Academic Search

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.

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



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


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


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

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



Exfoliated soluble graphite  

Microsoft Academic Search

Reduction of graphite by lithium in liquid ammonia yields graphite salts that can be reacted with dodecyl iodide to yield soluble dodecylated graphite. The height of the soluble graphite nanoplatelets was determined by scanning tunneling microscopy (STM) to be 3.5nm, corresponding to approximately 10 layers of graphene. Solubility in organic solvents was determined to be 20mg\\/L in chloroform and 70mg\\/L

Jayanta Chattopadhyay; Arnab Mukherjee; Soma Chakraborty; JungHo Kang; Peter J. Loos; Kevin F. Kelly; Howard K. Schmidt; W. E. Billups



Assessment of biomarkers of cardiovascular risk among HIV type 1-infected adolescents: role of soluble vascular cell adhesion molecule as an early indicator of endothelial inflammation.  


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

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



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

PubMed Central

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

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



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




EPA Science Inventory

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


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.



Parainfluenza Virus Type 3 Expressing the Native or Soluble Fusion (F) Protein of Respiratory Syncytial Virus (RSV) Confers Protection from RSV Infection in African Green Monkeys  

Microsoft Academic Search

Respiratory syncytial virus (RSV) causes respiratory disease in young children, the elderly, and immuno- compromised individuals, often resulting in hospitalization and\\/or death. After more than 40 years of research, a Food and Drug Administration-approved vaccine for RSV is still not available. In this study, a chimeric bovine\\/human (b\\/h) parainfluenza virus type 3 (PIV3) expressing the human PIV3 (hPIV3) fusion (F)

Roderick S. Tang; Mia MacPhail; Jeanne H. Schickli; Jasmine Kaur; Christopher L. Robinson; Heather A. Lawlor; Jeanne M. Guzzetta; Richard R. Spaete; Aurelia A. Haller



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

PubMed Central

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

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



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.



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



Lack of Evidence from Studies of Soluble Protein Fragments that Knops Blood Group Polymorphisms in Complement Receptor-Type 1 Are Driven by Malaria  

PubMed Central

Complement receptor-type 1 (CR1, CD35) is the immune-adherence receptor, a complement regulator, and an erythroid receptor for Plasmodium falciparum during merozoite invasion and subsequent rosette formation involving parasitized and non-infected erythrocytes. The non-uniform geographical distribution of Knops blood group CR1 alleles Sl1/2 and McCa/b may result from selective pressures exerted by differential exposure to infectious hazards. Here, four variant short recombinant versions of CR1 were produced and analyzed, focusing on complement control protein modules (CCPs) 15–25 of its ectodomain. These eleven modules encompass a region (CCPs 15–17) key to rosetting, opsonin recognition and complement regulation, as well as the Knops blood group polymorphisms in CCPs 24–25. All four CR1 15–25 variants were monomeric and had similar axial ratios. Modules 21 and 22, despite their double-length inter-modular linker, did not lie side-by-side so as to stabilize a bent-back architecture that would facilitate cooperation between key functional modules and Knops blood group antigens. Indeed, the four CR1 15–25 variants had virtually indistinguishable affinities for immobilized complement fragments C3b (KD?=?0.8–1.1 µM) and C4b (KD?=?5.0–5.3 µM). They were all equally good co-factors for factor I-catalysed cleavage of C3b and C4b, and they bound equally within a narrow affinity range, to immobilized C1q. No differences between the variants were observed in assays for inhibition of erythrocyte invasion by P. falciparum or for rosette disruption. Neither differences in complement-regulatory functionality, nor interactions with P. falciparum proteins tested here, appear to have driven the non-uniform geographic distribution of these alleles. PMID:22506052

Tetteh-Quarcoo, Patience B.; Schmidt, Christoph Q.; Tham, Wai-Hong; Hauhart, Richard; Mertens, Haydyn D. T.; Rowe, Arthur; Atkinson, John P.; Cowman, Alan F.; Rowe, J. Alexandra; Barlow, Paul N.



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.



Nickel solubility in intrinsic and doped silicon  

SciTech Connect

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

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



Multiplex Bead Array Assay for Detection of 25 Soluble Cytokines in Blister Fluid of Patients with Complex Regional Pain Syndrome Type 1  

PubMed Central

Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNF? compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1?, IL-1RA, IL-6, IL-8, and TNF-?; (2) Th1/Th2 distinguishing cytokines IFN-?, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-?, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1?, MIP-1?, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-?, IL-12p40/p70, MCP-1, and MIP-1? were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-? simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85, P < .001 for IL-6 and r = 0.88, P < .001 for TNF-?). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines. PMID:16864900

Heijmans-Antonissen, Claudia; Wesseldijk, Feikje; Munnikes, Renate JM; Huygen, Frank JPM; van der Meijden, Patrick; Hop, Wim C. J.; Hooijkaas, Herbert; Zijlstra, Freek J.



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


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

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



Exogenous GDF9 but not Activin A, BMP15 or TGF? alters tight junction protein transcript abundance in zebrafish ovarian follicles.  


The tight junction (TJ) complex plays an important role in regulating paracellular permeability and provides mechanical stability in vertebrate epithelia and endothelia. In zebrafish ovarian follicles, TJ complexes in the follicular envelope degenerate as the follicles develop towards maturation. In the current study, transcript abundance of claudins (cldn d, g, h, 1, and 12) and occludins (ocln, and ocln b) were assessed in mid-vitellogenic follicles in response to treatment with exogenous growth factors that are reported to be involved in zebrafish follicle development (i.e. Activin A, BMP15, GDF9 and TGF?). Exogenous GDF9 reduced the transcript abundance of cldn g, ocln and ocln b in mid-vitellogenic follicles, whereas Activin A, BMP15, and TGF? had no effect. Subsequent studies with GDF9 revealed that this factor did not alter TJ protein transcript abundance in pre-vitellogenic follicles but did increase the abundance of ocln b in fully grown (maturing) follicles. GDF9 was also seen to increase the abundance of StAR mRNA in all but primary stage follicles. These data suggest a role for GDF9 in the regulation of TJ integrity in zebrafish ovarian follicles, perhaps in the facilitation of ovulation, and support a previously postulated role for GDF9 in zebrafish ovarian follicle development. In addition, data also support the idea that endocrine factors play an important role in the regulation of TJ proteins during ovarian follicle development. PMID:21291886

Clelland, Eric S; Kelly, Scott P



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.



High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding  

SciTech Connect

BMPRII is a type II TGF-{beta} serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-{beta} type ligands, BMPs bind to type II receptors with lower affinity than type I receptors. Crystals of the BMPRII ectodomain were grown in two different forms, both of which diffracted to high resolution. The tetragonal form exhibited some disorder, whereas the entire polypeptide was seen in the orthorhombic form. The two structures retain the basic three-finger toxin fold of other TGF-{beta} receptor ectodomains, and share the main hydrophobic patch used by ActRII to bind various ligands. However, they present different conformations of the A-loop at the periphery of the proposed ligand-binding interface, in conjunction with rearrangement of a disulfide bridge within the loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and activin receptors, suggesting that it is important for their likely shared mode of binding. Evidence is presented that the two crystal forms represent ligand-bound and free conformations of BMPRII. Comparison with the solved structure of ActRII bound to BMP2 suggests that His87, unique amongst TGF-{beta} receptors, may play a key role in ligand recognition.

Mace, Peter D. [Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001 (New Zealand); Cutfield, John F. [Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001 (New Zealand); Cutfield, Sue M. [Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001 (New Zealand)]. E-mail:



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



Sequential CD4-coreceptor interactions in human immunodeficiency virus type 1 Env function: soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120.  


We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. PMID:10590121

Salzwedel, K; Smith, E D; Dey, B; Berger, E A



Preservation of nitric oxide-induced relaxation of porcine coronary artery: roles of the dimers of soluble guanylyl cyclase, phosphodiesterase type 5, and cGMP-dependent protein kinase.  


Soluble guanylyl cyclase (sGC), phosphodiesterase type 5 (PDE5), and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) are all dimeric. The present study was to determine the role of their dimeric status in nitric oxide-induced vasodilatation. In isolated porcine coronary arteries, after 20 h incubation with serum-free medium, serum-containing medium, or phosphate-buffered saline solution, the protein levels of the dimers of sGC, PDE5, and PKG were diminished while the monomer levels remained unchanged, associated with reduced cGMP elevation in response to DETA NONOate and decreased PDE5 activity; the activity of PKG was not significantly altered. DETA NONOate caused a greater relaxation in arteries incubated for 20 vs. 2 h. The relaxant response was largely abolished by 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor. Zaprinast, a PDE5 inhibitor, had no effect on relaxation caused by DETA NONOate of arteries incubated for 20 h but augmented the response incubated for 2 h. A greater relaxation to 8-bromo-guanosine 3'5'-cyclic monophosphate occurred in arteries incubated for 20 than for 2 h. The protein level of the dimers but not monomers of PDE5 was reduced by dithiothreitol and unaffected by hydrogen peroxide, accompanied with decreased PDE5 activity and reduced response to DETA NONOate. These results demonstrate that the dimeric but not monomeric status of sGC and PDE5 of coronary arteries are closely related to their activities. The preserved vasodilator response after 20 h incubation may result in part from a synchronous reduction of the dimer levels of sGC and PDE5 as well as an augmented response to cGMP. PMID:24413911

Liu, Juan; Chen, Zhengju; Ye, Liping; Liu, Huixia; Dou, Dou; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng



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.



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


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

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



Water soluble laser dyes  


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

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



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.



Pure Phase Solubility Limits: LANL  

SciTech Connect

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

C. Stockman



Soluble filler as a dissolution profile modulator for slightly soluble drugs in matrix tablets.  


The purpose of this experimental work was the development of hydrophilic-lipophilic matrix tablets for controlled release of slightly soluble drug represented here by diclofenac sodium (DS). Drug dissolution profile optimization provided by soluble filler was studied. Matrix tablets were based on cetyl alcohol as the lipophilic carrier, povidone as the gel-forming agent, and common soluble filler, that is lactose or sucrose of different particle size. Physical properties of tablets prepared by melt granulation and drug release in a phosphate buffer of pH 6.8 were evaluated. In vitro studies showed that used filler type, filler to povidone ratio and sucrose particle size influenced the drug release rate. DS dissolution profile could be changed within a wide range from about 50% per 24 hours to almost 100% in 10 hours. The release constant values confirmed that DS was released from matrices by the diffusion and anomalous transport. The influence of sucrose particle size on the drug release rate was observed. As the particle size decreased, the drug release increased significantly and its dissolution profile became more uniform. Soluble fillers participated in the pore-forming process according to their solubility and particle size. Formulations containing 100 mg of the drug, 80 mg of cetyl alcohol, 40 mg of povidone, and 80 mg of either lactose or sucrose (particle size 250-125 microm) were considered optimal for 24-hour lasting dissolution of DS. PMID:19274510

Dvorácková, Katerina; Rabisková, Miloslava; Masteiková, Ruta; Muselík, Jan; Krejcová, Katerina



Cloud droplet activation: solubility revisited  

NASA Astrophysics Data System (ADS)

Soluble compounds present in atmospheric aerosol facilitate their transformation into cloud droplets by depressing the equilibrium vapor pressure required for activation. Their impact depends on the amount of dissolved substance in the aerosol aqueous phase, which in turn is controlled by its solubility. This study explores the impact of particle curvature on solubility, expressed in terms of a Kelvin enhancement. The augmented solubility, termed "Curvature Enhanced Solubility" (CES), is then introduced into Köhler theory for assessment of its impact on CCN activity for several organic compounds with a wide range of aqueous solubility. The interfacial energy between solute and aqueous phase required for quantification of CES is determined from existing correlations based on bulk solubility, and concurrent measurements of contact angle and surface tension. A number of important findings arise from this study: i) CES can substantially increase solubility and impact CCN activity but only if the aerosol is initially wet, ii) CES can stabilize highly supersaturated solutions, and provide a mechanism for retention of an aerosol aqueous phase even at very low relative humidity (RH), and, iii) trace amounts of surfactant impurities can magnify the impact of CES.

Padró, L. T.; Nenes, A.



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.



Solubility of triazine pesticides in pure and modified subcritical water.  


Solubility measurements in pure and modified water serve as a basis for optimizing the subcritical water extraction of target analytes such as food contaminants. The solvent strength of the water is affected by both the system's temperature and the amount and type of cosolvent modifier that is added to the water, which causes a reduction in the dielectric constant of water. In the present work, the solubilities of the triazine pesticides atrazine, cyanazine, and simazine were measured in pure and modified water at temperatures ranging from 50 to 125 degrees C and at a pressure of 50 atm. The solubility data were obtained using a static solubility apparatus with on-line liquid chromatographic (LC) detection. By increasing the temperature of the water, the solubilities of the triazine pesticides increased approximately 3-fold in pure water for each 25 degrees C temperature increment. Cyanazine was 5 times more soluble than atrazine and an order of magnitude more soluble than simazine at 100 degrees C. The solubility of atrazine was also measured in ambient and hot water modified with ethanol and urea. At 100 degrees C, the solubility of atrazine is doubled when the water is modified with urea, and is increased over an order of magnitude when ethanol is used as modifier. The data, therefore, indicate that adding a cosolvent to water in addition to increasing the system temperature increases the solubilities of triazine pesticides in subcritical water. It was further determined that the solutes do not thermally degrade or hydrolyze at the temperatures reported in this study. PMID:11248886

Curren, M S; King, J W



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.



Solubility Characteristics of a Methacrylate Copolymer.  

National Technical Information Service (NTIS)

Solubility maps in several coordinate systems have been constructed to determine regions of solubility for a methacrylate copolymer. The general methodology followed was that of ASTM D 3132 Test Method for Solubility Range of Resins and Polymers. Over 90 ...

M. K. Potts



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-



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.



Mineral oil soluble borate compositions  

SciTech Connect

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

Dulat, J.



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)



Water-soluble vitamins.  


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

Konings, Erik J M



Prediction of drug solubility by the general solubility equation (GSE).  


The revised general solubility equation (GSE) proposed by Jain and Yalkowsky is used to estimate the aqueous solubility of a set of organic nonelectrolytes studied by Jorgensen and Duffy. The only inputs used in the GSE are the Celsius melting point (MP) and the octanol water partition coefficient (K(ow)). These are generally known, easily measured, or easily calculated. The GSE does not utilize any fitted parameters. The average absolute error for the 150 compounds is 0.43 compared to 0.56 with Jorgensen and Duffy's computational method, which utilitizes five fitted parameters. Thus, the revised GSE is simpler and provides a more accurate estimation of aqueous solubility of the same set of organic compounds. It is also more accurate than the original version of the GSE. PMID:11277722

Ran, Y; Yalkowsky, S H



How Important is Methodology to Estimates of Aerosol Solubility?  

NASA Astrophysics Data System (ADS)

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

Buck, C. S.; Paytan, A.



Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene  

PubMed Central

Muscle strength is important in functional activities of daily living and the prevention of common pathologies. We describe the two-staged fine mapping of a previously identified linkage peak for knee strength on chr12q12-14. First, 209 tagSNPs in/around 74 prioritized genes were genotyped in 500 Caucasian brothers from the Leuven Genes for Muscular Strength study (LGfMS). Combined linkage and family-based association analyses identified activin receptor 1B (ACVR1B) and inhibin ? C (INHBC), part of the transforming growth factor ? pathway regulating myostatin – a negative regulator of muscle mass – signaling, for follow-up. Second, 33 SNPs, selected in these genes based on their likelihood to functionally affect gene expression/function, were genotyped in an extended sample of 536 LGfMS siblings. Strong associations between ACVR1B genotypes and knee muscle strength (P-values up to 0.00002) were present. Of particular interest was the association with rs2854464, located in a putative miR-24-binding site, as miR-24 was implicated in the inhibition of skeletal muscle differentiation. Rs2854464 AA individuals were ?2% stronger than G-allele carriers. The strength increasing effect of the A-allele was also observed in an independent replication sample (n=266) selected from the Baltimore Longitudinal Study of Aging and a Flemish Policy Research Centre Sport, Physical Activity and Health study. However, no genotype-related difference in ACVR1B mRNA expression in quadriceps muscle was observed. In conclusion, we applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength. PMID:21063444

Windelinckx, An; De Mars, Gunther; Huygens, Wim; Peeters, Maarten W; Vincent, Barbara; Wijmenga, Cisca; Lambrechts, Diether; Delecluse, Christophe; Roth, Stephen M; Metter, E Jeffrey; Ferrucci, Luigi; Aerssens, Jeroen; Vlietinck, Robert; Beunen, Gaston P; Thomis, Martine A



Formulation of soluble oils with synthetic and petroleum sulfonates  

SciTech Connect

Metalworking fluids for metal removal are formulated to provide cooling, lubrication, and rust protection when cutting and machining metals. There are basically four types of cutting fluids: straight oils, synthetics, semisynthetic fluids and soluble oils. The last type is the most widely used for metal removal operations such as cutting, drilling and grinding. Soluble oils used for metalworking operations are normally the oil-in-water type, with oil as the internal phase and water as the external phase. The soluble oils can have rather complex compositions, usually containing two or more emulsifiers and coupling agents, as well as additives to provide rust inhibition, lubricity, detergency, resistance to bacterial attack and foam control. The dominant emulsifier in a soluble oil is usually sodium sulfonate which also has the secondary benefit of being a rust inhibitor. Soluble oil emulsions based on petroleum or synthetic sulfonates have been found to improve lubrication and cleaning of metal parts and equipment. As has been done previously, a series of emulsification studies were conducted using petroleum and synthetic sulfonates. Emulsifier level, coemulsifiers and minor formulation adjustments were made to optimize each system. This study was made using naphthenic oil basestock. Formulations were evaluated using criteria including concentrate stability, hard and soft water emulsion stability, emulsibility, foaming tendency and response to defoamers, antirust properties and cost effectiveness of individual formulations. The results of these evaluations are presented in the present paper.

Eckard, A.; Riff, I.; Weaver, J. [Witco Corp., Oakland, NJ (United States)



The Effect of Immune Factors, Tumor Necrosis Factor-? (TNF-?), and Agonistic Autoantibodies to the Angiotensin II Type I Receptor (AT1-AA) on Soluble fms-Like Tyrosine-1 (sFlt-1) and Soluble Endoglin (sEng) Production in Response to Hypertension During Pregnancy  

PubMed Central

BACKGROUND Preeclampsia is considered a disease of immunological origin associated with abnormalities in inflammatory cytokines, tumor necrosis factor-? (TNF-?), and activated lymphocytes secreting AT1-AA. Recent studies have also demonstrated that an imbalance of angiogenic factors, soluble fms-like tyrosine kinase (sFlt-1), and sEndoglin, exists in preeclampsia; however, the mechanisms that initiate their overproduction are unclear. METHODS To determine the role of immune regulation of these factors, circulating and placental sFlt-1 and/or sEndoglin was examined from pregnant rats chronically treated with TNF-? or AT1-AA. On day 19 of gestation blood pressure was analyzed and serum and tissues were collected. Placental villous explants were excised and cultured on matrigel coated inserts for 24 h and sFlt-1 and sEndoglin was measured from media. RESULTS In response to TNF-?-induced hypertension, sFlt-1 increased from 180 ± 5 to 2,907 ± 412 pg/ml. sFlt-1 was also increased from cultured placental explants of TNF-? induced hypertensive pregnant rats (n = 12) (2,544 ± 1,132 pg/ml) vs. explants from normal pregnant (NP) rats (n = 12) (2,189 ± 586 pg/ml) where as sEng was undetectable. Circulating sFlt-1 increased from 245 ± 38 to 3,920 ± 798 pg/ml in response to AT1-AA induced hypertension. sFlt-1 levels were higher (3,400 ± 350 vs. 2,480 ± 900 pg/ml) in placental explants from AT1-AA infused rats (n = 12) than NP rats (n = 7). In addition, sEndoglin increased from 30 ± 2.7 to 44 ± 3.3 pg/ml (P < 0.047) in AT1-AA infused rats but was undetectable in the media of the placental explants. CONCLUSIONS These data suggest that immune factors may serve as an important stimulus for both sFlt-1 and sEndoglin production in response to placental ischemia. PMID:20431529

Parrish, Marc R.; Murphy, Sydney R.; Rutland, Sarah; Wallace, Kedra; Wenzel, Katrin; Wallukat, Gerd; Keiser, Sharon; Ray, Lillian Fournier; Dechend, Ralf; Martin, James N.; Granger, Joey P.; LaMarca, Babbette



Aqueous Solubility of CL-20.  

National Technical Information Service (NTIS)

The Energetics and Warheads Division of the U.S. Army Armament Research, Development and Engineering Center has been involved in the development of CL-20. An aqueous solubility study was performed to better understand the fate and transport of CL-20 throu...

P. Karakaya, M. Sidhoum, C. Christodoulatos, W. Balas, S. Nicolich



Lubrication studies of aqueous mixtures of inversely soluble components  

Microsoft Academic Search

Phase and aggregational behavior of model metal working formulations of the inversely soluble type was studied with the aid of a new analytical tool. Correlations between these data and measured anti-wear performance data are discussed. The aim was to gain some insight into the mode of variation of the anti-wear effect with temperature and concentration depending on composition of inversely

S. K. Misra; Rolf O. Sköld



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





Microsoft Academic Search

In order to understand the behavior of water soluble organic matter (WSOM) in soil under different types of forest, soil samples from twenty sites were sampled and analyzed for each forest in the area of Huzhou, China. Each sample was extracted with both cool water (25°C) and hot water (100°C). Without exception, hot water soluble organic carbon (HWSOC) was more

Qiufang Xu; Zhengqian Ye; Jianming Xu; Peikun Jiang



Solubility of sparingly soluble drug derivatives of anthranilic acid.  


This work is a continuation of our systematic study of the solubility of pharmaceuticals (Pharms). All substances here are derivatives of anthranilic acid, and have an anti-inflammatory direction of action (niflumic acid, flufenamic acid, and diclofenac sodium). The basic thermal properties of pure Pharms, i.e., melting and glass-transition temperatures as well as the enthalpy of melting, have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The equilibrium mole fraction solubilities of three pharmaceuticals were measured in a range of temperatures from 285 to 355 K in three important solvents for Pharm investigations: water, ethanol, and 1-octanol using a dynamic method and spectroscopic UV-vis method. The experimental solubility data have been correlated by means of the commonly known G(E) equation: the NRTL, with the assumption that the systems studied here have revealed simple eutectic mixtures. pK(a) precise measurement values have been investigated with the Bates-Schwarzenbach spectrophotometric method. PMID:21366210

Doma?ska, Urszula; Pobudkowska, Aneta; Pelczarska, Aleksandra



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 limited due to the difficulty in obtaining...

Kramer, Ryan 1984-



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)



Diameter-dependent solubility of single-walled carbon nanotubes.  


We study the solubility and dispersibility of as-produced and purified HiPco single-walled carbon nanotubes (SWNTs). Variation in specific operating conditions of the HiPco process are found to lead to significant differences in the respective SWNT solubilities in oleum and surfactant suspensions. The diameter distributions of SWNTs dispersed in surfactant solutions are batch-dependent, as evidenced by luminescence and Raman spectroscopies, but are identical for metallic and semiconducting SWNTs within a batch. We thus find that small diameter SWNTs disperse at higher concentration in aqueous surfactants and dissolve at higher concentration in oleum than do large-diameter SWNTs. These results highlight the importance of controlling SWNT synthesis methods in order to optimize processes dependent on solubility, including macroscopic processing such as fiber spinning, material reinforcement, and films production, as well as for fundamental research in type selective chemistry, optoelectronics, and nanophotonics. PMID:20521799

Duque, Juan G; Parra-Vasquez, A Nicholas G; Behabtu, Natnael; Green, Micah J; Higginbotham, Amanda L; Price, B Katherine; Leonard, Ashley D; Schmidt, Howard K; Lounis, Brahim; Tour, James M; Doorn, Stephen K; Cognet, Laurent; Pasquali, Matteo



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


Aluminium solubility in rainwater and molten snow  

Microsoft Academic Search

Large variations of aluminium solubilities are found in marine and rural precipitations. The results of seven field experiments are used to produce a model of the solubilization of aluminium independent of the sampling site. Large variations of solubility appear, and the pH seems to be a major factor explaining this solubility changes. Thermodynamic calculations at T=278K suggest that, at higher

R. Losno; J. L. Colin; N. Bris; G. Bergametti; T. Jickells; B. Lim



Fosinopril-cyclodextrin inclusion complexes: phase solubility and physicochemical analysis.  


Fosinopril is one of the most hydrophobic substances among the angiotensin-converting enzyme inhibitors, exhibiting low water solubility and poor bioavailability following oral administration. Inclusion complexes between the drug substance and cyclodextrins (CDs) were obtained in order to improve its solubility. The purpose of this study was to investigate the guest-host interaction of fosinopril sodium (FOS) with beta-cyclodextrin (beta-CD) and its derivative, randomly methylated beta-cyclodextrin (RAMEB) in solution by phase solubility diagrams (PSD) and in solid state by using thermal analysis, powder X-ray diffractometry (PXRD) and Fourier transform infrared spectroscopy (FTIR). The phase solubility analysis indicated that the solubility of FOS in simulated gastric fluid was increased in the presence of CDs and revealed for RAMEB an A(L)-type diagram, suggesting the formation of a 1:1 inclusion complex, and for beta-CD a B(s)-type phase diagram. The estimated apparent stability constant (K1:1), according to the Higuchi and Connors method, is 3209.99 M(-1) and 1770.34 M(-1) for RAMEB and beta-CD complexes respectively. The binary systems FOS/CDs were prepared using the kneading method in the molar ratio 1:1. The PXRD patterns and the thermograms indicated a drug amorphization process, higher for FOS/RAMEB binary system and the FTIR analysis suggested that the ester group of FOS is probably enclosed in the CD's cavity. The results of this study confirm the formation of inclusion complexes both in solution and in solid state and suggest that the complexes formation between FOS and CDs could improve the bioavailability of the drug due to the enhancing absorption expected from increased drug solubility. PMID:21901980

Sbârcea, L; Udrescu, L; Dr?gan, L; Trandafirescu, C; Szabadai, Z; Boji??, M



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.


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 of California, One Shields Avenue, Davis, California 95616 Received January 31, 2005 Soluble epoxide hydrolase and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties

Hammock, Bruce D.


Measuring Soluble ICAM-1 in African Populations  

PubMed Central

The level of plasma soluble ICAM-1 (sICAM-1) has been associated with the pathogenesis of several diseases. Previously, a commercial antibody was reported not to recognize an ICAM-1 allele known as ICAM-1kilifi prevalent among African populations. However, that study was based on 19 samples from African Americans of whom 13 had the wild type allele, five heterozygotes and one homozygote. Here, we compare plasma sICAM-1 measures using three different commercial antibodies in samples from Kenyan children genotyped for ICAM-1kilifi allele. We show that two of these antibodies have some degree of deficiency in detecting the ICAM-1kilifi allele. Consideration of the antibody used to measure sICAM-1 is important as up to 30% of the populations in Africa harbour this allele. PMID:25289635

Abdi, Abdirahman I.; Muthui, Michelle; Kiragu, Esther; Bull, Peter C.



Hydrogen adsorption of ruthenium: Isosteres of solubility of adsorbed hydrogen  

SciTech Connect

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

Zaginaichenko, S.Y. [UAS, Kiev (Ukraine). Inst. for Problems of Materials Science; Matysina, Z.A. [State Univ., Dnepropetrovsk (Ukraine); Schur, D.V.; Pishuk, V.K. [Inst. of Hydrogen and Solar Energy, Kiev (Ukraine)



Review and Bibliography on Rock Solubility and Zeolite Minerals.  

National Technical Information Service (NTIS)

A bibliography was prepared and literature reviewed on the solubility of rock and rock-forming minerals, with emphasis on laboratory methods for solubility studies and the solubility of zeolites and calcium carbonate. As solubility is dependent on many va...

G. W. DePuy



Solubility enhancement of simvastatin: a review.  


Fairly soluble drugs in gastrointestinal (GI) media exhibit complete oral absorption, and thus good bioavailability. About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity. Thus, most exigent phase of drug development practice particularly for oral dosage forms is the enhancement of drug solubility and thereby its oral bioavailability. Solubility, an important factor to achieve desired plasma level of drug for pharmacological response, is the phenomenon of dissolution of solid in liquid phase resulting in a homogenous system. This review describes various traditional and novel methodologies proposed for solubility enhancement of simvastatin, and ultimately improvement in its bioavailability. For simvastatin, solubility is a crucial rate limiting factor to achieve its desired level in systemic circulation for pharmacological response. Thus, problematic solubility of simvastatin is a main challenge for dosage form developing researchers. Various procedures, illustrated in this review, have been successfully employed to improve the simvastatin solubility for its bioavailability enhancement; however, successful improvement essentially depends on the assortment of technique. Among all the solubility enhancement techniques, solid dispersion method, in terms of ease and efficiency is most promising and routinely employed technique to resolve the solubility problems of simvastatin. PMID:22876598

Murtaza, Ghulam



Investigation of interleukin-6 (IL6), soluble IL6 receptor (sIL6R) and soluble gp130 (sgp130) in sera of cancer patients  

Microsoft Academic Search

The serum levels of interleukin-6 (IL-6), sIL-6R and sgp130 were investigated in 76 cancer patients in comparison with 28 healthy controls. IL-6 is a multifunctional cytokine involved in certain malignant diseases. Soluble IL-6 receptor as agonist enhances the biological effect of released IL-6. Soluble gp130 as antagonist inhibits the effect of the IL-6\\/sIL-6R complex. Patients with different types of tumour

E Kovacs



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



Thorium(IV) hydrous oxide solubility  

SciTech Connect

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

Ryan, J.L.; Rai, D.



Water soluble pentacene Chandrani Pramanik,a  

E-print Network

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

Müller, Peter


Soluble polymer-supported organic synthesis.  


Soluble polymers have been used as supports for reagent/catalyst immobilization and synthesis. Two polymers are commonly used in this context, linear polystyrene and poly(ethylene glycol). The complementary solubility properties of these polymers allow access to a wide range of chemistries. Parallel and combinatorial libraries of small molecules have been prepared using these polymers, and reagents/catalysts that are easily recovered and recycled have been immobilized on them. To develop soluble polymers with novel properties, bifunctional polymerization initiators have been used in a parallel combinatorial methodology to prepare block copolymers that exhibit unique solubility profiles. PMID:10955985

Toy, P H; Janda, K D



Characterization of a soluble polyimide  

NASA Technical Reports Server (NTRS)

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

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



Enhancement of solubility of dexibuprofen applying mixed hydrotropic solubilization technique.  


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

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



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



Soluble kit receptor in human serum.  


c-kit encodes the transmembrane receptor tyrosine kinase (Kit) for the recently described ligand stem cell factor (SCF). We have developed an enzyme-linked immunosorbent assay for measuring soluble human Kit and we have used the assay to show high levels of soluble Kit in human serum. The distribution of soluble Kit levels was investigated among 112 normal human serum donors. The mean serum level (+/- SD) was found to be 324 +/- 105 ng/mL with the values falling between 163 ng/mL and 788 ng/mL. No correlation between soluble Kit levels and the sexes or ages of the donors was found. Partial purification using immunoaffinity chromatography allowed us to characterize the soluble Kit from pooled human serum. Antibodies generated to a 497-amino acid recombinant human soluble Kit corresponding to the N-terminal extracellular domain of the receptor recognized the serum-derived soluble Kit by immunoblotting. We found that the serum-derived soluble Kit is glycosylated, with mostly N-linked but also O-linked carbohydrate, and with terminal sialic acid residues. When compared with the recombinant human soluble Kit, the serum-derived material was similar both in size and glycosylation pattern. CNBr cleavage of the isolated serum-derived material followed by amino terminal sequencing confirmed the presence of five peptides expected for the extracellular portion of the Kit molecule. The immunoaffinity purified serum-derived soluble Kit inhibited binding of [125I]SCF to membrane-bound receptor in an in vitro assay. These results indicate that soluble Kit could modulate the activity and functions of SCF in vivo. PMID:7528574

Wypych, J; Bennett, L G; Schwartz, M G; Clogston, C L; Lu, H S; Broudy, V C; Bartley, T D; Parker, V P; Langley, K E



Collagen solubility correlates with skin optical  

E-print Network

Collagen solubility correlates with skin optical clearing Jason Hirshburg,a Bernard Choi,b J, biocompatible chemical agents can induce a reversible reduction in optical scatter- ing of collagenous tissues related to its collagen solubility, providing a rational design basis for effective, percutaneous

Choi, Bernard



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


Solubility prediction in octanol: a technical note.  


The purpose of this work was to derive an equation for the rapid estimation of octanol solubilities of organic compounds. Solubilities ranging over 4 orders of magnitude were predicted with an average absolute error of 0.39 logarithmic units using melting point alone. The greatest error in prediction occurred for strongly bonded compounds. PMID:16584157

Sepassi, Kia; Yalkowsky, Samuel H



Water Soluble Vitamins for Dairy Cattle  

Microsoft Academic Search

Research on effects of water soluble vitamins when fed to dairy cows and field supplementation of some water soluble vitamins has increased markedly in the past few years. In research studies, biotin supplementation (20 mg\\/ day) has consistently improved hoof health of cows and often increased milk production. Supplementation of niacin, although common, has little effect on milk production unless

William P. Weiss; Gonzalo Ferreira



Jodimetric estimation of water-soluble dithiocarbamates  

Microsoft Academic Search

Iodimetric estimation of dialkyl dithiocarbamate in alcoholic solution is not accurate. The method has not met with success for the water-soluble dithiocarbamates before. A simple and accurate iodimetric method has been developed for the estimation of water-soluble dithiocarbamates. The success of the method is due to the removal of the oxidation product which interferes during the titration with iodine.

M. L. Shankaranarayana; C. C. Patel



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



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.



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, Mahmoud (Sante Fe, NM)



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, Mahmoud (Sante Fe, NM)



Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility  

PubMed Central

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows lownanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants. PMID:23937980

Bollini, Mariela; Cisneros, Jose A.; Spasov, Krasimir A.



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



Solubility of the sesquiterpene alcohol patchoulol in supercritical carbon dioxide  

PubMed Central

The solubility of the sesquiterpene alcohol patchoulol in supercritical carbon dioxide was measured at P ranging from 10.0 MPa to 25.0 MPa and T of 40.0 and 50.0 °C using a simple microsampling type apparatus with a 100.5 µL sample loop to remove aliquots for off-line analysis. The system was first validated using vanillin with off-line spectrophotometric analysis, then utilized for patchoulol measurements with off-line GC-MS analysis. The measured solubility of patchoulol in supercritical CO2 ranged from mole fractions of 0.43 × 10?3 at 10.0 MPa and 50.0 °C to 9.45 × 10?3 at 25.0 MPa and 40.0 °C. PMID:19424449

Hybertson, Brooks 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



Drosophila Dpp signaling is mediated by the punt gene product: a dual ligand-binding type II receptor of the TGF beta receptor family.  


Signaling by TGF beta-related factors requires ligand-induced association between type I and type II transmembrane serine/threonine kinases. In Drosophila, the saxophone (sax) and thick veins (tkv) genes encode type I receptors that mediate signaling by decapentaplegic (dpp), a member of the bone morphogenetic protein (BMP) subgroup of TGF beta-type factors. In this report, we demonstrate that the Drosophila punt gene encodes atr-II, a previously described type II receptor that on its own is able to bind activin but not BMP2, a vertebrate ortholog of dpp. Mutations in punt produce phenotypes similar to those exhibited by tkv, sax, and dpp mutants. Furthermore, punt will bind BMP2 in concert with tkv or sax, forming complexes with these receptors. We suggest that punt functions as a type II receptors for dpp and propose that BMP signaling in vertebrates may also involve sharing of type II receptors by diverse ligands. PMID:7697720

Letsou, A; Arora, K; Wrana, J L; Simin, K; Twombly, V; Jamal, J; Staehling-Hampton, K; Hoffmann, F M; Gelbart, W M; Massagué, J



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



Solubility of Structurally Complicated Materials: II. Bone  

NASA Astrophysics Data System (ADS)

Bone is a structurally complex material, formed of both organic and inorganic chemicals. The organic compounds constitute mostly collagen and other proteins. The inorganic or bone mineral components constitute predominantly calcium, phosphate, carbonate, and a host of minor ingredients. The mineralized bone is composed of crystals which are closely associated with a protein of which collagen is an acidic polysaccharide material. This association is very close and the protein integrates into the crystalline structure. The mineralization involves the deposition of relatively insoluble crystals on an organic framework. The solubility process takes place when the outermost ions in the crystal lattice breakaway from the surface and become separated from the crystal. This is characteristic for ions dissolving in water or aqueous solutions at the specified temperature. The magnitude of solubility is temperature and pH dependent. Bone is sparingly soluble in most solvents. Enamel is less soluble than bone and fluoroapatite is the least soluble of all apatites in acid buffers. Collagen is less soluble in neutral salt solution than in dilute acid solutions at ambient temperatures. The solubility of collagens in solvents gradually decreases with increasing age of the bone samples.

Horvath, Ari L.



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


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

Microsoft Academic Search

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

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


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 16mg/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 2months 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



Solubility of Injectable Valium in Intravenous Solutions.  

National Technical Information Service (NTIS)

A study of the solubility of Valium in commonly used intravenous solutions showed Valium to be equally insoluble in 5% dextrose in saline, normal saline, and Ringer's lactate. However, the precipitate which was formed became completely resuspended when mi...

M. F. Grower, E. A. Russell, L. Getter




EPA Science Inventory

This report discusses sources, concentrations, characteristics and methods for removal of Soluble Organic Nitrogen (SON) in wastewater. Removal by various physical, chemical and biological processes are described and molecular weight distribution is characterized. A significant p...



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



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




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



Cu and Ni solubility in high-temperature aqueous fluids  

NASA Astrophysics Data System (ADS)

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

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



Soluble levels of cytosolic tubulin regulate ciliary length control  

PubMed Central

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

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



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

PubMed Central

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

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



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.



Preparation, characterization and solubility product constant of AmOHCO/sub 3/  

SciTech Connect

An investigation into the nature and solubility of a stable solid phase formed by a trivalent actinide, /sup 243/Am/sup 3 +/, in dilute aqueous carbonate solutions was conducted. The compound exhibited an x-ray powder diffraction pattern which was nearly identical to that reported for NdOHCO/sub 3/ - type A. The pattern could be indexed in the orthorhombic system with unit cell parameters a = 4.958, b = 8.487, and c = 7.215 A. The steady-state solubility of the compound was determined from the results of both dissolution and precipitation experiments. The average solubility product quotient for 0.1M ionic strength, 25 +- 1/sup 0/C and 1 atmosphere pressure was found to be 583 +- 206. The solubility product constant for zero ionic strength was estimated to be 335 +- 120. 22 references, 3 tables.

Silva, R.J.



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


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

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



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

Microsoft Academic Search

Cyclomaltodextrinases are multidomain and often dimeric proteins from the ?-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

Pernilla Turner; Olle Holst; Eva Nordberg Karlsson



High level soluble production of functional ribonuclease inhibitor in Escherichia coli by fusing it to soluble partners.  


Ribonuclease inhibitor (RI) is a 50-kDa cytosolic scavenger of pancreatic-type ribonucleases which inhibits ribonucleolytic activity. Expression of recombinant RI is extremely difficult to reach high levels in soluble form in the cytoplasm of Escherichia coli. Here, we utilized five N-terminal fusion partners to improve the soluble expression of RI. Among these five fusion partners which have been screened, maltose-binding protein (MBP), N-utilization substance A (NusA) and translation initiation factor 2 domain I (IF2) have greatly improved the soluble expression level of recombinant murine RI under the drive of T7 promoter, while glutathione S-transferase (GST) and small ubiquitin modifying protein (SUMO) were much less efficient. All these RI-fusion proteins remained to be highly active in inhibiting RNase A activity. Furthermore, all fusion tags can be efficiently removed by enterokinase digestion to generate native RI which results the highest yield to date (>30mg of native RI per liter culture). And a convenient two-step immobilized metal affinity chromatography (IMAC) method has been implemented in our study, comparing with the traditional RNase A affinity chromatography method. PMID:21292012

Guo, Wanhua; Cao, Lin; Jia, Zhijun; Wu, Gang; Li, Teng; Lu, Fengxia; Lu, Zhaoxin



Use of Fat-Soluble Fluorescent Brighteners on Microorganisms.  


We have applied a fat-soluble fluorescent aid to certain microorganisms. The aid, a stilbyl triazole compound, fluoresced more in the presence of certain strains of flocculating brewing yeasts than in the presence of nonflocculating types. The work suggested the possibility that flocculating yeasts may possess more surface lipids than the nonflocculating organisms. The performance of the compound on rapidly growing cell centers and bacterial spores is described, and the possible application of the technique to other areas of microbiology is outlined. PMID:17795765

Lycette, R M; Hedrick, L R



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.


Cyclodextrin-water soluble polymer ternary complexes enhance the solubility and dissolution behaviour of poorly soluble drugs. Case example: itraconazole.  


The aim of the present series of experiments was to improve the solubility and dissolution/precipitation behaviour of a poorly soluble, weakly basic drug, using itraconazole as a case example. Binary inclusion complexes of itraconazole with two commonly used cyclodextrin derivatives and a recently introduced cyclodextrin derivative were prepared. Their solubility and dissolution behaviour was compared with that of the pure drug and the marketed formulation Sporanox®. Ternary complexes were prepared by addition of Soluplus®, a new highly water soluble polymer, during the formation of the itraconazole/cyclodextrin complex. A solid dispersion made of itraconazole and Soluplus® was also studied as a control. Solid state analysis was performed for all formulations and for pure itraconazole using powder X-ray diffraction (pX-RD) and differential scanning calorimetry (DSC). Solubility tests indicated that with all formulation approaches, the aqueous solubility of itraconazole formed with hydroxypropyl-?-cyclodextrin (HP-?-CD) or hydroxybutenyl-?-cyclodextrin (HBen-?-CD) and Soluplus® proved to be the most favourable formulation approaches. Whereas the marketed formulation and the pure drug showed very poor dissolution, both of these ternary inclusion complexes resulted in fast and extensive release of itraconazole in all test media. Using the results of the dissolution experiments, a newly developed physiologically based pharmacokinetic (PBPK) in silico model was applied to compare the in vivo behaviour of Sporanox® with the predicted performance of the most promising ternary complexes from the in vitro studies. The PBPK modelling predicted that the bioavailability of itraconazole is likely to be increased after oral administration of ternary complex formulations, especially when itraconazole is formulated as a ternary complex comprising HP-?-CD or HBen-?-CD and Soluplus®. PMID:23201048

Taupitz, Thomas; Dressman, Jennifer B; Buchanan, Charles M; Klein, Sandra



Prediction of aqueous solubility from SCRATCH.  


This study proposes the SCRATCH model for the aqueous solubility estimation of a compound directly from its structure. The algorithm utilizes predicted melting points and predicted aqueous activity coefficients. It uses two additive, constitutive molecular descriptors (enthalpy of melting and aqueous activity coefficient) and two non-additive molecular descriptors (symmetry and flexibility). The latter are used to determine the entropy of melting. The melting point prediction is trained on over 2200 compounds whereas the aqueous activity coefficient is trained on about 1640 compounds, making the model very rigorous and robust. The model is validated using a 10-fold cross-validation on a dataset of 883 compounds for the aqueous solubility prediction. A comparison with the general solubility equation (GSE) suggests that the SCRATCH predicted aqueous solubilities have a slightly greater average absolute error. This could result from the fact that SCRATCH uses two predicted parameters whereas the GSE utilizes one measured property, the melting point. Although the GSE is simpler to use, the drawback of requiring an experimental melting point is overcome in SCRATCH which can predict the aqueous solubility of a compound based solely on its structure and no experimental values. PMID:19819319

Jain, Parijat; Yalkowsky, Samuel H



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

Boyer, Edmond


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

PubMed Central

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

Sareen, Swati; Mathew, George; Joseph, Lincy



Platinum solubility in phosphate laser glass  

SciTech Connect

Microscopic platinum inclusions ({approximately} 10--20 {mu}m), that originate from the melt containers, have been a major cause of optical damage in phosphate laser glasses. One way to eliminate such inclusions is to dissolve them in the glass matrix. The relative solubility of platinum in three commercial phosphate laser glasses is reported. The results show that the lowest Al{sub 2}O{sub 3}-containing phosphate glass has the highest Pt solubility. Moreover, the Pt solubility decreases linearly with increasing, Al{sub 2}O{sub 3} content. Activation energies for Pt dissolution are found to be nearly equivalent for the three glasses. Laser-excited fluorescence of the Pt-ion is reported. 6 refs., 6 figs., 1 tab.

Hayden, Y.T. (Schott Glass Technologies, Inc., Duryea, PA (USA)); Campbell, J.H.; Payne, S.A.; Wilke, G.D. (Lawrence Livermore National Lab., CA (USA))



AW-101 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 AW-101 low-activity waste (LAW) sample. BNFL requested Battelle to dilute the AW-1-1 sample using de-ionized water to mimic expected plant operating conditions. BNFL further requested Battelle to assess the solubility of the solids present in the diluted AW-101 sample versus temperature conditions of 30, 40, and 50 C. BNFL requested these tests to assess the composition of the LAW supernatant and solids versus expected plant-operating conditions. The work was conducted according to test plan BNFL-TP-29953-7, Rev. 0, Determination of the Solubility of LAW Entrained Solids. The test went according to plan, with no deviations from the test plan.

GJ Lumetta; RC Lettau; GF Piepel



Water soluble azo polymers for electronic and photonic applications  

NASA Astrophysics Data System (ADS)

The focus of this dissertation is the design and synthesis of novel water soluble azo polymers and their processing into molecular level multilayer films with unique electronic and optical phenomena. Conjugated main chain azo polymers are expected to exhibit interesting electrical and optical properties. Through an oxidative coupling reaction of 2,5-diaminobenzene sulfonic acid, a high molecular weight, conjugated, main chain azo polymer was synthesized. The polymer was soluble in water and organic solvents such as DMF and DMSO. Two classes of water soluble side chain azo polymers, one epoxy based and the other acrylic acid based, were also synthesized. The polymers were designed to contain ionizable groups in the azo chromophore. All these polymers can be processed in a manner similar to the conventional azo polymers. In addition, the water solubility of the polymers has been utilized in fabricating multilayer films through a recently reported layer-by-layer deposition process. Using the water soluble azo polymers in the ionized form and commercially available oppositely charged polyelectrolytes, multilayers were formed through an alternate deposition process. The azo chromophores in the multilayer films containing the epoxy based azo polymers self-assemble into an acentric arrangement during the deposition process. The films exhibit second order nonlinear optical (NLO) coefficients comparable to the poled, spin coated films of the same polymer. This result indicates that the chromophores in the multilayer films possess the same order of noncentrosymmetric alignment as in the case of the poled films. The self-organization of the chromophores in the multilayer films was confirmed using transmission electron microscopic (TEM) studies. Electron diffraction pattern from the films indicate that the chromophores assemble into a liquid crystal type of order with a d spacing of about 4.7 A. Additional evidence of orientational order was obtained from electroabsorption spectroscopy which is a useful technique in determining the nonlinear optical coefficients ?(3)1133 and ?(3)3333 of NLO films. The ratio ?(3)3333/?(3)1133 is an indication of the orientational order of the relevant chromophore. If the ratio is <3, it indicates that the chromophores lie preferentially in the plane of the film. If the ratio is =3, the film is isotropic. If the ratio is >3, the chromophores are predominantly oriented normal to the plane of the film. The electroabsorption results indicate that in the multilayer films the ratio is about 4, whereas in the spin coated film it is about 1.9. These results collectively indicate that we have achieved acentric ordering of azo NLO chromophores through a simple layer-by-layer deposition process. (Abstract shortened by UMI.)

Balasubramanian, Srinivasan


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



Nitrogen solubility in upper mantle minerals  

NASA Astrophysics Data System (ADS)

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

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



Physicochemical investigation of the effects of water-soluble polymers on vinpocetine complexation with ?-cyclodextrin and its sulfobutyl ether derivative in solution and solid state  

Microsoft Academic Search

The studies reported in this work aimed to elucidate the inclusion complex formation of vinpocetine (VP), a poorly water-soluble base type drug, with ?-cyclodextrin (?CD) and its sulfobutyl ether derivative (sulfobutyl ether ?-cyclodextrin (SBE?CD)), with or without water-soluble polymers (PVP and HPMC), by thoroughly investigating their interactions in solution and solid state. Phase solubility studies were carried out to evaluate

Laura S. S Ribeiro; Domingos C Ferreira; Francisco J. B Veiga



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


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

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



Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties.  


The purpose of this study was to produce a dry powder for inhalation (DPI) of a poorly soluble active ingredient (itraconazole: ITZ) that would present an improved dissolution rate and enhanced solubility with good aerosolization properties. Solid dispersions of amorphous ITZ, mannitol and, when applicable, D-?-tocopherol polyethylene glycol 1000 succinate (TPGS) were produced by spray-drying hydro-alcoholic solutions in which all agents were dissolved. These dry formulations were characterized in terms of their aerosol performances and their dissolution, solubility and physical properties. Modulate differential scanning calorimetry and X-ray powder diffraction analyses showed that ITZ recovered from the different spray-dried solutions was in an amorphous state and that mannitol was crystalline. The inlet drying temperature and, indirectly, the outlet temperature selected during the spray-drying were critical parameters. The outlet temperature should be below the ITZ glass transition temperature to avoid severe particle agglomeration. The formation of a solid dispersion between amorphous ITZ and mannitol allowed the dry powder to be produced with an improved dissolution rate, greater saturation solubility than bulk ITZ and good aerosol properties. The use of a polymeric surfactant (such as TPGS) was beneficial in terms of dissolution rate acceleration and solubility enhancement, but it also reduced aerosol performance. For example, significant dissolution rate acceleration (f(2)<50) and greater saturation solubility were obtained when introducing 1% (w/w) TPGS (mean dissolution time dropped from 50.4 min to 36.9 min and saturation solubility increased from 20 ± 3 ng/ml to 46 ± 2 ng/ml). However, the fine particle fraction dropped from 47 ± 2% to 37.2 ± 0.4%. This study showed that mannitol solid dispersions may provide an effective formulation type for producing DPIs of poorly soluble active ingredients, as exemplified by ITZ. PMID:22414388

Duret, Christophe; Wauthoz, Nathalie; Sebti, Thami; Vanderbist, Francis; Amighi, Karim



Solubility of Fullerenes C60 and C70 in Seven Normal Alcohols and Their Deduced Solubility in Water  

Microsoft Academic Search

The solubilities of C60 and C70 at 25°C in seven normal alcohols obey the relationship InY = a + bX + cX, where Y is solubility and X is the Hildebrand solubility parameter of the solvent. Extrapolation to the solubility parameter of water yields solubilities in water of 1.3?10 (C60) and 1.3?10(C70) ng\\/ml with an uncertainty of one order of

D. Heymann



The Role of Liquid Composition on the Argon Solubility of Silicate Melts  

NASA Astrophysics Data System (ADS)

Interpreting the abundance and ratios of noble gases in magmatic rocks requires an understanding of how these elements behave as a function of pressure, temperature and composition. In particular, knowledge of gas solubilities in the melt phase is critical. Previous studies have concluded that noble gas solubility in silicate melts is a function of ionic porosity, a measure of the 'free space' in the liquid. However, data for simplified synthetic melts such as CMAS do not overlap the trend of solubility as a function of ionic porosity observed for natural liquids. To understand the discrepancies between data for natural and synthetic melts we have determined the argon solubility of 38 liquids in the system NCMAS. The compositions were chosen to cover a wide range in molar silica content, molar Al/Si, average polymerization state, and identity of the cation which charge-balances Al. Beads of liquid, approximately 2 mm in diameter, were held for 24 hours at 1873 K and 1 bar under a flow of pure Ar. After quenching, glass chips typically 1 to 7 mg were analysed using a conventional noble gas mass spectrometer with a Nier type source (VG 5400 at the CRPG, Nancy, France). The gas was released from the chips by melting with a CO2 laser for periods of 1 to 5 minutes. The results confirm that liquid composition significantly affects argon solubility. When our data are considered in isolation, the covaration of argon solubility and ionic porosity is excellent. However, when literature data are added, no clear correlation is apparent. Based upon this observation and consideration of the temperature dependence of argon solubility, it is concluded that ionic porosity is not a universally applicable parameter for predicting noble gas solubility. Two new models for argon solubility are proposed, both employing the notion of partial molar argon solubilities. The model which works best uses tetrahedral rather than oxide units as the melt components, and successfully reproduces reported solubilities for Al-free and Al-bearing synthetic systems as well as data for natural liquids.

Marrocchi, Y.; Toplis, M. J.



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.



Golden rule for buttressing vulnerable soluble proteins.  


Local weaknesses in the structure of soluble proteins have received little attention. The structure may be inherently weak at sites where hydration of the protein backbone is locally hampered by formation of an intramolecular hydrogen bond which in turn is not fully stabilized through burial within a hydrophobic environment. The result is insufficient compensation for the thermodynamic cost of dehydrating the backbone polar groups. This work shows that these structural deficiencies, the unburied backbone hydrogen bonds, are compensated in natural proteins by disulfide bonds that are needed to maintain the structural integrity. Examination of all PDB-reported soluble structures reveals that, after suitable normalization, the number of disulfide bonds, X, correlates tightly with the number of unburied backbone hydrogen bonds, Y, beyond the baseline level Y = 20, revealing a simple balance relation: Y = 5X + 20. This equation introduces a 1:5 ratio associated with the buttressing of soluble proteins with structural deficiencies. The results are justified on thermodynamic grounds and have implications for biomolecular engineering as they introduce two constants of universal applicability determining the architecture of soluble proteins. PMID:20364868

Fernández, Ariel; Berry, R Stephen



Surface shear inviscidity of soluble surfactants  

PubMed Central

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

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



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.



Chemistry Students' Conceptions of Solubility: A Phenomenography.  

ERIC Educational Resources Information Center

Conceptions of (n=13) grade-11 chemistry students via interviews were grouped into 6 categories related to students' preferred explanations for solubility phenomena. Argues that an understanding of the typical conceptions used by students should form an integral component of chemistry teaching, both as points of origin for lesson planning and for…

Ebenezer, Jazlin V.; Erickson, Gaalen L.



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



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)



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)



A condition on finitely generated soluble groups  

Microsoft Academic Search

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

Alireza Abdollahi; Bijan Taeri



Combined Effect of Natural Organic Matter and Surfactants on the Apparent Solubility of Polycyclic Aromatic Hydrocarbons  

Microsoft Academic Search

and the types of ions in solution, as well as other physio- chemical parameters (Schlautman and Morgan, 1993). Both natural organic matter (NOM) and surfactants are known The partitioning of HOCs into dissolved humic sub- to enhance the apparent aqueous solubility of hydrophobic organic contaminants (HOCs) in aqueous systems. In this study, the combined stances parallels the partitioning behavior of

Hyun-Hee Cho; Jaeyoung Choi; Mark N. Goltz; Jae-Woo Park



Separation of Water Soluble Synthetic and Biological Macromolecules by Flow Field-Flow Fractionation  

Microsoft Academic Search

Because of the universal applicability of crossflow as a driving force in field-flow fractionation, flow FFF can be utilized for the separation of most classes of macromoleculcs and particles ranging from less than 1000 molecular weight up to 50 ?.m particle diameter. This paper focuses on water soluble macromoleculcs. Among the various types of macromolecular materials recently separated by flow

J. Calvin Giddings; Maria Anna Benincasa; Min-Kuang Liu; Ping Li



Three-coordinate, luminescent, water-soluble gold(I) phosphine complexes: structural characterization and photoluminescence  

E-print Network

Three-coordinate, luminescent, water-soluble gold(I) phosphine complexes: structural some beautiful work involving gold Abstract The trigonal planar Au(I) complex Cs8[Au(TPPTS)3]Ã?/5.25H2O The photoluminescent properties of several types of three-coordinate gold(I) complexes in organic solvents

Abdou, Hanan E.


Isolation and Characterization of Pepsin-Soluble Collagen from the Skin of Peru Squid (Dosidicus Gigas)  

Microsoft Academic Search

Pepsin-soluble collagen (PSC) was isolated from Peru squid (Dosidicus gigas) skin and physicochemical properties of the PSC were determined. The PSC exhibited a maximum absorbance at 220 nm. Sodium dodecyl sulfate polyacrylamide gel electrophoresis suggested the collagen containing a1 and a2 chain was classified as type I collagen. Amino acid composition indicated that the collagen had lower amino acid content

Wandong Fu; Yan Wang; Bin Zheng; Miaofei Liao; Weijie Zhang



Characterization of water soluble organic matter in soils by size exclusion chromatography and fractionation with polyvinylpyrrolidone  

Microsoft Academic Search

Water extracts were obtained from four types of soils (Brown Lowland soil, Yellow soil with manure application for 6 years, non-allophanic Andosol, and allophanic Andosol), and the organic matter in the water extracts was fractionated according to the solubility in acid and adsorption onto polyvinylpyrrolidone (PVP). For the water extracts and their fractions, the amounts of organic C, total N,

Masakazu Aoyama



Weight Loss Increases Soluble Leptin Receptor Levels and the Soluble Receptor Bound Fraction of Leptin  

Microsoft Academic Search

Objective: Soluble leptin receptor (sOB-R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound\\/free ratio after pronounced weight reduction.Research Methods and Procedures: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass,

Markus Laimer; Christoph F. Ebenbichler; Susanne Kaser; Anton Sandhofer; Helmut Weiss; Hermann Nehoda; Franz Aigner; Josef R. Patsch



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.; Cardenas, J.; Schabes-Retchkiman, P. S.



Preparations and properties of anti-corrosion additives of water-soluble metal working fluids for aluminum alloy materials.  


This short review describes various types of anti-corrosion additives of water-soluble metal working fluids for aluminum alloy materials. It is concerned with synthetic additives classified according to their functional groups; silicone compounds, carboxylic acids and dibasic acids, esters, Diels-Alder adducts, various polymers, nitrogen compounds, phosphoric esters, phosphonic acids, and others. Testing methods for water-soluble metal working fluids for aluminum alloy materials are described for a practical application in a laboratory. PMID:18075217

Watanabe, Shoji



Comparative Chemical Composition of Steam-Distilled and Water-Soluble Essential Oils of South American Marigold (Tagetes minuta L.)  

Microsoft Academic Search

Flowering shoot biomass of feld-grown South American marigold (Tagetes minuta L.) was hydrodistilled in Clevenger-type apparatus, steam-distilled in a feld distillation unit and the distillation water was collected. Chemical profles of hydrodistilled, steam-distilled and water-soluble (recovered from the distillation water of feld distillation unit employing hexane as the solvent) essential oils were analyzed by GC and GC\\/MS. The solubility of

B. R. Rajeswara Rao; P. N. Kaul; A. K. Bhattacharya; D. K. Rajput; K. V. Syamasundar; S. Ramesh



The effect of limited monomer solubility in heterogeneous step-growth polymerization.  


Limited monomer solubility imposes very intriguing features on poly(p-phenylenebenzobisoxazole) polymerization. Only one type of functional group is detected at oligomer chain ends, and a high-molecular-weight polymer is obtained even when an excess of the monomer with low solubility is used. These remarkable phenomena are interpreted as an unprecedented "spoon-feeding-of-monomer" mechanism. A novel apparatus for staged polymerization is described that was triggered by the uniqueness of the heterogeneous step-growth polymerization. Hyperbranched polyesters and a polyurethane/polyethylene blend, which represent two phases in the polymerization process, are also discussed. PMID:11560475

So, Y H



21 CFR 520.88d - Amoxicillin trihydrate soluble powder.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Amoxicillin trihydrate soluble powder. 520...ANIMAL DRUGS § 520.88d Amoxicillin trihydrate soluble powder. (a...Specifications. Each gram contains amoxicillin trihydrate equivalent to 115.4...



Water-soluble benzophenoxazine dyes: syntheses, derivatization and photophysical studies  

E-print Network

A set of three benzophenoxazine dyes, two completely soluble and one partially soluble in aqueous media, has been prepared and their spectroscopic properties examined. These dyes can be used as either donor or acceptor in synthesis of through...

Jose, Jiney




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...


Ethanol effects on apparent solubility of poorly soluble drugs in simulated intestinal fluid.  


Ethanol intake can lead to an unexpected and possibly problematic increase in the bioavailability of druglike compounds. In this work we investigated the effect of ethanol on the apparent solubility and dissolution rate of poorly soluble compounds in simulated intestinal fluid representing a preprandial state. A series of 22 structurally diverse, poorly soluble compounds were measured for apparent solubility and intrinsic dissolution rate (37 °C) in phosphate buffer pH 6.5 (PhB6.5) and fasted state simulated intestinal fluid (FaSSIF, pH 6.5) with and without ethanol at 5% v/v or 20% v/v. The obtained data were used to understand for which molecules ethanol results in an increased apparent solubility and, therefore, may increase the amount of drug absorbed. In FaSSIF20%ethanol 59% of the compounds displayed >3-fold higher apparent solubility than in pure FaSSIF, whereas the effects of 5% ethanol on solubility, in most cases, were negligible. Acidic and neutral compounds were more solubilized by the addition of ethanol than by lecithin/taurocholate aggregates, whereas bases showed a more substance-specific response to the additives in the buffer. The stronger solubilizing capacity of ethanol as compared to the mixed lipid aggregates in FaSSIF was further identified through Spearman rank analyses, which showed a stronger relationship between FaSSIF20%ethanol and PhB6.5,20%ethanol (rS of 0.97) than FaSSIF20%ethanol and FaSSIF (rS of 0.86). No relationships were found between solubility changes in media containing ethanol and single physicochemical properties, but multivariate data analysis showed that inclusion of ethanol significantly reduced the negative effect of compound lipophilicity on solubility. For this data set the higher concentration of ethanol gave a dose number (Do) <1 for 30% of the compounds that showed incomplete dissolution in FaSSIF. Significant differences were shown in the melting point, lipophilicity, and dose profiles between the compounds having a Do < 1 and Do > 1, with the latter having higher absolute values in all three parameters. In conclusion, this study showed that significant effects of ethanol on apparent solubility in the preprandial state can be expected for lipophilic compounds. The results herein indicate that acidic and neutral compounds are more sensitive to the addition of ethanol than to the mixed lipid aggregates present in the fasted intestine. PMID:22651218

Fagerberg, Jonas H; Al-Tikriti, Yassir; Ragnarsson, Gert; Bergström, Christel A S



Comparison of the solubility and pharmacokinetics of sildenafil salts  

Microsoft Academic Search

To develop sildenafil lactate, a salt form of sildenafil with improved solubility and bioavailability of poorly water-soluble\\u000a sildenafil base, this salt form was prepared using a spray dryer. Its solubility and pharmacokinetics in rabbits were evaluated\\u000a compared with sildenafil base and sildenafil citrate. Sildenafil lactate improved the solubility of sildenafil in various\\u000a solvents including distilled water compared with sildenafil citrate.

Si-Young Jung; Youn-Gee Seo; Gun Kook Kim; Jong Soo Woo; Chul Soon Yong; Han-Gon Choi



Solubility of fluoranthene, chrysene, and triphenylene in supercritical carbon dioxide  

SciTech Connect

The solubility of polycyclic aromatic hydrocarbons in supercritical carbon dioxide is very low, and very little experimental data exist. A method has been developed for the measurement of such low solubilities, and the solubilities of fluoranthene, chrysene, and triphenylene in a temperature range 308.15 K to 328.15 K and in a pressure range 84 bar to 251 bar have been determined. The solubilities have been fitted to the excess function-equation of state model.

Barna, L.; Blanchard, J.M. [Inst. National des Sciences Appliques, Villeurbanne (France). Lab. de Chimie Physique Appliquee et Environnement] [Inst. National des Sciences Appliques, Villeurbanne (France). Lab. de Chimie Physique Appliquee et Environnement; Rauzy, E.; Berro, C. [Faculte des Sciences de Luminy, Marseille (France). Lab. de Chimie Physique] [Faculte des Sciences de Luminy, Marseille (France). Lab. de Chimie Physique



Water-soluble polymers as corrosion inhibitors  

Microsoft Academic Search

Purpose – To determine the inhibition efficiency and adsorption characteristics of two water soluble polymers namely polyvinyl alcohol (PVA) and polyethyleneglycol (PGE) as corrosion inhibitors of mild steel in H2SO4. Design\\/methodology\\/approach – The inhibition efficiencies of PVA and PEG were evaluated using the weight loss and hydrogen evolution techniques at 30-60°C. Findings – The inhibition efficiency (I per cent) of

S. A. Umoren; E. E. Ebenso; P. C. Okafor; O. Ogbobe



Biologically derived water soluble conducting polyaniline  

Microsoft Academic Search

An enzymatic, polyelectrolyte (matrix) assisted polymerization of aniline that directly leads to the formation of water soluble, electrically conducting polyaniline is reported. This new biological route is advantageous in that it offers a mild (pH 4–5), benign, one pot synthesis where the desired product requires minimal purification prior to processing. UV-visnear-IR spectroscopy, FTIR, GPC and conductivity measurements all confirm that

W. Liu; A. Anagnostopoulos; F. F. Bruno; K. Senecal; J. Kumar; S. Tripathy; L. Samuelson



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 of lead(II) oxide and copper(II) oxide in subcritical and supercritical water  

SciTech Connect

The solubilities of lead oxide (PbO) and copper oxide (CuO) in subcritical and supercritical water were measured at temperatures from 250 C to 500 C and pressures from 26 MPa to 34 MPa, in a flow-type apparatus. The solubility of lead oxide varied from 351 {micro}mol/kg H{sub 2}O at 424.9 C and 25.9 MPa to 4,406 {micro}mol/kg H{sub 2}O at 350.3 C and 30.2 MPa. The solubility of copper oxide varied from 1.3 {micro}mol/kg H{sub 2}O at 339.8 C and 28.0 MPa to 8.0 {micro}mol/kg H{sub 2}O at 324.9 C and 28.1 MPa. A hydration reaction model was applied to correlate the data.

Sue, Kiwamu; Hakuta, Yukiya; Smith, R.L. Jr.; Adschiri, Tadafumi; Arai, Kunio



Aluminum Solubility in Complex Electrolytes - 13011  

SciTech Connect

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

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



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.



Structure and Aqueous Solubility of Sodium Isosaccharinate  

SciTech Connect

It has been recently shown that isosaccharinic acid, C6H12O6 (ISA), and its derivative salts have a great potential for practical application in the area of nuclear waste treatment and disposal sites management. Several studies demonstrated the effect of ISA complexation on radionuclide solubility and sorptive properties, especially on actinides in (+4) oxidation state like Np(IV) and Th(IV). The presence of ISA and/or its derivatives strongly affects the migration of radionuclides by increasing their solubility in water by several orders of magnitude and Na-ISA has been proposed as a component of decontamination formulations for actinide-contaminated surfaces. Here we report the synthesis, crystal's structure and characterization (FTIR, TGA) of sodium isosaccharate, NaC6H11O6-H2O (Na-ISA). The structure has been solved by single crystal X-ray diffraction methods. The solubility of Na-ISA has been evaluated and compared to that of Ca-ISA based on the structural features of both compounds.

Bontchev, Ranko P.; Moore, Robert; Tucker, Mark; Holt, Kathleen



Effect of sodium gluconate on the solubility of calcium lactate  

Microsoft Academic Search

Calcium and lactate are present in excess of their solubility in Cheddar cheese. Consequently, calcium lactate crystals (CLC) are a common defect in Cheddar cheese. A novel approach for preventing CLC is the addition of sodium gluconate. Sodium gluconate has the potential to increase the solubility of calcium and lactate by forming soluble complexes with calcium and lactate ions, and

C. Phadungath; L. E. Metzger



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


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.



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


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



E-print Network

NICKEL SOLUBILITY AND PRECIPITATION IN SOILS: A THERMODYNAMIC STUDY EDWARD PELTIER 1 on these thermodynamic data indicated that the formation of LDH phases on soil mineral substrates decreased Ni solubility compared to Ni(OH)2 over pH 5ÿ9 when soluble Al is present in the soil substrate. Over time, both

Sparks, Donald L.


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



E-print Network

HANSEN SOLUBILITY PARAMETERS FOR A CARBON FIBER/EPOXY COMPOSITE Hélène Launay* , Charles Medom assigned Hansen solubility (cohesion) parameters (HSP) by analysis of their interactions with a set of well Laboratory, Roskilde, Denmark #12;Launay, Hansen, Almdal analysis of the mechanical tests. Hansen solubility



E-print Network

LOCAL SOLUBILITY AND HEIGHT BOUNDS FOR COVERINGS OF ELLIPTIC CURVES T.A. FISHER AND G.F. SILLS efficient algorithms for testing local solubility and modify the classical formulae for the covering maps so- culation computes equations for the everywhere locally soluble n-coverings of E. Finding rational points

Fisher, Tom


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.


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



E-print Network


Venkataraman, Dhandapani "DV"


Solubility of fluoranthene, chrysene, and triphenylene in supercritical carbon dioxide  

Microsoft Academic Search

The solubility of polycyclic aromatic hydrocarbons in supercritical carbon dioxide is very low, and very little experimental data exist. A method has been developed for the measurement of such low solubilities, and the solubilities of fluoranthene, chrysene, and triphenylene in a temperature range 308.15 K to 328.15 K and in a pressure range 84 bar to 251 bar have been

Ligia Barna; Jean-Marie Blanchard; Evelyne Rauzy; Charles Berro



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:



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

Microsoft Academic Search

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

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



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

USGS Publications Warehouse

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

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



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

SciTech Connect

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

Barney, G.S.



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.


Serum Levels of Soluble IL-2R, CD4 and CD8 in Chronic Active HCV Positive Hepatitis  

PubMed Central

The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation ofthe immune system, in patients with histologically verified chronic active hepatitis associated to hepatitis C virus infection, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD8 were found in patients with chronic active hepatitis compared with controls. In contrast no difference was found for soluble CD4 values in the two groups. No correlations were found for both sIL-2R and sCD8 and these two molecules with other parameters of liver function. These results indicate that in these patients there is a general activation of the immune system, but the lack of correlation with parameters of liver function strengthens the suggestion that this activation does not play a role in the pathogenesis of chronic type C hepatitis. PMID:18472940

Candore, G.; Cigna, D.; Tripi, S.; Di Gaetano, G.; Migneco, G.; Montalto, G.; Ruggieri, I.; Notarbartolo, A.



Rapid Determination of Water-Soluble and Fat-Soluble Vitamins in Commercial Formulations by MEEKC  

Microsoft Academic Search

Microemulsion electrokinetic capillary chromatography has been successfully applied to the separation and determination of\\u000a water-soluble vitamins (thiamine hydrochloride, riboflavin, niacin, pyridoxine hydrochloride, folic acid, cobalamin, ascorbic\\u000a acid) and a fat-soluble vitamin (?-tocopherol acetate). The optimal microemulsion buffer contained sodium dodecylsulfate (SDS)\\u000a as surfactant, butan-1-ol as the co-surfactant, ethyl acetate as the oil and pH 9.2 tetraborate buffer, modified with 15%

María S. Aurora-Prado; Claudinei A. Silva; Marina F. M. Tavares; Kevin D. Altria



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

E-print Network

cel I wai ls, or the protoplasmic fraction against chal lenge with 700 arthrospores. In an attempt to isolate the component(s) which confer ed immuno- protection with cel I waf Is, Pappagianis et al . (39) extracted spherule cel I wal... was removed by centrifugation and the supernat- ant (containing C-ASWS-M) was f i itered again through a Mi I I i pore membrane, then lyophil Ized and stored at -20 C. C-ASWS-S, the alkali-soluble, water-soluble cel I wai I antigen derived from spherules...

Lecara, Grace




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.


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



Modelling of oxygen solubility in titanium  

SciTech Connect

The purpose of this work is to present a thermodynamic modeling of oxygen solubility data of metallic and liquid titanium and also of thermodynamic data of titanium alloys not applied up to now for such a work. In view of focusing this work on the metallic part of the system Ti-O an attempt will be made to use fewer model parameters in comparison with previous studies, where the thermodynamics of titanium oxides were also involved. Sublattice models are chosen taking structural features of the bcc and hcp titanium solid solutions into consideration. Since higher oxygen content increases the ionic character in he liquid phase an associate model is used.

Waldner, P. [Montauniversitaet Leoben (Austria). Institut fuer Physikalische Chemie] [Montauniversitaet Leoben (Austria). Institut fuer Physikalische Chemie



Soluble N-Substituted Organosilane Polybenzimidazoles  

SciTech Connect

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

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



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.

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



Water soluble sapphyrins: potential fluorescent phosphate anion sensors.  


As part of an ongoing effort to study the anion binding properties of sapphyrins in various media, a number of previously reported water solubilized sapphyrins were studied in methanol and in buffered, neutral aqueous solutions and found to undergo self-aggregation under these solution phase conditions. The nature of the species produced as the result of self-aggregation and the processes leading to their formation were studied via UV-vis absorbance and fluorescence spectroscopy. In previous work (V. Král, H. Furuta, K. Shreder, V. Lynch, and J. L. Sessler, J. Am. Chem. Soc. 1996, 118 1595-1607) it was found that the addition of phosphate-type anions to water soluble sapphyrins at pH 6.1 gives rise to visible spectroscopic changes consistent with the binding to the aggregated form and the concurrent formation of an anion-bound dimer with effective equilibrium constants on the order of 100-300 M(-1). In this study we show that at high phosphate-to-sapphyrin ratios in neutral, buffered aqueous solutions further deaggregation occurs to produce an anion-bound monomeric form. This highly fluorescent species is formed with effective equilibrium constants on the order of 6-19 M(-1) leading to considerations that sapphyrins could function as fluorescent phosphate anion sensors. In an effort to modulate the deaggregation properties, several new sapphyrin derivatives bearing two meso aryl substituents were prepared and studied. The aggregation properties of these latter systems were analyzed in methanol and, in the case of one water solublized system, in neutral aqueous media. In analogy to what was observed for the beta-alkyl substituted sapphyrins, H-type aggregates were seen for the water solubilized meso-substituted system in aqueous media. However, in contrast to the H-type dimers seen in the case of the meso-free systems in methanol, J-type dimers were observed in the case of the sapphyrins bearing two meso substituents in this solvent. The effective dimerization constants of several of the meso-diaryl sapphyrins were determined in methanol as were their pKa values in aqueous media. The solid state structure of the bis HBr salt of one of the meso-diaryl sapphyrins, specifically 10,15-bis(3,5-di-tert-butylphenyl)-3,22-diethyl-2,23-dimethylsapphyrin, was also determined and found to show elements in common with those of previously reported sapphyrin derivatives. In particular, the two counter anions were found to be hydrogen bound above and below the diprotonated sapphyrin plane. PMID:14664401

Sessler, Jonathan L; Davis, Julian M; Král, Vladimir; Kimbrough, Thomas; Lynch, Vincent



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.

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



Selective Water-Soluble Gelatinase Inhibitor Prodrugs  

PubMed Central

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

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



Solubility modeling of refrigerant/lubricant mixtures  

SciTech Connect

A general model for predicting the solubility properties of refrigerant/lubricant mixtures has been developed based on applicable theory for the excess Gibbs energy of non-ideal solutions. In our approach, flexible thermodynamic forms are chosen to describe the properties of both the gas and liquid phases of refrigerant/lubricant mixtures. After an extensive study of models for describing non-ideal liquid effects, the Wohl-suffix equations, which have been extensively utilized in the analysis of hydrocarbon mixtures, have been developed into a general form applicable to mixtures where one component is a POE lubricant. In the present study we have analyzed several POEs where structural and thermophysical property data were available. Data were also collected from several sources on the solubility of refrigerant/lubricant binary pairs. We have developed a computer code (NISC), based on the Wohl model, that predicts dew point or bubble point conditions over a wide range of composition and temperature. Our present analysis covers mixtures containing up to three refrigerant molecules and one lubricant. The present code can be used to analyze the properties of R-410a and R-407c in mixtures with a POE lubricant. Comparisons with other models, such as the Wilson or modified Wilson equations, indicate that the Wohl-suffix equations yield more reliable predictions for HFC/POE mixtures.

Michels, H.H.; Sienel, T.H.



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


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

Yuvaraja, K; Khanam, Jasmina



Characteristics of water-soluble fiber manufactured from carboxymethylcellulose synthesis  

Microsoft Academic Search

Carboxymethylcellulose (CMC), which is water-soluble fiber at room temperature, was manufactured from cellulose in this study.\\u000a Experimental parameters included reaction temperature, time, concentration of NaOH, and monochloroacetic acid. In mercerization\\u000a and etherification, the solubility and DS increased when NaOH (or MCA) concentration increased, and maximum solubility and\\u000a DS were achieved when NaOH or MCA was 30%. The effect of MCA

Youngmin Choi; Sanjeev Maken; Seungmoon Lee; Euihyun Chung; Byoungryul Min



Fractionation of Potato Proteins: Solubility, Thermal Coagulation and Emulsifying Properties  

Microsoft Academic Search

Water-soluble potato proteins were extracted and an acidic and a basic fraction were isolated by ion-exchange chromatography. The acidic fraction contained mainly patatin (67%), the major soluble protein of potato tubers. The basic fraction contained the 20–25-kDa proteins family (64%) and a 16-kDa polypeptide (22%), probably corresponding to the protease inhibitor potato II. Functionality as pH–solubility curves, thermocoagulation sensitivity, kinetics

Marie-Christine Ralet; Jacques Guéguen



Solubility of ruthenium dioxide in lead borosilicate glasses  

Microsoft Academic Search

The solubility of RuOâ in a lead borosilicate glass was measured in the range of 700° to 1000°C. The effect of dissolved alumina in the glass was studied in the same range using 2%, 4%, 6%, and 10% dissolved alumina. The solubility showed an exponential dependence on temperature, and the dissolved alumina decreased the solubility at any given temperature; however,

P. Polanisamy; Dwadasi H. R. Sarma; Robert W. Vest



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

Microsoft Academic Search

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

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



Interaction of water-soluble vitamins with a new HPLC stationary phase based on zinc phthalocyanate  

Microsoft Academic Search

The adsorption of water-soluble vitamins on the surface of Diaspher-110-C18 sorbent modified with zinc octa-4,5-carboxyphthalocyanate is studied. Adsorption isotherms are constructed and calculated\\u000a by the Glücauf method at 20°C. It is established that the shape of the isotherms depends on the nature of vitamins and their\\u000a structure: the isotherm of vitamin C is a Henry-type isotherm, the isotherms of vitamins

S. M. Matusova; G. D. Brykina; O. A. Shpigun



Study of the Behavior of Water-Soluble Vitamins in HILIC on a Diol Column  

Microsoft Academic Search

An effort has been made to investigate the chromatographic behavior and to understand the basic mechanisms in HILIC-based\\u000a separation of water-soluble vitamins with highly varied properties on a diol column. The water content of the mobile phase\\u000a is of utmost importance because it directly affects the type and extent of interactions of the solutes with the stationary\\u000a phase and with

Andreas E. Karatapanis; Yiannis C. Fiamegos; Constantine D. Stalikas



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


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

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



Rare earth and yttrium phosphate solubilities in aqueous solution  

NASA Astrophysics Data System (ADS)

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

Liu, Xuewu; Byrne, Robert H.



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)



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.




SciTech Connect

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

Per Redelius



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



Soluble pig for radioactive waste transfer lines  

SciTech Connect

Flushing transfer pipe after radioactive waste transfers generates thousands of gallons of additional radioactive waste each year at the Hanford site. The use of pneumatic pigging with waste soluble pigs as a means to clear transfer piping may be an effective alternative to raw water flushes. A feasibility study was performed by a group of senior mechanical engineering students for their senior design project as part of their curriculum at Washington State University. The students divided the feasibility study into three sub-projects involving: (1) materials research, (2) delivery system design, and (3) mockup fabrication and testing. The students screened through twenty-three candidate materials and selected a thermoplastic polymer combined 50:50 wt% with sucrose to meet the established material performance criteria. The students also prepared a conceptual design of a remote pneumatic delivery system and constructed a mockup section of transfer pipe for testing the prototype pigs.

Ohl, P.C., Westinghouse Hanford



A Census of Human Soluble Protein Complexes  

PubMed Central

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

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



Material characterization of porcine lenticular soluble proteins.  


The soluble proteins present in the ocular lens impart important optical and dynamic mechanical properties on the lens. The short-range order of crystallin proteins grants transparency to a very concentrated protein solution. This unique protein system directly enables proper visual function of the eye. These proteins were investigated in steady and oscillatory shear. Steady shear data were fitted with a modified Herschel-Bulkley yield stress model that allows for a Newtonian plateau at low shear rates. The Cox-Merz rule was used in conjunction with large amplitude oscillatory shear to give insight into the degradation of the fluid structure with increasing strain. The shear thinning viscoelastic behavior of these proteins gives rise to beneficial mechanical properties and results from the same short-range order granting optical transparency. PMID:18471013

Reilly, Matthew A; Rapp, Brian; Hamilton, Paul D; Shen, Amy Q; Ravi, Nathan



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


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

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



Improving the solubility of ampelopsin by solid dispersions and inclusion complexes.  


The aim of this study was to increase the solubility of ampelopsin (AMP) in water by two systems: solid dispersions with polyethylene glycol 6000 (PEG 6000) or polyvinylpyrrolidone K-30 (PVP K30) and inclusion complexes with beta-cyclodextrin (BCD) and hydroxypropyl-beta-cyclodextrin (HPBCD). The interaction of AMP with the hydrophilic polymers was evaluated by differential scanning calorimetry (DSC), Fourier transformation-infrared spectroscopy (FTIR), scanning electron microscopy (SEM). The results from DSC, FTIR and SEC analyses of solid dispersions and inclusion complexes showed that AMP might exist as an amorphous state or as a solid solution. On the other hand, the SEM images of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The influence of various factors (pH, temperature, type of polymer, ration of the drug to polymer) on the solubility and dissolution rate of the drug were also evaluated. The solubility and dissolution rates of AMP were significantly increased by solid dispersions and cyclodextrin complexes as well as their physical mixtures. The improvement of solubility using polymers was in the following order: HPBCD approximately BCD>PVP K30>PEG 6000. PMID:15925247

Ruan, Li-Ping; Yu, Bo-Yang; Fu, Guang-Miao; Zhu, Dan-Ni



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



A water-soluble luminescence oxygen sensor.  


We developed a water-soluble luminescent probe for dissolved oxygen. This probe is based on (Ru[dpp(SO3Na)2]3) cl2, which is a sulfonated analogue of the well-known oxygen probe (Ru[dpp]3)cl2. The compound dpp is 4,7-diphenyl-1,10-phenanthroline and dpp(SO3Na)2 is a disulfonated derivative of the same ligand. In aqueous solution in the absence of oxygen (Ru[dpp(SO3Na)2]3)cl2 displays a lifetime of 3.7 microseconds that decreases to 930 ns on equilibrium with air and 227 ns on equilibrium with 100% oxygen. The Stern-Volmer quenching constant is 11,330 M-1. This high oxygen-quenching constant means that the photoluminescence of Ru(dpp[SO3Na]2)3cl2 is 10% quenched at an oxygen concentration of 8.8 x 10(-6) M, or equilibration with 5.4 torr of oxygen. The oxygen probe dissolved in water displays minimal interactions with lipid vesicles composed of dipalmityl-L-alpha-phosphatidyl glycerol but does appear to interact with human serum albumin. The absorption maximum near 480 nm, long lifetime and large Stokes' shift allow this probe to be used with simple instrumentation based on a light-emitting diode light source, allowing low-cost oxygen sensing in aqueous solutions. To the best of our knowledge this is the first practical water-soluble oxygen sensor. PMID:9487796

Castellano, F N; Lakowicz, J R



Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations.  


The purpose of the present research work was to observe the effects of drug solubility on their release kinetics of water soluble verpamil hydrochloride and insoluble aceclofenac from hydrophilic polymer based matrix formulations. Matrix formulations were prepared by the direct compression method. The formulations were evaluated for various physical parameters. Along with the dynamics of water uptake and erosion, SEM and in vitro drug release of the tablets were studied. Applying an exponential equation, it was found that the kinetics of soluble drug release followed anomalous non-Fickian diffusion transport whereas insoluble drug showed zero-order release. SEM study showed pore formation on the tablet surface that differed depending on drug solubility. t-Test pointed to a significant difference in amount of both drugs released due to the difference in solubility. Solubility of the drug effects kinetics and the mechanism of drug release. PMID:19819827

Chakraborty, Santanu; Khandai, Madhusmruti; Sharma, Anuradha; Patra, Ch Niranjan; Patro, V Jagannath; Sen, Kalyan Kumar



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

PubMed Central

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

Syed, Neeraja; Kim, Haesun A.



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

Microsoft Academic Search

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

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



Prediction of aqueous solubility of organic compounds by the general solubility equation (GSE).  


The revised general solubility equation (GSE) is used along with four different methods including Huuskonen's artificial neural network (ANN) and three multiple linear regression (MLR) methods to estimate the aqueous solubility of a test set of the 21 pharmaceutically and environmentally interesting compounds. For the selected test sets, it is clear that the GSE and ANN predictions are more accurate than MLR methods. The GSE has the advantages of being simple and thermodynamically sound. The only two inputs used in the GSE are the Celsius melting point (MP) and the octanol water partition coefficient (K(ow)). No fitted parameters and no training data are used in the GSE, whereas other methods utilize a large number of parameters and require a training set. The GSE is also applied to a test set of 413 organic nonelectrolytes that were studied by Huuskonen. Although the GSE uses only two parameters and no training set, its average absolute errors is only 0.1 log units larger than that of the ANN, which requires many parameters and a large training set. The average absolute error AAE is 0.54 log units using the GSE and 0.43 log units using Huuskonen's ANN modeling. This study provides evidence for the GSE being a convenient and reliable method to predict aqueous solubilities of organic compounds. PMID:11604020

Ran, Y; Jain, N; Yalkowsky, S H



Apparatus automatically measures soluble residue content of volatile solvents  

NASA Technical Reports Server (NTRS)

Solvent Purity Meter /SPM/ automatically measures the soluble residue in volatile solvents used in cleaning or extraction of oils, greases, and other nonvolatile materials. The SPM gives instantaneous and continuous readout of soluble contaminant residues in concentrations as low as one part per million of solution.

Oswalt, F. W.



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




E-print Network

URANIUM PROJECT WATER-SOLUBLE SUBSTANCES IN KVANEFJELD LUJAVRITE NOVEMBER 1982 Emil S0rensen #12;I Water-soluble substances in Kvanefield lujavrite Introduction In the first description the water extractable material. During storage some of the cores grew whiskers of an alkaline substance


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.



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.



Human soluble epoxide hydrolase: Structural basis of inhibition by  

E-print Network

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

Hammock, Bruce D.


Solubility of sodium soaps in aqueous salt solutions  

Microsoft Academic Search

The solubility of sodium soaps in dilute aqueous salt solutions has been systematically investigated by direct visual phase behavior observations. The added electrolytes, including simple inorganic salts and bulky organic salts, influence the solubility of sodium soaps in water, as represented by the varied soap Krafft point. Two inorganic salts, sodium chloride and sodium perchlorate, demonstrate a “salting-out” property. On

Bin Lin; Alon V. McCormick; H. Ted Davis; Reinhard Strey



Effects of Acetate Buffer Concentration on Lysozyme Solubility.  

National Technical Information Service (NTIS)

The micro-solubility column technique was employed to systematically investigate the effects of buffer concentration on tetragonal lysozyme solubility. While keeping the NaCl concentrations constant at 2%, 3%, 4%, 5% and 7%, and the pH at 4.0, we have stu...

E. L. Forsythe, M. L. Pusey



The Differential Cytotoxicity of Water-Soluble Fullerenes  

E-print Network

The Differential Cytotoxicity of Water-Soluble Fullerenes Christie M. Sayes, John D. Fortner, Wenh, 2004 ABSTRACT We show that the cytotoxicity of water-soluble fullerene species is a sensitive function of surface derivatization; in two different human cell lines, the lethal dose of fullerene changed over 7

Tao, Yizhi Jane


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"


Solubility enhancement of phenol and phenol derivatives in perfluorooctyl bromide.  


Perfluorinated solvents are gaining popularity as pulmonary ventilation fluids, but they suffer from poor solvent quality in concurrent drug delivery applications. The present study examines the use of a hydrophobic solubilizing agent capable of interacting with model drug solutes by hydrogen bonding with the purpose of enhancing solubility in perfluorooctyl bromide (PFOB). A series of solubilizing agents containing a ketone carbonyl to act as a hydrogen bond acceptor and a perfluoroalkyl chain to maintain the solubility of the putative complex in PFOB are investigated. The solubility of phenol in PFOB is enhanced to the greatest extent by 1-(4-perfluorobutyl phenyl)-1-hexanone (III) where the ketone carbonyl is protected from the electron withdrawing effects of the perfluorobutyl chain by a phenyl ring. Experiments with solubilizers lacking the ketone group suggest that pi-pi bond interactions of III with phenol do not significantly enhance solubility. For a series of phenol derivatives, a rank-order correlation exists between the magnitude of solubility enhancement by III, as reflected by the calculated association constants, and the Hammett sigma parameter of the phenols. Because the O-methyl-substituted phenols do not have the ability to hydrogen bond, their solubility is not enhanced by the presence of III. The results of the present study indicate that solubility of model drug hydrogen bond donating compounds can be enhanced in PFOB by the presence of fluorocarbon-soluble hydrogen bond acceptors. PMID:10189271

Williams, T D; Jay, M; Lehmler, H J; Clark, M E; Stalker, D J; Bummer, P M



Microbial respiration activities related to sequentially separated, particulate and water-soluble organic matter fractions from arable and forest topsoils  

Microsoft Academic Search

This study aimed to reveal differences in the relevance of particulate as well as water-soluble organic matter (OM) fractions from topsoils to the easily biodegradable soil organic matter (SOM). We selected eight paired sites with quite different soil types and soil properties. For each of these sites, we took samples from adjacent arable and forest topsoils. Physically uncomplexed, macro-, and

M. Kaiser; S. Wirth; R. H. Ellerbrock; M. Sommer



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


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

Kumar, Sunny; Tummala, Hemachand



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



Development of an ALK2-biased BMP type I receptor kinase inhibitor  

PubMed Central

The bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and in the normal and pathophysiologic remodeling of tissues. Small molecule inhibitors of the BMP receptor kinase family have been useful for probing physiologic functions of BMP signaling in vitro and in vivo, and may have roles in the treatment of BMP-mediated diseases. Here we describe the development of a selective and potent inhibitor of the BMP type I receptor kinases, LDN-212854, which in contrast to previously described BMP receptor kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the closely related TGF-? and Activin type I receptors. In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity and function. LDN-212854 potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva. These findings represent a significant step towards developing selective inhibitors targeting individual members of the highly homologous BMP type I receptor family. Such inhibitors would provide greater resolution as probes of physiologic function, and improved selectivity against therapeutic targets. PMID:23547776

Mohedas, Agustin H.; Xing, Xuechao; Armstrong, Kelli A.; Bullock, Alex N.; Cuny, Gregory D.; Yu, Paul B.



Tetragonal Chicken Egg White Lysozyme Solubility in Sodium Chloride Solutions  

NASA Technical Reports Server (NTRS)

The solubility of chicken egg white lysozyme, crystallized in the tetragonal form was measured in sodium chloride solutions from 1.6 to 30.7 C, using a miniature column solubility apparatus. Sodium chloride solution concentrations ranged from 1 to 7% (w/v). The solutions were buffered with 0.1 M sodium acetate buffer with the solubility being measured at pH values in 0.2 pH unit increments in the range pH 4.0 to 5.4, with data also included at pH 4.5. Lysozyme solubility was found to increase with increases in temperature and decreasing salt concentration. Solution pH has a varied and unpredictable effect on solubility.

Forsythe, Elizabeth L.; Judge, Russell A.; Pusey, Marc L.



Sparingly soluble pesticide dissolved in ionic liquid aqueous.  


Ionic liquids may be considered as "environment-friendly solvents" for sparingly soluble pesticides. In this study, a series of aqueous ionic liquids (ILs) with different cations and different anions was used as environment-friendly alternative to harmful organic solvents sparingly dissolved in soluble pesticides (metolachlor, acetochlor, clethodim, thiamethoxam, and prochloraz). The aggregation behavior of aqueous ILs was investigated through surface tension measurement. Minimum area per IL molecule (Amin) values from the surface tension measurement showed that alkyl chain length and the halide anions strongly affect the aggregation behavior of ILs and the solubilization of pesticides. The solubility of metolachlor, acetochlor, clethodim, thiamethoxam, nitenpyram, and prochloraz in aqueous ILs increased. More importantly, the solubility of prochloraz in [C10mim][I] became 5771-fold higher than that in pure water. The substantially enhanced solubility of the above pesticides proved that aqueous ILs are promising environment-friendly solvents for pesticides that are commercially processed in emulsifiable concentrate (EC) formulation. PMID:25222470

Fan, Tengfei; Wu, Xuemin; Peng, Qingrong



Water-soluble metal working fluids additives derived from the esters of acid anhydrides with higher alcohols for aluminum alloy materials.  


Water-soluble metal working fluids are used for processing of aluminum alloy materials. This short article describes properties of new additives in water-soluble metal working fluids for aluminum alloy materials. Many half esters or diesters were prepared from the reactions of higher alcohols with acid anhydrides. Interestingly, diesters of PTMG (tetrahydrofuran oligomer, MW = 650 and 1000) and polybutylene oxide (MW = 650) with maleic anhydride and succinic anhydride showed both of an excellent anti-corrosion property for aluminum alloy and a good hard water tolerance. The industrial soluble type processing oils including these additives also showed anti-corrosion property and hard water tolerance. PMID:17898514

Yamamoto, Syutaro; Tomoda, Hideyuki; Watanabe, Shoji



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



Studies on Polymerization Activities by Soluble Catalysts Based on Compounds of Organotransition Metals and Aluminum Alkyls  

Microsoft Academic Search

Polymerization activities of the soluble Ziegler-type of catalyst systems, Ti(OR)4-AlEt3, Ti(NEt2)4-AlMe3, and V(NEt2)4-AlEt3, were investigated. In the catalyst system of Ti(OR)4-AlEt3, formation of two types of Ti(III) compounds, i.e., Ti(OR)2Et and its bridged complex with aluminum alkyl, was confirmed by IR and ESR measurements. With the addition of donor molecule to the system, it was found that the polymer yield

Naoyuki Koide; Kazuyoshi Iimura; Masatami Takeda



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



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


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

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



On the efficiency of water soluble antioxidants.  


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

Elia, Paz; Azoulay, Amnon; Zeiri, Yehuda



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.



Adjuvant and immunostimulating activities of water-soluble substances extracted from Mycobacterium tuberculosis (var. hominis).  


Water-soluble substances have been extracted from two strains of Mycobacterium tuberculosis var. hominis: the native hydrosoluble part (polysaccharide and peptidoglycan), a substance in which the polysaccharide moiety is less abundant than in the latter, the acetylated peptidoglycan and, finally a tetrasaccharide-heptapeptide. All four types of substances, when they were injected together with Freund's incomplete adjuvant, exerted an adjuvant effect on the production of delayed-type hypersensitivity to ovalbumin in the guinea pig and on the production of anti-influenza virus antibodies in the rabbit. Injected intravenously in the mouse, they increased the number of antibody-producing cells in the spleen and enhanced the graft versus host reaction; no effect was seen on the phagocytic activity of the reticulo-endothelial system. By contrast with wax D, the water-soluble substances were devoid of arthritis-inducing activity in the rat. Altogether, these water-soluble substances seem to be endowed with at least some of the adjuvant activities of Freund's complete adjuvant and some of the immunostimulant activities of a live Mycobacterium like BCG. PMID:4166

Werner, G H; Maral, R; Floch, F; Migliore-Samour, D; Jollès, P



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


Vertically averaged approaches for CO2 migration with solubility trapping  

NASA Astrophysics Data System (ADS)

The long-term storage security of injected carbon dioxide (CO2) is an essential component of geological carbon sequestration operations. In the postinjection phase, the mobile CO2 plume migrates in large part because of buoyancy forces, following the natural topography of the geological formation. The primary trapping mechanisms are capillary and solubility trapping, which evolve over hundreds to thousands of years and can immobilize a significant portion of the mobile CO2 plume. However, both the migration and trapping processes are inherently complex, spanning multiple spatial and temporal scales. Using an appropriate model that can capture both large- and small-scale effects is essential for understanding the role of these processes on the long-term storage security of CO2 sequestration operations. Traditional numerical models quickly become prohibitively expensive for the type of large-scale, long-term modeling that is necessary for characterizing the migration and immobilization of CO2 during the postinjection period. We present an alternative modeling option that combines vertically integrated governing equations with an upscaled representation of the dissolution-convection process. With this approach, we demonstrate the effect of different modeling choices for typical large-scale geological systems and show that practical calculations can be performed at the temporal and spatial scales of interest.

Gasda, S. E.; Nordbotten, J. M.; Celia, M. A.



Molecular dissection of mouse soluble guanylyl cyclase alpha1 promoter.  


Soluble guanylyl cyclase (sGC) is the only known receptor for nitric oxide (NO) and is downregulated in aging and hypertension. Little is known about sGC gene transcriptional regulation. In order to characterize the sGC transcriptional system, we cloned and sequenced the 5(') flanking region of mouse sGC alpha(1) gene (AY116663). Structurally, it is a non-canonical TATA-less promoter that we mapped to chromosome 3 with many putative regulation sites for Sp-1, NF-kappaB, and AP-1 transcription factors amongst others, and two (TG:CA)(n) dinucleotide microsatellites near the transcriptional start point. The cloned upstream sequence produced a 5-fold increase in luciferase activity in Cos7, HeLa, NIH3T3, and 293 cells as well as in mouse VSMC-like kidney mesangial cells. In the latter cell type, we showed that sGC alpha(1) promoter activity was dependent on the presence of its 5(') unstranslated region (5(')UTR). PMID:14715267

Vazquez-Padron, Roberto I; Pham, Si M; Pang, Manhui; Li, Sen; Aïtouche, Abdelouahab



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



Interaction of Phenol-Soluble Modulins with Phosphatidylcholine Vesicles  

PubMed Central

Several members of the staphylococcal phenol-soluble modulin (PSM) peptide family exhibit pronounced capacities to lyse eukaryotic cells, such as neutrophils, monocytes, and erythrocytes. This is commonly assumed to be due to the amphipathic, ?-helical structure of PSMs, giving PSMs detergent-like characteristics and allowing for a relatively non-specific destruction of biological membranes. However, the capacities of PSMs to lyse synthetic phospholipid vesicles have not been investigated. Here, we analyzed lysis of synthetic phosphatidylcholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC) vesicles by all Staphylococcus aureus and S. epidermidis PSMs. In addition, we investigated the lytic capacities of culture filtrates obtained from different S. aureus PSM deletion mutants toward POPC vesicles. Our results show that all staphylococcal PSMs have phospholipid vesicle-lysing activity and the capacity of S. aureus culture filtrate to lyse POPC vesicles is exclusively dependent on PSMs. Notably, we observed largely differing capacities among PSM peptides to lyse POPC vesicles. Interestingly, POPC vesicle-lytic capacities did not correlate with those previously seen for the lysis of eukaryotic cells. For example, the ?-type PSMs were strongly lytic for POPC vesicles, but are known to exhibit only very low lytic capacities toward neutrophils and erythrocytes. Thus our results also suggest that the interaction between PSMs and eukaryotic membranes is more specific than previously assumed, potentially depending on additional structural features of those membranes, such as phospholipid composition or yet unidentified docking molecules.

Duong, Anthony C.; Cheung, Gordon Y. C.; Otto, Michael



Hansen solubility parameter analysis on the dispersion of zirconia nanocrystals.  


Nanoparticle dispersible in a broad range of solvents is desirable when preparing an organic/inorganic nanocomposite. In this report, the dispersion behavior of carboxylate-grafted zirconia nanoparticle in 25 solvents covering a wide range of polarity was analyzed based on their Hansen solubility parameters (HSP). Particles grafted with alkyl-chain longer than four carbons could only be dispersed in non-polar solvents, while that grafted with acetic acid was dispersible in polar ones. However, particle modified with methacrylic acid (MA) was compatible with both types of solvents, which was rather unexpected. Further NMR analysis showed that the carboxylate-grafted samples contained a trace amount of triethanolamine (TEA) due to the particular ZrO2 synthesis process employed. The combination of the hydrophilic TEA ligand with the short hydrophobic tail of methacrylate broadened the range of compatible solvents from benzene to methanol. Such an extended solvent compatibility was observed previously only for nanoparticles covered with large polymer surfactants having both hydrophilic and hydrophobic groups. Achieving this with two small molecules having separate functional groups is crucial when one needs to maximize the inorganic content in a composite. PMID:23906862

Wang, Sho-Hsun; Liu, Jia-Hong; Pai, Chin-Tung; Chen, Chien-Wei; Chung, Pao-Tang; Chiang, Anthony Shiaw-Tseh; Chang, Shinn-Jen



Solubility control of regioregular 3-substituted polythiophenes bearing 2-phenylnaphthalene side chain by copolymerisation  

NASA Astrophysics Data System (ADS)

Two types of 2,5-dibromothiophene monomers having a dodecyl chain and a 2-phenylnaphthalene one were randomly copolymerised in different feed molar ratio by Ni-catalysed chain-growth polymerisation method. Regioregularity of all polymers were sufficiently high (88-97%). Absorption ?max due to ?-?* transition of polythiophene backbones in solutions were observed at 444-451 nm for all polymers, which were almost similar to each other and typical of the optical characteristics of regioregular poly(3-alkylthiophene)s. The homopolymer of the latter monomer that had the phenylnaphthalene side group showed poor solubility to common organic solvents, i.e., it was insoluble in chloroform at room temperature and could dissolve only in hot solvents above 100 °C. The copolymers, which had higher number average molecular weights (Mn), had better solubility than that of the homopolymer.

Watanabe, Mari; Kijima, Masashi



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


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

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



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 Watanabe of California, One Shields Avenue, Davis, California 95616 Received October 10, 2003 The soluble epoxideEH that are active both in vitro and in vivo. However, their poor solubility in either water or lipid reduces

Hammock, Bruce D.


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

E-print Network

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

de Gispert, Adrià


Investigating the role of small, acid-soluble spore proteins (SASPs) in the resistance of Clostridium perfringens spores to heat  

Microsoft Academic Search

BACKGROUND: Clostridium perfringens type A food poisoning is caused by enterotoxigenic C. perfringens type A isolates that typically possess high spore heat-resistance. The molecular basis for C. perfringens spore heat-resistance remains unknown. In the current study, we investigated the role of small, acid-soluble spore proteins (SASPs) in heat-resistance of spores produced by C. perfringens food poisoning isolates. RESULTS: Our current

Deepa Raju; Michael Waters; Peter Setlow; Mahfuzur R Sarker



Pressurized capillary electrochromatographic analysis of water-soluble vitamins by combining with on-line concentration technique  

Microsoft Academic Search

A pressurized capillary electrochromatography (pCEC) system was developed for the separation of water-soluble vitamins, in which UV absorbance was used as the detection method and a monolithic silica-ODS column as the separation column. The parameters (type and content of organic solvent in the mobile phase, type and concentration of electrolyte, pH of the electrolyte buffer, applied voltage and flow rate)

Li Jia; Yaling Liu; Yanyan Du; Da Xing



Solubility properties of synthetic and natural meta-torbernite  

NASA Astrophysics Data System (ADS)

Meta-torbernite, Cu(UO2)2(PO4)2?8H2O, is one of the most common secondary minerals resulting from the alteration of pitchblende. The determination of the thermodynamic data associated to this phase appears to be a crucial step toward the understanding the origin of uranium deposits or to forecast the fate and transport of uranium in natural media. A parallel approach based on the study of both synthetic and natural samples of meta-torbernite (H3O)0.4Cu0.8(UO2)2(PO4)2?7.6H2O was set up to evaluate its solubility constant. The two solids were first thoroughly characterized and compared by means of XRD, SEM, X-EDS analyses, Raman spectroscopy and BET measurements. The solubility constant was then determined in both under- and supersaturated conditions: the obtained value appeared close to logKs,0°(298 K) = -52.9 ± 0.1 whatever the type of experiment and the sample considered. The joint determination of Gibbs free energy (?RG°(298 K) = 300 ± 2 kJ mol-1) then allowed the calculation of ?RH°(298 K) = 40 ± 3 kJ mol-1 and ?RS°(298 K) = -879 ± 7 J mol-1 K-1. From these values, the thermodynamic data associated with the formation of meta-torbernite (H3O)0.4Cu0.8(UO2)2(PO4)2?7.6H2O were also evaluated and found to be consistent with those previously obtained by calorimetry, showing the reliability of the method developed in this work. Finally, the obtained data were implemented in a calculation code to determine the conditions of meta-torbernite formation in environmental conditions typical of a former mining site. SI=log({Q}/{Ks}) with Q=?i( where ?i is the stoichiometric coefficient (algebraic value) of species i and ai the nonequilibrium activity of i.

Cretaz, Fanny; Szenknect, Stéphanie; Clavier, Nicolas; Vitorge, Pierre; Mesbah, Adel; Descostes, Michael; Poinssot, Christophe; Dacheux, Nicolas



Solubility of simvastatin: A theoretical and experimental study  

NASA Astrophysics Data System (ADS)

Solubility experimental data from Simvastatin in a family of alcohols were obtained at different temperatures. Simvastatin was characterized by using thermal analysis and X-ray diffraction. From the experimental solubility data an anomalous behavior was observed, since an increase the number of alcohol carbon atoms shows an increase in solubility only for the three first alcohols, ethanol, 1-propanol and 1-butanol. A decrease in solubility was obtained for 1-pentanol, 1-hexanol and 1-octanol. Van't·Hoff equation was used to obtain the theoretical solubility value and the ideal activity coefficient. Experimental error was very low and does not affect the plots and equations used. No polymorphic phenomenon was found from the Simvastatin characterization. Theoretical calculations were carried out in order to corroborate the experimental solubility data. Trends and results are similar in both cases. The geometry optimizations of Simvastatin was carried out using density functional theory with Becke's three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-311++G?? basis set. The solvent effect was treated using a continuum model as modeled in water, methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol and 1-octanol. Moreover, dielectric constant, dipolar moment and solubility in the solvents were obtained for explaining the former behavior.

Aceves-Hernández, Juan M.; Hinojosa-Torres, Jaime; Nicolás-Vázquez, Inés; Ruvalcaba, Rene Miranda; García, Rosa María Lima



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.



Generation of a vector suite for protein solubility screening  

PubMed Central

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

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



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.



Cytokine soluble receptors in perinatal and early neonatal life.  

PubMed Central

BACKGROUND: In contrast to cellular receptors, soluble receptors do not enhance the cellular activation because they do not have transmembranic and cytoplasmic parts, acting thereby as endogenous regulatory mechanisms against systemic functions of cytokines. AIM: To measure serum concentrations of the soluble interleukin-2 receptor (sIL2R), soluble interleukin-4 receptor (sIL4R), soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-alpha receptor I and soluble tumor necrosis factor-alpha receptor II, during the perinatal and early neonatal period, in order to evaluate their role in activation of immune response in labor and the first days postpartum. METHODS: Soluble receptor serum concentrations were determined by enzyme-linked immunosorbent assay, in 45 healthy, full-termed neonates during the first and fifth days after birth, in 25 of their mothers (MS), in 25 samples of umbilical cords (UC) and in 25 healthy adult donors age-matched with the mothers (controls). RESULTS: Soluble receptor serum concentrations showed considerable changes during labor and early neonatal life, being significantly higher both in MS (except sIL6R) and in neonatal sample UC, first and fifth days after birth, compared with controls (p<0.0001). Neonatal serum sIL2R and sIL6R increased significantly from birth to the fifth day, while the remaining receptors showed a rapid increase in the first day (p<0.0001), declining significantly thereafter (p<0.0001). CONCLUSION: Our findings suggest that the elevated concentrations of all studied soluble cytokine receptors reflect the activation of immune response, and represent also regulatory protective mechanisms for mother and fetus-neonate against the systemic function of cytokines during labor and early neonatal life. PMID:12857603

Protonotariou, Efthimia; Rizos, Demetrios; Malamitsi-Puchner, Ariadne; Moira, Evangelia; Sarandakou, Angeliki; Salamalekis, Emmanuil



Factors affecting the solubility of calcium pyrophosphate dihydrate crystals.  

PubMed Central

The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are "shed" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response. PMID:423

Bennett, R M; Lehr, J R; McCarty, D J



Extended solubility and spin-glass behavior in a Ag-Gd solid solution prepared by mechanical alloying  

SciTech Connect

The effects of mechanical alloying on the solubility in a Ag-Gd solid solution have been investigated. The study shows that the solubility of Gd in Ag can be extended to about 5 at. % Gd by mechanical alloying from the equilibrium solubility of less than 0.95 at. % Gd. Ag{sub 85}Gd{sub 15} prepared by mechanical alloying exhibits a spin-glass-type transition at {similar_to}5 K. A Curie-Weiss behavior at higher temperatures and x-ray patterns of the material indicate that Gd atoms are either dissolved in the Ag matrix or in the form of small clusters of diameters of a few nanometers.

Tang, J.; Zhao, W.; O`Connor, C.J.; Tao, C. [Departments of Physics and of Chemistry, University of New Orleans, New Orleans, Louisiana 70148 (United States)] [Departments of Physics and of Chemistry, University of New Orleans, New Orleans, Louisiana 70148 (United States); Zhao, M.; Wang, L. [Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)] [Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)



Soluble opsin is present in human vitreous.  


The purpose of this research project was to evaluate if intravitreal opsins are present in human vitreous liquid which is, so far, unknown. Therefore a pilot study was conducted including 22 vitreal samples which were harvested at the beginning of a standard 23-gauge three-port pars plana vitrectomy for macular pucker, diabetic vitreous hemorrhage or vitreal floater removal as well as macular hole closure or vitreomacular traction relief from the central vitreous body. No adverse events or serious side effects occurred. All samples were immediately stabilized by human albumin and arginine and subsequently frozen. Short-wavelength cone opsin concentrations were analyzed by enzyme immune essay (EIA) with anti-proteolytic 400 mM arginine, pH 8.7, in the antigen capture phase. Intravitreal short-wavelength cone opsins were detected in all analyzed samples and respective concentrations ranged at levels of 157 pg/ml ± 73 pg/ml (MV ± SD; range: 27 pg/m-286 pg/ml). Eyes with MP/MH/DVH/VMT and VF exhibited intravitreal short-wavelength cone opsin concentrations of 189 pg/ml ± 68 pg/ml (range: 72 pg/ml-286 pg/ml)/96 pg/ml ± 39 pg/ml (range: 50 pg/ml-138 pg/ml)/126 pg/ml ± 88 pg/ml (range: 27 pg/ml-198 pg/ml)/224 pg/ml and 121 pg/ml. Further studies will quantify the intravitreal opsin pattern of all visual opsins and compare these concentrations between different vitreoretinal diseases. This in turn might offer a better pathophysiological understanding and new diagnostic and therapeutic strategies for various eye pathologies. As a hypothesis, soluble opsins might be a biomarker for retinal damage comparable to creatinine for kidney damage. PMID:24582891

Bertelmann, Thomas; Stief, Thomas; Sekundo, Walter



Equilibrium solubilities of spearmint oil components in supercritical carbon dioxide  

Microsoft Academic Search

The equilibrium solubilities of l-carvone and l-limonene in the binary (l-carvone–CO2 and l-limonene–CO2) and ternary (l-carvone–l-limonene–CO2) systems were obtained at 39°C and 49°C and at pressures ranging from 6 to 10 MPa. The solubilities of these components increased with a pressure increase or a temperature decrease. The solubility of l-limonene was higher than that of l-carvone at the same temperature

Kyoung Heon Kim; Juan Hong



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

NASA Technical Reports Server (NTRS)

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

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



The solubility of hen egg-white lysozyme  

NASA Technical Reports Server (NTRS)

The equilibrium solubility of chicken egg-white lysozyme in the presence of crystalline solid state was determined as a function of NaCl concentration, pH, and temperature. The solubility curves obtained represent a region of the lysozyme phase diagram. This diagram makes it possible to determine the supersaturation of a given set of conditions or to achieve identical supersaturations by different combinations of parameters. The temperature dependence of the solubility permits the evaluation of Delta-H of crystallization. The data indicate a negative heat of crystallization for the tetragonal crystal form but a positive heat of crystallization for the high-temperature orthorhombic form.

Howard, Sandra B.; Twigg, Pamela J.; Baird, James K.; Meehan, Edward J.



Improved water solubility of neohesperidin dihydrochalcone in sweetener blends.  


Significant technological advantages in terms of sweetness synergy and hence cost-saving can be obtained if neohesperidin dihydrochalcone (NHDC) is used in sweetener blends with other intense or bulk sweeteners. The combination of NHDC with sodium saccharin or sodium cyclamate is an excellent method to improve the water solubility at room temperature of NHDC. In the case of NHDC-sodium saccharin, two different methods for blend preparation, a simple mixture and a cosolubilized mixture, can be used, with similar results obtained for solubility and solution stability properties. To improve temporally the water solubility of NHDC in combination with sodium cyclamate, it is absolutely necessary to prepare cosolubilized blends. PMID:11170576

Benavente-García, O; Castillo, J; Del Baño, M J; Lorente, J



[Hydrophobic modification of water soluble drug and its reconstitutable liposomes].  


Water soluble drugs carried in liposomes have rather low encapsulation percentage (EP%) and poor stability. In this paper metronidazole (I) was chosen as a model of water soluble drugs which was modified by means of esterification. Its myristic ester (II) was synthesized. On studying the liposomes of I and II, the results have shown that EP% and stability of II were more than ten times as high as that of I. Furthermore, the reconstitutable liposomes of II were prepared successfully. The amoebacide activity of II liposomes was increased also. Therefore, the hydrophobic modification of water soluble drugs is a good way to improve the drug entrapped in liposomes. PMID:2099094

Hou, X P; Cui, D H; Yi, Y Y; Li, X Y; Yang, L P



Soluble aromatic polyimides for film and coating applications  

NASA Technical Reports Server (NTRS)

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

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



Soluble aromatic polyimides for film and coating applications  

NASA Technical Reports Server (NTRS)

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

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



[Non alcoholic fatty liver disease: treatment with soluble fibres].  


The pilot study evaluated the efficiency of oral soluble fibers to treat patients with nonalcoholic fatty liver disease. Twelve patients received 10 g/day of soluble fibers during 3 months. After the treatment 100% of patients presented reduction in body mass index, waist circumference and insulin resistance index. In 66.7% of the patients were observed reduction of the cholesterol levels and 75% presented normal liver enzymes (AST, ALT, and GGT). The present study suggests that oral soluble fibers may be useful to control risk factors and liver enzymes in patients with nonalcoholic fatty liver disease. However, future studies with histological controls are considered necessary. PMID:18317656

Rocha, Raquel; Cotrim, Helma P; Siqueira, Ana Cristina; Floriano, Shirley



Solubility of polycyclic aromatic hydrocarbons in supercritical carbon dioxide  

SciTech Connect

The equilibrium solubilities of three solid polycyclic aromatic hydrocarbons (acenaphthene, fluoranthene, and triphenylene) were determined at temperatures ranging from 308 K to 348 K and pressures from 121.6 to 354.6 bar in supercritical CO{sub 2}. The data were obtained by using a simple static sampling apparatus which was tested by measuring the solubility of naphthalene in compressed CO{sub 2}. The measured solubilities were correlated using a semiempirical model. The calculated results show satisfactory agreement with the experimental data.

Yamini, Y.; Bahramifar, N.



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


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



Contents of soluble, cell-wall-bound and exuded phlorotannins in the brown alga Fucus vesiculosus, with implications on their ecological functions.  


Phlorotannins are ubiquitous secondary metabolites in brown algae that are phenotypically plastic and suggested to have multiple ecological roles. Traditionally, phlorotannins have been quantified as total soluble phlorotannins. Here, we modify a quantification procedure to measure, for the first time, the amount of cell-wall-bound phlorotannins. We also optimize the quantification of soluble phlorotannins. We use these methods to study the responses of soluble and cell-wall-bound phlorotannin to nutrient enrichment in growing and nongrowing parts of the brown alga Fucus vesiculosus. We also examine the effects of nutrient shortage and herbivory on the rate of phlorotannin exudation. Concentrations of cell-wall-bound phlorotannins were much lower than concentrations of soluble phlorotannins; we also found that nutrient treatment over a period of 41 days affected only soluble phlorotannins. Concentrations of each phlorotannin type correlated positively between growing and nongrowing parts of individual seaweeds. However, within nongrowing thalli, soluble and cell-wall-bound phlorotannins were negatively correlated, whereas within growing thalli there was no correlation. Phlorotannins were exuded from the thallus in all treatments. Herbivory increased exudation, while a lack of nutrients had no effect on exudation. Because the amount of cell-wall-bound phlorotannins is much smaller than the amount of soluble phlorotannins, the major function of phlorotannins appears to be a secondary one. PMID:15839490

Koivikko, Riitta; Loponen, Jyrki; Honkanen, Tuija; Jormalainen, Veijo



The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFbeta family signaling pathways.  


Wishful thinking (Wit) is a Drosophila transforming growth factor-beta (TGFbeta) superfamily type II receptor most related to the mammalian bone morphogenetic protein (BMP) type II receptor, BMPRII. To better understand its function, we undertook a biochemical approach to establish the ligand binding repertoire and downstream signaling pathway. We observed that BMP4 and BMP7, bound to receptor complexes comprised of Wit and the type I receptor thickveins and saxophone to activate a BMP-like signaling pathway. Further we demonstrated that both myoglianin and its most closely related mammalian ligand, myostatin, interacted with a Wit and Baboon (Babo) type II-type I receptor complex to activate TGFbeta/activin-like signaling pathways. These results thereby demonstrate that Wit binds multiple ligands to activate both BMP and TGFbeta-like signaling pathways. Given that myoglianin is expressed in muscle and glial-derived cells, these results also suggest that Wit may mediate myoglianin-dependent signals in the nervous system. PMID:16098524

Lee-Hoeflich, Si Tuen; Zhao, Xin; Mehra, Arun; Attisano, Liliana



Analysis of Functional Groups by Solubility and Infrared Analysis.  

ERIC Educational Resources Information Center

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

Turek, William N.



21 CFR 520.110 - Apramycin sulfate soluble powder.  

Code of Federal Regulations, 2013 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...Specifications. A water soluble powder used...pounds of body weight. Water consumption should be monitored...adjusted according to water consumption which varies...



21 CFR 520.110 - Apramycin sulfate soluble powder.  

Code of Federal Regulations, 2011 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...Specifications. A water soluble powder used...pounds of body weight. Water consumption should be monitored...adjusted according to water consumption which varies...



21 CFR 520.110 - Apramycin sulfate soluble powder.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...Specifications. A water soluble powder used...pounds of body weight. Water consumption should be monitored...adjusted according to water consumption which varies...



Nanosuspension: An approach to enhance solubility of drugs  

PubMed Central

One of the major problems associated with poorly soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and nonaqueous media, belonging to BCS class II as classified by biopharmaceutical classification system. Formulation as nanosuspension is an attractive and promising alternative to solve these problems. Nanosuspension consists of the pure poorly water-soluble drug without any matrix material suspended in dispersion. Preparation of nanosuspension is simple and applicable to