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Sample records for activin type ii

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

    PubMed

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

    2015-01-01

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

  2. Development of Novel Activin-Targeted Therapeutics

    PubMed Central

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

    2015-01-01

    Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-β proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, “fastener” residues (Lys45, Tyr96, His97, and Ala98; activin A numbering) that confer latency to other TGF-β proteins were incorporated. For the activin A prodomain, these modifications generated a reagent that potently (IC50 5 nmol/l) and specifically inhibited activin A signaling in vitro, and activin A-induced muscle wasting in vivo. Interestingly, the modified activin B prodomain inhibited both activin A and B signaling in vitro (IC50 ~2 nmol/l) and in vivo, suggesting it could serve as a general activin antagonist. Importantly, unlike soluble ActRIIA/IIB, the modified prodomains did not inhibit myostatin or GDF-11 activity. To underscore the therapeutic utility of specifically antagonising activin signaling, we demonstrate that the modified activin prodomains promote significant increases in muscle mass. PMID:25399825

  3. ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma

    PubMed Central

    Su, Gloria H.; Bansal, Ravi; Murphy, Kathleen M.; Montgomery, Elizabeth; Yeo, Charles J.; Hruban, Ralph H.; Kern, Scott E.

    2001-01-01

    DPC4 is known to mediate signals initiated by type β transforming growth factor (TGFβ) as well as by other TGFβ superfamily ligands such as activin and BMP (bone morphogenic proteins), but mutational surveys of such non-TGFβ receptors have been negative to date. Here we describe the gene structure and novel somatic mutations of the activin type I receptor, ACVR1B, in pancreatic cancer. ACVR1B has not been described previously as a mutated tumor-suppressor gene. PMID:11248065

  4. Activin signaling as an emerging target for therapeutic interventions

    PubMed Central

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

    2009-01-01

    After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands. The functions of activins through activin receptors are pleiotrophic, cell type-specific and contextual, and they are involved in the etiology and pathogenesis of a variety of diseases. Accordingly, activin signaling may be a target for therapeutic interventions. In this review, we summarize the current knowledge on activin signaling and discuss the potential roles of

  5. Seasonal changes in immunoreactivity of activin signaling component proteins in wild ground squirrel testes.

    PubMed

    Sheng, Xia; Zhang, Haolin; Zhang, Mengyuan; Zhang, Wei; Hu, Xiao; Song, Moshi; Zhou, Jiao; Xu, Meiyu; Weng, Qiang; Watanabe, Gen; Taya, Kazuyoshi

    2012-01-01

    The seasonal spermatogenesis and localization of inhibin/activin subunits (alpha, betaA, betaB) in the testes of wild ground squirrel has been previously described; however, the expression pattern of activin receptors and cytoplasmic signaling SMADs has not been detected in any seasonal breeders. The objective of this study was to investigate the abundance and cellular localization of activin signaling components in testes of the wild ground squirrel during the breeding and nonbreeding seasons. The immunolocalizations of ActRIIB (activin type II receptor B) and activin-related SMADs (phospho-SMAD2/3, SMAD4 and SMAD7) were observed by immunohistochemistry. Total proteins were extracted from testicular tissues in the breeding and nonbreeding seasons and were used for Western blotting analysis for ActRIIB and SMADs. Immunoreactivities of activin signaling components were greater in the testes of the breeding season, and then decreased to a relatively low level in the nonbreeding season. ActRIIB and related SMADs were widely spread in the active testes, while spermatogonia were the predominant cellular sites of activin signal transduction during arrested spermatogenesis. The dynamic regulation of activin type II receptor and SMADs indicated that the activin signal pathway played an important paracrine role in seasonal spermatogenesis of the wild ground squirrel. Furthermore, the distinct localizations and immunoreactivity of ActRIIB and SMADs might suggest different functions of activin in seasonal spermatogenesis.

  6. Regulation of FSHbeta and GnRH receptor gene expression in activin receptor II knockout male mice.

    PubMed

    Kumar, T Rajendra; Agno, Julio; Janovick, Jo Ann; Conn, P Michael; Matzuk, Martin M

    2003-12-30

    To examine in vivo, the local effects of inhibins and activins within the anterior pituitary, independent of their endocrine effects exerted from the gonad, in mediating FSH homeostasis, we used castrated knockout mice lacking either inhibin alpha or activin receptor II (ACVR2) alone or in combination. Compared to castrated wild-type (WT) mice, FSHbeta mRNA levels in the pituitaries of Acvr2 null mice were significantly downregulated in the absence of gonadal feedback. FSHbeta mRNA levels were not significantly higher in the pituitaries of castrated inhibin alpha null mice compared to those in Acvr2 null mice and remained the same in the pituitaries of castrated double mutant mice lacking both inhibin and ACVR2. In contrast to FSHbeta mRNA expression changes, pituitary FSH content was significantly reduced in Acvr2 null mice whereas it was only slightly upregulated in inhibin alpha null mice. Combined absence of both ACVR2 signaling and inhibins caused a decrease in FSH content compared to that in the absence of inhibins alone. These changes in pituitary content were in parallel to those in serum FSH levels in these three groups of castrated mice, suggesting that the unopposed actions of locally produced inhibins are dominant over those effects mediated by ACVR2 signaling to regulate FSH biosynthesis and secretion. Thus, our in vivo results demonstrate that within the pituitary, locally produced activins and inhibins exert their actions at distinct phases of FSH homeostasis. In an independent set of experiments, we tested whether in vivo signaling via ACVR2 is necessary for hypothalamic GnRH biosynthesis and for GnRH receptor expression. Our results demonstrate that in contrast to previous in vitro studies, signaling through ACVR2 is neither required for hypothalamic synthesis of GnRH peptide nor for expression of GnRH receptors in the anterior pituitary. We conclude that within the hypothalamic-pituitary short loop, ACVR2 signaling is critical only for FSH

  7. Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development.

    PubMed

    Matzuk, M M; Kumar, T R; Shou, W; Coerver, K A; Lau, A L; Behringer, R R; Finegold, M J

    1996-01-01

    With the advent of gene targeting in pluripotent mouse embryonic stem cells, it is now possible to modify the mammalian genome to generate mutant strains of mice with precise genetic mutations. The major goal of my laboratory is to generate transgenic mice to use as physiologic models to study mammalian reproduction and development. The initial focus of our research has been to generate mice deficient in inhibins, activins, activin binding proteins (i.e., follistatin), and activin receptors (i.e., activin receptor type II) to understand their interactions and roles in the hypothalamic-pituitary-gonadal axis and mammalian development. Inhibins and activins, dimeric members of the TGF-beta superfamily, were discovered due to their role in pituitary follicle stimulating hormone homeostasis. However, these proteins have later been shown to have diverse endocrine, paracrine, and autocrine functions. Activins have been shown to mediate their signals through type I and type II serine/threonine kinase receptors. The high interspecies conservation of activins, inhibins, and activin receptors and the universal presence of activins in mammals, birds, amphibians, and fish suggest an evolutionarily conserved role of these proteins in animal development. Our initial studies have demonstrated a tumor suppressor role of inhibin in the gonads and adrenals and have also suggested a role of activins in cancer cachexia-like syndrome. To further study the gonadal tumor development and the cancer cachexia-like syndrome in these mice, we have begun to generate mice with multiple genetic alterations (e.g., mice deficient in both inhibin and Mullerian inhibiting substance). We have also generated mice deficient in other components of this complex system (e.g., activin beta A, activin receptor type II, follistatin). Analysis of these transgenic mutant models has aided our overall understanding of the critical roles these proteins play in the development of the reproductive system, in the

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

    PubMed Central

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

    2015-01-01

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

  9. Characterization of Follistatin-Type Domains and Their Contribution to Myostatin and Activin A Antagonism

    PubMed Central

    Cash, Jennifer N.; Angerman, Elizabeth B.; Keutmann, Henry T.

    2012-01-01

    Follistatin (FST)-type proteins are important antagonists of some members of the large TGF-β family of cytokines. These include myostatin, an important negative regulator of muscle growth, and the closely related activin A, which is involved in many physiological functions, including maintenance of a normal reproductive axis. FST-type proteins, including FST and FST-like 3 (FSTL3), differentially inhibit various TGF-β family ligands by binding each ligand with two FST-type molecules. In this study, we sought to examine features that are important for ligand antagonism by FST-type proteins. Previous work has shown that a modified construct consisting of the FST N-terminal domain (ND) followed by two repeating follistatin domains (FSD), herein called FST ND-FSD1-FSD1, exhibits strong specificity for myostatin over activin A. Using cell-based assays, we show that FST ND-FSD1-FSD1 is unique in its specificity for myostatin as compared with similar constructs containing domains from FSTL3 and that the ND is critical to its activity. Furthermore, we demonstrate that FSD3 of FST provides affinity to ligand inhibition and confers resistance to perturbations in the ND and FSD2, likely through the interaction of FSD3 of one FST molecule with the ND of the other FST molecule. Additionally, our data suggest that this contact provides cooperativity to ligand antagonism. Cross-linking studies show that this interaction also potentiates formation of 1:2 ligand-FST complexes, whereas lack of FSD3 allows formation of 1:1 complexes. Altogether, these studies support that domain differences generate FST-type molecules that are each uniquely suited ligand antagonists. PMID:22593183

  10. Activin A regulation of gonadotropin-releasing hormone synthesis and release in vitro.

    PubMed

    MacConell, L A; Lawson, M A; Mellon, P L; Roberts, V J

    1999-10-01

    Activin is essential for the regulation of normal mammalian reproductive function at both the pituitary and gonadal levels. However, its central actions in the control of the hypothalamic-pituitary-gonadal axis remain largely unexplored. The present study aims to determine whether activin could regulate the reproductive axis at the level of the hypothalamus, through control of the GnRH neuroendocrine system. Using the GnRH-secreting GT1-7 neuronal cell line as a model system, we demonstrate expression of mRNAs encoding activin receptor types I, IB, and II. We examined the effects of activin A on GnRH protein secretion and mRNA levels in GT1-7 cells. Treatment with rh-activin A regulated both GnRH protein secretion and GnRH mRNA expression in the GT1-7 cells in a time-dependent fashion. Using transient transfection assays, we explored a potential transcriptional basis for these changes. Activin A increased reporter gene activity driven by minimal GnRH enhancer and promoter elements, suggesting that activin may regulate GnRH gene expression at the level of transcription. Lastly, activin A treatment of male rat hypothalami, in vitro, increased GnRH protein secretion. Collectively, molecular and physiological evidence support the presence of an activin system which might act at a hypothalamic site to regulate mammalian reproduction via activation of GnRH synthesis and release.

  11. Activation of activin type IB receptor signals in pancreatic β cells leads to defective insulin secretion through the attenuation of ATP-sensitive K+ channel activity.

    PubMed

    Nomura, Masatoshi; Morinaga, Hidetaka; Zhu, Hai-Lei; Wang, Lixiang; Hasuzawa, Nao; Takayanagi, Ryoichi; Teramoto, Noriyoshi

    2014-07-18

    In studies of gene-ablated mice, activin signaling through activin type IIB receptors (ActRIIB) and Smad2 has been shown to regulate not only pancreatic β cell mass but also insulin secretion. However, it still remains unclear whether gain of function of activin signaling is involved in the modulation of pancreatic β cell mass and insulin secretion. To identify distinct roles of activin signaling in pancreatic β cells, the Cre-loxP system was used to activate signaling through activin type IB receptor (ActRIB) in pancreatic β cells. The resultant mice (pancreatic β cell-specific ActRIB transgenic (Tg) mice; ActRIBCAβTg) exhibited a defect in glucose-stimulated insulin secretion (GSIS) and a progressive impairment of glucose tolerance. Patch-clamp techniques revealed that the activity of ATP-sensitive K(+) channels (KATP channels) was decreased in mutant β cells. These results indicate that an appropriate level of activin signaling may be required for GSIS in pancreatic β cells, and that activin signaling involves modulation of KATP channel activity.

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

    SciTech Connect

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

    2013-01-04

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

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

    PubMed Central

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

    2011-01-01

    X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells. It was postulated that therapeutically increasing muscle fiber size would cause symptomatic improvement in myotubularin deficiency. Recent studies have elucidated an important role for the activin-receptor type IIB (ActRIIB) in regulation of muscle growth and have demonstrated that ActRIIB inhibition results in significant muscle hypertrophy. To evaluate whether promoting muscle hypertrophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1δ4) mice. Compared with wild-type mice, untreated Mtm1δ4 mice have decreased body weight, skeletal muscle hypotrophy, and reduced survival. Treatment of Mtm1δ4 mice with ActRIIB-mFC produced a 17% extension of lifespan, with transient increases in weight, forelimb grip strength, and myofiber size. Pathologic analysis of Mtm1δ4 mice during treatment revealed that ActRIIB-mFC produced marked hypertrophy restricted to type 2b myofibers, which suggests that oxidative fibers in Mtm1δ4 animals are incapable of a hypertrophic response in this setting. These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency. PMID:21281811

  14. Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient mice.

    PubMed

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

    2011-02-01

    X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells. It was postulated that therapeutically increasing muscle fiber size would cause symptomatic improvement in myotubularin deficiency. Recent studies have elucidated an important role for the activin-receptor type IIB (ActRIIB) in regulation of muscle growth and have demonstrated that ActRIIB inhibition results in significant muscle hypertrophy. To evaluate whether promoting muscle hypertrophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1δ4) mice. Compared with wild-type mice, untreated Mtm1δ4 mice have decreased body weight, skeletal muscle hypotrophy, and reduced survival. Treatment of Mtm1δ4 mice with ActRIIB-mFC produced a 17% extension of lifespan, with transient increases in weight, forelimb grip strength, and myofiber size. Pathologic analysis of Mtm1δ4 mice during treatment revealed that ActRIIB-mFC produced marked hypertrophy restricted to type 2b myofibers, which suggests that oxidative fibers in Mtm1δ4 animals are incapable of a hypertrophic response in this setting. These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency. PMID:21281811

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    1997-01-01

    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

  17. The Biology Of Activin: Recent Advances In Structure, Regulation And Function

    PubMed Central

    Xia, Yin; Schneyer, Alan L.

    2009-01-01

    Activin was discovered in the 1980’s as a gonadal protein that stimulated FSH release from pituitary gonadotropes and was thought of as a reproductive hormone. In the ensuing decades many additional activities of activin were described and it was found to be produced in a wide variety of cell types at nearly all stages of development. Its signaling and actions are regulated intracellularly as well as by extracellular antagonists. Over the past 5 years a number of important advances have been made that clarify our understanding of the structural basis for signaling and regulation, as well as the biological roles of activin in stem cells, embryonic development, and in adults. These include the crystallization of activin in complex with the activin type II receptor ActRIIB, or with the binding proteins follistatin and follistatin-like 3 (FSTL3), and identification of the activin roles in gonadal sex development, follicle development and luteolysis, in β-cell proliferation and function in the islet, in stem cell self-renewal and differentiation into different cell types, and in immune cells. These advances are reviewed to provide perspective for future studies. PMID:19273500

  18. Activins and activin antagonists in hepatocellular carcinoma

    PubMed Central

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

    2008-01-01

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

  19. BAFF and APRIL from Activin A-Treated Dendritic Cells Upregulate the Antitumor Efficacy of Dendritic Cells In Vivo.

    PubMed

    Shurin, Michael R; Ma, Yang; Keskinov, Anton A; Zhao, Ruijing; Lokshin, Anna; Agassandian, Marianna; Shurin, Galina V

    2016-09-01

    The members of the TGFβ superfamily play a key role in regulating developmental and homeostasis programs by controlling differentiation, proliferation, polarization, and survival of different cell types. Although the role of TGFβ1 in inflammation and immunity is well evident, the contribution of other TGFβ family cytokines in the modulation of the antitumor immune response remains less documented. Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI. In vivo, activin A-stimulated DCs demonstrate a significantly increased ability to induce tumor-specific CTLs and inhibit the growth of melanoma and lung carcinoma, which relies on DC-derived BAFF and APRIL, as knockdown of the BAFF and APRIL gene expression in activin A-treated DCs blocks augmentation of their antitumor potential. Although systemic administration of activin A, BAFF, or APRIL for the therapeutic purposes is not likely due to the pluripotent effects on malignant and nonmalignant cells, our data open a novel opportunity for improving the efficacy of DC vaccines. In fact, a significant augmentation of the antitumor activity of DC pretreated with activin A and the proven role of DC-derived BAFF and APRIL in the induction of antitumor immunity in vivo support this direction. Cancer Res; 76(17); 4959-69. ©2016 AACR. PMID:27364554

  20. Type II universal spacetimes

    NASA Astrophysics Data System (ADS)

    Hervik, S.; Málek, T.; Pravda, V.; Pravdová, A.

    2015-12-01

    We study type II universal metrics of the Lorentzian signature. These metrics simultaneously solve vacuum field equations of all theories of gravitation with the Lagrangian being a polynomial curvature invariant constructed from the metric, the Riemann tensor and its covariant derivatives of an arbitrary order. We provide examples of type II universal metrics for all composite number dimensions. On the other hand, we have no examples for prime number dimensions and we prove the non-existence of type II universal spacetimes in five dimensions. We also present type II vacuum solutions of selected classes of gravitational theories, such as Lovelock, quadratic and L({{Riemann}}) gravities.

  1. Activin A balance regulates epithelial invasiveness and tumorigenesis

    PubMed Central

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

    2015-01-01

    Activin A is a member of the TGFβ superfamily. Activin A and TGFβ 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 TGFβ receptor II results in epithelial cell invasion. When grown in three-dimensional organotypic reconstruct cultures, esophageal keratinocytes expressing dominant-negative mutants of E-cadherin and TGFβ receptor II showed activated Smad2 in the absence of functional TGFβ receptor II. However, we could show increased levels of Activin A secretion, and Activin A 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 Activin A antibody can increase cell invasion in organotypic cultures in a fibroblast- and MMP-dependent manner. Similarly, suppression of Activin A with shRNA increases cell invasion and tumorigenesis in vivo. Therefore, we conclude that maintaining a delicate balance of Activin A expression is critical for homeostasis in the esophageal microenvironment. PMID:25068654

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

    SciTech Connect

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

    2014-01-10

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

  3. Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion

    PubMed Central

    Loomans, Holli A.; Andl, Claudia D.

    2014-01-01

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

  4. The role of myostatin and activin receptor IIB in the regulation of unloading-induced myofiber type-specific skeletal muscle atrophy.

    PubMed

    Babcock, Lyle W; Knoblauch, Mark; Clarke, Mark S F

    2015-09-15

    Chronic unloading induces decrements in muscle size and strength. This adaptation is governed by a number of molecular factors including myostatin, a potent negative regulator of muscle mass. Myostatin must first be secreted into the circulation and then bind to the membrane-bound activin receptor IIB (actRIIB) to exert its atrophic action. Therefore, we hypothesized that myofiber type-specific atrophy observed after hindlimb suspension (HLS) would be related to myofiber type-specific expression of myostatin and/or actRIIB. Wistar rats underwent HLS for 10 days, after which the tibialis anterior was harvested for frozen cross sectioning. Simultaneous multichannel immunofluorescent staining combined with differential interference contrast imaging was employed to analyze myofiber type-specific expression of myostatin and actRIIB and myofiber type cross-sectional area (CSA) across fiber types, myonuclei, and satellite cells. Hindlimb suspension (HLS) induced significant myofiber type-specific atrophy in myosin heavy chain (MHC) IIx (P < 0.05) and MHC IIb myofibers (P < 0.05). Myostatin staining associated with myonuclei was less in HLS rats compared with controls, while satellite cell staining for myostatin remained unchanged. In contrast, the total number myonuclei and satellite cells per myofiber was reduced in HLS compared with ambulatory control rats (P < 0.01). Sarcoplasmic actRIIB staining differed between myofiber types (I < IIa < IIx < IIb) independent of loading conditions. Myofiber types exhibiting the greatest cytoplasmic staining of actRIIB corresponded to those exhibiting the greatest degree of atrophy following HLS. Our data suggest that differential expression of actRIIB may be responsible for myostatin-induced myofiber type-selective atrophy observed during chronic unloading. PMID:26205544

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

    PubMed

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

    2014-09-01

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

  6. Ligand trap for the activin type IIA receptor protects against vascular disease and renal fibrosis in mice with chronic kidney disease.

    PubMed

    Agapova, Olga A; Fang, Yifu; Sugatani, Toshifumi; Seifert, Michael E; Hruska, Keith A

    2016-06-01

    The causes of cardiovascular mortality associated with chronic kidney disease (CKD) are partly attributed to the CKD-mineral bone disorder (CKD-MBD). The causes of the early CKD-MBD are not well known. Our discovery of Wnt (portmanteau of wingless and int) inhibitors, especially Dickkopf 1, produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. In the search for such factors, we studied the effects of activin receptor type IIA (ActRIIA) signaling by using a ligand trap for the receptor, RAP-011 (a soluble extracellular domain of ActRIIA fused to a murine IgG-Fc fragment). In a mouse model of CKD that stimulated atherosclerotic calcification, RAP-011 significantly increased aortic ActRIIA signaling assessed by the levels of phosphorylated Smad2/3. Furthermore, RAP-011 treatment significantly reversed CKD-induced vascular smooth muscle dedifferentiation as assessed by smooth muscle 22α levels, osteoblastic transition, and neointimal plaque calcification. In the diseased kidneys, RAP-011 significantly stimulated αklotho levels and it inhibited ActRIIA signaling and decreased renal fibrosis and proteinuria. RAP-011 treatment significantly decreased both renal and circulating Dickkopf 1 levels, showing that Wnt activation was downstream of ActRIIA. Thus, ActRIIA signaling in CKD contributes to the CKD-MBD and renal fibrosis. ActRIIA signaling may be a potential therapeutic target in CKD. PMID:27165838

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

    PubMed Central

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

    2009-01-01

    Activin A is a potent growth and differentiation factor whose synthesis and bioactivity are tightly regulated. Both follistatin binding and inhibin subunit heterodimerization block access to the activin receptor and/or receptor activation. We postulated that the activin-βC subunit provides another mechanism regulating activin bioactivity. To test our hypothesis, we examined the biological effects of activin C and produced mice that overexpress activin-βC. Activin C reduced activin A bioactivity in vitro; in LNCaP cells, activin C abrogated both activin A-induced Smad signaling and growth inhibition, and in LβT2 cells, activin C antagonized activin A-mediated activity of an follicle-stimulating hormone-β promoter. Transgenic mice that overexpress activin-βC exhibited disease in testis, liver, and prostate. Male infertility was caused by both reduced sperm production and impaired sperm motility. The livers of the transgenic mice were enlarged because of an imbalance between hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased evidence of nuclear Smad-2 localization in the testis, liver, and prostate, indicating that overexpression of activin-βC antagonized Smad signaling in vivo. Underlying the significance of these findings, human testis, liver, and prostate cancers expressed increased activin-βC immunoreactivity. This study provides evidence that activin-βC is an antagonist of activin A and supplies an impetus to examine its role in development and disease. PMID:19095948

  8. [Oculocutaneous type II tyrosinosis].

    PubMed

    Podglajen-Wecxsteen, O; Delaporte, E; Piette, F; le Flohic, X; Bergoend, H

    1993-01-01

    Richner-Hanhart syndrome, also called oculo-cutaneous tyrosinosis type II, is a recessive autosomal genodermatosis consecutive to a disorder of tyrosine metabolism. It presents as a varying association of palmo-plantar keratosis, bilateral keratitis and mental retardation. The authors report a new case which is atypical in that palmoplantar keratosis made a late appearance. The diagnosis was confirmed by the presence of hypertyrosinaemia, hypertyrosinuria and urinary excretion of phenolic acids, and the absence of hepato-renal lesion. Needle biopsy of the liver, which demonstrates the deficiency of soluble cytosolic tyrosine aminotransferase, is not indispensable to the diagnosis and was not performed in our patient. Treatment consisted of a dietary measure: a controlled phenylalanine and tyrosine intake to obtain a tyrosinaemia below 10 mg/100 ml. This resulted in a favourable and durable course of the oculo-cutaneous lesions. In case of isolated skin lesion, retinoids can be prescribed either alone of combined with a diet, making it less strict.

  9. Activins and inhibins: Novel regulators of thymocyte development

    SciTech Connect

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

    2009-04-03

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

  10. Activins and Inhibins: novel regulators of thymocyte development

    PubMed Central

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

    2009-01-01

    Activins and inhibins are members of the transforming growth factor β 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+CD24hiTCRβlo 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 α 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

  11. Activation of signalling by the activin receptor complex.

    PubMed Central

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

    1996-01-01

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

  12. Case 22:Type II diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is characterized by elevated blood glucose levels. It is composed of two types depending on the pathogenesis. Type I diabetes is characterized by insulin deficiency and usually has its onset during childhood or teenage years. This is also called ketosis-prone diabetes. Type II diab...

  13. Pregnancy and tyrosinaemia type II.

    PubMed

    Cerone, R; Fantasia, A R; Castellano, E; Moresco, L; Schiaffino, M C; Gatti, R

    2002-08-01

    A female patient with tyrosinaemia type II is reported having undergone two untreated pregnancies. During pregnancies, plasma tyrosine was raised. The outcomes of both offspring show that maternal tyrosinaemia may have an adverse effect on the developing fetus.

  14. Type-II Weyl semimetals.

    PubMed

    Soluyanov, Alexey A; Gresch, Dominik; Wang, Zhijun; Wu, QuanSheng; Troyer, Matthias; Dai, Xi; Bernevig, B Andrei

    2015-11-26

    Fermions--elementary particles such as electrons--are classified as Dirac, Majorana or Weyl. Majorana and Weyl fermions had not been observed experimentally until the recent discovery of condensed matter systems such as topological superconductors and semimetals, in which they arise as low-energy excitations. Here we propose the existence of a previously overlooked type of Weyl fermion that emerges at the boundary between electron and hole pockets in a new phase of matter. This particle was missed by Weyl because it breaks the stringent Lorentz symmetry in high-energy physics. Lorentz invariance, however, is not present in condensed matter physics, and by generalizing the Dirac equation, we find the new type of Weyl fermion. In particular, whereas Weyl semimetals--materials hosting Weyl fermions--were previously thought to have standard Weyl points with a point-like Fermi surface (which we refer to as type-I), we discover a type-II Weyl point, which is still a protected crossing, but appears at the contact of electron and hole pockets in type-II Weyl semimetals. We predict that WTe2 is an example of a topological semimetal hosting the new particle as a low-energy excitation around such a type-II Weyl point. The existence of type-II Weyl points in WTe2 means that many of its physical properties are very different to those of standard Weyl semimetals with point-like Fermi surfaces.

  15. Achondrogenesis type II with polydactyly.

    PubMed

    Rittler, M; Orioli, I M

    1995-11-01

    We report on a newborn male infant who presented the typical findings of achondrogenesis type II (Langer-Saldino), and who also showed postaxial polydactyly on both feet and bilateral microtia. Polydactyly is frequently part of the short-rib syndromes, but has not been reported in achondrogenesis. The hypothesis of polydactyly as part of a contiguous gene syndrome is discussed. PMID:8588578

  16. Outcome in tyrosinaemia type II.

    PubMed

    Barr, D G; Kirk, J M; Laing, S C

    1991-10-01

    Tyrosinaemia type II was diagnosed in a boy with failure to thrive and in his sister on neonatal screening. On diet the outcome, at 12 and 10 years respectively, has been excellent in respect of oculocutaneous sequelae, growth, and psychomotor development, contrasting with the generally unfavourable outcome in most reported cases.

  17. The biological function of type I receptors of bone morphogenetic protein in bone

    PubMed Central

    Lin, Shuxian; Svoboda, Kathy K H; Feng, Jian Q; Jiang, Xinquan

    2016-01-01

    Bone morphogenetic proteins (BMPs) have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors (BMPRI and BMPRII). In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 (ALK2, also called type IA activin receptor), activin-like kinase 3 (ALK3, also called BMPRIA), and activin-like kinase 6 (ALK6, also called BMPRIB). The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future. PMID:27088043

  18. Type-II Quantum Computers

    NASA Astrophysics Data System (ADS)

    Yepez, Jeffrey

    This paper discusses a computing architecture that uses both classical parallelism and quantum parallelism. We consider a large parallel array of small quantum computers, connected together by classical communication channels. This kind of computer is called a type-II quantum computer, to differentiate it from a globally phase-coherent quantum computer, which is the first type of quantum computer that has received nearly exclusive attention in the literature. Although a hybrid, a type-II quantum computer retains the crucial advantage allowed by quantum mechanical superposition that its computational power grows exponentially in the number of phase-coherent qubits per node, only short-range and short time phase-coherence is needed, which significantly reduces the level of engineering facility required to achieve its construction. Therefore, the primary factor limiting its computational power is an economic one and not a technological one, since the volume of its computational medium can in principle scale indefinitely.

  19. [Tyrosinemia type II. Case report].

    PubMed

    Benatiya, A I; Bouayed, M A; Touiza, E; Daoudi, K; Bhalil, S; Elmesbahi, I; Tahri, H

    2005-01-01

    Tyrosinemia type II or Richner-Hanhart syndrome is a rare hereditary disease characterized by the association of pseudoherpetiform corneal ulcerations and palmoplantar hyperkeratosis. We report the case of a 12 year-old young man presenting a superficial punctate keratitis and a corneal dystrophy in both eyes, associated with a palmoplantar hyperkeratosis. The dosage of the serum level of tyrosine is meaningfully raised to 1236 micromol/l. A dietary treatment restraining tyrosine and phenylalanine is started with favorable results after an evolution of 6 months. Tyrosinemia type II is an autosomal recessive disease, due to an enzymatic deficit in tyrosine aminotransferase. The diagnosis is based on the clinic and high level of serum and urinary tyrosine as well as of its urinary metabolites. This disease must be suspected in all cases of dentritic keratitis not reacting on the antiviral treatment, and more especially if it is associated with cutaneous lesions such as palmo-plantar keratosis.

  20. Light echoes - Type II supernovae

    NASA Technical Reports Server (NTRS)

    Schaefer, Bradley E.

    1987-01-01

    Type II supernovae (SNs) light curves show a remarkable range of shapes. Data have been collected for the 12 Type II SNs that have light curve information for more than four months past maximum. Contrary to previous reports, it is found that (1) the decay rate after 100 days past maximum varies by almost an order of magnitude and (2) the light curve shapes are not bimodally distributed, but actually form a continuum. In addition, it is found that the extinctions to the SNs are related to the light curve shapes. This implies that the absorbing dust is local to the SNs. The dust is likely to be part of a circumstellar shell emitted by the SN progenitor that Dwek (1983) has used to explain infrared echoes. The optical depth of the shell can get quite large. In such cases, it is found that the photons scattered and delayed by reflection off dust grains will dominate the light curve several months after peak brightness. This 'light echo' offers a straightforward explanation of the diversity of Type II SN light curves.

  1. Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells.

    PubMed

    Chang, Hsun-Ming; Cheng, Jung-Chien; Huang, He-Feng; Shi, Feng-Tao; Leung, Peter C K

    2015-09-01

    Activins are homo- or heterodimers of inhibin β subunits that play important roles in the reproductive system. Our previous work has shown that activins A (βAβA), B (βBβB) and AB (βAβB) induce aromatase/estradiol, but suppress StAR/progesterone production in human granulosa-lutein cells. However, the underlying molecular determinants of these effects have not been examined. In this continuing study, we used immortalized human granulosa cells (SVOG) to investigate the effects of activins in regulating StAR/progesterone and the potential mechanisms of action. In SVOG cells, activins A, B and AB produced comparable down-regulation of StAR expression and progesterone production. In addition, all three activin isoforms induced equivalent phosphorylation of both SMAD2 and SMAD3. Importantly, the activin-induced down-regulation of StAR, increase in SMAD2/3 phosphorylation, and decrease in progesterone were abolished by the TGF-β type I receptor inhibitor SB431542. Interestingly, the small interfering RNA-mediated knockdown of ALK4 but not ALK5 reversed the activin-induced suppression of StAR. Furthermore, the knockdown of SMAD4 or SMAD2 but not SMAD3 abolished the inhibitory effects of all three activin isoforms on StAR expression. These results provide evidence that activins A, B and AB down-regulate StAR expression and decrease progesterone production in human granulosa cells, likely via an ALK4-mediated SMAD2/SMAD4-dependent pathway. Our findings provide important insights into the molecular mechanisms underlying the regulatory effects of activins on human granulosa cell steroidogenesis.

  2. Moving beyond Type I and Type II neuron types.

    PubMed

    Skinner, Frances K

    2013-01-01

    In 1948, Hodgkin delineated different classes of axonal firing.  This has been mathematically translated allowing insight and understanding to emerge.  As such, the terminology of 'Type I' and 'Type II' neurons is commonplace in the Neuroscience literature today.  Theoretical insights have helped us realize that, for example, network synchronization depends on whether neurons are Type I or Type II.  Mathematical models are precise with analyses (considering Type I/II aspects), but experimentally, the distinction can be less clear.  On the other hand, experiments are becoming more sophisticated in terms of distinguishing and manipulating particular cell types but are limited in terms of being able to consider network aspects simultaneously.   Although there is much work going on mathematically and experimentally, in my opinion it is becoming common that models are either superficially linked with experiment or not described in enough detail to appreciate the biological context.  Overall, we all suffer in terms of impeding our understanding of brain networks and applying our understanding to neurological disease.  I suggest that more modelers become familiar with experimental details and that more experimentalists appreciate modeling assumptions. In other words, we need to move beyond our comfort zones.

  3. Activin B promotes BMSC-mediated cutaneous wound healing by regulating cell migration via the JNK-ERK signaling pathway.

    PubMed

    Zhang, Min; Sun, Li; Wang, Xueer; Chen, Shixuan; Kong, Yanan; Liu, Nuyun; Chen, Yinghua; Jia, Qin; Zhang, Lu; Zhang, Lin

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are able to differentiate into various types of skin cells and participate in skin regeneration and repair. Activin signaling can regulate wound healing and reepithelialization. The present study assessed the impact of activin B on BMSC-mediated cutaneous wound healing in rats and explored the possible mechanism involved. We found that CFSE-labeled BMSCs participated in wound healing in vivo, and compared to administration with PBS, activin B, or BMSCs, activin B plus BMSCs significantly promoted wound healing and hair follicle regeneration. Activin B induced actin stress fiber formation and cell migration in BMSCs in vitro. Activation of JNK and ERK, but not p38, was required for activin B-induced actin stress fiber formation and BMSC migration. These results show that activin B may promote BMSC-mediated wound healing by inducing actin stress fiber formation and BMSC migration via the ERK and JNK signal pathways. Combined administration of BMSCs and cytokines may be a promising therapeutic strategy for the management of skin wounds.

  4. Type II Transmembrane Serine Proteases*

    PubMed Central

    Bugge, Thomas H.; Antalis, Toni M.; Wu, Qingyu

    2009-01-01

    Analysis of genome and expressed sequence tag data bases at the turn of the millennium unveiled a new protease family named the type II transmembrane serine proteases (TTSPs) in a Journal of Biological Chemistry minireview (Hooper, J. D., Clements, J. A., Quigley, J. P., and Antalis, T. M. (2001) J. Biol. Chem. 276, 857–860). Since then, the number of known TTSPs has more than doubled, and more importantly, our understanding of the physiological functions of individual TTSPs and their contribution to human disease has greatly increased. Progress has also been made in identifying molecular substrates and endogenous inhibitors. This minireview summarizes the current knowledge of the rapidly advancing TTSP field. PMID:19487698

  5. Activin-like factor from a Xenopus laevis cell line responsible for mesoderm induction.

    PubMed

    van den Eijnden-Van Raaij, A J; van Zoelent, E J; van Nimmen, K; Koster, C H; Snoek, G T; Durston, A J; Huylebroeck, D

    1990-06-21

    Induction of mesoderm during early amphibian embryogenesis can be mimicked in vitro by adding growth factors, including heparin-binding and type-beta transforming growth factors (TGF-beta), to isolated ectoderm explants from Xenopus laevis embryos. Although the mesoderm-inducing factor (MIF) from X. laevis XTC cells (XTC-MIF) has properties similar to TGF-beta, this factor is still unidentified. Recently, we obtained a number of homogeneous cell lines from the heterogeneous XTC population, which differ in their MIF production. Only one, XTC-GTX-11, produced MIF, although it was similar to the rest of the clones in its production of known growth factors, including TGF-beta activity. This observation, together with the identification of activin A as a potent MIF led us to study the parallel activities of MIF and activin. Here we report an analysis of activin-like activity from XTC cells and some of the XTC clones, including XTC-GTX-11. There is a clear consistent correlation between MIF activity and presence of activin activity, indicating that XTC-MIF is the Xenopus homologue of mammalian activin.

  6. Mucopolysaccharidosis type II, Hunter's syndrome.

    PubMed

    Tylki-Szymańska, Anna

    2014-09-01

    Hunter syndrome is caused by deficiency of the lysososmal enzyme iduronate-2-sulphatase that cleaves O-linked sulphate moieties from dermatan sulphate and heparan sulphate and leads to accumulation of GAGs. The disease is a X-linked condition affecting males and rarely females, clinically divided into severe (2/3) and attenuated types. Children with severe form, diagnosed at 12-36 months, have coarse facial feature, short stature, joint stiffness, short neck, broad chest, large head circumference, watery diarrhea, skeletal changes, progressive and profound mental retardation, retinal degeneration' hearing loss, cardiomyopathy, valvular involvement, with progressive thickening and stiffening of the valve leaflets leading to mitral and aortic regurgitation and stenosis . Recurrent and prolonged rhinitis with persistent nasal discharge are the first symptoms of airway disease that manifests itself as noisy breathing and later sleep apnea. Some patients develop ivory-colored skin lesions on the upper back and sides of the upper arms, pathogenomic of Hunter syndrome. The scalp hair becomes coarse, straight and bristly. Inguinal and umbilical hernias occur caused by the disturbed structure of connective tissue and increased liver and spleen volume. Patients with attenuated form have normal intelligence and a milder phenotype. Physical features diagnosed later are similar but less pronounced but progress to severe disease. Sceening is by quantitative assessment of urinary GAGs excretion. Qualitative assessment of GAG by electrophoresis can distinguish the type of mucopolysaccharidosis. Definitive diagnosis is based on enzyme activity assay in leukocytes, fibroblasts or plasma. Molecular testing is recommended mainly for genetic counseling and carrier detection. Limited experience of Haematopoietic stem cell therapy in MPS II showed progressive neurodegeneration. Recombinant 125 Idursulfase, is indicated for long-term treatment. The response appears to depend on the

  7. Mucopolysaccharidosis type II, Hunter's syndrome.

    PubMed

    Tylki-Szymańska, Anna

    2014-09-01

    Hunter syndrome is caused by deficiency of the lysososmal enzyme iduronate-2-sulphatase that cleaves O-linked sulphate moieties from dermatan sulphate and heparan sulphate and leads to accumulation of GAGs. The disease is a X-linked condition affecting males and rarely females, clinically divided into severe (2/3) and attenuated types. Children with severe form, diagnosed at 12-36 months, have coarse facial feature, short stature, joint stiffness, short neck, broad chest, large head circumference, watery diarrhea, skeletal changes, progressive and profound mental retardation, retinal degeneration' hearing loss, cardiomyopathy, valvular involvement, with progressive thickening and stiffening of the valve leaflets leading to mitral and aortic regurgitation and stenosis . Recurrent and prolonged rhinitis with persistent nasal discharge are the first symptoms of airway disease that manifests itself as noisy breathing and later sleep apnea. Some patients develop ivory-colored skin lesions on the upper back and sides of the upper arms, pathogenomic of Hunter syndrome. The scalp hair becomes coarse, straight and bristly. Inguinal and umbilical hernias occur caused by the disturbed structure of connective tissue and increased liver and spleen volume. Patients with attenuated form have normal intelligence and a milder phenotype. Physical features diagnosed later are similar but less pronounced but progress to severe disease. Sceening is by quantitative assessment of urinary GAGs excretion. Qualitative assessment of GAG by electrophoresis can distinguish the type of mucopolysaccharidosis. Definitive diagnosis is based on enzyme activity assay in leukocytes, fibroblasts or plasma. Molecular testing is recommended mainly for genetic counseling and carrier detection. Limited experience of Haematopoietic stem cell therapy in MPS II showed progressive neurodegeneration. Recombinant 125 Idursulfase, is indicated for long-term treatment. The response appears to depend on the

  8. Activins and inhibins in mammalian testis development: new models, new insights.

    PubMed

    Barakat, B; Itman, C; Mendis, S H; Loveland, K L

    2012-08-15

    The discovery of activin and inhibins as modulators of the hypothalamic-pituitary-gonadal axis has set the foundation for understanding their central importance to many facets of development and disease. This review contains an overview of the processes and cell types that are central to testis development and spermatogenesis and then provides an update focussed on information gathered over the past five years to address new concepts about how these proteins function to control testis development in fetal and juvenile life. Current knowledge about the interactive nature of the transforming growth factor-β (TGFβ) superfamily signalling network is applied to recent findings about activins and inhibins in the testis. Information about the regulated synthesis of signalling components and signalling regulators in the testis is integrated with new concepts that demonstrate their functional significance. The importance of activin bioactivity levels or dosage in controlling balanced growth of spermatogonial cells and their niche at different stages of testis development is highlighted.

  9. Hearing Restoration in Neurofibromatosis Type II Patients

    PubMed Central

    Lee, Jeon Mi; Chang, Jin Woo; Choi, Jae Young

    2016-01-01

    Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID:27189272

  10. Isolation and characterization of Xenopus follistatin and activins.

    PubMed

    Fukui, A; Nakamura, T; Sugino, K; Takio, K; Uchiyama, H; Asashima, M; Sugino, H

    1993-09-01

    Xenopus follistatin and activins were purified from a Xenopus laevis cell line (XTC-F1) by four purification steps consisting of consecutive affinity chromatography on dextran sulfate-Sepharose and Sulfate Cellulofine, fast protein liquid chromatography gel permeation, and reverse-phase high performance liquid chromatography (HPLC). Our results thus obtained indicated that almost equimolar amounts of activins A, AB, and B were found to be present as a complex with follistatin (activin-binding protein) in the conditioned medium of XTC-F1 cells. Reverse-phase HPLC of the complex gave Xenopus follistatin and activins A, AB, and B. The purified Xenopus follistatin showed four major bands in a molecular mass range from 34 to 39 kDa by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by activin-binding assay and ligand blotting analysis. Each protein was found to have the same NH2-terminus and its sequence was very homologous to that of mammalian follistatin. Several criteria including immunoblotting analysis and various functional assays revealed the existence of three isoforms of activins A, AB, and B in Xenopus, as in mammals. Xenopus activins significantly induced both ventral and dorsal mesoderm in explants of Xenopus blastula cells that would otherwise form epidermis. In a dose-dependent manner of each isoform of activin, the induced explants were able to differentiate into blood-like cells, coelomic epithelium, mesenchyme, muscle, and notochord. The induction patterns of three Xenopus activins were essentially the same. The mesoderm induction by the purified Xenopus activins was shown to be inhibited stoichiometrically by the purified Xenopus follistatin. These results indicate that Xenopus XTC-F1 cells secrete several molecular forms of follistatin/activin-binding protein and three isoforms of activins AB and B in addition to activin A.

  11. Resistance domain in type II superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1980-01-05

    We show that traveling domains with a finite resistance can exist in type II superconductors in the presence of a transport current. An experiment in which this effect generates an alternating electric field and current is proposed.

  12. Achondrogenesis type II, abnormalities of extracellular matrix.

    PubMed

    Horton, W A; Machado, M A; Chou, J W; Campbell, D

    1987-09-01

    Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation. PMID:3309860

  13. Antenatal diagnosis of achondrogenesis type II.

    PubMed

    Kodandapani, S; Ramkumar, V

    2009-01-01

    Achondrogenesis is a lethal congenital chondrodystrophy characterized by extreme micromelia, small thorax and polyhydramnios. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis). Prenatal ultrasonography at 22-weeks gestation revealed a fetus with large head, short neck and chest, prominent abdomen and short limbs. Pregnancy was terminated. Radiologic examination of neonate revealed features of achondrogenesis type II. Routine ultrasound screening made early detection and timely management possible. PMID:20387359

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

    PubMed Central

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

    2015-01-01

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

  15. Coronal type II bursts and interplanetary type II bursts: Distinct shock drivers

    NASA Astrophysics Data System (ADS)

    Suryanarayana, G. S.

    2012-02-01

    We study solar radio type II bursts combining with Wind/WAVES type II bursts and coronal mass ejections (CMEs). The aim of the present work is to investigate the effectiveness of shocks to cause type II bursts in the solar corona and the interplanetary space. We consider the following findings. The distribution of the cessation heights of type II emission is confined to a rather narrow range of height than the distribution of the heights of start frequencies. This is suggestive of the presence of a gradient for the Alfvén speed from the heliocentric height of ˜1.4 solar radii. The range of the kinetic energy of CMEs associated with coronal type II emission taken together with the suggested computation method and the Alfvén speed gradient, indicates the limit to the height up to which type II emission could be expected. This height is ˜2 solar radii from the center of the Sun. Further, the large time gap between the cessation time and heights of coronal type II emission and the commencement time and heights of most of the IP type II bursts do not account for the difference between the two heights and the average shock speed. Also, there is clear difference in the magnitude of the kinetic energies and the distinct characteristics of the CMEs associated with coronal and IP type II bursts. Hence, we suggest that in most instances the coronal type II bursts and IP type II bursts occur due to distinct shocks. We also address the question of the origin of type II bursts and discuss the possible explanation of observed results.

  16. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

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

    PubMed

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

    2015-11-01

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

  18. Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen.

    PubMed

    Godfrey, M; Hollister, D W

    1988-12-01

    We have extended the study of a mild case of type II achondrogenesis-hypochondrogenesis to include biochemical analyses of cartilage, bone, and the collagens produced by dermal fibroblasts. Type I collagen extracted from bone and types I and III collagen produced by dermal fibroblasts were normal, as was the hexosamine ratio of cartilage proteoglycans. Hyaline cartilage, however, contained approximately equal amounts of types I and II collagen and decreased amounts of type XI collagen. Unlike the normal SDS-PAGE mobility. Two-dimensional SDS-PAGE revealed extensive overmodification of all type II cyanogen bromide peptides in a pattern consistent with heterozygosity for an abnormal pro alpha 1(II) chain which impaired the assembly and/or folding of type II collagen. This interpretation implies that dominant mutations of the COL2A1 gene may cause type II achondrogenesis-hypochondrogenesis. More generally, emerging data implicating defects of type II collagen in the type II achondrogenesis-hypochondrogenesis-spondyloepiphyseal dysplasia congenita spectrum and in the Kniest-Stickler syndrome spectrum suggest that diverse mutations of this gene may be associated with widely differing phenotypic outcome. PMID:3195588

  19. DO GIANT PLANETS SURVIVE TYPE II MIGRATION?

    SciTech Connect

    Hasegawa, Yasuhiro; Ida, Shigeru E-mail: ida@geo.titech.ac.jp

    2013-09-10

    Planetary migration is one of the most serious problems to systematically understand the observations of exoplanets. We clarify that the theoretically predicted type II, migration (like type I migration) is too fast, by developing detailed analytical arguments in which the timescale of type II migration is compared with the disk lifetime. In the disk-dominated regime, the type II migration timescale is characterized by a local viscous diffusion timescale, while the disk lifetime is characterized by a global diffusion timescale that is much longer than the local one. Even in the planet-dominated regime where the inertia of the planet mass reduces the migration speed, the timescale is still shorter than the disk lifetime except in the final disk evolution stage where the total disk mass decays below the planet mass. This suggests that most giant planets plunge into the central stars within the disk lifetime, and it contradicts the exoplanet observations that gas giants are piled up at r {approx}> 1 AU. We examine additional processes that may arise in protoplanetary disks: dead zones, photoevaporation of gas, and gas flow across a gap formed by a type II migrator. Although they make the type II migration timescale closer to the disk lifetime, we show that none of them can act as an effective barrier for rapid type II migration with the current knowledge of these processes. We point out that gas flow across a gap and the fraction of the flow accreted onto the planets are uncertain and they may have the potential to solve the problem. Much more detailed investigation for each process may be needed to explain the observed distribution of gas giants in extrasolar planetary systems.

  20. Type II endoleaks: challenges and solutions

    PubMed Central

    Brown, Andrew; Saggu, Greta K; Bown, Matthew J; Sayers, Robert D; Sidloff, David A

    2016-01-01

    Type II endoleaks are the most common endovascular complications of endovascular abdominal aortic aneurysm repair (EVAR); however, there has been a divided opinion regarding their significance in EVAR. Some advocate a conservative approach unless there is clear evidence of sac expansion, while others maintain early intervention is best to prevent adverse late outcomes such as rupture. There is a lack of level-one evidence in this challenging group of patients, and due to a low event rate of complications, large numbers of patients would be required in well-designed trials to fully understand the natural history of type II endoleak. This review will discuss the imaging, management, and outcome of patients with isolated type II endoleaks following infra-renal EVAR. PMID:27042087

  1. Type II seesaw dominance in SO(10)

    SciTech Connect

    Melfo, Alejandra; Ramirez, Alba; Senjanovic, Goran

    2010-10-01

    Grand unified theories where the neutrino mass is given by type II seesaw have the potential to provide interesting connections between the neutrino and charged fermion sectors. We explore the possibility of having a dominant type II seesaw contribution in supersymmetric SO(10). We show that this can be achieved in the model where symmetry breaking is triggered by 54 and 45 dimensional representations, without the need for additional fields other than those already required to have a realistic charged fermion mass spectrum. Physical consequences, such as the implementation of the Bajc, Senjanovic, and Vissani mechanism, the possibility of the fields responsible for type II seesaw dominance being messengers of supersymmetry breaking, and the realization of baryo and leptogenesis in these theories, are discussed.

  2. Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF.

    PubMed

    Chang, Hsun-Ming; Cheng, Jung-Chien; Liu, Yingtao; Klausen, Christian; Xu, Congjian; Leung, Peter C K

    2016-10-01

    Lysyl oxidase (LOX) is the key enzyme involved in the crosslinking of collagen and elastin that is essential for the formation of extracellular matrix (ECM). LOX-mediated ECM remodeling plays a critical role in follicle development, oocyte maturation and corpus luteum formation. To date, the regulation of LOX in human ovary has never been elucidated. Activin A and its functional receptors are highly expressed in ovarian follicles from an early developmental stage. They locally regulate follicle progression. The aim of this study was to investigate the effects of activin A on the expression of LOX and its extracellular enzyme activity in primary and immortalized human granulosa-lutein cells obtained from patients undergoing an in vitro fertilization procedure. We demonstrated that activin A significantly upregulated the expression of connective tissue growth factor (CTGF) and LOX via an activin/TGF-β type I receptor mediated-signaling pathway. Using a target depletion small interfering RNA knockdown approach, we further confirmed that the upregulation of CTGF expression resulted in an activin-A-induced increases in LOX expression and activity. These findings may provide insight into the mechanisms by which intrafollicular growth factors regulate the expression of LOX for ECM formation and tissue remodeling in the human ovary. PMID:27530347

  3. Seasonal changes in spermatogenesis and immunolocalization of inhibin/activin subunits in the wild male ground squirrel (Citellus dauricus Brandt).

    PubMed

    Sheng, Xia; Zhang, Haolin; Zhang, Wei; Song, Moshi; Zhang, Mengyuan; Li, Ben; Weng, Qiang; Watanabe, Gen; Taya, Kazuyoshi

    2008-12-01

    The objective of this study was to investigate the seasonal changes in spermatogenesis and the immunolocalization of the inhibin alpha and inhibin/activin (betaA and betaB) subunits during the breeding and non-breeding seasons in the wild male ground squirrel. The testicular weight and size and seminiferous tubule diameter were measured, and histological observations of testes were performed. The sections of the testes were immunostained by the avidin-biotin-peroxidase complex method (ABC) using polyclonal antisera raised against porcine inhibin alpha, inhibin/activin betaA and inhibin/activin betaB during the breeding and non-breeding seasons. There were marked variations in testicular weight and size and seminiferous tubule diameter between the breeding and non-breeding seasons, and all types of spermatogenic cells, including spermatozoa, were found in the breeding season. In addition, immunoreactivity was also detected for the inhibin alpha, betaA and betaB subunits in Sertoli and Leydig cells during the breeding season, but immunostaining was only present for the inhibin alpha and inhibin/activin betaB subunits in Sertoli cells during the non-breeding season. These results suggest that seasonal changes in testicular weight and size and seminiferous tubule diameter of wild ground squirrels are correlated with changes in spermatogenesis, and the cellular localization of the inhibin/activin subunits showed season related changes in the breeding and non-breeding seasons.

  4. The role of activin in mammary gland development and oncogenesis.

    PubMed

    Dunphy, Karen A; Schneyer, Alan L; Hagen, Mary J; Jerry, D Joseph

    2011-06-01

    TGFβ contributes to mammary gland development and has paradoxical roles in breast cancer because it has both tumor suppressor and tumor promoter activity. Another member of the TGFβ superfamily, activin, also has roles in the developing mammary gland, but these functions, and the role of activin in breast cancer, are not well characterized. TGFβ and activin share the same intracellular signaling pathways, but divergence in their signaling pathways are suggested. The purpose of this review is to compare the spatial and temporal expression of TGFβ and activin during mammary gland development, with consideration given to their functions during each developmental period. We also review the contributions of TGFβ and activin to breast cancer resistance and susceptibility. Finally, we consider the systemic contributions of activin in regulating obesity and diabetes; and the impact this regulation has on breast cancer. Elevated levels of activin in serum during pregnancy and its influence on pregnancy associated breast cancer are also considered. We conclude that evidence demonstrates that activin has tumor suppressing potential, without definitive indication of tumor promoting activity in the mammary gland, making it a good target for development of therapeutics.

  5. Biceps Tenodesis for Type II SLAP Tears.

    PubMed

    Tayrose, Gregory A; Karas, Spero G; Bosco, Joseph

    2015-06-01

    Tears of the superior glenoid labrum are a common cause of shoulder pain and disability, especially in overhead athletes such as pitchers, swimmers, and volleyball players. Type II SLAP lesions have been the most clinically important superior labral pathology, and the management of this lesion has been a very controversial topic. Currently, there are no high level studies in the literature to guide treatment. While the few level 3 and level 4 evidence studies that are available following arthroscopic repair of type II SLAP lesions all report reasonable overall patient satisfaction, persistent postoperative pain is common and associated with a low return to pre-injury level of sports participation. There has been a recent school of thought that biceps tenodesis, which maintains the length-tension relationship of the long head of biceps, should be the procedure of choice for patients with isolated type II SLAP lesions. The current paper reviews the role biceps tenodesis plays in the management of type II SLAP tears. PMID:26517164

  6. Neurofibromatosis types I and II: radiological appearance.

    PubMed

    Romanowski, C A; Cavallin, L I

    1998-02-01

    The neurocutaneous disorders frequently involve the central nervous system. This, the first in a pair of articles which describe and illustrate the radiological appearances of the central nervous system manifestations of the most common neurocutaneous disorders, looks at neurofibromatosis types I and II.

  7. Biceps Tenodesis for Type II SLAP Tears.

    PubMed

    Tayrose, Gregory A; Karas, Spero G; Bosco, Joseph

    2015-06-01

    Tears of the superior glenoid labrum are a common cause of shoulder pain and disability, especially in overhead athletes such as pitchers, swimmers, and volleyball players. Type II SLAP lesions have been the most clinically important superior labral pathology, and the management of this lesion has been a very controversial topic. Currently, there are no high level studies in the literature to guide treatment. While the few level 3 and level 4 evidence studies that are available following arthroscopic repair of type II SLAP lesions all report reasonable overall patient satisfaction, persistent postoperative pain is common and associated with a low return to pre-injury level of sports participation. There has been a recent school of thought that biceps tenodesis, which maintains the length-tension relationship of the long head of biceps, should be the procedure of choice for patients with isolated type II SLAP lesions. The current paper reviews the role biceps tenodesis plays in the management of type II SLAP tears.

  8. [A case of type II achondrogenesis].

    PubMed

    Micheli, E; Perrone, C; Quarta Colosso, L; Vetrugno, M; Zecca, G; Indirli, G C; Greco, F; Elia, G; Ciancio, S

    1996-01-01

    We describe a rare case of type II achondrogenesis (gestational age = thirty-two weeks) dead forty-five minutes after birth. This congenital skeletal dysplasia is classified among the lethal osteochondrodysplasias. Clinical features were enough for diagnosis and autopsy added nothing to our clinical knowledges. PMID:8685014

  9. Calcitonin metabolism in senile (type II) osteoporosis.

    PubMed

    Reginster, J Y; Deroisy, R; Bruwier, M; Franchimont, P

    1992-05-01

    The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic clearance rate (MCR) and production rate (PR) of iCT and eCT were measured in 41 postmenopausal women, including 14 hip fractures (OP II) and 27 healthy controls. No significant difference appeared for basal iCT levels between OP II (mean +/- SEM: 41.9 +/- 3.4 pg/ml) and controls (mean +/- SEM: 46.2 +/- 5 pg/ml). eCT basal levels were similar in OP II (mean +/- SEM: 5.42 +/- 0.5 pg/ml) and in controls (mean +/- SEM: 7.3 +/- 0.7 pg/ml). MCR were similar in the two groups. iCT PR were similar in OP II (mean +/- SEM: 17.2 +/- 1.5 micrograms/24 h) and controls (mean +/- SEM: 18.6 +/- 1.1 micrograms/24 h). No difference appeared between eCT PR in OP II (mean +/- SEM: 2.3 +/- 0.2 micrograms/24 h) and controls (mean +/- SEM: 3.2 +/- 0.3 pg/ml). From these data, no evidence appears that calcitonin might be one of the determinant factors in the pathogenesis of senile osteoporosis.

  10. Theoretical models for Type I and Type II supernova

    SciTech Connect

    Woosley, S.E.; Weaver, T.A.

    1985-01-01

    Recent theoretical progress in understanding the origin and nature of Type I and Type II supernovae is discussed. New Type II presupernova models characterized by a variety of iron core masses at the time of collapse are presented and the sensitivity to the reaction rate /sup 12/C(..cap alpha..,..gamma..)/sup 16/O explained. Stars heavier than about 20 M/sub solar/ must explode by a ''delayed'' mechanism not directly related to the hydrodynamical core bounce and a subset is likely to leave black hole remnants. The isotopic nucleosynthesis expected from these massive stellar explosions is in striking agreement with the sun. Type I supernovae result when an accreting white dwarf undergoes a thermonuclear explosion. The critical role of the velocity of the deflagration front in determining the light curve, spectrum, and, especially, isotopic nucleosynthesis in these models is explored. 76 refs., 8 figs.

  11. Uric acid: a modulator of prostate cells and activin sensitivity.

    PubMed

    Sangkop, Febbie; Singh, Geeta; Rodrigues, Ely; Gold, Elspeth; Bahn, Andrew

    2016-03-01

    Elevated serum uric acid (SUA) or urate is associated with inflammation and gout. Recent evidence has linked urate to cancers, but little is known about urate effects in prostate cancer. Activins are inflammatory cytokines and negative growth regulators in the prostate. A hallmark of prostate cancer progression is activin insensitivity; however, mechanisms underlying this are unclear. We propose that elevated SUA is associated with prostate cancer counteracting the growth inhibitory effects of activins. The expression of activins A and B, urate transporter GLUT9 and tissue urate levels were examined in human prostate disease. Intracellular and secreted urate and GLUT9 expression were assessed in human prostate cancer cell lines. Furthermore, the effects of urate and probenecid, a known urate transport inhibitor, were determined in combination with activin A. Activin A expression was increased in low-grade prostate cancer, whereas activin B expression was reduced in high-grade prostate cancer. Intracellular urate levels decreased in all prostate pathologies, while GLUT9 expression decreased in benign prostatic hyperplasia, prostatitis and high-grade prostate cancer. Activin responsive LNCaP cells had higher intracellular and lower secreted urate levels than activin-insensitive PC3 cells. GLUT9 expression in prostate cancer cells was progressively lower than in prostate epithelial cells. Elevated extracellular urate was growth promoting in vitro, which was abolished by the gout medication probenecid, and it antagonized the growth inhibitory effects of activins. This study shows for the first time that a change in plasma or intracellular urate levels, possibly involving GLUT9 and a urate efflux transporter, has an impact on prostate cancer cell growth, and that lowering SUA levels in prostate cancer is likely to be therapeutically beneficial. PMID:26910779

  12. Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A.

    PubMed

    Smith, J C; Price, B M; Van Nimmen, K; Huylebroeck, D

    1990-06-21

    The first inductive interaction in amphibian development is mesoderm induction, when a signal from the vegetal hemisphere of the blastula induces mesoderm from overlying equatorial cells. Recently, several 'mesoderm-inducing factors' (MIFs) have been discovered. These cause isolated Xenopus animal caps to form mesodermal cell types such as muscle, instead of their normal fate of epidermis. The MIFs fall into two classes. One comprises members of the fibroblast growth factor (FGF) family, and the other members of the transforming growth factor type beta (TGF-beta) family. Of the latter group, the most potent is XTC-MIF, a protein produced by Xenopus XTC cells. Here we show that XTC-MIF is the homologue of mammalian activin A. Activins modulate the release of follicle-stimulating hormone from cultured anterior pituitary cells and cause the differentiation of two erythroleukaemia cell lines. Our results indicate that these molecules may also act in early development during formation of the mesoderm.

  13. Magnetization of anisotropic Type II superconductors

    SciTech Connect

    Mints, R.G.

    1989-04-10

    Peculiarities of magnetization of anisotropic type II superconductors are of considerable interest in view of the discovery of high-T/sub c/ superconductors characterized by strongly asymmetric layered structure. Specifics of the penetration of magnetic flux into an anisotropic type II superconductor were discussed in the literature. This analysis gave the distribution of induction in an isolated vortex, its energy, and critical magnetic field H/sub c1/. However, the magnetization curve of anisotropic superconductors was not considered. This paper deals with the magnetic moment of uniaxial London superconductor in the interval H/sub c1/ /le/ H/sub 0/ << H/sub c2/, where H/sub 0/ is the external magnetic field strength.

  14. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

    PubMed

    Shahid, Mohd; Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A; Leyton, Patricio A; Cheng, Juan; Tainsh, Robert E T; Mayeur, Claire; Rhee, David K; Wu, Mei X; Scherrer-Crosbie, Marielle; Buys, Emmanuel S; Zapol, Warren M; Bloch, Kenneth D; Bloch, Donald B

    2016-04-15

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

  15. Activin Signaling in the Pathogenesis and Therapy of Neuropsychiatric Diseases

    PubMed Central

    Link, Andrea S.; Zheng, Fang; Alzheimer, Christian

    2016-01-01

    Activins are members of the transforming growth factor β (TGFβ) family and serve as multifunctional regulatory proteins in many tissues and organs. In the brain, activin A, which is formed by two disulfide-linked βA subunits, is recognized as the predominant player in activin signaling. Over the last years, considerable progress has been made in elucidating novel and unexpected functions of activin in the normal and diseased brain and in deciphering the underlying molecular mechanisms. Initially identified as a neurotrophic and protective factor during development and in several forms of acute injury, the scope of effects of activin A in the adult central nervous system (CNS) has been considerably broadened by now. Here, we will highlight recent findings that bear significance for a better understanding of the pathogenesis of various neuropsychiatric diseases and might hold promise for novel therapeutic strategies. While the basal level of activin A in the adult brain is low, significant short-term up-regulation occurs in response to increased neuronal activity. In fact, brief exposure to an enriched environment (EE) is already sufficient to considerably strengthen activin signaling. Enhancement of this pathway tunes the performance of glutamatergic and GABAergic synapses in a fashion that impacts on cognitive functions and affective behavior, counteracts death-inducing signals through extrasynaptic NMDA receptors (NMDARs), and stimulates adult neurogenesis in the hippocampus. We will discuss how impaired activin signaling is involved in anxiety disorders, depression, drug dependence, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and how reinforcement of activin signaling might be exploited for therapeutic interventions. PMID:27242425

  16. UBIQUITOUS TORSIONAL MOTIONS IN TYPE II SPICULES

    SciTech Connect

    De Pontieu, B.; Hansteen, V. H.; Carlsson, M.; Rouppe van der Voort, L. H. M.; Rutten, R. J.; Watanabe, H.

    2012-06-10

    Spicules are long, thin, highly dynamic features that jut out ubiquitously from the solar limb. They dominate the interface between the chromosphere and corona and may provide significant mass and energy to the corona. We use high-quality observations with the Swedish 1 m Solar Telescope to establish that so-called type II spicules are characterized by the simultaneous action of three different types of motion: (1) field-aligned flows of order 50-100 km s{sup -1}, (2) swaying motions of order 15-20 km s{sup -1}, and (3) torsional motions of order 25-30 km s{sup -1}. The first two modes have been studied in detail before, but not the torsional motions. Our analysis of many near-limb and off-limb spectra and narrowband images using multiple spectral lines yields strong evidence that most, if not all, type II spicules undergo large torsional modulation and that these motions, like spicule swaying, represent Alfvenic waves propagating outward at several hundred km s{sup -1}. The combined action of the different motions explains the similar morphology of spicule bushes in the outer red and blue wings of chromospheric lines, and needs to be taken into account when interpreting Doppler motions to derive estimates for field-aligned flows in spicules and determining the Alfvenic wave energy in the solar atmosphere. Our results also suggest that large torsional motion is an ingredient in the production of type II spicules and that spicules play an important role in the transport of helicity through the solar atmosphere.

  17. Ubiquitous Torsional Motions in Type II Spicules

    NASA Astrophysics Data System (ADS)

    De Pontieu, B.; Carlsson, M.; Rouppe van der Voort, L. H. M.; Rutten, R. J.; Hansteen, V. H.; Watanabe, H.

    2012-06-01

    Spicules are long, thin, highly dynamic features that jut out ubiquitously from the solar limb. They dominate the interface between the chromosphere and corona and may provide significant mass and energy to the corona. We use high-quality observations with the Swedish 1 m Solar Telescope to establish that so-called type II spicules are characterized by the simultaneous action of three different types of motion: (1) field-aligned flows of order 50-100 km s-1, (2) swaying motions of order 15-20 km s-1, and (3) torsional motions of order 25-30 km s-1. The first two modes have been studied in detail before, but not the torsional motions. Our analysis of many near-limb and off-limb spectra and narrowband images using multiple spectral lines yields strong evidence that most, if not all, type II spicules undergo large torsional modulation and that these motions, like spicule swaying, represent Alfvénic waves propagating outward at several hundred km s-1. The combined action of the different motions explains the similar morphology of spicule bushes in the outer red and blue wings of chromospheric lines, and needs to be taken into account when interpreting Doppler motions to derive estimates for field-aligned flows in spicules and determining the Alfvénic wave energy in the solar atmosphere. Our results also suggest that large torsional motion is an ingredient in the production of type II spicules and that spicules play an important role in the transport of helicity through the solar atmosphere.

  18. Dietary fibre in type II diabetes.

    PubMed

    Asp, N G; Agardh, C D; Ahrén, B; Dencker, I; Johansson, C G; Lundquist, I; Nyman, M; Sartor, G; Scherstén, B

    1981-01-01

    Recent studies have indicated that diets rich in digestible carbohydrates and dietary fibre might be beneficial in the regulation of type II non insulin dependent diabetes (NIDD). Addition of the gel forming type of dietary fibre such as pectin and guar gum to meals or glucose solutions reduces post-prandial glucose and insulin response. Addition of cereal fibres in the form of bran seems to have long term beneficial effect improving glucose tolerance. Little is known, however, concerning effects of dietary fibre naturally occurring in food on postprandial glucose and hormone response. In the present study we prepared two breakfast meals which were similar regarding digestible carbohydrates but differed in their dietary fibre content. One of the meals, including whole grain bread and whole apples, contained 8.4 g of dietary fibre, and the other one, containing white bread and apple juice, 3.1 g. When given to eight NIDD, the fibre rich breakfast gave significantly lower blood glucose increment during the three hours following ingestion. The results indicate that foods rich in dietary fibre might be useful in the regulation of type II diabetes.

  19. A novel mutation in type II methemoglobinemia.

    PubMed

    Hudspeth, Michelle P; Joseph, Sumy; Holden, Kenton R

    2010-01-01

    Type II methemoglobinemia is a somatic deficiency of cytochrome b5 reductase with severe global neurologic impairment. We report a novel mutation in exon 3 of the CYB5R3 gene on chromosome 22 consisting of homozygous 1-base pair (bp) deletion noted as c.215delG; p.Gly72AlafsX100. The patient had improvement of gross motor skills, chewing, and swallowing that may be due to the initiation of daily ascorbic acid therapy. We hypothesize that a possible response to ascorbic acid may be related to the effect of making additional ferrous iron available for its role as a cofactor in carnitine synthesis. PMID:19471045

  20. INTERPLANETARY SHOCKS LACKING TYPE II RADIO BURSTS

    SciTech Connect

    Gopalswamy, N.; Kaiser, M. L.; Xie, H.; Maekelae, P.; Akiyama, S.; Yashiro, S.; Howard, R. A.; Bougeret, J.-L.

    2010-02-20

    We report on the radio-emission characteristics of 222 interplanetary (IP) shocks detected by spacecraft at Sun-Earth L1 during solar cycle 23 (1996 to 2006, inclusive). A surprisingly large fraction of the IP shocks ({approx}34%) was radio quiet (RQ; i.e., the shocks lacked type II radio bursts). We examined the properties of coronal mass ejections (CMEs) and soft X-ray flares associated with such RQ shocks and compared them with those of the radio-loud (RL) shocks. The CMEs associated with the RQ shocks were generally slow (average speed {approx}535 km s{sup -1}) and only {approx}40% of the CMEs were halos. The corresponding numbers for CMEs associated with RL shocks were 1237 km s{sup -1} and 72%, respectively. Thus, the CME kinetic energy seems to be the deciding factor in the radio-emission properties of shocks. The lower kinetic energy of CMEs associated with RQ shocks is also suggested by the lower peak soft X-ray flux of the associated flares (C3.4 versus M4.7 for RL shocks). CMEs associated with RQ CMEs were generally accelerating within the coronagraph field of view (average acceleration {approx}+6.8 m s{sup -2}), while those associated with RL shocks were decelerating (average acceleration {approx}-3.5 m s{sup -2}). This suggests that many of the RQ shocks formed at large distances from the Sun, typically beyond 10 Rs, consistent with the absence of metric and decameter-hectometric (DH) type II radio bursts. A small fraction of RL shocks had type II radio emission solely in the kilometric (km) wavelength domain. Interestingly, the kinematics of the CMEs associated with the km type II bursts is similar to those of RQ shocks, except that the former are slightly more energetic. Comparison of the shock Mach numbers at 1 AU shows that the RQ shocks are mostly subcritical, suggesting that they were not efficient in accelerating electrons. The Mach number values also indicate that most of these are quasi-perpendicular shocks. The radio-quietness is predominant

  1. Genetics Home Reference: microcephalic osteodysplastic primordial dwarfism type II

    MedlinePlus

    ... Genetics Home Health Conditions MOPDII microcephalic osteodysplastic primordial dwarfism type II Enable Javascript to view the expand/ ... Open All Close All Description Microcephalic osteodysplastic primordial dwarfism type II ( MOPDII ) is a condition characterized by ...

  2. Activin A is essential for neurogenesis following neurodegeneration.

    PubMed

    Abdipranoto-Cowley, Andrea; Park, Jin Sung; Croucher, David; Daniel, James; Henshall, Susan; Galbraith, Sally; Mervin, Kyle; Vissel, Bryce

    2009-06-01

    It has long been proposed that excitotoxicity contributes to nerve cell death in neurodegenerative diseases. Activin A, a member of the transforming growth factor-beta superfamily, is expressed by neurons following excitotoxicity. We show for the first time that this activin A expression is essential for neurogenesis to proceed following neurodegeneration. We found that intraventricular infusion of activin A increased the number of newborn neurons in the dentate gyrus, CA3, and CA1 layers of the normal adult hippocampus and also, following lipopolysaccharide administration, had a potent inhibitory effect on gliosis in vivo and on microglial proliferation in vivo and in vitro. Consistent with the role of activin A in regulating central nervous system inflammation and neurogenesis, intraventricular infusion of follistatin, an activin A antagonist, profoundly impaired neurogenesis and increased the number of microglia and reactive astrocytes following onset of kainic acid-induced neurodegeneration. These results show that inhibiting endogenous activin A is permissive for a potent underlying inflammatory response to neurodegeneration. We demonstrate that the anti-inflammatory actions of activin A account for its neurogenic effects following neurodegeneration because co-administration of nonsteroidal anti-inflammatory drugs reversed follistatin's inhibitory effects on neurogenesis in vivo. Our work indicates that activin A, perhaps working in conjunction with other transforming growth factor-beta superfamily molecules, is essential for neurogenesis in the adult central nervous system following excitotoxic neurodegeneration and suggests that neurons can regulate regeneration by suppressing the inflammatory response, a finding with implications for understanding and treating acute and chronic neurodegenerative diseases. PMID:19489097

  3. Type-II superlattices: the Fraunhofer perspective

    NASA Astrophysics Data System (ADS)

    Rehm, Robert; Walther, Martin; Schmitz, Johannes; Rutz, Frank; Wörl, Andreas; Scheibner, Ralf; Ziegler, Johann

    2010-04-01

    In the past years, the development of the type-II InAs/GaSb superlattice technology at the Fraunhofer-Institute for Applied Solid State Physics (IAF) has been focused on achieving series-production readiness for third generation dualcolor superlattice detector arrays for the mid-wavelength infrared spectral range. The technology is ideally suited for airborne missile threat warning systems, due to its ability of low false alarm remote imaging of hot carbon dioxide signatures on a millisecond time scale. In a multi-wafer molecular beam epitaxy based process eleven 288×384 dualcolor detector arrays are fabricated on 3" GaSb substrates. Very homogeneous detector arrays with an excellent noise equivalent temperature difference have been realized. The current article presents the type-II superlattice dual-color technology developed at IAF and delivers insights into a range of test methodologies employed at various stages during the fabrication process, which ensure that the basic requirements for achieving high detector performance are met.

  4. Type II secretion and Legionella virulence.

    PubMed

    Cianciotto, Nicholas P

    2013-01-01

    Type II secretion (T2S) is one of six systems that can occur in Gram-negative bacteria for the purpose of secreting proteins into the extracellular milieu and/or into host cells. This chapter will describe the T2S system of Legionella pneumophila. Topics to be covered include the genetic basis of T2S in L. pneumophila, the numbers (>25), types, and novelties of Legionella proteins that are secreted via T2S, and the many ways in which T2S and its substrates promote L. pneumophila physiology, ecology, and virulence. Within the aquatic environment, T2S plays a major role in L. pneumophila intracellular infection of multiple types of (Acanthamoeba, Hartmannella, and Naegleria) amoebae. Within the mammalian host, T2S promotes bacterial persistence in lungs, intracellular infection of both macrophages and epithelial cells, and a dampening of the host innate immune response. In this context, T2S may represent a potential target for both industrial and biomedical application. PMID:23900831

  5. Characterizing spiking in noisy type II neurons.

    PubMed

    Boďová, Katarína; Paydarfar, David; Forger, Daniel B

    2015-01-21

    Understanding the dynamics of noisy neurons remains an important challenge in neuroscience. Here, we describe a simple probabilistic model that accurately describes the firing behavior in a large class (type II) of neurons. To demonstrate the usefulness of this model, we show how it accurately predicts the interspike interval (ISI) distributions, bursting patterns and mean firing rates found by: (1) simulations of the classic Hodgkin-Huxley model with channel noise, (2) experimental data from squid giant axon with a noisy input current and (3) experimental data on noisy firing from a neuron within the suprachiasmatic nucleus (SCN). This simple model has 6 parameters, however, in some cases, two of these parameters are coupled and only 5 parameters account for much of the known behavior. From these parameters, many properties of spiking can be found through simple calculation. Thus, we show how the complex effects of noise can be understood through a simple and general probabilistic model.

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

    PubMed

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

    2015-09-01

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

  7. High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

    PubMed Central

    Hoda, Mir Alireza; Rozsas, Anita; Lang, Elisabeth; Klikovits, Thomas; Lohinai, Zoltan; Torok, Szilvia; Berta, Judit; Bendek, Matyas; Berger, Walter; Hegedus, Balazs; Klepetko, Walter; Renyi-Vamos, Ferenc; Grusch, Michael; Dome, Balazs; Laszlo, Viktoria

    2016-01-01

    Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases. PMID:26950277

  8. Type II Migration and Giant Planet Survival

    NASA Technical Reports Server (NTRS)

    Ward, William R.

    2003-01-01

    Type II migration, in which a newly formed large planet opens a gap in its precursor circumstellar nebula and subsequently evolves with it, has been implicated as a delivery mechanism responsible for close stellar companions. Large scale migration is possible in a viscously spreading disk of surface density sigma (r,t) when most of it is sacrificed to the primary in order to promote a small portion of the disk to much higher angular momentum orbits. Embedded planets generally follow its evolution unless their own angular momentum is comparable to that of the disk. The fraction of the starting disk mass, M (sub d) = 2pi integral rsigma(r,0)dr, that is consumed by the star depends on the distance at which material escapes the disk's outer boundary. If the disk is allowed to expand indefinitely, virtually all of the disk will fall into the primary in order to send a vanishingly small portion to infinity. For such a case, it is difficult to explain the survival of any giant planets, including Jupiter and Saturn. Realistically, however, there are processes that could truncate a disk at a finite distance, r(sub d). Recent numerical modeling has illustrated that planets can survive in this case. We show here that much of these results can be understood by simple conservation arguments.

  9. Multispectral imaging with type II superlattice detectors

    NASA Astrophysics Data System (ADS)

    Ariyawansa, Gamini; Duran, Joshua M.; Grupen, Matt; Scheihing, John E.; Nelson, Thomas R.; Eismann, Michael T.

    2012-06-01

    Infrared (IR) focal plane arrays (FPAs) with multispectral detector elements promise significant advantages for airborne threat warning, surveillance, and targeting applications. At present, the use of type II superlattice (T2SL) structures based on the 6.1Å-family materials (InAs, GaSb, and AlSb) has become an area of interest for developing IR detectors and their FPAs. The ability to vary the bandgap in the IR range, suppression of Auger processes, prospective reduction of Shockley-Read-Hall centers by improved material growth capabilities, and the material stability are a few reasons for the predicted dominance of the T2SL technology over presently leading HgCdTe and quantum well technologies. The focus of the work reported here is on the development of T2SL based dual-band IR detectors and their applicability for multispectral imaging. A new NpBPN detector designed for the detection of IR in the 3-5 and 8-12 μm atmospheric windows is presented; comparing its advantages over other T2SL based approaches. One of the key challenges of the T2SL dual-band detectors is the spectral crosstalk associated with the LWIR band. The properties of the state-of-the-art T2SLs (i.e., absorption coefficient, minority carrier lifetime and mobility, etc.) and the present growth limitations that impact spectral crosstalk are discussed.

  10. Learning Objects, Type II Applications, and Embedded Pedagogical Models

    ERIC Educational Resources Information Center

    Gadanidis, George; Schindler, Karen

    2006-01-01

    In this paper we consider the extent to which learning objects that focus on higher level thinking might be seen as Type II applications, as defined by Maddux, Johnson, and Willis (2001). We conclude that learning objects are at best hybrid applications, with some Type I and some Type II characteristics. We also consider whether the educational…

  11. Annexin II contains two types of Ca(2+)-binding sites.

    PubMed Central

    Jost, M; Weber, K; Gerke, V

    1994-01-01

    The annexins are a multigene family of Ca(2+)-dependent phospholipid-binding proteins which contain novel types of Ca2+ sites. Using site-directed mutagenesis, we generated mutant proteins that show defects in the Ca(2+)-binding sites in a particular member of this family, the src tyrosine kinase substrate annexin II. Analysis of the relative Ca(2+)-binding affinities of annexin II mutants in a combined Ca2+/phospholipid-binding assay revealed two distinct types of Ca(2+)-binding sites. Three so-called type II sites are found in annexin repeats 2, 3 and 4 respectively. Two so-called type III sites are located in the first repeat and involve the glutamic acid residues at positions 52 and 95. Both types of sites were recently identified by X-ray crystallography in annexins V and I [Huber, Schneider, Mayr, Römisch and Paques (1990) FEBS Lett. 275, 15-21; Weng, Luecke, Song, Kang, Kim and Huber (1993) Protein Sci. 2, 448-458], indicating that similar principles govern Ca2+ binding to annexins in crystals and in solution. The two types of Ca(2+)-binding sites differ not only in their architecture but also in their affinity for the bivalent cation. The Ca2+ concentration needed for half-maximal phosphatidylserine binding is 5-10 microM for an annexin II derivative with intact type II but defective type III sites (TM annexin II) whereas a mutant protein containing defective type II but unaltered type III sites (CM annexin II) requires 200-300 microM Ca2+ for the same activity. Annexin II mutants with defects in the type II and/or type III sites also show different subcellular distributions. When expressed transiently in HeLa cells, TM annexin II acquires the typical location in the cortical cytoskeleton observed for the wild-type molecule. In contrast, CM annexin II remains essentially cytosolic, as does a mutant protein containing defects in both type II and type III Ca(2+)-binding sites (TCM annexin II). This indicates that the intracellular association of annexin II

  12. Self-dual nonsupersymmetric Type II String Compactifications

    SciTech Connect

    Kachru, Shamit; Silverstein, Eva

    1998-08-17

    It has recently been proposed that certain nonsupersymmetric type II orbifolds have vanishing perturbative contributions to the cosmological constant. We show that techniques of Sen and Vafa allow one to construct dual type II descriptions of these models (some of which have no weakly coupled heterotic dual). The dual type II models are given by the same orbifolds with the string coupling S and a T{sup 2} volume T exchanged. This allows us to argue that in various strongly coupled limits of the original type II models, there are weakly coupled duals which exhibit the same perturbative cancellations as the original models.

  13. [Achondrogenesis type I and II and hypochondrogenesis (author's transl)].

    PubMed

    Bueno, M; Toledo, F; Toledo, J; Villegas, T; López, S; Remírez, J; García-Julián, G

    1980-10-01

    A study is made of achondrogenesis in relation to four observations of early fatal development. One case corresponds to type I (Parenti-Fraccaro); another to type II (Langer-Saldino); the final two, brothers, seem to come under the variation of hypochondrogenesis. In this study, authors stress the heterogenous nature of lethal, neonatal (short-limb) nanisms of which currently include: Type I and II achondrogenesis, hypochondrogenesis, homozygote achondroplasia, classical Torrance-type and San Diego-type thanatophoric dysplasia. PMID:7469190

  14. Type-II Superlattice Avalanche Photodiodes

    NASA Astrophysics Data System (ADS)

    Huang, Jun

    Type-II superlattice avalanche photodiodes have shown advantages compared to conventional mercury cadmium telluride photodiodes for infrared wavelength detection. However, surface or interface leakage current has been a major issue for superlattice avalanche photodiodes, especially in infrared wavelength region. First, passivation of the superlattice device with ammonium sulfide and thioacetamide was carried out, and its surface quality was studied by X-ray Photoelectron Spectroscopy. The study showed that both ammonium sulfide and thiacetamide passivation can actively remove the native oxide at the surface. Thiacetamide passivation combine more sulfur bonds with III-V elements than that of ammonium sulfide. Another X-ray photoelectron spectra of thiacetamide-treated atomic layer deposited zinc sulfide capped InAs/GaSb superlattice was performed to investigate the interface sulfur bond conditions. Sb--S and As--S bonds disappear while In-S bond gets enhanced, indicating that Indium Sulfide should be the major components at the interface after ZnS deposition. Second, the simulation of electrical characteristics for zinc sulfide, silicon nitride and silicon dioxide passivated superlattice devices was performed by SILVACO software to fit the experimental results and to discover the surface current mechanism. Different surface current mechanism strengths were found. Third, several novel dual-carrier avalanche photodiode structures were designed and simulated. The structures had alternate carrier multiplication regions, placed next to a wider electron multiplication region, creating dual-carrier multiplication feedback systems. Gain and excess noise factor of these structures were simulated and compared based on the dead space multiplication theory under uniform electric field. From the simulation, the applied bias can be greatly lowered or the thickness can be shrunk to achieve the same gain from the conventional device. The width of the thin region was the most

  15. Type II superlattice technology for LWIR detectors

    NASA Astrophysics Data System (ADS)

    Klipstein, P. C.; Avnon, E.; Azulai, D.; Benny, Y.; Fraenkel, R.; Glozman, A.; Hojman, E.; Klin, O.; Krasovitsky, L.; Langof, L.; Lukomsky, I.; Nitzani, M.; Shtrichman, I.; Rappaport, N.; Snapi, N.; Weiss, E.; Tuito, A.

    2016-05-01

    SCD has developed a range of advanced infrared detectors based on III-V semiconductor heterostructures grown on GaSb. The XBn/XBp family of barrier detectors enables diffusion limited dark currents, comparable with MCT Rule-07, and high quantum efficiencies. This work describes some of the technical challenges that were overcome, and the ultimate performance that was finally achieved, for SCD's new 15 μm pitch "Pelican-D LW" type II superlattice (T2SL) XBp array detector. This detector is the first of SCD's line of high performance two dimensional arrays working in the LWIR spectral range, and was designed with a ~9.3 micron cut-off wavelength and a format of 640 x 512 pixels. It contains InAs/GaSb and InAs/AlSb T2SLs, engineered using k • p modeling of the energy bands and photo-response. The wafers are grown by molecular beam epitaxy and are fabricated into Focal Plane Array (FPA) detectors using standard FPA processes, including wet and dry etching, indium bump hybridization, under-fill, and back-side polishing. The FPA has a quantum efficiency of nearly 50%, and operates at 77 K and F/2.7 with background limited performance. The pixel operability of the FPA is above 99% and it exhibits a stable residual non uniformity (RNU) of better than 0.04% of the dynamic range. The FPA uses a new digital read-out integrated circuit (ROIC), and the complete detector closely follows the interfaces of SCD's MWIR Pelican-D detector. The Pelican- D LW detector is now in the final stages of qualification and transfer to production, with first prototypes already integrated into new electro-optical systems.

  16. Inhibins and activins in human ovulation, conception and pregnancy.

    PubMed

    Lockwood, G M; Muttukrishna, S; Ledger, W L

    1998-01-01

    The activins and inhibins are glycoproteins that belong to the transforming growth factor-beta superfamily and, as such, have diverse effects at many stages during growth and development. Originally identified by their effects on follicle stimulating hormone in males and females, the recent development of specific and sensitive assays for this group of polypeptides has permitted the elucidation of their role in 'fine-tuning' the hypothalamic-pituitary-gonadal axis. This review article focuses on the roles of inhibin and activin in female reproductive physiology with reference to possible future clinical applications in the investigation of infertility and abnormal pregnancy.

  17. Activin Enhances α- to β-Cell Transdifferentiation as a Source For β-Cells In Male FSTL3 Knockout Mice.

    PubMed

    Brown, Melissa L; Andrzejewski, Danielle; Burnside, Amy; Schneyer, Alan L

    2016-03-01

    Diabetes results from inadequate β-cell number and/or function to control serum glucose concentrations so that replacement of lost β-cells could become a viable therapy for diabetes. In addition to embryonic stem cell sources for new β-cells, evidence for transdifferentiation/reprogramming of non-β-cells to functional β-cells is accumulating. In addition, de-differentiation of β-cells observed in diabetes and their subsequent conversion to α-cells raises the possibility that adult islet cell fate is malleable and controlled by local hormonal and/or environmental cues. We previously demonstrated that inactivation of the activin antagonist, follistatin-like 3 (FSTL3) resulted in β-cell expansion and improved glucose homeostasis in the absence of β-cell proliferation. We recently reported that activin directly suppressed expression of critical α-cell genes while increasing expression of β-cell genes, supporting the hypothesis that activin is one of the local hormones controlling islet cell fate and that increased activin signaling accelerates α- to β-cell transdifferentiation. We tested this hypothesis using Gluc-Cre/yellow fluorescent protein (YFP) α-cell lineage tracing technology combined with FSTL3 knockout (KO) mice to label α-cells with YFP. Flow cytometry was used to quantify unlabeled and labeled α- and β-cells. We found that Ins+/YFP+ cells were significantly increased in FSTL3 KO mice compared with wild type littermates. Labeled Ins+/YFP+ cells increased significantly with age in FSTL3 KO mice but not wild type littermates. Sorting results were substantiated by counting fluorescently labeled cells in pancreatic sections. Activin treatment of isolated islets significantly increased the number of YFP+/Ins+ cells. These results suggest that α- to β-cell transdifferentiation is influenced by activin signaling and may contribute substantially to β-cell mass.

  18. Type II collagenopathies: Are there additional family members?

    SciTech Connect

    Freisinger, P.; Pontz, B.F.; Emmrich, P.; Stoess, H.; Bonaventure, J.

    1996-05-03

    The type II collagenopathies represent a group of chondrodysplasia sharing clinical and radiological manifestations which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal to very mild conditions. Their common molecular bases are mutations in the type II collagen gene (COL2A1). We describe one case of lethal platyspondylic dysplasia, Torrance type, and a variant of lethal Kniest dysplasia, neither of which has been reported as a type II collagenopathy. Biochemical studies of cartilage collagens and morphological analysis of cartilage sections suggest that abnormalities of type II collagen structure and biosynthesis are the main pathogenetic factors in both cases. Thus, the phenotypic spectrum of type II collagenopathies might be greater than hitherto suspected. 20 refs., 6 figs.

  19. [Osteochondrodysplasia determined genetically by a collagen type II gene mutation].

    PubMed

    Czarny-Ratajczak, M; Rogala, P; Wolnik-Brzozowska, D; Latos-Bieleńska, A

    2001-01-01

    Chondrodysplasias are a heterogenous group of skeletal dysplasias, affecting the growing cartilage. The main part of chondrodysplasias is caused by mutations in various types of collagen genes. The current classification within this group of disorder relies on clinical, histological and radiographic features. Type II collagenopathies comprise part of chondrodysplasias, consisting of hereditary disorders caused by defects in the type II collagen. Collagen type II is coded by a large gene--COL2A1. The chromosomal location for the human COL2A1 gene is 12q13.11-q13.12. Defects in collagen type II are caused by point mutations in the COL2A1 gene. Type II collagenopathies form a wide spectrum of clinical severity ranging from lethal achondrogenesis type II, hypochondrogenesis, through severe forms like spondyloepiphyseal dysplasia congenita, spondyloepimetaphyseal dysplasia congenita, Marshall syndrome, to the mild forms--Stickler syndrome and early osteoarthritis. The pathological changes in the patients are observed in the growth plate, nucleus pulposus and vitreous body, where the abnormal collagen type II is distributed. This article presents the genetic background of collagenopathies type II and the results of current molecular studies of the patients. Both the molecular and the clinical studies may promise a better understanding of the relationship between the genotype and the phenotype. We present the patients, who were diagnosed at the Department of Medical Genetics and in the Orthopaedic Department in Poznań. PMID:11481990

  20. A drug delivery hydrogel system based on activin B for Parkinson's disease.

    PubMed

    Li, Juan; Darabi, Mohammadali; Gu, Jingjing; Shi, Junbin; Xue, Jinhua; Huang, Lu; Liu, Yutong; Zhang, Lei; Liu, N; Zhong, Wen; Zhang, Lin; Xing, Malcolm; Zhang, Lu

    2016-09-01

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Activins are members of the superfamily of transforming growth factors and have many potential neuroprotective effects. Herein, at the first place, we verified activin B's neuroprotective role in a PD model, and revealed that activin B's fast release has limited function in the PD therapy. To this end, we developed a multi-functional crosslinker based thermosensitive injectable hydrogels to deliver activin B, and stereotactically injected the activin B-loaded hydrogel into the striatum of a mouse model of PD. The histological evaluation showed that activin B can be detected even 5 weeks post-surgery in PD mice implanted with activin B-loaded hydrogels, and activin B-loaded hydrogels can significantly increase the density of tyrosine hydroxylase positive (TH(+)) nerve fibers and reduce inflammatory responses. The behavioral evaluation demonstrated that activin B-loaded hydrogels significantly improved the performance of the mice in the PD model. Meanwhile, we found that hydrogels can slightly induce the activation of microglia cells and astrocytes, while cannot induce apoptosis in the striatum. Overall, our data demonstrated that the developed activin B-loaded hydrogels provide sustained release of activin B for over 5 weeks and contribute to substantial cellular protection and behavioral improvement, suggesting their potential as a therapeutic strategy for PD.

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

    PubMed Central

    Howell, M; Hill, C S

    1997-01-01

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

  2. Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater Fish

    PubMed Central

    2014-01-01

    Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions. PMID:24868555

  3. The type II collagenopathies: a spectrum of chondrodysplasias.

    PubMed

    Spranger, J; Winterpacht, A; Zabel, B

    1994-02-01

    With the application of molecular techniques the aetiopathogenesis of skeletal dysplasias is gradually elucidated. Recent advances show that some bone dysplasias result from defects in the biosynthesis of type II (cartilage) collagen. Clinical entities caused by mutations in the COL2A1 gene coding for type II collagen comprise achondrogenesis II, hypochondrogenesis, spondyloepiphyseal dysplasia congenita, Kniest dysplasia, Stickler arthroophthalmopathy and mild dominant spondyloarthropathy. The mutations are expressed in the heterozygous state, and inheritance of type II collagenopathies is autosomal dominant. The wide range of clinical manifestations is not well understood but characterization of the basic defect may provide clues to establish specific genotype-phenotype correlations. PMID:8157027

  4. Type II lepra reaction--an unusual presentation.

    PubMed

    Ray, Avas Chandra; Sen, Sumit; Banerjee, Sabyasachi; Mukhopadhyay, Jotideb

    2012-06-01

    Type II lepra reaction usually present with skin lesions. We report a 23 years old male patient presented with fever for two weeks with no visible skin lesion suggestive of leprosy and with no history of either completion or concurrent anti leprosy drug treatment was eventually turned out to be a case of Hansen's presenting with type II lepra reaction. PMID:23409423

  5. Unmyelinated type II afferent neurons report cochlear damage

    PubMed Central

    Liu, Chang; Glowatzki, Elisabeth; Fuchs, Paul Albert

    2015-01-01

    In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term “noxacusis” to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage. Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear. PMID:26553995

  6. Structure and activation of pro-activin A

    PubMed Central

    Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

    2016-01-01

    Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

  7. Structure and activation of pro-activin A.

    PubMed

    Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

    2016-01-01

    Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

  8. IMMUNOLOCALIZATION OF INHIBIN/ACTIVIN SUBUNITS AND STEROIDOGENIC ENZYMES IN THE TESTES OF AN ADULT AFRICAN ELEPHANT (LOXODONTA AFRICANA).

    PubMed

    Li, Qinglin; Lu, Lu; Weng, Qiang; Kawakami, Shigehisa; Saito, Eriko; Yamamoto, Tatsuya; Yamamoto, Yuki; Kaewmanee, Saroch; Nagaoka, Kentaro; Watanabe, Gen; Taya, Kazuyoshi

    2016-06-01

    In this case report, the authors investigated immunolocalization of inhibin α and inhibin/activin βA and βB subunits, as well as steroidogenic enzymes, in the testes of an African elephant. Testes were collected from a reproductively active male African elephant (24 yr old) at autopsy. Histologically, all types of spermatogenic cells including mature-phase spermatozoa were found in the seminiferous tubules. Positive immunostaining for inhibin α and inhibin/activin βA and βB subunits was observed in Sertoli and Leydig cells. In addition, P450scc, 3βHSD, P450c17, and P450arom were also detected in the cytoplasm of Leydig cells. These results suggested that Leydig cells of adult African elephant testes have the ability to synthesize progestin, androgen, and estrogen, whereas both Sertoli and Leydig cells appear as a major source of inhibin secretion in the male African elephant.

  9. Prediction of Type II Burst Radiation for Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Schmidt, J. M.

    2013-12-01

    Type IIs are associated with shocks in the corona and solar wind, either driven by CMEs or else blast waves. Recent quantitative theories for type II radiation show that the amount of radiation depends on the speed and spatial extent of the 3D shock, as well as on the background plasma, magnetic field configuration, and the number of superthermal electrons available for acceleration by the shock. In principle, then, Type II bursts may provide 1-3 day warnings of large and fast CMEs that might produce space weather at Earth. In this paper we couple the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our new ``bolt-on'' theory for type II emission. The modeling includes initialization with coronal and active region magnetic fields reconstructed from solar magnetograms, coronal densities determined by 1 AU data, and CMEs modelled using STEREO coronagraph data. Two events with type IIs and strong CMEs are analyzed: 15 February 2011 and 7 March 2012. We demonstrate impressive accuracy in time, frequency, and intensity for both type II bursts. This strongly supports the type II theory, implies real understanding of the physics involved, and supports the near-term development of a capability to predict and track these events for space weather prediction.

  10. Phase II Evaluation of Dalantercept, a Soluble Recombinant Activin Receptor-Like Kinase 1 (ALK1) Receptor Fusion Protein, for the Treatment of Recurrent or Persistent Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study 0229N

    PubMed Central

    Makker, Vicky; Filiaci, Virginia L.; Chen, Lee-may; Darus, Christopher J.; Kendrick, James E.; Sutton, Gregory; Moxley, Katherine; Aghajanian, Carol

    2015-01-01

    Objective This two-stage phase II study assessed activity of single agent dalantercept in patients with recurrent/persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent/recurrent EMC after 1–2 prior cytotoxic regimens, measurable disease (RECIST 1.1), and GOG performance ≤ 2. Dalantercept 1.2 mg/kg subcutaneous was administered once every 3 weeks until disease progression (PD)/development of prohibitory toxicity. Primary objectives were to estimate the proportion of patients with persistent/recurrent EMC, who survive progression-free without receiving non-protocol therapy (TPFS) for at least 6 months and to estimate the proportion having objective tumor response. Results All 28 enrolled patients were eligible and evaluable. Median age: 62 years. Most common histologies: 32% Grade 1/2 endometrioid and 54% serous tumors. Prior treatment: 1 or 2 regimens in 82% and 18% of patients, respectively. Eighteen patients received prior radiation therapy. Patients received 1–12 cycles of dalantercept, and 46% of patients received ≤2 cycles. The most common adverse events (AE) were fatigue, anemia, constipation and peripheral edema. Grade 3/4 AEs occurred in 39% and 4% of patients. One grade 5 gastric hemorrhage in a patient with a history of radiation fibrosis/small bowel obstruction was deemed possibly dalantercept-related. All patients are off study: 86% for PD. No ORs were observed; 57% had stable disease and 11% had TPFS ≥ 6 mos. Median progression-free and overall survival: 2.1 months (90% CI: 1.4–3.2) and 14.5 months (90% CI: 7.0–17.5), respectively. Conclusions Dalantercept has insufficient single agent activity in recurrent EMC to warrant further investigation at this dose level and schedule. PMID:25888978

  11. Potassium currents in rat type II alveolar epithelial cells.

    PubMed Central

    DeCoursey, T E; Jacobs, E R; Silver, M R

    1988-01-01

    1. Type II alveolar epithelial cells isolated from adult rats and grown in primary culture were studied using the whole-cell configuration of the gigohm-seal voltage clamp technique. 2. The average specific capacitance of type II cells was 2.5 microF/cm2, suggesting that type II cell membranes in vitro are irregular, with an actual area more than twice the apparent area. 3. Most type II cells have time- and voltage-dependent outward currents carried by potassium ions. Potassium currents activate with a sigmoid time course upon membrane depolarization, and inactivate during maintained depolarization. The average maximum whole-cell K+ conductance was 1.6 nS. 4. Two distinct types of K+-selective channels underlie outward currents in type II cells. Most cells have currents resembling delayed rectifier K+ currents in skeletal muscle, nerve and immune cells. A few cells had a different type of K+ conductance which is more sensitive to block by tetraethylammonium ions, has faster 'tail currents', and activates at more positive potentials. 5. In some experiments, individual type II cells were identified by staining with phosphine, a fluorescent dye which is concentrated in lamellar bodies. Both types of K+ channels were seen in type II cells identified with this dye. 6. Phosphine added to the bathing solution reversibly reduced K+ currents and shifted K+ channel activation to more positive potentials. Excitation of phosphine to fluoresce reduced irreversibly K+ currents in type II cells. The usefulness of phosphine as a means of identifying cells for study is discussed. PMID:2457683

  12. Type II collagen screening in the human chondrodysplasias.

    PubMed

    Horton, W A; Campbell, D; Machado, M A; Chou, J

    1989-12-01

    Abnormalities of type II collagen have been considered strong candidates for causing human condrodysplasias. We have employed peptide mapping to screen for several types of type II colagen abnormalities in cartilage samples from 66 patients with 20 separate disorders. Except for achondrogenesis type II (Langer-Saldino) and spondyloepiphyseal dysplasia (SED) congenita in which abnormalities have been described and diastrophic dysplasia in which the changes were probably secondary, no abnormalities were detected. Within the limitations of the screening technique, the results combined with other data from the literature suggest that abnormalities of this molecule are not common causes of chondrodysplasias outside of the achondrogenesis type II-SED congenita family of disorders. PMID:2624272

  13. Dentinogenesis imperfecta type II: an affected family saga.

    PubMed

    Kamboj, Mala; Chandra, Anil

    2007-09-01

    Dentinogenesis imperfecta (DI) type II or hereditary opalescent dentin is inherited in simple autosomal dominant mode with high penetrance and low mutation rate. It generally affects both the deciduous and permanent dentitions. DI type II corresponds to a localized form of mesodermal dysplasia, observed in histodifferentiation. Early diagnosis and treatment are therefore, fundamental, aiming at obtaining a favourable prognosis since late intervention makes treatment more complex. We present two cases of DI type II with the disease affecting three generations of a family in India, and briefly highlight the molecular basis of this disease.

  14. Type II oestrogen binding sites in human colorectal carcinoma.

    PubMed Central

    Piantelli, M; Ricci, R; Larocca, L M; Rinelli, A; Capelli, A; Rizzo, S; Scambia, G; Ranelletti, F O

    1990-01-01

    Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. PMID:2266171

  15. Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies.

    PubMed Central

    Godfrey, M; Keene, D R; Blank, E; Hori, H; Sakai, L Y; Sherwin, L A; Hollister, D W

    1988-01-01

    A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3057886

  16. Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies.

    PubMed

    Godfrey, M; Keene, D R; Blank, E; Hori, H; Sakai, L Y; Sherwin, L A; Hollister, D W

    1988-12-01

    A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen. PMID:3057886

  17. Serum markers for type II diabetes mellitus

    DOEpatents

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Polpitiya, Ashoka D; Camp, II, David G; Smith, Richard D

    2014-03-18

    A method for identifying persons with increased risk of developing type 2 diabetes mellitus utilizing selected biomarkers described hereafter either alone or in combination. The present invention allows for broad based, reliable, screening of large population bases and provides other advantages, including the formulation of effective strategies for characterizing, archiving, and contrasting data from multiple sample types under varying conditions.

  18. Type II cochlear ganglion cells in the chinchilla.

    PubMed

    Ruggero, M A; Santi, P A; Rich, N C

    1982-12-01

    In order to ascertain whether Type II cochlear ganglion cells project to the brain, we have studied the retrograde transport of horseradish peroxidase (HRP) from the cochlear nucleus to the spiral ganglion of the chinchilla. In this animal there exist two types of ganglion neurons, which closely correspond to those previously described in guinea pigs, cats and rats. As in the guinea pig, the majority population (Type I) consists of relatively large, myelinated neurons. The minority population (Type II, 10% of the total population) consists of small, mostly unmyelinated cells, with filamentous cytoplasm and finely grained nuclear chromatin. Type II neurons tend to be clustered toward the peripheral side of Rosenthal's canal, often in close proximity to the intraganglionic spiral bundle. By 24 h after injections of HRP into the cochlear nucleus, incubation of the cochlear ganglion in diaminobenzidine/H2O2 reveals abundant HRP label in both Type I and Type II neurons. Type II neurons, however, tend to be labelled less intensely than Type I neurons. Control experiments, consisting of spillage of HRP solution over the cochlear nucleus, were carried out to determine how much HRP might be picked up by neurons after HRP diffusion. Comparison of cochleae from injected animals and from the control animals suggests that most of the label that was found in ganglion neurons after cochlear nucleus injections represents axonally transported HRP. We conclude, at least tentatively, that Type II neurons project to the brain. The fact that less label is found in Type II neurons that in Type I neurons suggests that the former have thinner axons and/or finer terminals in the cochlear nucleus. PMID:6185462

  19. A COL2A1 mutation in achondrogenesis type II results in the replacement of type II collagen by type I and III collagens in cartilage.

    PubMed

    Chan, D; Cole, W G; Chow, C W; Mundlos, S; Bateman, J F

    1995-01-27

    An autosomal dominant mutation in the COL2A1 gene was identified in a fetus with achondrogenesis type II. A transition of G2853 to A in exon 41 produced a substitution of Gly769 by Ser within the triple helical domain of the alpha 1(II) chain of type II collagen, interrupting the mandatory Gly-X-Y triplet sequence required for the normal formation of stable triple helical type II collagen molecules, resulting in the complete absence of type II collagen in the cartilage, which had a gelatinous composition. Type I and III collagens were the major species found in cartilage tissue and synthesized by cultured chondrocytes along with cartilage type XI collagen. However, cultured chondrocytes produced a trace amount of type II collagen, which was retained within the cells and not secreted. In situ hybridization of cartilage sections showed that the chondrocytes produced both type II and type I collagen mRNA. As a result, it is likely that the chondrocytes produced type II collagen molecules, which were then degraded. The close proximity of the Gly769 substitution by Ser to the mammalian collagenase cleavage site at Gly775-Leu776 may have produced an unstable domain that was highly susceptible to proteolysis. The type I and III collagens that replaced type II collagen were unable to maintain the normal structure of the hyaline cartilage but did support chondrocyte maturation, evidenced by the expression of type X collagen in the hypertrophic zone of the growth plate cartilage. PMID:7829510

  20. Imaging Observations of a Very High Frequency Type II Burst

    NASA Astrophysics Data System (ADS)

    White, S. M.; Mercier, C.; Bradley, R.; Bastian, T.; Kerdraon, A.; Pick, M.

    2006-05-01

    A remarkable Type II burst was detected by the high-frequency system of the Green Bank Solar Radio Burst Spectrometer on 2005 November 14. The harmonic branch of the Type II extended up to 800 MHz, making it one of the highest frequency Type II bursts ever detected, but it failed to propagate to heights corresponding to frequencies below 100 MHz. At such high frequencies, it implies the formation of a shock relatively low in the corona. No coronal mass ejection was evident in the LASCO data for this east limb event. It is one of the few Type II bursts to be observable at every frequency of observation of the Nancay Radio Heliograph (164-432 MHz). Here we present analysis of images of the event, including simultaneous imaging of the fundamental and harmonic branches.

  1. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... when tested in accordance with 40 CFR Part 136. (b) The 40 samples must be taken from the device as...: Type II devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of...

  2. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... when tested in accordance with 40 CFR Part 136. (b) The 40 samples must be taken from the device as...: Type II devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of...

  3. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... when tested in accordance with 40 CFR Part 136. (b) The 40 samples must be taken from the device as...: Type II devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of...

  4. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... when tested in accordance with 40 CFR Part 136. (b) The 40 samples must be taken from the device as...: Type II devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of...

  5. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... when tested in accordance with 40 CFR part 136. (b) The 40 samples must be taken from the device as...: Type II devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of...

  6. PKMiner: a database for exploring type II polyketide synthases

    PubMed Central

    2012-01-01

    Background Bacterial aromatic polyketides are a pharmacologically important group of natural products synthesized by type II polyketide synthases (type II PKSs) in actinobacteria. Isolation of novel aromatic polyketides from microbial sources is currently impeded because of the lack of knowledge about prolific taxa for polyketide synthesis and the difficulties in finding and optimizing target microorganisms. Comprehensive analysis of type II PKSs and the prediction of possible polyketide chemotypes in various actinobacterial genomes will thus enable the discovery or synthesis of novel polyketides in the most plausible microorganisms. Description We performed a comprehensive computational analysis of type II PKSs and their gene clusters in actinobacterial genomes. By identifying type II PKS subclasses from the sequence analysis of 280 known type II PKSs, we developed highly accurate domain classifiers for these subclasses and derived prediction rules for aromatic polyketide chemotypes generated by different combinations of type II PKS domains. Using 319 available actinobacterial genomes, we predicted 231 type II PKSs from 40 PKS gene clusters in 25 actinobacterial genomes, and polyketide chemotypes corresponding to 22 novel PKS gene clusters in 16 genomes. These results showed that the microorganisms capable of producing aromatic polyketides are specifically distributed within a certain suborder of Actinomycetales such as Catenulisporineae, Frankineae, Micrococcineae, Micromonosporineae, Pseudonocardineae, Streptomycineae, and Streptosporangineae. Conclusions We could identify the novel candidates of type II PKS gene clusters and their polyketide chemotypes in actinobacterial genomes by comprehensive analysis of type II PKSs and prediction of aromatic polyketides. The genome analysis results indicated that the specific suborders in actinomycetes could be used as prolific taxa for polyketide synthesis. The chemotype-prediction rules with the suggested type II PKS

  7. Achondrogenesis type II (Langer-Saldino)--a case report.

    PubMed

    Swar, M O; Srikrishna, B V

    1995-09-01

    Achondrogenesis is a lethal form of congenital chondrodystophy characterised by extreme micromelia. Definitive clinical and radiographic criteria have been established to differentiate Type II Achondrogenesis (Langer-Saldino) from type I Achondrogenesis (Parenti-Fraccaro). The mode of inheritance is autosomal recessive for both types. We are presenting a case of Type II Achondrogenesis, a still born male to consanguinous parents. The clinical features included an enlarged head, protuberant abdomen and short stubby limbs. The mother had earlier delivered two still born males presumably with similar features. Radiographic characteristics of absence of rib fractures and well ossified iliac bones with concave medial margins and absent or deficient ossification of the sacrum, ischiae, and pubic bones differentiated Type II Achondrogenesis from Type I Achondrogenesis. PMID:8798967

  8. Achondrogenesis type II with normally developed extremities: a case report.

    PubMed

    Kocakoc, Ercan; Kiris, Adem

    2002-07-01

    We present a case of achondrogenesis type II with normally developed extremities that was confirmed with postmortem ultrasonographic and radiographic examination. The length of the long bones may vary and the diagnosis of achondrogenesis should not be ruled out with normally developed extremities. Intrauterine sonographic examination of the vertebrae is very important and the absence of vertebral body ossification may be the unique finding of achondrogenesis type II. Axial ultrasonographic images and postmortem plain radiographs are useful to clarify the pathology. PMID:12124695

  9. Richner-Hanhart syndrome and tyrosinemia type II.

    PubMed

    Hunziker, N

    1980-01-01

    A patient already published a case of Richner-Hanhart syndrome (RHS) (stabilized corneal lesions and hyperkeratotic lesions on the palms and soles) proved to be associated with tyrosinemia type II. 2 other cases (sister and brother) with only typical dermatologic features of RHS and tyrosinemia type II are described. The treatment with a low phenylalanine and tyrosine diet improves the cutaneous lesions in our 3 cases.

  10. Unsupervised Clustering of Type II Supernova Light Curves

    NASA Astrophysics Data System (ADS)

    Rubin, Adam; Gal-Yam, Avishay

    2016-09-01

    As new facilities come online, the astronomical community will be provided with extremely large data sets of well-sampled light curves (LCs) of transients. This motivates systematic studies of the LCs of supernovae (SNe) of all types, including the early rising phase. We performed unsupervised k-means clustering on a sample of 59 R-band SN II LCs and find that the rise to peak plays an important role in classifying LCs. Our sample can be divided into three classes: slowly rising (II-S), fast rise/slow decline (II-FS), and fast rise/fast decline (II-FF). We also identify three outliers based on the algorithm. The II-FF and II-FS classes are disjoint in their decline rates, while the II-S class is intermediate and “bridges the gap.” This may explain recent conflicting results regarding II-P/II-L populations. The II-FS class is also significantly less luminous than the other two classes. Performing clustering on the first two principal component analysis components gives equivalent results to using the full LC morphologies. This indicates that Type II LCs could possibly be reduced to two parameters. We present several important caveats to the technique, and find that the division into these classes is not fully robust. Moreover, these classes have some overlap, and are defined in the R band only. It is currently unclear if they represent distinct physical classes, and more data is needed to study these issues. However, we show that the outliers are actually composed of slowly evolving SN IIb, demonstrating the potential of such methods. The slowly evolving SNe IIb may arise from single massive progenitors.

  11. Histological types of polypoid cutaneous melanoma II.

    PubMed

    Knezević, Fabijan; Duancić, Vjekoslav; Sitić, Sanda; Horvat-Knezević, Anica; Benković, Vesna; Ramić, Snjezana; Kostović, Kresimir; Ramljak, Vesna; Vrdoljak, Danko Velemir; Stanec, Mladen; Bozović, Angelina

    2007-12-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type. PMID:18217457

  12. The initial hyperglycemia in acute type II pyrethroid poisoning.

    PubMed

    Kim, Dongseob; Moon, Jeongmi; Chun, Byeongjo

    2015-04-01

    This retrospective observational case series study was conducted to describe the clinical feature of acute type II pyrethroid poisoning, and to investigate whether hyperglycemia at presentation can predict the outcome in patients with type II pyrethroid poisoning. This study included 104 type II pyrethroid poisoned patients. The complication rate and mortality rate was 26.9% and 2.9% in type II pyrethroid poisoned patients. The most common complication was respiratory failure followed by acidosis and hypotension. In non-diabetic type II pyrethroid poisoned patients, patients with complications showed a higher frequency of hyperglycemia, abnormalities on the initial X ray, depressed mentality, lower PaCO2 and HCO3- levels, and a higher WBC and AST levels at the time of admission compared to patients without complication. Hyperglycemia was an independent factor for predicting complications in non-diabetic patients. Diabetic patients had a significantly higher incidence of complications than non-diabetic patients. However, there was no significant predictive factor for complications in patients with diabetes mellitus probably because of small number of diabetes mellitus. In contrast to the relatively low toxicity of pyrethroids in mammals, type II pyrethroid poisoning is not a mild disease. Hyperglycemia at presentation may be useful to predict the critical complications in non-diabetic patients. PMID:25829802

  13. The initial hyperglycemia in acute type II pyrethroid poisoning.

    PubMed

    Kim, Dongseob; Moon, Jeongmi; Chun, Byeongjo

    2015-04-01

    This retrospective observational case series study was conducted to describe the clinical feature of acute type II pyrethroid poisoning, and to investigate whether hyperglycemia at presentation can predict the outcome in patients with type II pyrethroid poisoning. This study included 104 type II pyrethroid poisoned patients. The complication rate and mortality rate was 26.9% and 2.9% in type II pyrethroid poisoned patients. The most common complication was respiratory failure followed by acidosis and hypotension. In non-diabetic type II pyrethroid poisoned patients, patients with complications showed a higher frequency of hyperglycemia, abnormalities on the initial X ray, depressed mentality, lower PaCO2 and HCO3- levels, and a higher WBC and AST levels at the time of admission compared to patients without complication. Hyperglycemia was an independent factor for predicting complications in non-diabetic patients. Diabetic patients had a significantly higher incidence of complications than non-diabetic patients. However, there was no significant predictive factor for complications in patients with diabetes mellitus probably because of small number of diabetes mellitus. In contrast to the relatively low toxicity of pyrethroids in mammals, type II pyrethroid poisoning is not a mild disease. Hyperglycemia at presentation may be useful to predict the critical complications in non-diabetic patients.

  14. Mg II 2800 A emission in late type stars

    NASA Technical Reports Server (NTRS)

    Doherty, L. R.

    1972-01-01

    The largest body of data on ultraviolet spectra of late-type stars now available is the series of scans made with the long wavelength spectrometer onboard OAO-2. Some features of selected scans from this series and estimates of Mg II emission fluxes were reported earlier. Since that time, the effects of sky background, scattered light and variable instrumental sensitivity have become better understood. Additional stars are used to define more clearly the transition from Mg II 2800 A absorption to emission with advancing spectral type, and additional scans of alpha Sco provide a better estimate of Mg II emission strength for this supergiant in OAO observations.

  15. Activin A and follistatin during the oestrous cycle and early pregnancy in ewes.

    PubMed

    O'Connell, Anne R; McNatty, Kenneth P; Hurst, Peter R; Spencer, Thomas E; Bazer, Fuller W; Reader, Karen L; Johnstone, Peter D; Davis, George H; Juengel, Jennifer L

    2016-03-01

    The activin pathway has been postulated to be involved in regulation of multiple reproductive processes important for survival of the conceptus. These processes include luteinisation of the follicular cells and thus function of the corpus luteum, early embryo development and uterine function including implantation of the conceptus. Therefore, the aim of the current study was to determine whether the concentrations of activin A and follistatin (FST), an activin-binding protein, differed between ewes with a lifetime history of enhanced or reduced embryonic survival (ES). The mRNAs encoding FST and activin A (inhibin beta A subunit; INHBA) were present in the uterus and abundant in the uterine luminal or glandular epithelia by day 18 of gestation. A peak of activin A was observed in the systemic circulation around the time of oestrus, and activin A concentrations were elevated in animals with reduced ES during the oestrous cycle and early gestation. Concentrations of activin A in uterine fluid were approximately twofold greater on day 16 of gestation in ewes with reduced ES compared to those with enhanced ES. No consistent differences in FST were observed between these groups. Treatment of luteinising ovine granulosa cells with activin A in vitro suppressed progesterone secretion providing evidence of a potential pathway whereby increased concentrations of activin A may decrease ES. PMID:26733604

  16. Novel ovarian regulatory peptides: inhibin, activin, and follistatin.

    PubMed

    Ling, N; DePaolo, L V; Bicsak, T A; Shimasaki, S

    1990-09-01

    Based on the extensive amount of research on inhibin and related polypeptides accomplished during the past 5 years, the inhibin concept put forth more than 50 years ago has not only become well established but also more complex than originally imagined. The closed-loop feedback mechanism of ovarian inhibin and pituitary FSH has been joined by possible "inhibin-like" actions of follistatin and FSH-stimulatory effects of activin. In addition, in vitro experiments suggest possible autocrine and paracrine functions for the gonadal polypeptide hormones. Figure 3 shows a simplistic diagram summarizing our current understanding of inhibin/activin and follistatin action along the hypothalamic-pituitary-gonadal axis. Hopefully, research in the coming years will allow us to remove the many question marks still remaining but will undoubtedly add others.

  17. Biceps instability and Slap type II tear in overhead athletes.

    PubMed

    Osti, Leonardo; Soldati, Francesco; Cheli, Andrea; Pari, Carlotta; Massari, Leo; Maffulli, Nicola

    2012-10-01

    Type II lesions are common lesions encountered in overhead athletes with controversies arising in term of timing for treatment, surgical approach, rehabilitation and functional results. The aim of our study was to evaluate the outcomes of arthroscopic repair of type II SLAP tears in overhead athletes, focusing on the time elapsed from diagnosis and treatment, time needed to return to sport, rate of return to sport and to previous level of performance, providing an overview concerning evidence for the effectiveness of different surgical approaches to type II SLAP tears in overhead athletes. A internet search on peer reviewed Journal from 1990, first descriprion of this pathology, to 2012, have been conducted evaluating the outcomes for both isolated Slap II tear overhead athletes and those who presented associated lesions treated. The results have been analyzed according to the scale reported focusing on return to sport and level of activity. Apart from a single study, non prospective level I and II studies were detected. Return to play at the same level ranged form 22% to 94% with different range of technique utilized with the majority of the authors recommending the fixation of these lesions but biceps tenodesis can lead to higher satisfaction racte when directly compated to the anchor fixation. Associated pathologies such as partial or full tickness rotator cuff tear did not clearly affect the outcomes and complications rate. There is no consensus regarding timing and treatment for type II SLAP, especially in overhead athletes who need to regain a high level of performance.

  18. Prenatal diagnosis of Smith-Lemli-Opitz syndrome, type II.

    PubMed

    Johnson, J A; Aughton, D J; Comstock, C H; von Oeyen, P T; Higgins, J V; Schulz, R

    1994-01-15

    Smith-Lemli-Opitz syndrome, type II (SLOS-II) is a severe autosomal recessive disorder characterized by a distinctive face, unusual cleft palate, postaxial polydactyly, congenital heart defects, renal anomalies, and male pseudohermaphroditism. We present the first report of prenatal diagnosis of SLOS-II, as well as an additional report of prenatal detection of multiple anomalies, in which a positive diagnosis of SLOS II was made postnatally. In neither case was the pregnancy known prospectively to be at risk for SLOS-II. In the former case, targeted sonographic examination at 31 weeks of gestation showed intrauterine growth retardation, atrioventricular septal defect, mesomelic shortening of the arms, small kidneys, overlapping fingers, and female external genitalia; a 46,XY chromosome constitution had been ascertained previously. A provisional diagnosis of SLOS-II was made prenatally. In the latter case, targeted sonographic examination at 18 weeks of gestation showed severe oligohydramnios, atrioventricular septal defect, and Dandy-Walker malformation. The kidneys and bladder were not visualized. The chromosome constitution was 46,XX. The diagnosis of SLOS-II was made postnatally. In both cases, additional findings compatible with SLOS-II were noted postnatally. Prenatal detection of congenital heart defects and renal abnormalities, in combination with certain additional findings (most notably, female external genitalia in the presence of a 46,XY karyotype, polydactyly, disproportionately short limbs, or intrauterine growth retardation) and a normal karyotype, suggests the diagnosis of SLOS-II, and warrants further investigation.

  19. A sample of Type II-L supernovae

    NASA Astrophysics Data System (ADS)

    Faran, T.; Poznanski, D.; Filippenko, A. V.; Chornock, R.; Foley, R. J.; Ganeshalingam, M.; Leonard, D. C.; Li, W.; Modjaz, M.; Serduke, F. J. D.; Silverman, J. M.

    2014-11-01

    What are Type II-Linear supernovae (SNe II-L)? This class, which has been ill defined for decades, now receives significant attention - both theoretically, in order to understand what happens to stars in the ˜15-25 M⊙ range, and observationally, with two independent studies suggesting that they cannot be cleanly separated photometrically from the regular hydrogen-rich SNe II-P characterized by a marked plateau in their light curve. Here, we analyse the multiband light curves and extensive spectroscopic coverage of a sample of 35 SNe II and find that 11 of them could be SNe II-L. The spectra of these SNe are hydrogen deficient, typically have shallow Hα absorption, may show indirect signs of helium via strong O I λ7774 absorption, and have faster line velocities consistent with a thin hydrogen shell. The light curves can be mostly differentiated from those of the regular, hydrogen-rich SNe II-P by their steeper decline rates and higher luminosity, and we propose to define them based on their decline in the V band: SNe II-L decline by more than 0.5 mag from peak brightness by day 50 after explosion. Using our sample we provide template light curves for SNe II-L and II-P in four photometric bands.

  20. HLA class II genes: typing by DNA analysis.

    PubMed

    Bidwell, J L; Bidwell, E A; Bradley, B A

    1990-04-01

    A detailed understanding of the structure and function of the human major histocompatibility complex (MHC) has ensued from studies by molecular biologist during the last decade. Virtually all of the HLA genes have now been cloned, and the nucleotide sequences of their different allelic forms have been determined. Typing for these HLA alleles is a fundamental prerequisite for tissue matching in allogeneic organ transplantation. Until very recently, typing procedures have been dominated by serological and cellular methods. The availability of cloned DNA from HLA genes has now permitted the technique of restriction fragment length polymorphism (RFLP) analysis to be applied, with remarkable success and advantage, to phenotyping of both HLA Class I and Class II determinants. For the HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the accurate identification of all specificities defined by serology, and of many which are defined by cellular typing. At the present time, however, RFLP typing of HLA Class I genes is not as practicable or as informative as that for HLA Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing are predominantly in phenotyping of living donors, including selection of HLA-matched volunteer bone marrow donors, in allograft survival studies, and in studies of HLA Class II-associated diseases. However, the time taken to perform RFLP analysis precludes its use for the typing of cadaveric kidney donors. Nucleotide sequence data for the alleles of HLA Class II genes have now permitted the development of allele-specific oligonucleotide (ASO) typing, a second category of DNA analysis. This has been greatly facilitated by the ability to amplify specific HLA Class II DNA 'target' sequences using the polymerase chain reaction (PCR) technique. The accuracy of DNA typing techniques should ensure that this methodology will eventually replace conventional HLA phenotyping.

  1. Painful keratoderma and photophobia: hallmarks of tyrosinemia type II.

    PubMed

    Rabinowitz, L G; Williams, L R; Anderson, C E; Mazur, A; Kaplan, P

    1995-02-01

    Tyrosinemia type II (Richner-Hanhart syndrome), which is caused by a deficiency of hepatic tyrosine aminotransferase, results in elevated plasma and urinary tyrosine concentrations. We describe a young boy who was seen at 6 months of age with red eyes, photophobia, and eye pain that were not suspected to be caused by tyrosinemia II until painful plantar keratoderma developed at 2 1/2 years of age. Treatment with a diet low in tyrosine and phenylalanine reversed the manifestations of the disease.

  2. Comparison of type I and type II bovine viral diarrhea virus infection in swine.

    PubMed

    Walz, P H; Baker, J C; Mullaney, T P; Kaneene, J B; Maes, R K

    1999-04-01

    Some isolates of type II bovine viral diarrhea virus (BVDV) are capable of causing severe clinical disease in cattle. Bovine viral diarrhea virus infection has been reported in pigs, but the ability of these more virulent isolates of type II BVDV to induce severe clinical disease in pigs is unknown. It was our objective to compare clinical, virologic, and pathologic findings between type I and type II BVDV infection in pigs. Noninfected control and BVDV-infected 2-month-old pigs were used. A noncytopathic type I and a noncytopathic type II BVDV isolate were chosen for evaluation in feeder age swine based upon preliminary in vitro and in vivo experiments. A dose titration study was performed using 4 groups of 4 pigs for each viral isolate. The groups were inoculated intranasally with either sham (control), 10(3), 10(5), or 10(7) TCID50 of virus. The pigs were examined daily and clinical findings were recorded. Antemortem and postmortem samples were collected for virus isolation. Neither the type I nor type II BVDV isolates resulted in clinical signs of disease in pigs. Bovine viral diarrhea virus was isolated from antemortem and postmortem samples from groups of pigs receiving the 10(5) and the 10(7) TCID50 dose of the type I BVDV isolate. In contrast, BVDV was only isolated from postmortem samples in the group of pigs receiving the 10(7) TCID50 dose of the type II BVDV isolate. Type I BVDV was able to establish infection in pigs at lower doses by intranasal instillation than type II BVDV. Infection of pigs with a type II isolate of BVDV known to cause severe disease in calves did not result in clinically apparent disease in pigs.

  3. Nephrocalcinosis as adult presentation of Bartter syndrome type II.

    PubMed

    Huang, L; Luiken, G P M; van Riemsdijk, I C; Petrij, F; Zandbergen, A A M; Dees, A

    2014-02-01

    Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome. PMID:24659592

  4. Type II supernovae as probes of environment metallicity: observations of host H II regions

    NASA Astrophysics Data System (ADS)

    Anderson, J. P.; Gutiérrez, C. P.; Dessart, L.; Hamuy, M.; Galbany, L.; Morrell, N. I.; Stritzinger, M. D.; Phillips, M. M.; Folatelli, G.; Boffin, H. M. J.; de Jaeger, T.; Kuncarayakti, H.; Prieto, J. L.

    2016-05-01

    Context. Spectral modelling of type II supernova atmospheres indicates a clear dependence of metal line strengths on progenitor metallicity. This dependence motivates further work to evaluate the accuracy with which these supernovae can be used as environment metallicity indicators. Aims: To assess this accuracy we present a sample of type II supernova host H ii-region spectroscopy, from which environment oxygen abundances have been derived. These environment abundances are compared to the observed strength of metal lines in supernova spectra. Methods: Combining our sample with measurements from the literature, we present oxygen abundances of 119 host H ii regions by extracting emission line fluxes and using abundance diagnostics. These abundances are then compared to equivalent widths of Fe ii 5018 Å at various time and colour epochs. Results: Our distribution of inferred type II supernova host H ii-region abundances has a range of ~0.6 dex. We confirm the dearth of type II supernovae exploding at metallicities lower than those found (on average) in the Large Magellanic Cloud. The equivalent width of Fe ii 5018 Å at 50 days post-explosion shows a statistically significant correlation with host H ii-region oxygen abundance. The strength of this correlation increases if one excludes abundance measurements derived far from supernova explosion sites. The correlation significance also increases if we only analyse a "gold" IIP sample, and if a colour epoch is used in place of time. In addition, no evidence is found of a correlation between progenitor metallicity and supernova light-curve or spectral properties - except for that stated above with respect to Fe ii 5018 Å equivalent widths - suggesting progenitor metallicity is not a driving factor in producing the diversity that is observed in our sample. Conclusions: This study provides observational evidence of the usefulness of type II supernovae as metallicity indicators. We finish with a discussion of the

  5. Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa.

    PubMed

    de Chial, Magaly; Ghysels, Bart; Beatson, Scott A; Geoffroy, Valérie; Meyer, Jean Marie; Pattery, Theresa; Baysse, Christine; Chablain, Patrice; Parsons, Yasmin N; Winstanley, Craig; Cordwell, Stuart J; Cornelis, Pierre

    2003-04-01

    Pseudomonas aeruginosa produces, under conditions of iron limitation, a high-affinity siderophore, pyoverdine (PVD), which is recognized at the level of the outer membrane by a specific TonB-dependent receptor, FpvA. So far, for P. aeruginosa, three different PVDs, differing in their peptide chain, have been described (types I-III), but only the FpvA receptor for type I is known. Two PVD-producing P. aeruginosa strains, one type II and one type III, were mutagenized by a mini-TnphoA3 transposon. In each case, one mutant unable to grow in the presence of the strong iron chelator ethylenediaminedihydroxyphenylacetic acid (EDDHA) and the cognate PVD was selected. The first mutant, which had an insertion in the pvdE gene, upstream of fpvA, was unable to take up type II PVD and showed resistance to pyocin S3, which is known to use type II FpvA as receptor. The second mutant was unable to take up type III PVD and had the transposon insertion in fpvA. Cosmid libraries of the respective type II and type III PVD wild-type strains were constructed and screened for clones restoring the capacity to grow in the presence of PVD. From the respective complementing genomic fragments, type II and type III fpvA sequences were determined. When in trans, type II and type III fpvA restored PVD production, uptake, growth in the presence of EDDHA and, in the case of type II fpvA, pyocin S3 sensitivity. Complementation of fpvA mutants obtained by allelic exchange was achieved by the presence of cognate fpvA in trans. All three receptors posses an N-terminal extension of about 70 amino acids, similar to FecA of Escherichia coli, but only FpvAI has a TAT export sequence at its N-terminal end. PMID:12686625

  6. [Bacterial type II topoisomerases as targets for antibacterial drugs].

    PubMed

    Pietrusiński, Michał; Staczek, Paweł

    2006-01-01

    Bacterial type II DNA topoisomerases are essential enzymes for correct genome functioning and cell growth. Gyrase is responsible for maintaining negative supercoiling of bacterial chromosome, whereas topoisomerase IV acts in disentangling daughter chromosomes following replication. Type II DNA topoisomerases possess an ATP binding site, which can be treated as a target for antibacterial drugs. Resolving crystal structures of protein fragments consisting of an ATP binding site complexed with ADPNP/antibiotics have proven to be valuable for the understanding of the mode of action of existing antibacterial agents and presented new possibilities for novel drug design. Coumarins, quinolones and cyclothialidines are diverse group of antibiotics that interfere with type II DNA topoisomerases, however their mode of action is different. Recently a new class of antibiotics, simociclinones, was characterized. Their mechanism of action towards gyrase is entirely distinct from already known modes of action, therefore demonstrating the potential for development of novel anti-bacterial agents.

  7. Asymptomatic type II hyperprolinaemia associated with hyperglycinaemia in three sibs.

    PubMed Central

    Pavone, L; Mollica, F; Levy, H L

    1975-01-01

    Three clinically normal sibs were discovered to have type II hyperprolinaemia in a routine serum amino acid screening programme in Sicily. In addition to the basic biochemical features of type II hyperprolinaemia, all 3 children had marked hyperglycinaemia, whereas their parents had both normal blood proline and glycine concentrations. Clinical normality in individuals with hyperprolinaemia may suggest that these two metabolic disorders (types I and II) are benign entities. Furthermore, the absence of clinical abnormality in these sibs, despite the presence of marked hyperprolinaemia and hyperglycinaemia, may suggest that neither of these findings alone causes brain damage. The hyperglycinaemia in these sibs is unexplained and is an unusual if not unique finding in association with hyperprolinaemia. PMID:1200680

  8. A TYPE II RADIO BURST WITHOUT A CORONAL MASS EJECTION

    SciTech Connect

    Su, W.; Cheng, X.; Ding, M. D.; Chen, P. F.; Sun, J. Q. E-mail: dmd@nju.edu.cn

    2015-05-10

    Type II radio bursts are thought to be a signature of coronal shocks. In this paper, we analyze a short-lived type II burst that started at 07:40 UT on 2011 February 28. By carefully checking white-light images, we find that the type II radio burst is not accompanied by a coronal mass ejection, only by a C2.4 class flare and narrow jet. However, in the EUV images provided by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we find a wave-like structure that propagated at a speed of ∼600 km s{sup −1} during the burst. The relationship between the type II radio burst and the wave-like structure is, in particular, explored. For this purpose, we first derive the density distribution under the wave by the differential emission measure method, which is used to restrict the empirical density model. We then use the restricted density model to invert the speed of the shock that produces the observed frequency drift rate in the dynamic spectrum. The inverted shock speed is similar to the speed of the wave-like structure. This implies that the wave-like structure is most likely a coronal shock that produces the type II radio burst. We also examine the evolution of the magnetic field in the flare-associated active region and find continuous flux emergence and cancellation taking place near the flare site. Based on these facts, we propose a new mechanism for the formation of the type II radio burst, i.e., the expansion of the strongly inclined magnetic loops after reconnecting with a nearby emerging flux acts as a piston to generate the shock wave.

  9. A Type II Radio Burst without a Coronal Mass Ejection

    NASA Astrophysics Data System (ADS)

    Su, W.; Cheng, X.; Ding, M. D.; Chen, P. F.; Sun, J. Q.

    2015-05-01

    Type II radio bursts are thought to be a signature of coronal shocks. In this paper, we analyze a short-lived type II burst that started at 07:40 UT on 2011 February 28. By carefully checking white-light images, we find that the type II radio burst is not accompanied by a coronal mass ejection, only by a C2.4 class flare and narrow jet. However, in the EUV images provided by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we find a wave-like structure that propagated at a speed of ˜600 km s-1 during the burst. The relationship between the type II radio burst and the wave-like structure is, in particular, explored. For this purpose, we first derive the density distribution under the wave by the differential emission measure method, which is used to restrict the empirical density model. We then use the restricted density model to invert the speed of the shock that produces the observed frequency drift rate in the dynamic spectrum. The inverted shock speed is similar to the speed of the wave-like structure. This implies that the wave-like structure is most likely a coronal shock that produces the type II radio burst. We also examine the evolution of the magnetic field in the flare-associated active region and find continuous flux emergence and cancellation taking place near the flare site. Based on these facts, we propose a new mechanism for the formation of the type II radio burst, i.e., the expansion of the strongly inclined magnetic loops after reconnecting with a nearby emerging flux acts as a piston to generate the shock wave.

  10. Nonlinear convective pulsation models of type II Cepheids

    NASA Astrophysics Data System (ADS)

    Smolec, Radoslaw

    2015-08-01

    We present a grid of nonlinear convective pulsation models of type-II Cepheids: BL Her stars, W Vir stars and RV Tau stars. The models cover a wide range of masses, luminosities, effective temperatures and chemical compositions. The most interesting result is detection of deterministic chaos in the models. Different routes to chaos are detected (period doubling, intermittent route) as well as variety of phenomena intrinsic to chaotic dynamics (periodic islands within chaotic bands, crisis bifurcation, type-I and type-III intermittency). Some of the phenomena (period doubling in BL Her and in RV Tau stars, irregular pulsation of RV Tau stars) are well known in the pulsation of type-II Cepheids. Prospects of discovering the other are briefly discussed. Transition from BL Her type pulsation through W Vir type till RV Tau type is analysed. In the most luminous models a dynamical instability is detected, which indicates that pulsation driven mass loss is important process occurring in type-II Cepheids.

  11. Predicted Unusual Magnetoresponse in Type-II Weyl Semimetals

    NASA Astrophysics Data System (ADS)

    Yu, Zhi-Ming; Yao, Yugui; Yang, Shengyuan A.

    2016-08-01

    We show several distinct signatures in the magnetoresponse of type-II Weyl semimetals. The energy tilt tends to squeeze the Landau levels (LLs), and, for a type-II Weyl node, there always exists a critical angle between the B field and the tilt, at which the LL spectrum collapses, regardless of the field strength. Before the collapse, signatures also appear in the magneto-optical spectrum, including the invariable presence of intraband peaks, the absence of absorption tails, and the special anisotropic field dependence.

  12. Predicted Unusual Magnetoresponse in Type-II Weyl Semimetals.

    PubMed

    Yu, Zhi-Ming; Yao, Yugui; Yang, Shengyuan A

    2016-08-12

    We show several distinct signatures in the magnetoresponse of type-II Weyl semimetals. The energy tilt tends to squeeze the Landau levels (LLs), and, for a type-II Weyl node, there always exists a critical angle between the B field and the tilt, at which the LL spectrum collapses, regardless of the field strength. Before the collapse, signatures also appear in the magneto-optical spectrum, including the invariable presence of intraband peaks, the absence of absorption tails, and the special anisotropic field dependence. PMID:27563994

  13. Ricci inheritance collineations in Bianchi type II spacetime

    NASA Astrophysics Data System (ADS)

    Hussain, Tahir; Akhtar, Sumaira Saleem; Bokhari, Ashfaque H.; Khan, Suhail

    2016-06-01

    In this paper, we present a complete classification of Bianchi type II spacetime according to Ricci inheritance collineations (RICs). The RICs are classified considering cases when the Ricci tensor is both degenerate as well as non-degenerate. In case of non-degenerate Ricci tensor, it is found that Bianchi type II spacetime admits 4-, 5-, 6- or 7-dimensional Lie algebra of RICs. In the case when the Ricci tensor is degenerate, majority cases give rise to infinitely many RICs, while remaining cases admit finite RICs given by 4, 5 or 6.

  14. Stability conditions for the Bianchi type II anisotropically inflating universes

    SciTech Connect

    Kao, W.F.; Lin, Ing-Chen E-mail: g9522528@oz.nthu.edu.tw

    2009-01-15

    Stability conditions for a class of anisotropically inflating solutions in the Bianchi type II background space are shown explicitly in this paper. These inflating solutions were known to break the cosmic no-hair theorem such that they do not approach the de Sitter universe at large times. It can be shown that unstable modes of the anisotropic perturbations always exist for this class of expanding solutions. As a result, we show that these set of anisotropically expanding solutions are unstable against anisotropic perturbations in the Bianchi type II space.

  15. Achondrogenesis type II (Langer-Saldino achondrogenesis): a case report.

    PubMed

    Lee, H S; Doh, J W; Kim, C J; Chi, J G

    2000-10-01

    Achondrogenesis is a lethal form of congenital chondrodystrophy characterized by extreme micromelia. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis) detected by prenatal ultrasonography at 20-week gestation. A dwarfed fetus with large head, short neck and chest, prominent abdomen and short limbs was terminated transvaginally. Radiologic and histopathologic examination revealed features of mild form of achondrogenesis type II. Although the case had no known risk factor and the phenotypic abnormality was mild, modern development in prenatal screening made the early detection possible. PMID:11069003

  16. A large TAT deletion in a tyrosinaemia type II patient.

    PubMed

    Legarda, Maria; Wlodarczyk, Katarzyna; Lage, Sergio; Andrade, Fernando; Kim, Gwang-Jin; Bausch, Elke; Scherer, Gerd; Aldamiz-Echevarria, Luis Jose

    2011-11-01

    A girl, born to unrelated Spanish parents, presented at 6 months of age with photophobia, keratitis, palmar hyperkeratosis and high plasma tyrosine levels, indicative of tyrosinaemia type II. Analysis of the tyrosine aminotransferase (TAT) gene revealed a paternally inherited frameshift mutation c.1213delCinsAG at codon 405 causing a premature stop codon, and a maternally inherited deletion of 193kb encompassing the complete TAT gene and three neighbouring genes. This is the first complete TAT deletion in tyrosinaemia type II described so far.

  17. Towards a Cosmological Hubble Diagram for Type II-PSupernovae

    SciTech Connect

    Nugent, Peter; Sullivan, Mark; Ellis, Richard; Gal-Yam, Avishay; Leonard, Douglas C.; Howell, D. Andrew; Astier, Pierre; Carlberg, RaymondG.; Conley, Alex; Fabbro, Sebastien; Fouchez, Dominique; Neill, James D.; Pain, Reynald; Perrett, Kathy; Pritchet, Chris J; Regnault, Nicolas

    2006-03-20

    We present the first high-redshift Hubble diagram for Type II-P supernovae (SNe II-P) based upon five events at redshift upto z {approx}0.3. This diagram was constructed using photometry from the Canada-France-Hawaii Telescope Supernova Legacy Survey and absorption line spectroscopy from the Keck observatory. The method used to measure distances to these supernovae is based on recent work by Hamuy&Pinto (2002) and exploits a correlation between the absolute brightness of SNeII-P and the expansion velocities derived from the minimum of the Fe II 516.9 nm P-Cygni feature observed during the plateau phases. We present three refinements to this method which significantly improve the practicality of measuring the distances of SNe II-P at cosmologically interesting redshifts. These are an extinction correction measurement based on the V-I colors at day 50, across-correlation measurement for the expansion velocity and the ability to extrapolate such velocities accurately over almost the entire plateau phase. We apply this revised method to our dataset of high-redshift SNe II-P and find that the resulting Hubble diagram has a scatter of only 0.26 magnitudes, thus demonstrating the feasibility of measuring the expansion history, with present facilities, using a method independent of that based upon supernovae of Type Ia.

  18. Pharmacophore modeling studies of type I and type II kinase inhibitors of Tie2.

    PubMed

    Xie, Qing-Qing; Xie, Huan-Zhang; Ren, Ji-Xia; Li, Lin-Li; Yang, Sheng-Yong

    2009-02-01

    In this study, chemical feature based pharmacophore models of type I and type II kinase inhibitors of Tie2 have been developed with the aid of HipHop and HypoRefine modules within Catalyst program package. The best HipHop pharmacophore model Hypo1_I for type I kinase inhibitors contains one hydrogen-bond acceptor, one hydrogen-bond donor, one general hydrophobic, one hydrophobic aromatic, and one ring aromatic feature. And the best HypoRefine model Hypo1_II for type II kinase inhibitors, which was characterized by the best correlation coefficient (0.976032) and the lowest RMSD (0.74204), consists of two hydrogen-bond donors, one hydrophobic aromatic, and two general hydrophobic features, as well as two excluded volumes. These pharmacophore models have been validated by using either or both test set and cross validation methods, which shows that both the Hypo1_I and Hypo1_II have a good predictive ability. The space arrangements of the pharmacophore features in Hypo1_II are consistent with the locations of the three portions making up a typical type II kinase inhibitor, namely, the portion occupying the ATP binding region (ATP-binding-region portion, AP), that occupying the hydrophobic region (hydrophobic-region portion, HP), and that linking AP and HP (bridge portion, BP). Our study also reveals that the ATP-binding-region portion of the type II kinase inhibitors plays an important role to the bioactivity of the type II kinase inhibitors. Structural modifications on this portion should be helpful to further improve the inhibitory potency of type II kinase inhibitors. PMID:19138543

  19. Pharmacophore modeling studies of type I and type II kinase inhibitors of Tie2.

    PubMed

    Xie, Qing-Qing; Xie, Huan-Zhang; Ren, Ji-Xia; Li, Lin-Li; Yang, Sheng-Yong

    2009-02-01

    In this study, chemical feature based pharmacophore models of type I and type II kinase inhibitors of Tie2 have been developed with the aid of HipHop and HypoRefine modules within Catalyst program package. The best HipHop pharmacophore model Hypo1_I for type I kinase inhibitors contains one hydrogen-bond acceptor, one hydrogen-bond donor, one general hydrophobic, one hydrophobic aromatic, and one ring aromatic feature. And the best HypoRefine model Hypo1_II for type II kinase inhibitors, which was characterized by the best correlation coefficient (0.976032) and the lowest RMSD (0.74204), consists of two hydrogen-bond donors, one hydrophobic aromatic, and two general hydrophobic features, as well as two excluded volumes. These pharmacophore models have been validated by using either or both test set and cross validation methods, which shows that both the Hypo1_I and Hypo1_II have a good predictive ability. The space arrangements of the pharmacophore features in Hypo1_II are consistent with the locations of the three portions making up a typical type II kinase inhibitor, namely, the portion occupying the ATP binding region (ATP-binding-region portion, AP), that occupying the hydrophobic region (hydrophobic-region portion, HP), and that linking AP and HP (bridge portion, BP). Our study also reveals that the ATP-binding-region portion of the type II kinase inhibitors plays an important role to the bioactivity of the type II kinase inhibitors. Structural modifications on this portion should be helpful to further improve the inhibitory potency of type II kinase inhibitors.

  20. Antidepressants in type II versus type I bipolar depression: A randomized discontinuation trial

    PubMed Central

    Vöhringer, Paul A.; Ostacher, Michael J.; El-Mallakh, Rif S.; Holtzman, Niki S.; Thommi, Sairah B.; Whitham, Elizabeth A.; Sullivan, Matthew C.; Baldassano, Claudia F.; Goodwin, Fredrick K.; Baldessarini, Ross J.; Ghaemi, S. Nassir

    2015-01-01

    Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among type-II over type-I bipolar disorder (BD) patients. Methods DSM-IV BD-I (n=21) and -II patients (n=49) in acute major depressive episodes were treated with ADs plus mood-stabilizers to euthymia sustained for two months, and then randomized openly to continue or discontinue ADs for up to three years. Outcomes were episode-recurrences and changes in standardized symptom-ratings. Results In follow-up averaging 1.64±0.98 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in type I than in type II bipolar depression (for type II, mean decrease in depressive episodes per year 0.21 ± 0.26 [CI:0.05, 0.37]; for type I: mean decrease 0.35 ± 0.15 [CI:0.30, 0.41]). Type II subjects continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than BD-I subjects. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. Conclusions The findings do not confirm the hypothesis that long-term AD treatment in BP-II has better outcomes than in BD-I patients, except somewhat lower risk of manic/hypomanic episodes. PMID:26267418

  1. Using Type II Computer Network Technology To Reach Distance Students.

    ERIC Educational Resources Information Center

    Eastmond, Dan; Granger, Dan

    1998-01-01

    This article, in a series on computer technology and distance education, focuses on "Type II Technology," courses using textbooks and course guides for primary delivery, but enhancing them with computer conferencing as the main vehicle of instructional communication. Discusses technology proficiency, maximizing learning in conferencing…

  2. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  3. Type II seesaw and the PAMELA/ATIC signals

    NASA Astrophysics Data System (ADS)

    Gogoladze, Ilia; Okada, Nobuchika; Shafi, Qaisar

    2009-08-01

    We discuss how the cosmic ray signals reported by the PAMELA and ATIC/PPB-BETS experiments may be understood in a Standard Model (SM) framework supplemented by type II seesaw and a stable SM singlet scalar boson as dark matter. A particle physics explanation of the 'boost' factor can be provided by including an additional SM singlet scalar field.

  4. High Cell Surface Death Receptor Expression Determines Type I Versus Type II Signaling*

    PubMed Central

    Meng, Xue Wei; Peterson, Kevin L.; Dai, Haiming; Schneider, Paula; Lee, Sun-Hee; Zhang, Jin-San; Koenig, Alexander; Bronk, Steve; Billadeau, Daniel D.; Gores, Gregory J.; Kaufmann, Scott H.

    2011-01-01

    Previous studies have suggested that there are two signaling pathways leading from ligation of the Fas receptor to induction of apoptosis. Type I signaling involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to amplify a more modest death receptor-initiated signal. The biochemical basis for this dichotomy has previously been unclear. Here we show that type I cells have a longer half-life for Fas message and express higher amounts of cell surface Fas, explaining the increased recruitment of FADD and subsequent signaling. Moreover, we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can signal through a type I pathway upon forced receptor overexpression and that shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to type II signaling. Importantly, the same cells can exhibit type I signaling for Fas and type II signaling for TRAIL (TNF-α-related apoptosis-inducing ligand), indicating that the choice of signaling pathway is related to the specific receptor, not some other cellular feature. Additional experiments revealed that up-regulation of cell surface death receptor 5 levels by treatment with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells from type II to type I. Collectively, these results suggest that the type I/type II dichotomy reflects differences in cell surface death receptor expression. PMID:21865165

  5. Hippocampal type I and type II corticosteroid receptors are differentially regulated by chronic prazosin treatment.

    PubMed

    Kabbaj, M; Le Moal, M; Maccari, S

    1996-08-01

    Two types of hippocampal corticosteroid receptors play an important role in regulating the secretion of corticosterone: type I receptors are thought to regulate both the basal and stress induced release of corticosterone whereas type II receptors seem to be involved only in the stress response. Although these receptors are known to be regulated by circulating levels of corticosterone, there is also evidence for a direct neural control independent of hormonal influences. Furthermore, several studies suggest differential regulation of type I and type II corticosteroid receptors, with greater hormonal control of type II and greater neural control of type I. In order to investigate this theory of differential regulation of type I and type II corticosteroid receptors, we studied the effect of chronic treatment with either vehicle or the alpha 1 noradrenergic antagonist prazosin (0.5 mg/kg, i.p), on hippocampal corticosteroid receptors. Rats in one group had intact adrenal glands, whereas rats in a second group were adrenalectomized, their plasma corticosterone levels being maintained in the physiological range by implantation of corticosterone pellets. Thus, in the first group, the effects of drug-induced changes in both noradrenergic transmission and corticosterone secretion on corticosteroid receptors were investigated, whereas in the second group, the influence of altered noradrenergic transmission was effectively isolated. The results of this experiment show that, in comparison to the vehicle treatment, chronic treatment with the alpha 1 receptor antagonist prazosin decreased the number of type I corticosteroid receptors in adrenalectomized animals with corticosterone substitutive therapy. This effect on type I was not evident in adrenal-intact animals. In contrast, the prazosin treatment reduced the number of type II corticosteroid receptors in adrenal-intact animals, but not in adrenalectomized animals with corticosterone substitutive therapy. It has also been

  6. Comparing the host galaxies of type Ia, type II, and type Ibc supernovae

    SciTech Connect

    Shao, X.; Liang, Y. C.; Chen, X. Y.; Zhong, G. H.; Deng, L. C.; Zhang, B.; Shi, W. B.; Zhou, L.; Dennefeld, M.; Hammer, F.; Flores, H. E-mail: ycliang@bao.ac.cn

    2014-08-10

    We compare the host galaxies of 902 supernovae (SNe), including SNe Ia, SNe II, and SNe Ibc, which are selected by cross-matching the Asiago Supernova Catalog with the Sloan Digital Sky Survey (SDSS) Data Release 7. We selected an additional 213 galaxies by requiring the light fraction of spectral observations to be >15%, which could represent well the global properties of the galaxies. Among these 213 galaxies, 135 appear on the Baldwin-Phillips-Terlevich diagram, which allows us to compare the hosts in terms of whether they are star-forming (SF) galaxies, active galactic nuclei (AGNs; including composites, LINERs, and Seyfert 2s) or absorption-line galaxies (Absorps; i.e., their related emission lines are weak or non-existent). The diagrams related to the parameters D{sub n}(4000), Hδ{sub A}, stellar masses, star formation rates (SFRs), and specific SFRs for the SNe hosts show that almost all SNe II and most of the SNe Ibc occur in SF galaxies, which have a wide range of stellar masses and low D{sub n}(4000). The SNe Ia hosts as SF galaxies following similar trends. A significant fraction of SNe Ia occurs in AGNs and absorption-line galaxies, which are massive and have high D{sub n}(4000). The stellar population analysis from spectral synthesis fitting shows that the hosts of SNe II have a younger stellar population than hosts of SNe Ia. These results are compared with those of the 689 comparison galaxies where the SDSS fiber captures less than 15% of the total light. These comparison galaxies appear biased toward higher 12+log(O/H) (∼0.1 dex) at a given stellar mass. Therefore, we believe the aperture effect should be kept in mind when the properties of the hosts for different types of SNe are discussed.

  7. SPECTRA OF TYPE II CEPHEID CANDIDATES AND RELATED STARS

    SciTech Connect

    Schmidt, E. G.; Rogalla, Danielle; Thacker-Lynn, Lauren E-mail: drogall1@bigred.unl.edu

    2011-02-15

    We present low-resolution spectra for variable stars in the Cepheid period range from the ROTSE-I Demonstration Project and the All Sky Automated Survey, some of which were previously identified as type II Cepheid candidates. We have derived effective temperatures, gravities, and metallicities from the spectra. Based on this, three types of variables were identified: Cepheid strip stars, cool stars that lie along the red subgiant and giant branch, and cool main-sequence stars. Many fewer type II Cepheids were found than expected and most have amplitudes less than 0.4 mag. The cool variables include many likely binaries as well as intrinsic variables. Variation among the main-sequence stars is likely to be mostly due to binarity or stellar activity.

  8. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    SciTech Connect

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

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

    PubMed

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

    2015-01-01

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

  10. Coronal magnetic fields from multiple type II bursts

    NASA Astrophysics Data System (ADS)

    Honnappa, Vijayakumar; Raveesha, K. H.; Subramanian, K. R.

    Coronal magnetic fields from multiple type II bursts Vijayakumar H Doddamani1*, Raveesha K H2 and Subramanian3 1Bangalore University, Bangalore, Karnataka state, India 2CMR Institute of Technology, Bangalore, Karnataka state, India 3 Retd, Indian Institute of Astrophysics, Bangalore, Karnataka state, India Abstract Magnetic fields play an important role in the astrophysical processes occurring in solar corona. In the solar atmosphere, magnetic field interacts with the plasma, producing abundant eruptive activities. They are considered to be the main factors for coronal heating, particle acceleration and the formation of structures like prominences, flares and Coronal Mass Ejections. The magnetic field in solar atmosphere in the range of 1.1-3 Rsun is especially important as an interface between the photospheric magnetic field and the solar wind. Its structure and time dependent change affects space weather by modifying solar wind conditions, Cho (2000). Type II doublet bursts can be used for the estimation of the strength of the magnetic field at two different heights. Two type II bursts occur sometimes in sequence. By relating the speed of the type II radio burst to Alfven Mach Number, the Alfven speed of the shock wave generating type II radio burst can be calculated. Using the relation between the Alfven speed and the mean frequency of emission, the magnetic field strength can be determined at a particular height. We have used the relative bandwidth and drift rate properties of multiple type II radio bursts to derive magnetic field strengths at two different heights and also the gradient of the magnetic field in the outer corona. The magnetic field strength has been derived for different density factors. It varied from 1.2 to 2.5 gauss at a solar height of 1.4 Rsun. The empirical relation of the variation of the magnetic field with height is found to be of the form B(R) = In the present case the power law index ‘γ’ varied from -3 to -2 for variation of

  11. Type II and Type III Radio Bursts and their Correlation with Solar Energetic Proton Events

    NASA Astrophysics Data System (ADS)

    Winter, L. M.; Ledbetter, K.

    2015-08-01

    Using the Wind/WAVES radio observations from 2010 to 2013, we present an analysis of the 123 decametric–hectometric (DH) type II solar radio bursts during this period, the associated type III burst properties, and their correlation with solar energetic proton (SEP) properties determined from analysis of the Geostationary Operational Environmental Satellite (GOES) observations. We present a useful catalog of the type II burst, type III burst, Langmuir wave, and proton flux properties for these 123 events, which we employ to develop a statistical relationship between the radio properties and peak proton flux that can be used to forecast SEP events. We find that all SEP events with a peak \\gt 10 MeV flux above 15 protons cm‑2 s‑1 sr‑1 are associated with a type II burst and virtually all SEP events, 92%, are also associated with a type III radio burst. Based on a principal component analysis, the radio burst properties that are most highly correlated with the occurrence of gradual SEP events and account for the most variance in the radio properties are the type III burst intensity and duration. Further, a logistic regression analysis with the radio-derived principal component (dominated by the type III and type II radio burst intensity and type III duration) obtains SEP predictions approaching the human forecaster rates, with a false alarm rate of 22%, a probability of detection of 62%, and with 85% of the classifications correct. Therefore, type III radio bursts that occur along with a DH type II burst are shown to be an important diagnostic that can be used to forecast SEP events.

  12. Type II and Type III Radio Bursts and their Correlation with Solar Energetic Proton Events

    NASA Astrophysics Data System (ADS)

    Winter, L. M.; Ledbetter, K.

    2015-08-01

    Using the Wind/WAVES radio observations from 2010 to 2013, we present an analysis of the 123 decametric-hectometric (DH) type II solar radio bursts during this period, the associated type III burst properties, and their correlation with solar energetic proton (SEP) properties determined from analysis of the Geostationary Operational Environmental Satellite (GOES) observations. We present a useful catalog of the type II burst, type III burst, Langmuir wave, and proton flux properties for these 123 events, which we employ to develop a statistical relationship between the radio properties and peak proton flux that can be used to forecast SEP events. We find that all SEP events with a peak \\gt 10 MeV flux above 15 protons cm-2 s-1 sr-1 are associated with a type II burst and virtually all SEP events, 92%, are also associated with a type III radio burst. Based on a principal component analysis, the radio burst properties that are most highly correlated with the occurrence of gradual SEP events and account for the most variance in the radio properties are the type III burst intensity and duration. Further, a logistic regression analysis with the radio-derived principal component (dominated by the type III and type II radio burst intensity and type III duration) obtains SEP predictions approaching the human forecaster rates, with a false alarm rate of 22%, a probability of detection of 62%, and with 85% of the classifications correct. Therefore, type III radio bursts that occur along with a DH type II burst are shown to be an important diagnostic that can be used to forecast SEP events.

  13. Type II restriction endonucleases—a historical perspective and more

    PubMed Central

    Pingoud, Alfred; Wilson, Geoffrey G.; Wende, Wolfgang

    2014-01-01

    This article continues the series of Surveys and Summaries on restriction endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss ‘Type II’ REases, the kind used for DNA analysis and cloning. We focus on their biochemistry: what they are, what they do, and how they do it. Type II REases are produced by prokaryotes to combat bacteriophages. With extreme accuracy, each recognizes a particular sequence in double-stranded DNA and cleaves at a fixed position within or nearby. The discoveries of these enzymes in the 1970s, and of the uses to which they could be put, have since impacted every corner of the life sciences. They became the enabling tools of molecular biology, genetics and biotechnology, and made analysis at the most fundamental levels routine. Hundreds of different REases have been discovered and are available commercially. Their genes have been cloned, sequenced and overexpressed. Most have been characterized to some extent, but few have been studied in depth. Here, we describe the original discoveries in this field, and the properties of the first Type II REases investigated. We discuss the mechanisms of sequence recognition and catalysis, and the varied oligomeric modes in which Type II REases act. We describe the surprising heterogeneity revealed by comparisons of their sequences and structures. PMID:24878924

  14. On the nature of rapidly fading Type II supernovae

    NASA Astrophysics Data System (ADS)

    Moriya, Takashi J.; Pruzhinskaya, Maria V.; Ergon, Mattias; Blinnikov, Sergei I.

    2016-01-01

    It has been suggested that Type II supernovae with rapidly fading light curves (a.k.a. Type IIL supernovae) are explosions of progenitors with low-mass hydrogen-rich envelopes which are of the order of 1 M⊙. We investigate light-curve properties of supernovae from such progenitors. We confirm that such progenitors lead to rapidly fading Type II supernovae. We find that the luminosity of supernovae from such progenitors with the canonical explosion energy of 1051 erg and 56Ni mass of 0.05 M⊙ can increase temporarily shortly before all the hydrogen in the envelope recombines. As a result, a bump appears in their light curves. The bump appears because the heating from the nuclear decay of 56Ni can keep the bottom of hydrogen-rich layers in the ejecta ionized, and thus the photosphere can stay there for a while. We find that the light-curve bump becomes less significant when we make explosion energy larger (≳2 × 1051 erg), 56Ni mass smaller (≲0.01 M⊙), 56Ni mixed in the ejecta, or the progenitor radius larger. Helium mixing in hydrogen-rich layers makes the light-curve decline rates large but does not help reducing the light-curve bump. Because the light-curve bump we found in our light-curve models has not been observed in rapidly fading Type II supernovae, they may be characterized by not only low-mass hydrogen-rich envelopes but also higher explosion energy, larger degrees of 56Ni mixing, and/or larger progenitor radii than slowly fading Type II supernovae, so that the light-curve bump does not become significant.

  15. Activin A Predicts Left Ventricular Remodeling and Mortality in Patients with ST-Elevation Myocardial Infarction

    PubMed Central

    Lin, Jeng-Feng; Hsu, Shun-Yi; Teng, Ming-Sheng; Wu, Semon; Hsieh, Chien-An; Jang, Shih-Jung; Liu, Chih-Jen; Huang, Hsuan-Li; Ko, Yu-Lin

    2016-01-01

    Background Activin A levels increase in a variety of heart diseases including ST-elevation myocardial infarction (STEMI). The aim of this study is to investigate whether the level of activin A can be beneficial in predicting left ventricular remodeling, heart failure, and death in patients with ST-elevation myocardial infarction (STEMI). Methods We enrolled 278 patients with STEMI who had their activin A levels measured on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Thereafter, the clinical events of these patients were followed for a maximum of 3 years, including all-cause death and readmission for heart failure. Results During hospitalization, higher activin A level was associated with higher triglyceride level, lower left ventricular ejection fraction (LVEF), and lower left ventricular end diastolic ventricular volume index (LVEDVI) in multivariable linear regression model. During follow-up, patients with activin A levels > 129 pg/ml had significantly lower LVEF, and higher LVEDVI at 6 months. Kaplan-Meier survival curves showed that activin A level > 129 pg/ml was a predictor of all-cause death (p = 0.022), but not a predictor of heart failure (p = 0.767). Conclusions Activin A level > 129 pg/ml predicts worse left ventricular remodeling and all-cause death in STEMI. PMID:27471355

  16. Constitutively active FOXO1 diminishes activin induction of Fshb transcription in immortalized gonadotropes.

    PubMed

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

    2014-01-01

    In the present study, we investigate whether the FOXO1 transcription factor modulates activin signaling in pituitary gonadotropes. Our studies show that overexpression of constitutively active FOXO1 decreases activin induction of murine Fshb gene expression in immortalized LβT2 cells. We demonstrate that FOXO1 suppression of activin induction maps to the -304/-95 region of the Fshb promoter containing multiple activin response elements and that the suppression requires the FOXO1 DNA-binding domain (DBD). FOXO1 binds weakly to the -125/-91 region of the Fshb promoter in a gel-shift assay. Since this region of the promoter contains a composite SMAD/FOXL2 binding element necessary for activin induction of Fshb transcription, it is possible that FOXO1 DNA binding interferes with SMAD and/or FOXL2 function. In addition, our studies demonstrate that FOXO1 directly interacts with SMAD3/4 but not SMAD2 in a FOXO1 DBD-dependent manner. Moreover, we show that SMAD3/4 induction of Fshb-luc and activin induction of a multimerized SMAD-binding element-luc are suppressed by FOXO1 in a DBD-dependent manner. These results suggest that FOXO1 binding to the proximal Fshb promoter as well as FOXO1 interaction with SMAD3/4 proteins may result in decreased activin induction of Fshb in gonadotropes.

  17. Upregulation of activin A gene by butyrate in human colon cancer cell lines.

    PubMed

    Sonoyama, Kei; Pholnukulkit, Pimara; Toyoda, Masahiko; Rutatip, Suriya; Kasai, Takanori

    2003-06-01

    Activin A has been reported to play a role in the progression of colorectal cancer. Because dietary fiber protects against colorectal cancer, we hypothesized that butyrate, a fermentation product of dietary fiber, may affect the expression of activin A in colon cancer cells. Semiquantitative RT-PCR demonstrated that the activin A gene was upregulated by sodium butyrate in the human colon cancer cell lines HT-29 and Caco-2 in a concentration- and time-dependent manner. However, the activin A gene did not respond to sodium butyrate in the human normal colonic cell line FHC, rat normal intestinal epithelial cell (IEC) line IEC-6, and the explant of rat colon. Flow cytometry and agarose gel electrophoresis of genomic DNA revealed that cell cycle arrest and apoptosis were induced by sodium butyrate but not exogenous activin A in HT-29 cells, indicating that activin A could not act as an autocrine factor in colon cancer cells. By assuming that activin A promotes colorectal cancer spread as a paracrine factor, our findings suggest that butyrate could act as a tumor promoter in some circumstances.

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2014-09-01

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

  20. THE CONNECTION OF TYPE II SPICULES TO THE CORONA

    SciTech Connect

    Judge, Philip G.; McIntosh, Scott W.; De Pontieu, Bart; Olluri, Kosovare

    2012-02-20

    We examine the hypothesis that plasma associated with 'Type II' spicules is heated to coronal temperatures, and that the upward moving hot plasma constitutes a significant mass supply to the solar corona. One-dimensional hydrodynamical models including time-dependent ionization are brought to bear on the problem. These calculations indicate that heating of field-aligned spicule flows should produce significant differential Doppler shifts between emission lines formed in the chromosphere, transition region, and corona. At present, observational evidence for the computed 60-90 km s{sup -1} differential shifts is weak, but the data are limited by difficulties in comparing the proper motion of Type II spicules with spectral and kinematic properties of an associated transition region and coronal emission lines. Future observations with the upcoming infrared interferometer spectrometer instrument should clarify if Doppler shifts are consistent with the dynamics modeled here.

  1. K3-fibrations and heterotic-type II string duality

    NASA Astrophysics Data System (ADS)

    Klemm, A.; Lerche, W.; Mayr, P.

    1995-02-01

    We analyze the map between heterotic and type II N = 2 supersymmetric string theories for certain two and three moduli examples found by Kachru and Vafa. The appearance of elliptic j-functions can be traced back to specializations of the Picard-Fuchs equations to systems for K3 surfaces. For the three-moduli example we write the mirror maps and Yukawa couplings in the weak coupling limit in terms of j-functions; the expressions agree with those obtained in perturbative calculations in the heterotic string in an impressive way. We also discuss symmetries of the world-sheet instanton numbers in the type II theory, and interpret them in terms of S-duality of the non-perturbative heterotic string.

  2. Structure of type II dehydroquinase from Pseudomonas aeruginosa

    PubMed Central

    Reiling, Scott; Kelleher, Alan; Matsumoto, Monica M.; Robinson, Gonteria; Asojo, Oluwatoyin A.

    2014-01-01

    Pseudomonas aeruginosa causes opportunistic infections and is resistant to most antibiotics. Ongoing efforts to generate much-needed new antibiotics include targeting enzymes that are vital for P. aeruginosa but are absent in mammals. One such enzyme, type II dehydroquinase (DHQase), catalyzes the interconversion of 3-dehydroquinate and 3-dehydroshikimate, a necessary step in the shikimate pathway. This step is vital for the proper synthesis of phenylalanine, tryptophan, tyrosine and other aromatic metabolites. The recombinant expression, purification and crystal structure of catalytically active DHQase from P. aeruginosa (PaDHQase) are presented. Cubic crystals belonging to space group F23, with unit-cell parameters a = b = c = 125.39 Å, were obtained by vapor diffusion in sitting drops and the structure was refined to an R factor of 16% at 1.74 Å resolution. PaDHQase is a prototypical type II DHQase with the classical flavodoxin-like α/β topology. PMID:25372814

  3. Unification of type-II strings and T duality.

    PubMed

    Hohm, Olaf; Kwak, Seung Ki; Zwiebach, Barton

    2011-10-21

    We present a unified description of the low-energy limits of type-II string theories. This is achieved by a formulation that doubles the space-time coordinates in order to realize the T-duality group O(10,10) geometrically. The Ramond-Ramond fields are described by a spinor of O(10,10), which couples to the gravitational fields via the Spin(10,10) representative of the so-called generalized metric. This theory, which is supplemented by a T-duality covariant self-duality constraint, unifies the type-II theories in that each of them is obtained for a particular subspace of the doubled space.

  4. Two different molecular conformations found in chitosan type II salts.

    PubMed

    Lertworasirikul, Amornrat; Tsue, Shin-ichiro; Noguchi, Keiichi; Okuyama, Kenji; Ogawa, Kozo

    2003-05-23

    The type II structure of chitosan acidic salts prepared from crab tendon in solid state was studied using an X-ray fiber diffraction technique together with the linked-atom least-squares (LALS) technique. The cylindrical Patterson method was applied to confirm the molecular conformation of the chitosan. It was shown that there are two different helical conformations for type II salts. One is the relaxed twofold helix having a tetrasaccharide as an asymmetric unit as found in chitosan.HCl salt, which was previously reported as a conformation of chitosan.HCOOH salt. The other is the fourfold helix having a disaccharide as an asymmetric unit newly found in chitosan.HI salt.

  5. Unification of type-II strings and T duality.

    PubMed

    Hohm, Olaf; Kwak, Seung Ki; Zwiebach, Barton

    2011-10-21

    We present a unified description of the low-energy limits of type-II string theories. This is achieved by a formulation that doubles the space-time coordinates in order to realize the T-duality group O(10,10) geometrically. The Ramond-Ramond fields are described by a spinor of O(10,10), which couples to the gravitational fields via the Spin(10,10) representative of the so-called generalized metric. This theory, which is supplemented by a T-duality covariant self-duality constraint, unifies the type-II theories in that each of them is obtained for a particular subspace of the doubled space. PMID:22107505

  6. Study of interacting CMEs and DH type II radio bursts

    NASA Astrophysics Data System (ADS)

    Prasanna Subramanian, S.; Shanmugaraju, A.

    2013-04-01

    The subject of interaction between the Corona Mass Ejections (CMEs) is important in the concept of space-weather studies. In this paper, we analyzed a set of 15 interacting events taken from the list compiled by Manoharan et al. (in J. Geophys. Res. 109:A06109, 2004) and their associated DH type II radio bursts. The pre and primary CMEs, and their associated DH type II bursts are identified using the SOHO/LASCO catalog and Wind/WAVES catalog, respectively. All the primary CMEs are associated with shocks and interplanetary CMEs. These CMEs are found to be preceded by secondary slow CMEs. Most of primary CMEs are halo type CME and much faster (Mean speed = 1205 km s-1) than the pre CME (Mean speed = 450 km s-1). The average delay between the pre and primary CMEs, drift rate of DH type IIs and interaction height are found to be 211 min, 0.878 kHz/s and 17.87 Ro, respectively. The final observed distance (FOD) of all pre CMEs are found to be less than 15 Ro and it is seen that many of the pre CMEs got merged with the primary CMEs, and, they were not traced as separate CMEs in the LASCO field of view. Some radio signatures are identified for these events in the DH spectrum around the time of interaction. The interaction height obtained from the height-time plots of pre and primary CMEs is found to have correlations with (i) the time delay between the two CMEs and (ii) the central frequency of emission in the radio signatures in the DH spectrum around the time of interaction. The centre frequency of emission in the DH spectrum around the time of interaction seems to decrease when the interaction height increases. This result is compared with an interplanetary density model of Saito et al. (in Solar Phys. 55:121, 1977).

  7. [Renal histological lesions in patients with type II diabetes mellitus].

    PubMed

    Castellano, I; Covarsí, A; Novillo, R; Gómez-Martino, J R; Ferrando, L

    2002-01-01

    Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary.

  8. Asymptotic stability of vacuum twisting type II metrics

    NASA Astrophysics Data System (ADS)

    Natorf, Włodzimierz

    2012-02-01

    We generalize the result of Lukács et al. on asymptotic stability of the Schwarzschild metric with respect to perturbations in the Robinson-Trautman class of metrics to the case of Petrov type II twisting metrics, under the condition of asymptotic flatness at future null infinity. The Bondi energy is used as the Lyapunov functional and we prove that the "final state" of such metrics is the Kerr metric.

  9. Shock waves and nucleosynthesis in type II supernovae

    NASA Technical Reports Server (NTRS)

    Aufderheide, M. B.; Baron, E.; Thielemann, F.-K.

    1991-01-01

    In the study of nucleosynthesis in type II SN, shock waves are initiated artificially, since collapse calculations do not, as yet, give self-consistent shock waves strong enough to produce the SN explosion. The two initiation methods currently used by light-curve modelers are studied, with a focus on the peak temperatures and the nucleosynthetic yields in each method. The various parameters involved in artificially initiating a shock wave and the effects of varying these parameters are discussed.

  10. Nitric oxide alters metabolism in isolated alveolar type II cells.

    PubMed

    Miles, P R; Bowman, L; Huffman, L

    1996-07-01

    Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells. PMID:8760128

  11. Gaia16alo is a Type II SN

    NASA Astrophysics Data System (ADS)

    Fraser, M.; Hodgkin, S. T.; Mattila, S.; Harrison, D.; Wyrzykowski, L.; Kostrzewa-Rutkowska, Z.; Blagorodnova, N.

    2016-05-01

    Gaia16alo (aka PS16cct) was observed using the robotic Liverpool Telescope + SPRAT (R~350; 400-800 nm) on the night of 2016 May 6. The spectrum was compared to a set of templates using SNID (Blondin & Tonry, 2007, ApJ, 666, 1024), and we find a best match to a range of Type II SNe at z=0.03.

  12. Tyrosinemia type II: a challenge for ophthalmologists and dermatologists.

    PubMed

    Benoldi, D; Orsoni, J B; Allegra, F

    1997-01-01

    Tyrosinemia type II was suspected in a 13-month-old child with recurrent photophobia, tearing, and hyperkeratotic lesions on the palms and soles. Laboratory tests revealed high tyrosine levels in blood and urine. All the symptoms promptly improved after the institution of a low tyrosine diet. We emphasize the importance of an early diagnosis in order to avoid the risk of mental retardation in these patients.

  13. Transforming growth factor receptor type II (ec-TβR II) behaves as a halophile.

    PubMed

    Saini, Komal; Khan, M Ashhar I; Chakrapani, Sumit; Deep, Shashank

    2015-01-01

    The members of transforming growth factor β family (TGF-β) are multifunctional proteins but their main role is to control cell proliferation and differentiation. Polypeptides of TGF-β family function by binding to two related, functionally distinct transmembrane receptor kinases, first to the type II (TβR II) followed by type I receptor (TβR I). The paper describes, in details, the stability of wt-ec-TβR II under different conditions. The stability of wt-ec-TβR II was observed at different pH and salt concentration using fluorescence spectroscopy. Stability of ec-TβR II decreases with decrease in pH. Interestingly, the addition of salt increases the stability of the TβRII at pH 5.0 as observed for halophiles. Computational analysis using DELPHI suggests that this is probably due to the decrease in repulsion between negatively charged residues at surface on the addition of salt. This is further confirmed by the change in the stability of receptor on mutation of some of the residues (D32A) at surface.

  14. Retinopathy and microalbuminuria in type II diabetic patients

    PubMed Central

    Manaviat, Masoud R; Afkhami, Mohammad; Shoja, Mohammad R

    2004-01-01

    Background The aim of this study was to identify risk factors for the development of retinopathy and microalbuminuria and their correlation in type II diabetic patients. Methods In this cross-sectional study 590 patients suffering from diabetis type II were examined. Fundoscopy was performed by practising ophthalmologist. The ratio of urinary albumin to creatinine was assessed by clinitek 100 (Bayer corporation–USA). HbA1C, height and weight also were measured. Results The overall prevalence of retinopathy was 39.3% (232 patients), 5.4% of which showed to be prolifrative diabetic retinopathy (PDR). The diabetic retinopathy had significant inverse correlation with body mass index (BMI) (P = 0.02). HbA1C was higher in patients with PDR (mean = 10.5%) than in patients with no signs of retinopathy (mean = 9.5%) and this difference was statistically significant (P = 0.001). The prevalence of microalbuminuria was 25.9% while 14.5% of the patients revealed to have macroalbuminuria. As expected, diabetic retinopathy and renal involvement were highly positively correlated. (P = 0.001). Conclusion Microalbuminuria is associated with diabetic retinopathy in type II diabetic patients and is a reliable marker of retinopathy. PMID:15228626

  15. Type-II superlattice infrared detector technology at Fraunhofer IAF

    NASA Astrophysics Data System (ADS)

    Rehm, Robert; Daumer, Volker; Hugger, Tsvetelina; Kohn, Norbert; Luppold, Wolfgang; Müller, Raphael; Niemasz, Jasmin; Schmidt, Johannes; Rutz, Frank; Stadelmann, Tim; Wauro, Matthias; Wörl, Andreas

    2016-05-01

    For more than two decades, Antimony-based type-II superlattice photodetectors for the infrared spectral range between 3-15 μm are under development at the Fraunhofer Institute for Applied Solid State Physics (IAF). Today, Fraunhofer IAF is Germany's only national foundry for InAs/GaSb type-II superlattice detectors and we cover a wide range of aspects from basic materials research to small series production in this field. We develop single-element photodetectors for sensing systems as well as two-dimensional detector arrays for high-performance imaging and threat warning systems in the mid-wavelength and long-wavelength region of the thermal infrared. We continuously enhance our production capabilities by extending our in-line process control facilities. As a recent example, we present a semiautomatic wafer probe station that has developed into an important tool for electrooptical characterization. A large amount of the basic materials research focuses on the reduction of the dark current by the development of bandgap engineered device designs on the basis of heterojunction concepts. Recently, we have successfully demonstrated Europe's first LWIR InAs/GaSb type-II superlattice imager with 640x512 pixels with 15 μm pitch. The demonstrator camera already delivers a good image quality and achieves a thermal resolution better than 30 mK.

  16. Coronas Mass Ejections, Shocks, and Type II Radio Bursts

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Natchimuthuk

    2010-01-01

    Coronal mass ejections (CMEs) are the most energetic phenomena in the interplanetary medium. Type II radio bursts are the earliest indicators of particle acceleration by CME-driven shocks. There is one-to-one correspondence between large solar energetic particle (SEP) events and long wavelength type II bursts because the same CME-driven shock is supposed to accelerate electrons and ions. However, there are some significant deviations: some CMEs lacking type II bursts (radio-quiet or RQ CMEs) are associated with small SEP events while some radioloud (RL) CMEs are not associated with SEP events, suggesting subtle differences in the acceleration of electrons and protons. Not all CME-driven shocks are radio loud: more than one third of the interplanetary shocks during solar cycle 23 were radio quiet. Some RQ shocks were associated with energetic storm particle (ESP) events, which are detected when the shocks arrive at the observing spacecraft. This paper attempts to explain these contradictory results in terms of the properties of CMEs, shocks, and the ambient medium.

  17. Defects and noise in Type-II superlattice infrared detectors

    NASA Astrophysics Data System (ADS)

    Walther, Martin; Wörl, Andreas; Daumer, Volker; Rehm, Robert; Kirste, Lutz; Rutz, Frank; Schmitz, Johannes

    2013-06-01

    To examine defects in InAs/GaSb type-II superlattices we investigated GaSb substrates and epitaxial InAs/GaSb layers by synchrotron white beam X-ray topography to characterize the distribution of threading dislocations. Those measurements are compared with wet chemical etch pit density measurements on GaSb substrates and InAs/GaSb type-II superlattices epitaxial layer structures. The technique uses a wet chemical etch process to decorate threading dislocations and an automated optical analyzing system for mapping the defect distribution. Dark current and noise measurements on processed InAs/GaSb type-II superlattice single element photo diodes reveal a generation-recombination limited dark current behavior without contributions by surface leakage currents for midwavelength infrared detectors. In the white noise part of the noise spectrum, the extracted diode noise closely matches the theoretically expected shot noise behavior. For diodes with an increased dark current in comparison to the dark current of generation-recombination limited material, the standard shot-noise model fails to describe the noise experimentally observed in the white part of the spectrum. Instead, we find that McIntyre's noise model for avalanche multiplication processes fits the data quite well. We suggest that within high electric field domains localized around crystallographic defects, electrons initiate avalanche multiplication processes leading to increased dark current and excess noise.

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

    PubMed

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

    2015-01-01

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

  19. Perinatal lethal type II osteogenesis imperfecta: a case report

    PubMed Central

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure. PMID:26401205

  20. Systematic identification of type I and type II interferon-induced antiviral factors.

    PubMed

    Liu, Su-Yang; Sanchez, David Jesse; Aliyari, Roghiyh; Lu, Sun; Cheng, Genhong

    2012-03-13

    Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses. PMID:22371602

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

    PubMed

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

    2013-01-01

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

  2. A study of low-energy type II supernovae

    NASA Astrophysics Data System (ADS)

    Lisakov, Sergey M.; Dessart, Luc; Hillier, D. John; Waldman, Roni; Livne, Eli

    2015-08-01

    All stars with an initial mass greater than 8Msun, but not massive enough to encounter the pair-production instability, eventually form a degenerate core and collapse to form a compact object, either a neutron star or a black hole.At the lower mass end, these massive stars die as red-supergiant stars and give rise to Type II supernovae (SNe). The diversity of observed properties of SNe II suggests a range of progenitor mass, radii, but also explosion energy.We have performed a large grid simulations designed to cover this range of progenitor and explosion properties. Using MESA STAR, we compute a set of massive star models (12-30Msun) from the main sequence until core collapse. We then generate explosions with V1D to produce ejecta with a range of explosion energies and yields. Finally, all ejecta are evolved with CMFGEN to generate multi-band light curves and spectra.In this poster, we focus our attention on the properties of low-energy explosions that give rise to low-luminosity Type II Plateau (II-P) SNe. In particular, we present a detailed study of SN 2008bk, but also include other notorious low-energy SNe II-P like 2005cs, emphasising their non-standard properties by comparing to models that match well events like SN 1999em. Such low-energy explosions, characterised by low ejecta expansion rates, are more suitable for reliable spectral line identifications.Based on our models, we discuss the distinct signatures of low-energy explosions in lower and higher mass models. One important goal is to identify whether there is a progenitor-mass bias leading to such events.

  3. Monoclonal antibodies against type II rat brain protein kinase

    SciTech Connect

    Nakabayashi, C.H.; Huang, K.P.

    1987-05-01

    Three monoclonal antibodies (8/1, 10/10, and 25/3) against rat brain type II protein kinase C (PKC) were used to carry out the immunochemical characterization of this kinase. These antibodies immunoprecipitated the type II PKC in a dose-dependent manner but did neither to type I nor type III isozyme. Purified type II PKC has a molecular weight of 82,000 and consists of heterogeneous isoelectric point species, all of which are cross reactive with these antibodies. Immunoblot analysis of the tryptic fragments from PKC revealed that all three antibodies recognized the 33-38-KDa fragments, the phospholipid/phorbol ester-binding domain, but not the 45-48-KDa fragments, the kinase catalytic domain. The immune complexes of the kinase and the antibodies retained the kinase activity which was dependent on Ca/sup 2 +/ and phosphatidylserine (PS) and further activated by diacylglycerol. With antibody 8/1, the apparent Km values of the kinase for Ca/sup 2 +/ and PS were not influenced. The initial rate and final extent of autophosphorylation were reduced. The concentration of PS required for half-maximal (/sup 3/H)phorbol 12,13-dibutyrate (PDBu) binding was increased and the total PDBu binding was reduced. In the presence of optimum concentrations of Ca/sup 2 +/ and PS, the Kd of PDBu was unaffected by the antibody but the total binding was reduced. These results demonstrate that the PS/PDBu-binding domain contains the major epitope for the antibodies and the antibody mainly influences the PS/PDBu binding to the kinase.

  4. Observations of On-Disk Type I and II Spicules

    NASA Astrophysics Data System (ADS)

    Deng, Na; Denker, C.; Verma, M.; Shimizu, T.; Liu, C.; Wang, H.

    2011-05-01

    A coordinated observing campaign was carried out during 2010 November 16-30 using German Vacuum Tower Telescope (VTT) and Hinode to investigate properties of small-scale spicules on the solar disk. The high-spectral resolution Echelle spectrograph at the VTT on Tenerife acquired spectra of the chromospheric halpha (656.28 nm) and photospheric Fe I (656.92 nm) lines in a region centered on a small pore. Hinode mission provides high-cadence vector magnetograms, G-band and Ca II H images, EIS and XRT observations of the same region. We present statistical properties of spicules (type I and II), such as spectral characteristics, velocities, spatial distribution and temporal evolution, paying particular attention to type II spicules or chromospheric jets. We investigate the photospheric magnetic structure, flow field and their evolution attempting to find the origin of chromospheric jets. The vertical extent of identified chromospheric jets in the transition region and corona will be studied using EIS and XRT observations in conjunction with SDO observations.

  5. Hippocampal type I and type II corticosteroid receptors are modulated by central noradrenergic systems.

    PubMed

    Maccari, S; Mormède, P; Piazza, P V; Simon, H; Angelucci, L; Le Moal, M

    1992-01-01

    The effects of corticosteroids on various brain functions, including the negative feedback control of hypothalamo-pituitary-adrenal (HPA) axis activity, are mediated by two types of receptors (type I, or mineralocorticoid, and type II, or glucocorticoid) in the central nervous system. Although receptor numbers are thought to be regulated by circulating levels of corticosterone, there may be a direct neural control of corticosteroid receptors. In the present experiments, we demonstrate that 6-OHDA lesioning of noradrenergic (NA) ascending pathways in the pedunculus cerebellaris superior (PCS) reduces corticosterone secretion in response to novelty and increases the number of hippocampal type I corticosteroid receptors in rats 24 hr after adrenalectomy. The same lesion in adrenalectomized animals in which corticosterone levels were maintained within normal limits by corticosterone replacement implants also led to an increase in the number of type I corticosterone receptors and a decrease in the apparent affinity (Kd) of type II receptors in the hippocampus. These results suggest that the NA system may regulate HPA axis activity via a direct control of the number of type I receptors and the apparent affinity of type II receptors in the hippocampus. The possibility that there is a neural control of corticosteroid receptors may throw light on mechanisms controlling HPA axis activity and may suggest other approaches to the treatment of dysregulation of the HPA axis observed during stress and in certain psychopathological conditions. PMID:1332096

  6. Geochemistry of the alginite and amorphous organic matter from type II-S kerogens

    USGS Publications Warehouse

    Stankiewicz, B.A.; Kruge, M.A.; Mastalerz, Maria; Salmon, G.L.

    1996-01-01

    Maceral fractions of the Type II-S kerogens from the Monterey Formation (Miocene. California. U.S.A.) and Duwi Formation (Campanian/Maastrichtian, Egypt) were separated by density gradient centrifugation. The Monterey Fm. kerogen sample was comprised chiefly of light red-fluorescing amorphous organic matter (AOM), the flash pyrolyzate of which was characterized by a predominance of alkylbenzenes, alkylthiophenes and alkylpyrroles. In contrast, the pyrolyzates of its alginite concentrate showed a highly aliphatic character, typical of this maceral, with the series of n-alkenes and n-alkanes (C6- C26) predominating. The pyrolyzate of the dominant light brown-fluorescing AOM of the Duwi Fm. kerogen had a relatively high concentration of alkylbenzenes and alkylthiophenes, while its elginite concentrate showed a more aliphatic character upon pyrolysis. There was a marked enrichment of thiophenic sulfur in the light-colored AOM of both samples (and also pyrrolic nitrogen in the case of the Monterey) relative to the alginite. The results support a bacterially-mediated, degradative origin for Type II-S amorphous organic matter, with algal remains as the primary source of the kerogen.

  7. Dentinogenesis imperfecta type II: ultrastructure of teeth in sagittal sections.

    PubMed

    Wieczorek, Aneta; Loster, Jolanta

    2013-01-01

    The morphological abnormalities of the teeth of patients affected by dentinogenesis imperfecta type 2 (DI-II) may underlie the difficulties with the clinical restoration of such teeth. We therefore performed a scanning electron microscopy (SEM) study of four permanent first mandibular molars of four DI-II patients with periapical pathosis. The teeth were prepared for SEM evaluation by standard methods. In the crown, the enamel presented a highly irregular surface with a number of cracks and crevices. In some places, only granular remains of the enamel were found, while in other parts of the crown, the enamel was absent. SEM examination revealed the structural changes responsible for the lower enamel's hardness and resistance to attrition, and for tooth wear, while the structural changes in the dentin may explain the failure of some adhesive restorative materials. This SEM study thus revealed structural defects which underlie the problems of attrition and restoration loss found in patients with this genetic dental condition.

  8. The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy

    PubMed Central

    Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

    2015-01-01

    Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings. PMID:26226340

  9. ACTIVIN IIB RECEPTOR BLOCKADE ATTENUATES DYSTROPHIC PATHOLOGY IN A MOUSE MODEL OF DUCHENNE MUSCULAR DYSTROPHY

    PubMed Central

    Morine, Kevin J.; Bish, Lawrence T.; Selsby, Joshua T.; Gazzara, Jeffery A.; Pendrak, Klara; Sleeper, Meg M.; Barton, Elisabeth R.; Lee, Se-Jin; Sweeney, H. Lee

    2015-01-01

    Modulation of transforming growth factor-β (TGF-β) signaling to promote muscle growth holds tremendous promise for the muscular dystrophies and other disorders involving the loss of functional muscle mass. Previous studies have focused on the TGF-β family member myostatin and demonstrated that inhibition of myostatin leads to muscle growth in normal and dystrophic mice. We describe a unique method of systemic inhibition of activin IIB receptor signaling via adeno-associated virus (AAV)-mediated gene transfer of a soluble form of the extracellular domain of the activin IIB receptor to the liver. Treatment of mdx mice with activin IIB receptor blockade led to increased skeletal muscle mass, increased force production in the extensor digitorum longus (EDL), and reduced serum creatine kinase. No effect on heart mass or function was observed. Our results indicate that activin IIB receptor blockade represents a novel and effective therapeutic strategy for the muscular dystrophies. PMID:20730876

  10. Abnormal concentration of maternal serum activin-A in gestational diseases.

    PubMed

    Petraglia, F; De Vita, D; Gallinelli, A; Aguzzoli, L; Genazzani, A R; Romero, R; Woodruff, T K

    1995-02-01

    Serum plasma activin-A is measurable in the maternal circulation of healthy pregnant women, increases in specimens collected during the third trimester of gestation, and is highest at parturition. Hormone abnormalities are known to be associated with preterm labor or diabetes in pregnancy. Therefore, in the present study serum activin-A levels in normal controls were compared to those in pregnant women with preterm labor or gestational diabetes. In some cases, values were obtained before and after insulin therapy. In other controls and patients with preterm labor, the activin-A concentration in cord serum was also studied. A newly developed two-site immunotest was used to determine activin-A levels. Subjects included normal controls (n = 7), who were sampled throughout gestation every 5 weeks; pregnant women at term (38-40 weeks) not in labor (n = 22); pregnant women at term in spontaneous labor (< 3.0 cm dilated; n = 42); women in preterm labor (25-35 weeks; n = 38); and women with gestational diabetes (20-39 weeks; n = 9). In control women, serum activin-A levels increased from 4.8 +/- 5.5 micrograms/L (mean +/- SD) at 20 weeks to 25.4 +/- 27.8 micrograms/L at 40 weeks (P < 0.01), and values correlated with gestational age. Pregnant women in preterm labor had serum activin-A concentrations (89.04 +/- 173.31 micrograms/L) higher than those in normal controls (P < 0.01), and no significant correlation to gestational age was found in this group of pregnant women. Healthy women in labor showed serum activin-A concentrations higher than those in women at term but not in labor (P < 0.01). Diabetic patients had serum activin-A concentrations (52.39 +/- 23.32 micrograms/L) significantly higher than those in normal controls. In these patients, maternal serum activin-A concentrations significantly decreased to the range in healthy controls at the same gestational age after insulin therapy (9.48 +/- 3.82 micrograms/L). The present study shows that preterm labor is

  11. Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells

    PubMed Central

    Lobato-Márquez, Damián; Moreno-Córdoba, Inmaculada; Figueroa, Virginia; Díaz-Orejas, Ramón; García-del Portillo, Francisco

    2015-01-01

    Toxin-antitoxin (TA) modules contribute to the generation of non-growing cells in response to stress. These modules abound in bacterial pathogens although the bases for this profusion remain largely unknown. Using the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as a model, here we show that a selected group of TA modules impact bacterial fitness inside eukaryotic cells. We characterized in this pathogen twenty-seven TA modules, including type I and type II TA modules encoding antisense RNA and proteinaceous antitoxins, respectively. Proteomic and gene expression analyses revealed that the pathogen produces numerous toxins of TA modules inside eukaryotic cells. Among these, the toxins HokST, LdrAST, and TisBST, encoded by type I TA modules and T4ST and VapC2ST, encoded by type II TA modules, promote bacterial survival inside fibroblasts. In contrast, only VapC2ST shows that positive effect in bacterial fitness when the pathogen infects epithelial cells. These results illustrate how S. Typhimurium uses distinct type I and type II TA modules to regulate its intracellular lifestyle in varied host cell types. This function specialization might explain why the number of TA modules increased in intracellular bacterial pathogens. PMID:25792384

  12. Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells.

    PubMed

    Lobato-Márquez, Damián; Moreno-Córdoba, Inmaculada; Figueroa, Virginia; Díaz-Orejas, Ramón; García-del Portillo, Francisco

    2015-01-01

    Toxin-antitoxin (TA) modules contribute to the generation of non-growing cells in response to stress. These modules abound in bacterial pathogens although the bases for this profusion remain largely unknown. Using the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as a model, here we show that a selected group of TA modules impact bacterial fitness inside eukaryotic cells. We characterized in this pathogen twenty-seven TA modules, including type I and type II TA modules encoding antisense RNA and proteinaceous antitoxins, respectively. Proteomic and gene expression analyses revealed that the pathogen produces numerous toxins of TA modules inside eukaryotic cells. Among these, the toxins HokST, LdrAST, and TisBST, encoded by type I TA modules and T4ST and VapC2ST, encoded by type II TA modules, promote bacterial survival inside fibroblasts. In contrast, only VapC2ST shows that positive effect in bacterial fitness when the pathogen infects epithelial cells. These results illustrate how S. Typhimurium uses distinct type I and type II TA modules to regulate its intracellular lifestyle in varied host cell types. This function specialization might explain why the number of TA modules increased in intracellular bacterial pathogens.

  13. Change in the Gastro-Intestinal Tract by Overexpressed Activin Beta A

    PubMed Central

    Kim, Mi-Nyeu; Kim, Young Il; Cho, Chunghee; Mayo, Kelly E.; Cho, Byung-Nam

    2015-01-01

    Originally, activins were identified as stimulators of FSH release in reproduction. Other activities, including secondary axis formation in development, have since been revealed. Here, we investigated the influence of activin βA on the body, including the gastro-intestinal (GI) tract. Initially, the activin βA protein was detected in the serum proportional to the amount of pCMV-rAct plasmid injected. The induced level of activin βA in muscle was higher in female than male mice. Subsequent results revealed that stomach and intestine were severely damaged in pCMV-rAct-injected mice. At the cellular level, loss of parietal cells was observed, resulting in increased pH within the stomach. This phenomenon was more severe in male than female mice. Consistent with damage of the stomach and intestine, activin βA often led to necrosis in the tip of the tail or foot, and loss of body weight was observed in pCMV-rAct-injected male but not female mice. Finally, in pCMV-rAct-injected mice, circulating activin βA led to death at supraphysiological doses, and this was dependent on the strain of mice used. Taken together, these results indicate that activin βA has an important role outside of reproduction and development, specifically in digestion. These data also indicate that activin βA must be controlled within a narrow range because of latent lethal activity. In addition, our approach can be used effectively for functional analysis of secreted proteins. PMID:26608361

  14. Activin A is associated with asthma in underweight and overweight patients.

    PubMed

    Zhang, L L; Liu, C T

    2015-01-01

    There are limited data regarding the effects of activin A on underweight, normal weight, and overweight patients with asthma. We determined serum levels of activin A in asthmatic patients in relation to body mass index. The study protocol included questionnaires, measurement of exhaled nitric oxide, blood sampling for inflammatory biomarkers, and high-resolution computed tomography of the lungs to identify bronchial wall thickening. Serum and sputum activin A levels were measured using an enzyme-linked immunosorbent assay in 94 asthmatic patients. Mean serum levels of activin A were significantly (P = 0.001) higher in underweight (1781 ± 327.3 pg/mL) than in normal weight and overweight asthmatic patients, regardless of gender. After stratification by gender, significantly higher mean values of activin A were observed in females compared to males in the normal and underweight groups (P = 0.003 and P = 0.0002, respectively). Significant differences between groups were found in airway wall area (%) (P < 0.0001). We also observed a much higher percentage of sputum lymphocytes in the underweight group compared to the other groups (P < 0.0001). Correlations between bronchial wall thickness and activin A were found in the underweight (r = 0.67, P = 0.48) and normal weight groups (r = 0.51, P = 0.042). Correlations between fractional of exhaled nitric oxide, forced expiratory volume in 1 s, delayed treatment years, and activin A in different groups were also observed. Increased serum level of activin A indicates its role in the pathogenesis of asthma, particularly in underweight and overweight patients.

  15. On the Intrinsic Diversity of Type II-Plateau Supernovae

    NASA Astrophysics Data System (ADS)

    Pejcha, Ondřej; Prieto, Jose L.

    2015-06-01

    Hydrogen-rich Type II-Plateau supernovae (SNe) exhibit correlations between the plateau luminosity {L}{pl}, the nickel mass {M}{Ni}, the explosion energy {E}{exp}, and the ejecta mass {M}{ej}. Using our global, self-consistent, multi-band model of nearby well-observed SNe, we find that the covariances of these quantities are strong and that the confidence ellipsoids are oriented in the direction of the correlations, which reduces their significance. By proper treatment of the covariance matrix of the model, we discover a significant intrinsic width to the correlations between {L}{pl}, {E}{exp} and {M}{Ni}, where the uncertainties due to the distance and the extinction dominate. For fixed {E}{exp}, the spread in {M}{Ni} is about 0.25 dex, which we attribute to the differences in the progenitor internal structure. We argue that the effects of incomplete γ-ray trapping are not important in our sample. Similarly, the physics of the Type II-Plateau SN light curves leads to inherently degenerate estimates of {E}{exp} and {M}{ej}, which makes their observed correlation weak. Ignoring the covariances of SN parameters or the intrinsic width of the correlations causes significant biases in the slopes of the fitted relations. Our results imply that Type II-Plateau SN explosions are not described by a single physical parameter or a simple one-dimensional trajectory through the parameter space, but instead reflect the diversity of the core and surface properties of their progenitors. We discuss the implications for the physics of the explosion mechanism and possible future observational constraints.

  16. Oral magnesium supplementation in type II diabetic patients

    PubMed Central

    Solati, Mehrdad; Ouspid, Elham; Hosseini, Saeedeh; Soltani, Nepton; Keshavarz, Mansoor; Dehghani, Mohsen

    2014-01-01

    Background: Magnesium is the second most abundant intracellular cation. It plays an important role in insulin homeostasis and glucose metabolism through multiple enzymatic reactions. With increasing data on magnesium deficiency in diabetic patients and epidemiological studies demonstrating magnesium deficiency as a risk factor for diabetes, it is logical to search for its possible beneficial effects on diabetes control and prevention. We aimed to determine whether oral magnesium supplementation improves metabolic control, lipid profile and blood pressure in patients with type II diabetes. Methods: Fifty four patients with type II diabetes were included in a randomized double blind placebocontrolled clinical trial.Patients received either placebo or 300 mg elemental magnesium (as magnesium sulfate -MgSo4-) daily, for 3 months. Metabolic control, lipid profile, blood pressure, magnesium status, hepatic enzymes, hemoglobin concentration, and anthropometric indices were determined in the beginning and at the end of the study. Results: Daily administration of 300 mg elemental magnesium for 3 months, significantly improved fasting blood glucose (183.9±15.43 to 125.8±6.52 vs. 196.5±28.12 to 136.5±7.94, p< 0.0001), 2-hour post prandial glucose (239.1±74.75 to 189.1±60mg/dl vs. 246.4±97.37 to 247.8±86.74mg/dl, p< 0.01), lipid profile, blood pressure and hepatic enzymes. Conclusion: Oral magnesium supplementation with proper dosage has beneficial effects on blood glucose, lipid profile, and blood pressure in patients with type II diabetes. PMID:25405132

  17. Kelly West Lecture. Primary prevention of type II diabetes mellitus.

    PubMed

    Stern, M P

    1991-05-01

    A useful paradigm for developing a public health strategy for combating chronic diseases consists of three phases: observational epidemiological studies, first cross-sectional and then prospective; intervention trials; and, finally, public health action. Although the field of cardiovascular epidemiology is well advanced into the third phase, i.e., public health action, the field of diabetes epidemiology is at least a generation behind and has only recently entered the phase of prospective observational studies. Part of the reason for this lag may be that, unlike cardiovascular disease, non-insulin-dependent (type II) diabetes has not been traditionally viewed as an epidemic, thereby detracting from a sense of urgency about the disease. Although this perspective may be appropriate for white populations, data from around the world make it increasingly apparent that type II diabetes has indeed reached epidemic proportions in non-white populations. Prospective studies are needed to firmly establish risk factors on which public health actions can be confidently based. Although anthropometric and metabolic risk factors such as obesity, body fat distribution, and circulating glucose and insulin concentrations are becoming well established as risk factors for type II diabetes, much less is known about behavioral risk factors. These latter risk factors are especially important because they are often amenable to public health action. There are preliminary data suggesting that decreased physical activity and increased fat consumption may be behavioral risk factors for diabetes. Decreased total energy intake, reflecting either low levels of physical activity or an intrinsically low metabolic rate, perhaps genetic in origin, may also be a diabetes risk factor. Unlike the field of cardiovascular epidemiology, in which there is already a critical mass of intervention trials on primary prevention, such trials are essentially nonexistent in the field of diabetes epidemiology; they

  18. Interaction of ultrasound with vortices in type-II superconductors

    SciTech Connect

    Sonin, E.B.

    1996-04-01

    The theory of ultrasound in the mixed state of type-II superconductors is suggested which takes into account the Magnus force on vortices, the anti-Magnus force on ions, and diamagnetism of the mixed state. The acoustic Faraday effect (rotation of polarization of the transverse ultrasonic wave propagating along vortices) is linear in the Magnus force in any regime of the flux flow for wavelengths now used in the ultrasound experiments. Therefore, in contrast to previous predictions, the Faraday effect should be looked for only in clean superconductors with a strong Magnus force. {copyright} {ital 1996 The American Physical Society.}

  19. Paradoxical hypertension and salt wasting in Type II Bartter syndrome.

    PubMed

    Chan, Winnie Kwai-Yu; To, Ka Fai; Tong, Joanna H M; Law, Chi Wai

    2012-06-01

    Ante/neonatal Bartter syndrome (BS) is a rare hereditary disorder. It is characterized by renal salt wasting, hypokalaemic metabolic alkalosis, high renin and aldosterone but normal blood pressure. We report a low birth weight newborn baby who presented with repeated apnoea shortly after birth as well as hyponatraemia, hypochloraemia, hyperkalaemia and metabolic acidosis. Her biochemical features mimicked pseudohypoaldosteronism but with initial hypertension, which had not been described in BS. Her subsequent genetic study confirmed two novel heterozygous mutations in the Exon 5 of KCNJ1 compatible with Type II BS. PMID:26069767

  20. Parameters, limits and higher derivative type II string corrections

    NASA Astrophysics Data System (ADS)

    Gubay, Finn; West, Peter

    2012-11-01

    String theory in d dimensions has n + 1 = 11 - d parameters that may be thought of as being inherited from the geometry of an n + 1 torus which may be used to construct the theory using dimensional reduction from eleven dimensions. We give the precise relationship between these parameters and the expectation values of the scalar fields that parameterise the E n+1 coset of the d dimensional theory. This allows us to examine all possible limits of the automorphic forms which occur as the coefficient functions of the higher derivative corrections to the d dimensional type II string effective action.

  1. d-Brane Instantons in Type II Orientifolds

    NASA Astrophysics Data System (ADS)

    Blumenhagen, Ralph; Cvetič, Mirjam; Kachru, Shamit; Weigand, Timo

    2009-11-01

    We review recent progress in determining the effects of d-brane instantons in [Formula: see text] supersymmetric compactifications of Type II string theory to four dimensions. We describe the abstract d-brane instanton calculus for holomorphic couplings such as the superpotential, the gauge kinetic function, and higher fermionic F-terms, and we briefly discuss the implications of background fluxes for the instanton sector. We then summarize the concrete consequences of stringy d-brane instantons for the construction of semirealistic models of particle physics or supersymmetry breaking in compact and noncompact geometries.

  2. Type II reaction without erythema nodosum leprosum masquerading as lymphoma.

    PubMed

    Mahajan, Rahul; Dogra, Sunil; Kaur, Inderjeet; Yadav, Savita; Saikia, Uma Nahar; Budania, Anil

    2012-12-01

    Lepromatous leprosy is a multisystem disease that can involve many organ systems, with lymph nodes a common extra-cutaneous site to be affected. Rarely, multibacillary leprosy can be confused with other diseases like lymphomas and connective tissue diseases. Herein we report a patient of lepromatous leprosy with Type II lepra reaction involving lymph nodes who presented with generalised lymphadenopathy, acquired ichthyosis and constitutional symptoms but no cutaneous lesions to suggest erythema nodosum leprosum, and who was initially misdiagnosed as a case of Hodgkin's lymphoma. PMID:23614256

  3. Anaphase chromatid motion: involvement of type II DNA topoisomerases.

    PubMed Central

    Duplantier, B; Jannink, G; Sikorav, J L

    1995-01-01

    Sister chromatids are topologically intertwined at the onset of anaphase: their segregation during anaphase is known to require strand-passing activity by type II DNA topoisomerase. We propose that the removal of the intertwinings involves at the same time the traction of the mitotic spindle and the activity of topoisomerases. This implies that the velocity of the chromatids is compatible with the kinetic constraints imposed by the enzymatic reaction. We show that the greatest observed velocities (about 0.1 microns s-1) are close to the theoretical upper bound compatible with both the diffusion rate (calculated here within a probabilistic model) and the measured reaction rate of the enzyme. PMID:8534830

  4. Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

    PubMed Central

    Le Bras, Gregoire F.; Koumangoye, Rainelli B.; Romero-Morales, Alejandra I.; Quast, Laura L.; Zaika, Alexander I.; El-Rifai, Wael; Andl, Thomas; Andl, Claudia D.

    2015-01-01

    TGFβ signaling has been implicated in the metaplasia from squamous epithelia to Barrett's esophagus and, ultimately, esophageal adenocarcinoma. The role of the family member Activin A in Barrett's tumorigenesis is less well established. As tumorigenesis is influenced by factors in the tumor microenvironment, such as fibroblasts and the extracellular matrix, we aimed to determine if epithelial cell-derived Activin affects initiation and progression differently than Activin signaling stimulation from a mimicked stromal source. Using Barrett's esophagus cells, CPB, and the esophageal adenocarcinoma cell lines OE33 and FLO-1, we showed that Activin reduces colony formation only in CPB cells. Epithelial cell overexpression of Activin increased cell migration and invasion in Boyden chamber assays in CPB and FLO-1 cells, which exhibited mesenchymal features such as the expression of the CD44 standard form, vimentin, and MT1-MMP. When grown in organotypic reconstructs, OE33 cells expressed E-cadherin and Keratin 8. As mesenchymal characteristics have been associated with the acquisition of stem cell-like features, we analyzed the expression and localization of SOX9, showing nuclear localization of SOX9 in esophageal CPB and FLO-1 cells. In conclusion, we show a role for autocrine Activin signaling in the regulation of colony formation, cell migration and invasion in Barrett's tumorigenesis. PMID:26447543

  5. Immunohistochemical localization of inhibin/activin subunits in the wild ground squirrel (Citellus dauricus Brandt) ovary.

    PubMed

    Sheng, Xia; Weng, Jiaju; Zhang, Haolin; Li, Xiaonan; Zhang, Mengyuan; Xu, Meiyu; Weng, Qiang; Watanabe, Gen; Taya, Kazuyoshi

    2012-01-01

    The intraovarian function of gonadally produced inhibin and activin has been extensively studied in experimental models for decades, yet their presence and function have been rarely reported in wild rodents. With our seasonal breeding model, the wild ground squirrel, we aimed to investigate the possible roles of these peptides in the seasonal folliculogenesis. Immunohistochemical staining and Western blotting have been used to detect the cellular localization and expression patterns of inhibin/activin subunits (α, β(A) and β(B)). In the breeding season ovary, all three subunits were present in granulosa cells, theca cells of antral follicles and interstitial cells, with the strongest immunostaining in granulosa cells. Following ovulation, the corpora lutea become a major site of inhibin/activin synthesis. In the nonbreeding season ovary, inhibin/activin α and β(A) subunits were weakly immunopositive in granulosa cells of early stage follicles, while β(B) subunit was undetectable. The expression level of inhibin/activin subunit proteins were generally higher in the ovaries of the breeding season, and then decreased to a relatively low level during the nonbreeding season. The dynamic expression of inhibin/activin subunits indicated that they might play important paracrine and/or autocrine roles during the seasonal folliculogenesis of the wild ground squirrel.

  6. Activin B promotes initiation and development of hair follicles in mice.

    PubMed

    Jia, Qin; Zhang, Min; Kong, Yanan; Chen, Shixuan; Chen, Yinghua; Wang, Xueer; Zhang, Lei; Lang, Weiya; Zhang, Lu; Zhang, Lin

    2013-01-01

    Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated. In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice.

  7. Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

    ERIC Educational Resources Information Center

    Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.

    2012-01-01

    Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…

  8. [Achondrogenesis type II-hypochondrogenesis: radiological features.Case report].

    PubMed

    Delgado Carrasco, J; Casanova Morcillo, A; Zabalza Alvillos, M; Ayala Garcés, A

    2001-12-01

    We present a case of lethal dysplasia in the neonatal period. The abnormality was suspected after ultrasonography of a pregnant woman presenting weak fetal movements revealed shortening of the extremities, voluminous cranium and polyhydramnios. Clinical and radiological findings showed platyspondylic dwarfism with short extremities, narrow thorax and hydropic appearance. The infant died on the third day of life from progressive respiratory distress. In the absence of histological, chondro-osseus and molecular studies, detailed clinical and radiological studies, as well as the lethal evolution during the neonatal period, guided the diagnosis of hypochondrogenesis. This entity, together with achondrogenesis II (and other dysplasias), forms part of the same spectrum of collagen type II abnormalities produced by a defect in the gene (COL2A1) that codifies collagen II, located in chromosome 12 I(12q13.1-13.2). When a heterozygote is produced, transmission is dominant autosomal. The phenotype shows wide variation and severity depends on the mechanism and location of the mutation. The definitive diagnosis is given by cytomolecular studies, while individualization of the different entities is based on histological data from the cartilage; clinical findings and skeletal radiology serve as a guide. PMID:11730591

  9. Creatine kinase activity in patients with diabetes mellitus type I and type II.

    PubMed

    Jevrić-Causević, Adlija; Malenica, Maja; Dujić, Tanja

    2006-08-01

    Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  10. Acylation of Streptomyces type II polyketide synthase acyl carrier proteins.

    PubMed

    Crosby, J; Byrom, K J; Hitchman, T S; Cox, R J; Crump, M P; Findlow, I S; Bibb, M J; Simpson, T J

    1998-08-14

    Acyl derivatives of type II PKS ACPs are required for in vitro studies of polyketide biosynthesis. The presence of an exposed cysteine residue prevented specific chemical acylation of the phosphopantetheine thiol of the actinorhodin PKS holo ACP. Acylation studies were further complicated by intramolecular disulphide formation between cysteine 17 and the phosphopantetheine. The presence of this intramolecular disulphide was confirmed by tryptic digestion of the ACP followed by ESMS analysis of the fragments. An act Cys17Ser ACP was engineered by site-directed mutagenesis. S-Acyl adducts of act C17S, oxytetracycline and griseusin holo ACPs were rapidly formed by reaction with hexanoyl, 5-ketohexanoyl and protected acetoacetyl imidazolides. Comparisons with type 11 FAS ACPs were made.

  11. Type-II Weyl cone transitions in driven semimetals

    NASA Astrophysics Data System (ADS)

    Chan, Ching-Kit; Oh, Yun-Tak; Han, Jung Hoon; Lee, Patrick A.

    2016-09-01

    Periodically driven systems provide tunable platforms to realize interesting Floquet topological phases and phase transitions. In electronic systems with Weyl dispersions, the band crossings are topologically protected even in the presence of time-periodic perturbations. This robustness permits various routes to shift and tilt the Weyl spectra in the momentum and energy space using circularly polarized light of sufficient intensity. We show that type-II Weyl fermions, in which the Weyl dispersions are tilted with the appearance of pocketlike Fermi surfaces, can be induced in driven Dirac semimetals and line node semimetals. Under a circularly polarized drive, both semimetal systems immediately generate Weyl node pairs whose types can be further controlled by the driving amplitude and direction. The resultant phase diagrams demonstrate experimental feasibilities.

  12. Type II Hermite-Pade approximation to the exponential function

    NASA Astrophysics Data System (ADS)

    Kuijlaars, A. B. J.; Stahl, H.; van Assche, W.; Wielonsky, F.

    2007-10-01

    We obtain strong and uniform asymptotics in every domain of the complex plane for the scaled polynomials a(3nz), b(3nz), and c(3nz) where a, b, and c are the type II Hermite-Pade approximants to the exponential function of respective degrees 2n+2, 2n and 2n, defined by and as z-->0. Our analysis relies on a characterization of these polynomials in terms of a 3x3 matrix Riemann-Hilbert problem which, as a consequence of the famous Mahler relations, corresponds by a simple transformation to a similar Riemann-Hilbert problem for type I Hermite-Pade approximants. Due to this relation, the study that was performed in previous work, based on the Deift-Zhou steepest descent method for Riemann-Hilbert problems, can be reused to establish our present results.

  13. Structural insight into the type-II mitochondrial NADH dehydrogenases.

    PubMed

    Feng, Yue; Li, Wenfei; Li, Jian; Wang, Jiawei; Ge, Jingpeng; Xu, Duo; Liu, Yanjing; Wu, Kaiqi; Zeng, Qingyin; Wu, Jia-Wei; Tian, Changlin; Zhou, Bing; Yang, Maojun

    2012-11-15

    The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.

  14. Corneal lesion as the initial manifestation of tyrosinemia type II.

    PubMed

    Tsai, Chun-Pin; Lin, Pei-Yu; Lee, Ni-Chung; Niu, Dau-Ming; Lee, Shui-Mei; Hsu, Wen-Ming

    2006-06-01

    Tyrosinemia type II (Richner-Hanhart syndrome) is a rare autosomal recessive disease with deficiency of tyrosine aminotransferase and subsequently increasing level of serum tyrosine. We report the case of a 2-year-old girl who was referred due to bilateral corneal lesions. Slit-lamp examination showed small granular white deposits arranged in a dendritic pattern in the superficial central cornea of both eyes. Physical examination revealed painful, non-pruritic, hyperkeratotic plaques on the soles, palms and fingertips. Mental evaluation demonstrated developmental delay for her age. Blood examination revealed serum tyrosine level to be 1868 microM (normal range, 30-110 microM), which decreased to 838 microM with 2-month diet on tyrosine and phenylalanine restriction. The corneal and skin lesions resolved completely. However, the corneal deposits recurred a month later as her mother failed to strictly control the diet because the little girl was losing weight and activity. With specific formula and adjusted diet regimen, the corneal lesions decreased again. Corneal pseudodendritic deposits may be the initial manifestation in patients with tyrosinemia type II. Early diagnosis and intervention with diet control are crucial for preventing permanent visual and developmental deficits. Corneal deposits can be one of the parameters in monitoring the efficacy of diet control.

  15. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.

    PubMed

    Lee, K-E; Kang, H-Y; Lee, S-K; Yoo, S-H; Lee, J-C; Hwang, Y-H; Nam, K H; Kim, J-S; Park, J-C; Kim, J-W

    2011-04-01

    The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non-collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non-syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon-intron boundaries of the DSPP gene based on the candidate gene approach. Direct sequencing of PCR products and allele-specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.

  16. Vitamin D - Dependent Rickets, Type II Case Report

    PubMed Central

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Hoxha, Rina; Grajçevci-Uka, Violeta; Hoxha-Kamberi, Teuta

    2014-01-01

    Aim: The aim of this work the report of one case with vitamin D-dependent rickets, type II. Methods: Diagnosis has been established based on anamnesis, physical examination, laboratory findings and radiological examination. Results: A female child (age 25 months) has been hospitalized due to bone deformity, bone pain, alopecia and walking difficulties. The laboratory findings have revealed that the calcium values was low (1.20 mmol/L), phosphates in the reference value (1.30 mmol/L) the alkaline phosphatase value was quite high (852 IU/L), high value of parathyroid hormone (9.21 pmol/L), normal value of 25- hydroxyvitamin D, whereas the values of 1,25-dihydroxyvitamin D was high (185 μmol/L). Radiographic changes were evident and typical in the distal metaphysis of radius and ulna as well as in the bones of lower limbs (distal metaphysis of femur and proximal metaphysis of tibia and fibula). After treatment with calcium and calcitriol, the above mentioned clinical manifestations, laboratory test values and the radiographic changes in bones withdrew. Conclusions: Vitamin D-dependent rickets, type II is a rare genetic recessive disease, and its treatment includes a constant use of calcium and calcitriol. PMID:24757409

  17. Progress with type-II superlattice IR detector arrays

    NASA Astrophysics Data System (ADS)

    Rhiger, David R.; Kvaas, Robert E.; Harris, Sean F.; Bornfreund, Richard E.; Thai, Yen N.; Hill, Cory J.; Li, Jian V.; Gunapala, Sarath D.; Mumolo, Jason M.

    2007-04-01

    We report progress in the development of long wavelength infrared (LWIR) focal plane arrays (FPAs) built on type-II strained layer InAs/GaSb superlattice materials. Work at Raytheon Vision Systems and Jet Propulsion Laboratory has led to successful devices with cutoff wavelengths in the 10 to 12 μm range. Pixels have been formed by wet etching and surface passivation by plasma-deposited silicon dioxide. We present test results on arrays hybridized with indium bump bonding to silicon readout integrated circuits, as well as analyses of current-voltage characteristics of individual diodes. In particular, we find that, at temperatures below about 70 K the leakage current is dominated by generation-recombination effects near zero bias and by trap-assisted tunneling in reverse bias. Although other authors have demonstrated imaging for SWIR and MWIR type-II superlattice devices, to our knowledge no one has done so prior to 2006 in the LWIR range. We have obtained both still and video imaging with 256×256 arrays with 30-μm pixels operating at 78 K, having high operability and a cutoff wavelength of 10.5 μm.

  18. Zeta functional equation on Jordan algebras of type II

    NASA Astrophysics Data System (ADS)

    Kayoya, J. B.

    2005-02-01

    Using the Jordan algebras methods, specially the properties of Peirce decomposition and the Frobenius transformation, we compute the coefficients of the zeta functional equation, in the case of Jordan algebras of type II. As particular cases of our result, we can cite the case of studied by Gelbart [Mem. Amer. Math. Soc. 108 (1971)] and Godement and Jacquet [Zeta functions of simple algebras, Lecture Notes in Math., vol. 260, Springer-Verlag, Berlin, 1972], and the case of studied by Muro [Adv. Stud. Pure Math. 15 (1989) 429]. Let us also mention, that recently, Bopp and Rubenthaler have obtained a more general result on the zeta functional equation by using methods based on the algebraic properties of regular graded algebras which are in one-to-one correspondence with simple Jordan algebras [Local Zeta Functions Attached to the Minimal Spherical Series for a Class of Symmetric Spaces, IRMA, Strasbourg, 2003]. The method used in this paper is a direct application of specific properties of Jordan algebras of type II.

  19. Characterization of hearing loss in aged type II diabetics.

    PubMed

    Frisina, Susan T; Mapes, Frances; Kim, SungHee; Frisina, D Robert; Frisina, Robert D

    2006-01-01

    Presbycusis - age-related hearing loss - is the number one communicative disorder and a significant chronic medical condition of the aged. Little is known about how type II diabetes, another prevalent age-related medical condition, and presbycusis interact. The present investigation aimed to comprehensively characterize the nature of hearing impairment in aged type II diabetics. Hearing tests measuring both peripheral (cochlea) and central (brainstem and cortex) auditory processing were utilized. The majority of differences between the hearing abilities of the aged diabetics and their age-matched controls were found in measures of inner ear function. For example, large differences were found in pure-tone audiograms, wideband noise and speech reception thresholds, and otoacoustic emissions. The greatest deficits tended to be at low frequencies. In addition, there was a strong tendency for diabetes to affect the right ear more than the left. One possible interpretation is that as one develops presbycusis, the right ear advantage is lost, and this decline is accelerated by diabetes. In contrast, auditory processing tests that measure both peripheral and central processing showed fewer declines between the elderly diabetics and the control group. Consequences of elevated blood sugar levels as possible underlying physiological mechanisms for the hearing loss are discussed.

  20. Critical role of the endogenous interferon ligand-receptors in type I and type II interferons response.

    PubMed

    Lasfar, Ahmed; Cook, Jeffry R; Cohen Solal, Karine A; Reuhl, Kenneth; Kotenko, Sergei V; Langer, Jerome A; Laskin, Debra L

    2014-07-01

    Separate ligand-receptor paradigms are commonly used for each type of interferon (IFN). However, accumulating evidence suggests that type I and type II IFNs may not be restricted to independent pathways. Using different cell types deficient in IFNAR1, IFNAR2, IFNGR1, IFNGR2 and IFN-γ, we evaluated the contribution of each element of the IFN system to the activity of type I and type II IFNs. We show that deficiency in IFNAR1 or IFNAR2 is associated with impairment of type II IFN activity. This impairment, presumably resulting from the disruption of the ligand-receptor complex, is obtained in all cell types tested. However, deficiency of IFNGR1, IFNGR2 or IFN-γ was associated with an impairment of type I IFN activity in spleen cells only, correlating with the constitutive expression of type II IFN (IFN-γ) observed on those cells. Therefore, in vitro the constitutive expression of both the receptors and the ligands of type I or type II IFN is critical for the enhancement of the IFN activity. Any IFN deficiency can totally or partially impair IFN activity, suggesting the importance of type I and type II IFN interactions. Taken together, our results suggest that type I and type II IFNs may regulate biological activities through distinct as well as common IFN receptor complexes.

  1. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer. PMID:27648033

  2. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer.

  3. Neutrinos from type II supernovae - The first 100 milliseconds

    NASA Technical Reports Server (NTRS)

    Myra, Eric S.; Burrows, Adam

    1990-01-01

    The collapse of a 1.17 solar mass iron core is numerically followed through infall to 100 ms past core bounce, and the emergent neutrino spectra during each phase are highlighted. It is found that, even with fairly optimistic conditions for producing a strong, sustained core-bounce shock wave, the prompt shock stalls within 9 ms of core bounce at a radius of less than 250 km. It appears that a radical change in the character of the progenitor core or in our understanding of the relevant physics of stellar collapse is needed before the direct mechanism for type II supernovae can become viable. Expanding the number of neutrino types from one to six magnifies the debilitating effect of neutrino loss on shock propagation. At shock breakout, prompt bursts of all neutrino types are observed. The luminosities of the nonelectron types show a sudden turn-on in luminosity while that of the electron neutrinos steadily increases throughout infall as a result of accelerating electron capture.

  4. Relationships between type I and type II chondrules: Implications on chondrule formation processes

    NASA Astrophysics Data System (ADS)

    Villeneuve, Johan; Libourel, Guy; Soulié, Camille

    2015-07-01

    In unequilibrated chondrites, the ferromagnesian silicates in chondrules exhibit wide ranges of mg# = Mg/(Mg + Fe), allowing to sub-divide porphyritic chondrules into either type I (mg# > 0.9) or type II (mg# < 0.9). Although both chondrule types formed under oxidizing conditions relative to the canonical solar nebula, it is generally inferred that type II chondrules formed in more oxidizing conditions than type I. In order to check whether this redox difference was established during chondrule formation, or reflects differences in their precursors, we have undertaken a set of experiments aimed at heating type I olivine-rich (A) chondrule proxy, i.e. forsterite + Fe metal + Ca-Mg-Si-Al glass mixtures, under oxidizing conditions. We show that high temperature (isothermal) oxidation of type IA-like assemblages is a very efficient and rapid process (e.g. few tens of minutes) to form textures similar to type IIA chondrules. Due to the rapid dissolution of Fe metal blebs, a FeO increase in the melt and in combination with the dissolution of magnesian olivine allows the melt to reach ferroan olivine saturation. Crystallization of ferroan olivine occurs either as new crystal in the mesostasis or as overgrowths on the remaining unresorbed forsterite grains (relicts). Interruption of this process at any time before its completion by rapid cooling allows to reproduce the whole range of textures and chemical diversity observed in type A chondrules, i.e. from type I to type II. Several implications on chondrule formation processes can be inferred from the presented experiments. Type I chondrules or fragments of type I chondrules are very likely the main precursor material involved in the formation of most type II chondrules. Formation of porphyritic olivine type II chondrules is very likely the result of processes generating crystal growth by chemical disequilibrium at high temperature rather than processes generating crystallization only by cooling rates. This questions the

  5. Discovery and Observations of the Unusually Luminous Type-Defying II-P/II-L Supernova ASASSN-13co

    NASA Astrophysics Data System (ADS)

    Holoien, T. W.-S.; Prieto, J. L.; Pejcha, O.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Grupe, D.; Morrell, N.; Thorstensen, J. R.; Basu, U.; Beacom, J. F.; Bersier, D.; Brimacombe, J.; Davis, A. B.; Pojmański, G.; Skowron, D. M.

    2016-06-01

    We present photometric and spectroscopic observations of ASASSN-13co, an unusually luminous Type II supernova and the first core-collapse supernova discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN). First detection of the supernova was on UT 2013 August 29 and the data presented span roughly 3.5 months after discovery. We use the recently developed model by Pejcha and Prieto to model the multi-band light curves of ASASSN-13co and derive the bolometric luminosity curve. We compare ASASSN-13co to other Type II supernovae to show that it was unusually luminous for a Type II supernova and that it exhibited an atypical light curve shape that does not cleanly match that of either a standard Type II-L or Type II-P supernova.

  6. The Standardized Candle Method for Type II-Plateau Supernovae

    NASA Astrophysics Data System (ADS)

    Olivares, Felipe; Hamuy, Mario

    The determination of extragalactic distances allows us to constrain the cosmological parameters which drive the universe dynamics. The large luminosities of type II supernovae (SNe) (those with a hydrogen-rich envelope) make this class of objects as interesting distance indicators. Their luminosities can be standardized using the expansion velocity of the photosphere estimated from P-Cygni line profiles. However, one of the problems that hampers their use in distance determinations is the uncertainty in the host-galaxy extinction. The physics of the photosphere suggests the existence of a unique asymptotic color for all SNe toward the end of the optically thick phase (which corresponds to a period of constant luminosity of about 100 days called plateau). The purpose of this work is to examine the validity of this hypothesis and to contruct Hubble diagrams standardizing the luminosities of these objects. A usual problem with the measurement of such asymptotic color is that there is no obvious maximum during the plateau phase (unlike their cousins, the type Ia SNe), so it proves hard to bring all light curves to the same time scale. One way around this is to use the end of the plateau as an estimate of the time origin for each event. This time origin also serves as a uniform reference epoch to measure magnitudes and expansion velocities. Although simple in theory, in practice it is usually hard to measure magnitudes, colors and expansion velocities owing to the coarse sampling of the observations. Thus, our aims are 1) perform adequate fits to the light, color and velocity curves, 2) determine the asymptotic color, 3) explore the usefulness of such color as reddening indicator, 4) calibrate the relation between luminosity and expansion velocity, and 5) measure distances, which will lead us to the contruction a Hubble diagram. In this talk we present fits made by means of analytic function modeling. We discuss the usefulness of the (V-R) and (V-I) colors for the

  7. HTLV type I and HTLV type II infection among Indians and natives from Argentina.

    PubMed

    Bouzas, M B; Zapiola, I; Quiruelas, S; Gorvein, D; Panzita, A; Rey, J; Carnese, F P; Corral, R; Perez, C; Zala, C

    1994-11-01

    Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution.

  8. The importance of type II error and falsifiability.

    PubMed

    Matsuda, Hiroyuki

    2004-01-01

    Before intergovernmental consensus under the Rio Declaration in 1992, ignorance of type I errors had been disfavored in science. However, the Precautionary Principle (PP) counsels the avoidance of type II errors, rather than of type I errors. We need a new academic code for the PP. The risk of extinction has usually been evaluated based on conservative estimates of the present population size. I define the weight of evidence as the extinction risk of Japanese vascular plants based on unbiased estimates. Catch quotas in the fisheries are usually decided by precautionary approach. I calculate the long-term yield and risk of stock collapse under a simple stock dynamics model. The weight of evidence depends on the frequency of grids with size unknown. In a few plant species, rankings based on conservative estimates have differed from rankings based on unbiased estimates. In fishery management, a catch quota based on a precautionary approach proved neither sufficient nor necessary to avoid stock collapse. The precautionary approach is one of the reasons that prevent us from maximizing a sustainable yield. We need to clarify the end-point of risks, and check whether it is necessary to adopt a PP. We can obtain the weight of evidence that is measured under unbiased estimates, while the risk based on a PP is measured under conservative estimates.

  9. Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep

    PubMed Central

    2013-01-01

    Background It was recently shown that niacin supplementation counteracts the obesity-induced muscle fiber transition from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PPARδ (encoded by PPARD), PGC-1α (encoded by PPARGC1A) and PGC-1β (encoded by PPARGC1B), leading to type II to type I fiber transition and upregulation of genes involved in oxidative metabolism. The aim of the present study was to investigate whether niacin administration also influences fiber distribution and the metabolic phenotype of different muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. semitendinosus (ST)] in sheep as a model for ruminants. For this purpose, 16 male, 11 wk old Rhoen sheep were randomly allocated to two groups of 8 sheep each administered either no (control group) or 1 g niacin per day (niacin group) for 4 wk. Results After 4 wk, the percentage number of type I fibers in LD, SM and ST muscles was greater in the niacin group, whereas the percentage number of type II fibers was less in niacin group than in the control group (P < 0.05). The mRNA levels of PPARGC1A, PPARGC1B, and PPARD and the relative mRNA levels of genes involved in mitochondrial fatty acid uptake (CPT1B, SLC25A20), tricarboxylic acid cycle (SDHA), mitochondrial respiratory chain (COX5A, COX6A1), and angiogenesis (VEGFA) in LD, SM and ST muscles were greater (P < 0.05) or tended to be greater (P < 0.15) in the niacin group than in the control group. Conclusions The study shows that niacin supplementation induces muscle fiber transition from type II to type I, and thereby an oxidative metabolic phenotype of skeletal muscle in sheep as a model for ruminants. The enhanced capacity of skeletal muscle to utilize fatty acids in ruminants might be particularly useful during metabolic states in which fatty acids are

  10. D-brane Instantons in Type II String Theory

    SciTech Connect

    Blumenhagen, Ralph; Cvetic, Mirjam; Kachru, Shamit; Weigand, Timo; /SLAC

    2009-06-19

    We review recent progress in determining the effects of D-brane instantons in N=1 supersymmetric compactifications of Type II string theory to four dimensions. We describe the abstract D-brane instanton calculus for holomorphic couplings such as the superpotential, the gauge kinetic function and higher fermionic F-terms. This includes a discussion of multi-instanton effects and the implications of background fluxes for the instanton sector. Our presentation also highlights, but is not restricted to the computation of D-brane instanton effects in quiver gauge theories on D-branes at singularities. We then summarize the concrete consequences of stringy D-brane instantons for the construction of semi-realistic models of particle physics or SUSY-breaking in compact and non-compact geometries.

  11. Type II congenital pulmonary airway malformation in an esophageal lung

    PubMed Central

    Martínez-Martínez, Blanca Estela; Furuya, María Elena Yuriko; Martínez-Muñiz, Irma; Vargas, Mario H; Flores-Salgado, Rosalinda

    2013-01-01

    A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung. PMID:23762890

  12. Quantum oscillation in vortex states of type-II superconductors

    SciTech Connect

    Maki, K. )

    1991-08-01

    We examine theoretically magnetic quantum oscillations like the de Haas--van Alphen and Subnikov--de Haas effects in vortex states in type-II superconductors. For a magnetic field {ital B} not very small compared with {ital H}{sub {ital c}3}({ital T}), the main effect of superconductivity is introduction of the extra quasiparticle scattering rate proportional to {vert bar}{Delta}{vert bar}{sup 2}, the square of the superconducting order parameter. Therefore the detectability of the magnetic quantum oscillation is determined from the condition that the extra Dingle temperature due to {vert bar}{Delta}{vert bar}{sup 2} is not too large. For example in a magnetic field {similar to}10 T, the superconducting transition temperature {ital T}{sub {ital c}} has to be less than 30 K in order to have a reasonable signal.

  13. Type II Diabetes Mellitus in Arabic-Speaking Countries

    PubMed Central

    Badran, Mohammad; Laher, Ismail

    2012-01-01

    The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries. PMID:22851968

  14. Unusual approach for the treatment of a type II endoleak.

    PubMed

    Ciampi Dopazo, J J; Gastaldo, F; Lanciego Pérez, C

    2016-01-01

    This case presentation is about an 88 years-old male patient with previous endovascular aortic aneurysm repairment history and aortic endoleak type II (EL2). The direct lumbar artery catheterization was considered an alternative to solve EL2, associated with aortic endovascular prosthesis and due to an incomplete sealing or exclusion of the aneurysmal sac or a vascular segment demonstrated by imaging studies, when other treatment alternative failed (transarterial embolization) to control the aneurysm growing. Performing translumbar approach was decided by puncturing the artery lumbar (L4) left, previously the lumbar arteries (L4) were evaluated in the abdominal CT arterial phase to guide a puncture/access under flouroscopy control. Diagnostic angiogram clearly demonstrated the median sacral and right lumbar arteries inflow into the aneurysm sac. Transcatheter embolization with fibered platinum microcoils was performed of the median sacral artery and lumbar left and right arteries (L4), showing satisfactory endoleak devascularization.

  15. Electrodynamics of type-II superconductor with periodic pinning array

    NASA Astrophysics Data System (ADS)

    Hung, R. F.; Berco, D.; Shapiro, I. Ya.; Shapiro, B.; Rosenstein, B.

    2011-01-01

    Static and dynamic distribution of the superconducting condensate order parameters and current density is studied by numerical simulation of the 2D time-dependent Ginzburg-Landau equations. The vortex flux lattice in layered type-II superconductors under magnetic field above the lower critical field is described by the order parameters. Moreover, the pinning effect has been considered in this work. The Abrikosov lattice which is hexagonal in the static case is deformed due to the size of pinning centers. The dynamical order parameters distribution shows that the vortex transport (flux flow) is conducted via diffusive motion of the so-called interstitial vortices. The trajectories for interstitial vortices with different sizes of pinning centers are shown.

  16. Sweet taste and diet in type II diabetes.

    PubMed

    Tepper, B J; Hartfiel, L M; Schneider, S H

    1996-07-01

    The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

  17. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

    PubMed Central

    Wei, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

    2016-01-01

    Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group. We found that Ramipril significantly attenuates collagen-I and III deposition (col-I and III). Notably, we determined that expression of ACT A and II activin receptor (ActRII) were significantly down-regulated in the non-infarcted area of the left ventricle in the Ramipril group, whereas the mRNA and protein levels of FS were markedly up-regulated. Our data suggested that Ramipril benefited left ventricular remodeling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction. This observation was also associated with down-regulation of ACT A expression. This study elucidated a new protective mechanism of Ramipril and suggests a novel strategy for treatment of post-infarct remodeling and subsequent heart failure. PMID:27642098

  18. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure.

    PubMed

    Wei, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

    2016-01-01

    Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group. We found that Ramipril significantly attenuates collagen-I and III deposition (col-I and III). Notably, we determined that expression of ACT A and II activin receptor (ActRII) were significantly down-regulated in the non-infarcted area of the left ventricle in the Ramipril group, whereas the mRNA and protein levels of FS were markedly up-regulated. Our data suggested that Ramipril benefited left ventricular remodeling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction. This observation was also associated with down-regulation of ACT A expression. This study elucidated a new protective mechanism of Ramipril and suggests a novel strategy for treatment of post-infarct remodeling and subsequent heart failure. PMID:27642098

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

    PubMed Central

    2014-01-01

    Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all). Conclusions Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure. PMID:24885241

  20. Phospholipid-transfer activities in cytosols from lung, isolated alveolar type II cells and alveolar type II cell-derived adenomas.

    PubMed Central

    Pool, G L; Bubacz, D G; Lumb, R H; Mason, R J

    1983-01-01

    We have examined phospholipid-transfer activities in cytosols from rat and mouse whole lung, isolated rat alveolar type II cells and alveolar type II cell-derived mouse pulmonary adenomas. We report an enrichment in phosphatidylcholine and phosphatidylglycerol (but not phosphatidylinositol) protein-catalysed transfer in the type II cell and adenoma cytosols compared with the whole-lung cytosols. The activities from these cytosols were resolved using column chromatofocusing, which clearly demonstrated the presence of a phosphatidylcholine-specific transfer protein in each of the four tissues. In addition, two proteins (rat) or three proteins (mouse) catalysing both phosphatidylcholine and phosphatidylglycerol transfer were resolved from whole lung, whereas in both the rat isolated alveolar type II cells and the mouse type II cell-derived adenomas one of these less specific proteins is not present. PMID:6661189

  1. Activin Modulates the Transcriptional Response of LβT2 Cells to Gonadotropin-Releasing Hormone and Alters Cellular Proliferation

    PubMed Central

    Zhang, Hao; Bailey, Janice S.; Coss, Djurdjica; Lin, Bo; Tsutsumi, Rie; Lawson, Mark A.; Mellon, Pamela L.; Webster, Nicholas J. G.

    2009-01-01

    Both GnRH and activin are crucial for the correct function of pituitary gonadotrope cells. GnRH regulates LH and FSH synthesis and secretion and gonadotrope proliferation, whereas activin is essential for expression of FSH. Little is known, however, about the interplay of signaling downstream of these two hormones. In this study, we undertook expression profiling to determine how activin pre-treatment alters the transcriptional response of LβT2 gonadotrope cells to GnRH stimulation. Activin treatment alone altered the transcriptional profile of 303 genes including inducing that of the 17β-hydroxysteroid dehydrogenase B1 gene that converts estrone to 17β-estradiol, altering the sensitivity of the cells to estrone. Furthermore, activin had a dramatic effect on the response of LβT2 cells to GnRH. Hierarchical clustering of 2453 GnRH-responsive genes identified groups of genes the response of which to GnRH was either enhanced or blunted after activin treatment. Mapping of these genes to gene ontology classifications or signaling pathways highlighted significant differences in the classes of altered genes. In the presence of activin, GnRH regulates genes in pathways controlling cell energetics, cytoskeletal rearrangements, organelle organization, and mitosis in the absence of activin, but genes controlling protein processing, cell differentiation, and secretion. Therefore, we demonstrated that activin enhanced GnRH induction of p38MAPK activity, caused GnRH-dependent phosphorylation of p53, and reduced the ability of GnRH to cause G1 arrest. Thus, although activin alone changes a modest number of transcripts, activin pretreatment dramatically alters the response to GnRH from an antiproliferative response to a more differentiated, synthetic response appropriate for a secretory cell. PMID:16772531

  2. Magnetic-Field-Induced Relativistic Properties in Type-I and Type-II Weyl Semimetals

    NASA Astrophysics Data System (ADS)

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O.

    2016-08-01

    We investigate Weyl semimetals with tilted conical bands in a magnetic field. Even when the cones are overtilted (type-II Weyl semimetal), Landau-level quantization can be possible as long as the magnetic field is oriented close to the tilt direction. Most saliently, the tilt can be described within the relativistic framework of Lorentz transformations that give rise to a rich spectrum, displaying new transitions beyond the usual dipolar ones in the optical conductivity. We identify particular features in the latter that allow one to distinguish between semimetals of different types.

  3. Magnetic-Field-Induced Relativistic Properties in Type-I and Type-II Weyl Semimetals.

    PubMed

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O

    2016-08-19

    We investigate Weyl semimetals with tilted conical bands in a magnetic field. Even when the cones are overtilted (type-II Weyl semimetal), Landau-level quantization can be possible as long as the magnetic field is oriented close to the tilt direction. Most saliently, the tilt can be described within the relativistic framework of Lorentz transformations that give rise to a rich spectrum, displaying new transitions beyond the usual dipolar ones in the optical conductivity. We identify particular features in the latter that allow one to distinguish between semimetals of different types. PMID:27588870

  4. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    PubMed Central

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  5. Neutrino masses and leptogenesis in type I and type II seesaw models

    NASA Astrophysics Data System (ADS)

    Borah, Debasish; Das, Mrinal Kumar

    2014-07-01

    The baryon to photon ratio in the present Universe is very accurately measured to be (6.065±0.090)×10-10. We study the possible origin of this baryon asymmetry in the neutrino sector through the generic mechanism of baryogenesis through leptogenesis. We consider both the type I and type II seesaw origin of neutrino masses within the framework of left-right symmetric models (LRSM). Using the latest best-fit global neutrino oscillation data of mass squared differences, mixing angles and Dirac CP phase, we compute the predictions for baryon to photon ratio keeping the Majorana CP phases as free parameters for two different choices of lightest neutrino mass eigenvalue for both normal and inverted hierarchical patterns of neutrino masses. We do our calculation with and without lepton flavor effects being taken into account. We choose different diagonal Dirac neutrino mass matrix for different flavor effects in such a way that the lightest right-handed neutrino mass is in the appropriate range. We also study the predictions for baryon asymmetry when the neutrino masses arise from a combination of both type I and type II seesaw (with dominating type I term) and discriminate between several combinations of Dirac and Majorana CP phases by demanding successful predictions for baryon asymmetry.

  6. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    PubMed Central

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  7. XIAP discriminates between type I and type II FAS-induced apoptosis.

    PubMed

    Jost, Philipp J; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D; Nachbur, Ueli; Huang, David C S; Bouillet, Philippe; Thomas, Helen E; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-08-20

    FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

  8. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides.

    PubMed

    Du, Yuzhe; Nomura, Yoshiko; Luo, Ningguang; Liu, Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong, Ke

    2009-01-15

    Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an alpha-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G(1111) and two positively charged lysines immediately downstream of G(1111) in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G(1111), a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G(1111) had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.

  9. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

    SciTech Connect

    Du Yuzhe; Nomura, Yoshiko; Luo Ningguang; Liu Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong Ke

    2009-01-15

    Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an {alpha}-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G{sup 1111} and two positively charged lysines immediately downstream of G{sup 1111} in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G{sup 1111}, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G{sup 1111} had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.

  10. PTF11iqb: Bridging the gap between Type IIN and normal Type II

    NASA Astrophysics Data System (ADS)

    Smith, Nathan; Mauerhan, Jon; Ofek, Eran; Cenko, Stephen B.; Kasliwal, Mansi M.; Silverman, Jeffrey M.; Filippenko, Alexei V.; Gal-Yam, Avishay

    2015-01-01

    The recent supernova (SN) PTF11iqb was classified as a Type IIn event caught very early after explosion. It showed narrow Wolf-Rayet (WR) spectral features on day 2, but the narrow emission weakened quickly and the spectrum morphed through several stages resembling normal Types II-P and II-L. At late times, Hα emission ex- hibited a complex, multi-peaked profile reminiscent of SN 1998S. Overall, we find that PTF11iqb was a near twin of the classic object SN 1998S, except with a factor of 2- 4 weaker interaction with circumstellar material (CSM) at early times, and stronger CSM interaction at late times. We match the main light curve with a simple model for weak CSM interaction (with a mass loss rate of roughly 10-4 M⊙ yr-1 ) added to the light curve of a normal SN II-P (the relatively weak CSM interaction allowed this plateau to be seen more clearly than in other SNe IIn). This plateau in the underlying light curve requires that the progenitor had an extended hydrogen envelope like a cool (red or yellow) supergiant at the moment that it exploded. The likely cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum. Overall, PTF11iqb seems to bridge SNe IIn with weaker pre-SN mass loss seen in SNe II-L and II-P, thereby implying that episodic pre-SN mass loss on a wide range of time and mass scales could be more frequent than implied by standard SNe IIn.

  11. Replication of parainfluenza (Sendai) virus in isolated rat pulmonary type II alveolar epithelial cells.

    PubMed Central

    Castleman, W. L.; Northrop, P. J.; McAllister, P. K.

    1989-01-01

    The major objectives of this study were to determine whether alveolar type II epithelial cells isolated from rat lung and maintained in tissue culture would support productive replication of parainfluenza type 1 (Sendai) virus and to determine whether isolated type II cells from neonatal (5-day-old) rats that are more susceptible to viral-induced alveolar dysplasia supported viral replication to a greater extent than those from weanling (25-day-old) rats. Isolated and cultured type II cells from neonatal and weanling rats that were inoculated with Sendai virus supported productive replication as indicated by ultrastructural identification of budding virions and viral nucleocapsids in type II cells and by demonstration of rising titers of infectious virus from inoculated type II cell cultures. Alveolar macrophages from neonatal and weanling rats also supported viral replication, although infectious viral titers in macrophage cultures were lower than those from type II cell cultures. Only minor differences were detected between viral titers from neonatal and weanling type II epithelial cell cultures. Higher densities of viral nucleocapsids were observed in neonatal type II cells than in those from weanling rats. The results indicate that isolated type II alveolar epithelial cells support productive replication of parainfluenza virus and that type II cells are probably more efficient in supporting productive viral replication than are alveolar macrophages. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2541612

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1993-06-01

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

  15. Relative potencies of Type I and Type II pyrethroids for inhibition of spontaneous firing in neuronal networks.

    EPA Science Inventory

    Pyrethroids insecticides commonly used in pest control disrupt the normal function of voltage-sensitive sodium channels. We have previously demonstrated that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) inhibit sodium channel-dependent spontaneous netw...

  16. Targeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function.

    PubMed

    de Vinuesa, Amaya García; Bocci, Matteo; Pietras, Kristian; Ten Dijke, Peter

    2016-08-15

    Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs). ALK1 has been shown to play a pivotal role in regulating angiogenesis by binding to bone morphogenetic protein (BMP)9 and 10. Two main pharmacological inhibitors, an ALK1-Fc fusion protein (Dalantercept/ACE-041) and a fully human antibody against the extracellular domain of ALK1 (PF-03446962) are currently under clinical development. Herein, we briefly recapitulate the role of ALK1 in blood vessel formation and the current status of the preclinical and clinical studies on inhibition of ALK1 signalling as an anti-angiogenic strategy. Future directions in terms of new combination regimens will also be presented. PMID:27528762

  17. Hereditary sensory and autonomic neuropathies: types II, III, and IV.

    PubMed

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-01-01

    The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive. PMID:17915006

  18. Solar flares associated coronal mass ejections in case of type II radio bursts

    NASA Astrophysics Data System (ADS)

    Bhatt, Beena; Prasad, Lalan; Chandra, Harish; Garia, Suman

    2016-08-01

    We have statistically studied 220 events from 1996 to 2008 (i.e. solar cycle 23). Two set of flare-CME is examined one with Deca-hectometric (DH) type II and other without DH type II radio burst. Out of 220 events 135 (flare-halo CME) are accompanied with DH type II radio burst and 85 are without DH type II radio burst. Statistical analysis is performed to examine the distribution of solar flare-halo CME around the solar disk and to investigate the relationship between solar flare and halo CME parameters in case of with and without DH type II radio burst. In our analysis we have observed that: (i) 10-20° latitudinal belt is more effective than the other belts for DH type II and without DH type II radio burst. In this belt, the southern region is more effective in case of DH type II radio burst, whereas in case of without DH type II radio burst dominance exits in the northern region. (ii) 0-10° longitudinal belt is more effective than the other belts for DH type II radio burst and without DH type II radio burst. In this belt, the western region is more effective in case of DH type II radio burst, while in case of without DH type II radio burst dominance exits in the eastern region. (iii) Mean speed of halo CMEs (1382 km/s) with DH type II radio burst is more than the mean speed of halo CMEs (775 km/s) without DH type II radio burst. (iv) Maximum number of M-class flares is found in both the cases. (v) Average speed of halo CMEs in each class accompanied with DH type II radio burst is higher than the average speed of halo CMEs in each class without DH type II radio burst. (vi) Average speed of halo CMEs, associated with X-class flares, is greater than the other class of solar flares in both the cases.

  19. Novel behavior of magnetic flux lines in type II superconductors

    NASA Astrophysics Data System (ADS)

    Mohler, Gregory Allan

    In this thesis we present several studies in the properties of magnetic flux lines in type II superconductors. We have carried out a model calculation of the flux noise produced by vortex avalanches in a Type-II superconductor, using a simple kinetic model proposed by Bassler and Paczuski. Over a broad range of frequencies, we find that the flux noise SFw has a power-law dependence on frequency, SFw ˜ w-s , with s ˜ 1.4 in reasonable agreement with experiment. In addition, for small lattices, the calculated SFw has a high-frequency knee, which is seen in some experiments, and which is due to the finite lattice size. We have analyzed the Lawrence-Doniach free energy in a tilted magnetic field within the lowest Landau level (LLL) approximation for the case of a highly anisotropic high temperature superconductor. The free energy maps onto that of a strictly c-axis field, but with a reduced interlayer coupling. We use this result to calculate the tilt modulus C44 of a vortex lattice and vortex liquid. The vortex contribution to C44 can be expressed in terms of the squared c-axis Josephson plasmon frequency w2pl . We find that the transverse component of the field has very little effect on the position of the melting curve. We present a simple numerical model for the IV characteristics of a highly anisotropic high temperature superconductor in different geometries. An array of grains coupled together by Josephson junctions is used, with a triangular structure in the planes normal to an applied magnetic field and a square structure otherwise. Overdamped junctions are used to describe the CuO2 planes, while underdamped junctions are used to describe the interplanar coupling. Each grain has a capacitive shunt to ground. We measure the depinning current strength, decoupling current strength, and the critical coupling value in the "flux-transformer geometry." We also examine voltage branches in the I--V hysteresis curve for c-axis transport. Finally, we have used a simple

  20. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

    PubMed

    Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

    2005-08-01

    DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted. PMID:16050819

  1. II-Q restriction endonucleases--new class of type II enzymes.

    PubMed Central

    Degtyarev, S K; Rechkunova, N I; Kolyhalov, A A; Dedkov, V S; Zhilkin, P A

    1990-01-01

    Unique restriction endonucleases Bpu 10l and Bsil have been isolated from Bacillus pumilas and Bacillus sphaericus, respectively. The recognition sequences and cleavage points of these enzymes have been determinated as 5'-CC1TNAGC-3'/3'-GGANT1CG-5' for Bpu 10l and 5'-C1TCGTG-3'/3'-GAGCA1C-5' for Bsil. Restriction endonucleases Bpu 10l and Bsil represent a new class of enzymes which recognize non-palindromic nucleotide sequences and hydrolize DNA within the recognition sequence. Bpu 10l and Bsil recognition sequences may be regarded as quasipalindromic and the enzymes may be designated as type II-Q restriction endonucleases. Images PMID:2216771

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

    PubMed Central

    Papanayotou, Costis; Collignon, Jérôme

    2014-01-01

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

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

    PubMed

    Papanayotou, Costis; Collignon, Jérôme

    2014-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Unified Model of Type I and Type II Turbulence in the Equitorial E-Layer Plasma

    NASA Astrophysics Data System (ADS)

    Horton, W., Jr.; Hassan, E.; Smolyakov, A.; Litt, S.; Hatch, D. R.

    2014-12-01

    A new unified two-fluid model for the E-layer for the Type I and Type II plasma instabilities is developed and simulated for the nonlinear dynamics of the electron density, the electric fields, and ion fluid acceleration. Profiles and parameters are taken from the IRI data for the equitorial region ionosphere. Large, spectral simulations for the turbulence and the coherent structures are carried out. The fields are recorded for each sub-second time step in both physical space and wavenubmer space. The growth rate has two peaks in horizontal wavenumber and the nonlinear cascades go both to small scales [~10cm] and large scales [~10-50m]. Horizontal and vertical wavenumber spectra are shown as well as the isotropized energy spectrum of k-n. The S4 scintillation index computed from the density fluctuations and the PDFs for intermittency from the density fluctuations are computed. The PDFs and the net electron density fluxes are computed. Examples are run where the upward density gradient (Type II) is the dominant instability mechanism.

  6. Implementing type I & type II error spending for two-sided group sequential designs.

    PubMed

    Rudser, Kyle D; Emerson, Scott S

    2008-05-01

    Group sequential designs have become the mainstay for addressing efficacy and ethical issues when monitoring clinical trials. Several different procedures of defining stopping rules have been developed for the formulation of a sequential design, one of these being direct specification of type I and type II error spending. There are also different methods that have been proposed to fit a two-sided design for a given error spending function. Two methods that differ on when type II error begins to be spent are the flexible implementation of the unified family by Kittelson and Emerson and the method of Chang, Hwang, and Shih. Trial designs formulated by the latter are unable to mimic the boundaries of the unified family, which includes the two-sided symmetric designs of Emerson and Fleming, the two-sided designs of Pampallona and Tsiatis, and the double triangular designs of Whitehead and Stratton. Design operating characteristics of these two methods are compared over a wide range of commonly used size, power and error spending function combinations. PMID:17933592

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

    PubMed Central

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

    2012-01-01

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

  8. TYPE II SUPERNOVAE: MODEL LIGHT CURVES AND STANDARD CANDLE RELATIONSHIPS

    SciTech Connect

    Kasen, Daniel; Woosley, S. E.

    2009-10-01

    A survey of Type II supernovae explosion models has been carried out to determine how their light curves and spectra vary with their mass, metallicity, and explosion energy. The presupernova models are taken from a recent survey of massive stellar evolution at solar metallicity supplemented by new calculations at subsolar metallicity. Explosions are simulated by the motion of a piston near the edge of the iron core and the resulting light curves and spectra are calculated using full multi-wavelength radiation transport. Formulae are developed that describe approximately how the model observables (light curve luminosity and duration) scale with the progenitor mass, explosion energy, and radioactive nucleosynthesis. Comparison with observational data shows that the explosion energy of typical supernovae (as measured by kinetic energy at infinity) varies by nearly an order of magnitude-from 0.5 to 4.0 x 10{sup 51} ergs, with a typical value of approx0.9 x 10{sup 51} ergs. Despite the large variation, the models exhibit a tight relationship between luminosity and expansion velocity, similar to that previously employed empirically to make SNe IIP standardized candles. This relation is explained by the simple behavior of hydrogen recombination in the supernova envelope, but we find a sensitivity to progenitor metallicity and mass that could lead to systematic errors. Additional correlations between light curve luminosity, duration, and color might enable the use of SNe IIP to obtain distances accurate to approx20% using only photometric data.

  9. Type-II histone deacetylases: elusive plant nuclear signal transducers.

    PubMed

    Grandperret, Vincent; Nicolas-Francès, Valérie; Wendehenne, David; Bourque, Stéphane

    2014-06-01

    Since the beginning of the 21st century, numerous studies have concluded that the plant cell nucleus is one of the cellular compartments that define the specificity of the cellular response to an external stimulus or to a specific developmental stage. To that purpose, the nucleus contains all the enzymatic machinery required to carry out a wide variety of nuclear protein post-translational modifications (PTMs), which play an important role in signal transduction pathways leading to the modulation of specific sets of genes. PTMs include protein (de)acetylation which is controlled by the antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Regarding protein deacetylation, plants are of particular interest: in addition to the RPD3-HDA1 and Sir2 HDAC families that they share with other eukaryotic organisms, plants have developed a specific family called type-II HDACs (HD2s). Interestingly, these HD2s are well conserved in plants and control fundamental biological processes such as seed germination, flowering or the response to pathogens. The aim of this review was to summarize current knowledge regarding this fascinating, but still poorly understood nuclear protein family. PMID:24236403

  10. Polyglandular endocrinopathy type II (Schmidt's syndrome) in a Dobermann pinscher.

    PubMed

    Cartwright, J A; Stone, J; Rick, M; Dunning, M D

    2016-09-01

    A three-year-old, female neutered, Dobermann pinscher was presented for investigation of lethargy, episodic collapse, ataxia and myxoedema. Primary hypothyroidism and primary cortisol-deficient hypoadrenocorticism were diagnosed based on history, physical examination and compatible hormonal analysis. Increased serum concentrations of thyroglobulin autoantibodies and 21-hydroxylase autoantibodies indicated an immune-mediated aetiology. The case was complicated by lymphadenopathy with hand-mirror lymphocytes, classically identified in lymphoma. A polymerase chain reaction test for antigen receptor rearrangement indicated polyclonality and therefore reactive lymphadenopathy. The dog's clinical signs resolved following introduction of levothyroxine and prednisolone. Prioritising the problem-based approach in this case facilitated the diagnosis of hypoadrenocorticism in addition to hypothyroidism due to the persistence of clinical signs despite thyroxine replacement. Importantly, atypical adrenal gland dysfunction was not misinterpreted as inadequate therapeutic response to thyroxine supplementation. The observation that polyglandular endocrinopathy type II can occur in dogs suggests that in dogs with a suboptimal response to treatment for hypothyroidism or hypoadrenocorticism comorbid endocrinopathies should be investigated. PMID:27487017

  11. Type II Radio Bursts as an Indicator of CME Location

    NASA Astrophysics Data System (ADS)

    Quirk, C. A.; St Cyr, O. C.; Henning, C.; Xie, H.; Gilbert, H. R.; Orlove, M.; Gopalswamy, N.; Odstrcil, D.

    2011-12-01

    We examined a subset of nine low-frequency radio events with type II radio bursts that drifted below 2 megahertz and were detected by the WAVES investigation on the WIND spacecraft. For each event, we identified the associated coronal mass ejection (CME) and derived the electron density using a model of solar wind plasma frequency (fp ≈ 9 * ne1/2, where fp is plasma frequency in kHz and ne is electron density in cm-3) . We also used the pb_inverter program in SolarSoft developed by Howard and Hayes to examine the electron density structure. Expanding on the Van De Hulst process of inverting polarized brightness measurements, the program inverts total brightness measurements from SOHO LASCO images to extract electron density information. From the electron density inferred from radio spectra, we derived the location of the CME using five standard electron density to height models (Leblanc, 1996; Saito, 1977; Bougeret, 1984; Alvarez, 1973; and Fainberg, 1971). Using images from the LASCO instrument on SOHO and the SECCHI instrument on STEREO, we extracted locations of the leading edge of the CME and compared the heights and velocities to those found using the frequency data. For the lowest frequency events, we also compared our results to the outputs of ENLIL, a time-dependent, three-dimensional, MHD model of the heliosphere hosted by the Community Coordinated Modeling Center (CCMC) at NASA Goddard Space Flight Center.

  12. Simvastatin enhances bone morphogenetic protein receptor type II expression

    SciTech Connect

    Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N. . E-mail: peterkao@stanford.edu

    2006-01-06

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function.

  13. Hetero-engineering infrared detectors with type-II superlattices

    NASA Astrophysics Data System (ADS)

    Tian, Z.-B.; DeCuir, E. A.; Gautam, N.; Krishna, S.; Wijewarnasuriya, P. S.; Pattison, J. W.; Dhar, N.; Welser, R. E.; Sood, A. K.

    2013-09-01

    InAs/GaSb type-II superlattices (T2-SLs) are of great interest as they provide a lot of band engineering flexibility. A wide variety of unipolar barrier structures have been investigated with this material system. In this report, we will present our recent work on the development of low noise long-wave infrared (LWIR) InAs/GaSb T2-SLs photodetectors. By adopting a so-called pBiBn design, the dark current of LWIR photodetectors is greatly suppressed. The LWIR pBiBn device has demonstrated a dark current density as low as 1.42×10-5 A/cm2 at -60 mV, and R0A of 5365 Ωcm2 at 76 K. A peak detectivity at 7.8 μm of 7.7×1011 cmHz1/2W-1 is obtained at 76 K. Further effort to reduce the operating bias is also reported. By refining the energy-band alignment, a 2-μm-thick LWIR pBiBn device has demonstrated a single pass (no AR coating) quantum efficiency of 20% at 10 μm under zero-bias at 77 K. We have recently extended our efforts to further reduce the dark current by using an interband cascade (IC) photodetector structure. Some further details about the device operation and results will be discussed.

  14. Alveolar epithelial type II cell: defender of the alveolus revisited

    PubMed Central

    Fehrenbach, Heinz

    2001-01-01

    In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today. PMID:11686863

  15. General critical states in type-II superconductors

    NASA Astrophysics Data System (ADS)

    Badía-Majós, A.; López, C.; Ruiz, H. S.

    2009-10-01

    The magnetic flux dynamics of type-II superconductors within the critical state regime is posed in a generalized framework by using a variational theory supported by well-established physical principles. The equivalence between the variational statement and more conventional treatments based on the solution of the differential Maxwell equations together with appropriate conductivity laws is shown. Advantages of the variational method are emphasized, focusing on its numerical performance that allows us to explore a number of physical scenarios. In particular, we present the extension of the so-called double critical state model to three-dimensional (3D) configurations in which only flux transport ( T states), cutting ( C states), or both mechanisms ( CT states) occur. The theory is applied to several problems. First, we show the features of the transition from T to CT states. Second, we give a generalized expression for the flux cutting threshold in 3D and show its relevance in the slab geometry. In addition, several models that allow us to treat flux depinning and cutting mechanisms are compared. Finally, the longitudinal transport problem (current is applied parallel to the external magnetic field) is analyzed both under T and CT conditions. The complex interaction between shielding and transport is solved.

  16. Smooth ocular pursuit in Chiari type II malformation.

    PubMed

    Salman, Michael S; Sharpe, James A; Lillakas, Linda; Steinbach, Martin J; Dennis, Maureen

    2007-04-01

    Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, both important structures for processing smooth ocular pursuit. CII is associated with myelomeningocele and hydrocephalus. We investigated the effects of CII on smooth pursuit (SP) eye movements, and determined the effects of spinal lesion level, number of shunt revisions, nystagmus, and brain dysmorphology on SP. SP was recorded using an infrared eye tracker in 21 participants with CII (11 males, 10 females; age range 8-19y, mean 14y 3mo [SD 3y 2mo]). Thirty-eight healthy children (21 males, 17 females) constituted the comparison group. Participants followed a visual target moving sinusoidally at +/- 10 degrees amplitude, horizontally and vertically at 0.25 or 0.5Hz. SP gains, the ratio of eye to target velocities, were abnormal in the CII group with nystagmus (n= 8). The number of shunt revisions (range 0-10), brain dysmorphology, or spinal lesion level (n= 15 for lower and n= 6 for upper spinal lesion level) did not correlate with SP gains. SP is impaired in children with CII and nystagmus. Abnormal pursuit might be related to the CII dysgenesis or to effects of hydrocephalus. The lack of effect of shunt revisions and abnormal tracking in participants with nystagmus provide evidence that it is related primarily to the cerebellar and brainstem malformation.

  17. Inert dark matter in type-II seesaw

    NASA Astrophysics Data System (ADS)

    Chen, Chuan-Hung; Nomura, Takaaki

    2014-09-01

    Weakly interacting massive particle (WIMP) as a dark matter (DM) candidate is further inspired by recent AMS-02 data, which confirm the excess of positron fraction observed earlier by PAMELA and Fermi-LAT experiments. Additionally, the excess of positron+electron flux is still significant in the measurement of Fermi-LAT. For solving the problems of massive neutrinos and observed excess of cosmic-ray, we study the model with an inert Higgs doublet (IHD) in the framework of type-II seesaw model by imposing a Z 2 symmetry on the IHD, where the lightest particle of IHD is the DM candidate and the neutrino masses originate from the Yukawa couplings of Higgs triplet and leptons. We calculate the cosmic-ray production in our model by using three kinds of neutrino mass spectra, which are classified by normal ordering, inverted ordering and quasi-degeneracy. We find that when the constraints of DM relic density and comic-ray antiproton spectrum are taken into account, the observed excess of positron/electron flux could be explained well in normal ordered neutrino mass spectrum. Moreover, excess of comic-ray neutrinos is implied in our model. We find that our results on < σv> are satisfied with and close to the upper limit of IceCube analysis. More data from comic-ray neutrinos could test our model.

  18. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  19. Current developments for type-II superlattice imaging systems

    NASA Astrophysics Data System (ADS)

    Rutz, Frank; Rehm, Robert; Walther, Martin; Kirste, Lutz; Masur, Michael; Wörl, Andreas; Schmitz, Johannes; Wauro, Matthias; Niemasz, Jasmin; Scheibner, Ralf; Ziegler, Johann

    2011-06-01

    InAs/GaSb-based type-II superlattice photodiodes have considerably gained interest as high-performance infrared detectors. Beside the excellent properties of InAs/GaSb superlattices, like the relatively high effective electron mass suppressing tunneling currents, the low Auger recombination rate, and a high quantum efficiency, the bandgap can be widely adjusted within the infrared spectral range from 3 - 30 μm depending on the layer thickness rather than on composition. Superlattice growth and process technology have shown tremendous progress during the last years. Fully integrated superlattice cameras have been demonstrated by several groups worldwide. Within very few years, the InAs/GaSb superlattice technology has proven its suitability for high-performance infrared imaging detector arrays. At Fraunhofer IAF and AIM, the efforts have been focused on developing a mature fabrication technology for bispectral InAs/GaSb superlattice focal plane arrays for a simultaneous, co-located detection at 3-4 μm and 4-5 μm in the mid-wavelength infrared atmospheric transmission window. A very low number of pixel outages and cluster defects is mandatory for dual-color detector arrays. Sources for pixel outages are manifold and might be caused by dislocations in the substrate, the epitaxial growth process or by imperfections during the focal plane array fabrication process. Process refinements, intense root cause analysis and specific test methodologies employed at various stages during the process have proven to be the key for yield enhancements.

  20. Type I and Type II Interferons Inhibit the Translation of Murine Norovirus Proteins▿

    PubMed Central

    Changotra, Harish; Jia, Yali; Moore, Tara N.; Liu, Guangliang; Kahan, Shannon M.; Sosnovtsev, Stanislav V.; Karst, Stephanie M.

    2009-01-01

    Human noroviruses are responsible for more than 95% of nonbacterial epidemic gastroenteritis worldwide. Both onset and resolution of disease symptoms are rapid, suggesting that components of the innate immune response are critical in norovirus control. While the study of the human noroviruses has been hampered by the lack of small animal and tissue culture systems, our recent discovery of a murine norovirus (MNV) and its in vitro propagation have allowed us to begin addressing norovirus replication strategies and immune responses to norovirus infection. We have previously demonstrated that interferon responses are critical to control MNV-1 infection in vivo and to directly inhibit viral replication in vitro. We now extend these studies to define the molecular basis for interferon-mediated inhibition. Viral replication intermediates were not detected in permissive cells pretreated with type I interferon after either infection or transfection of virion-associated RNA, demonstrating a very early block to virion production that is after virus entry and uncoating. A similar absence of viral replication intermediates was observed in infected primary macrophages and dendritic cells pretreated with type I IFN. This was not due to degradation of incoming genomes in interferon-pretreated cells since similar levels of genomes were present in untreated and pretreated cells through 6 h of infection, and these genomes retained their integrity. Surprisingly, this block to the translation of viral proteins was not dependent on the well-characterized interferon-induced antiviral molecule PKR. Similar results were observed in cells pretreated with type II interferon, except that the inhibition of viral translation was dependent on PKR. Thus, both type I and type II interferon signaling inhibit norovirus translation in permissive myeloid cells, but they display distinct dependence on PKR for this inhibition. PMID:19297466

  1. Redesigning the type II' β-turn in green fluorescent protein to type I': implications for folding kinetics and stability.

    PubMed

    Madan, Bharat; Sokalingam, Sriram; Raghunathan, Govindan; Lee, Sun-Gu

    2014-10-01

    Both Type I' and Type II' β-turns have the same sense of the β-turn twist that is compatible with the β-sheet twist. They occur predominantly in two residue β-hairpins, but the occurrence of Type I' β-turns is two times higher than Type II' β-turns. This suggests that Type I' β-turns may be more stable than Type II' β-turns, and Type I' β-turn sequence and structure can be more favorable for protein folding than Type II' β-turns. Here, we redesigned the native Type II' β-turn in GFP to Type I' β-turn, and investigated its effect on protein folding and stability. The Type I' β-turns were designed based on the statistical analysis of residues in natural Type I' β-turns. The substitution of the native "GD" sequence of i+1 and i+2 residues with Type I' preferred "(N/D)G" sequence motif increased the folding rate by 50% and slightly improved the thermodynamic stability. Despite the enhancement of in vitro refolding kinetics and stability of the redesigned mutants, they showed poor soluble expression level compared to wild type. To overcome this problem, i and i + 3 residues of the designed Type I' β-turn were further engineered. The mutation of Thr to Lys at i + 3 could restore the in vivo soluble expression of the Type I' mutant. This study indicates that Type II' β-turns in natural β-hairpins can be further optimized by converting the sequence to Type I'.

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

    PubMed Central

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

    2015-01-01

    Cocaine addiction is a life-long relapsing disorder that results from long-term adaptations within the brain. We find that Activin-receptor signaling, including the transcription factor Smad3, is upregulated in the rat nucleus accumbens shell following withdrawal from cocaine. Direct genetic and pharmacological manipulations of this pathway bidirectionally alter cocaine seeking, while governing morphological plasticity in nucleus accumbens neurons. These findings reveal that Activin/Smad3 signaling is induced following withdrawal from cocaine, and such regulation may be a key molecular mechanism underlying behavioral and cellular plasticity in the brain following cocaine self-administration. PMID:26030849

  3. Regulation of the activin-inhibin-follistatin system by bone morphogenetic proteins in the zebrafish ovary.

    PubMed

    Li, Cheuk Wun; Ge, Wei

    2013-09-01

    In the zebrafish, the dynamic expression of the activin-inhibin-follistatin system during folliculogenesis and its exclusive localization (except follistatin) in follicle cells suggests that the system plays important roles in follicle development and that its expression is subject to tight controls, probably by external factors including those derived from the oocyte. We have previously identified zebrafish bone morphogenetic proteins (BMPs) as oocyte factors that may act on follicle cells; however, the targets of BMPs in the follicle cells remain unknown. Considering their spatiotemporal expression in the follicle, we hypothesized that members of the activin-inhibin-follistatin system in follicle cells could be potential target genes of BMPs. In the present study, we developed a novel coculture system to co-incubate zebrafish bone morphogenetic protein 2b or 4 (zfBMP2b/4)-producing Chinese hamster ovary (CHO) cells with zebrafish follicle cells. During incubation, the zfBMPs secreted from the CHO cells would act directly on the follicle cells in a paracrine manner. Our results showed that all activin beta subunits (inhbaa, inhbab, and inhbb) were down-regulated by both zfBMP2b and zfBMP4, while follistatin (fst, an activin-binding protein) and inhibin alpha (inha, an activin antagonist) were significantly up-regulated. The specificity of bone morphogenetic protein (BMP) actions was confirmed by short interfering RNA knockdown of zfBMP4 expression in the CHO cells. The robust response of inha to zfBMPs, together with our previous observation that inha expression surged at the full-grown stage prior to oocyte maturation, led us to hypothesize that the full-grown oocyte may signal upper levels of the hypothalamic-pituitary-gonadal axis its readiness to mature by releasing BMPs, which in turn stimulate inhibin production. As an ovarian hormone and activin antagonist, inhibin may suppress the action of activin in the pituitary to reduce follicle-stimulating hormone

  4. Higgs potential in the type II seesaw model

    SciTech Connect

    Arhrib, A.; Benbrik, R.; Chabab, M.; Rahili, L.; Ramadan, J.; Moultaka, G.; Peyranere, M. C.

    2011-11-01

    The standard model Higgs sector, extended by one weak gauge triplet of scalar fields with a very small vacuum expectation value, is a very promising setting to account for neutrino masses through the so-called type II seesaw mechanism. In this paper we consider the general renormalizable doublet/triplet Higgs potential of this model. We perform a detailed study of its main dynamical features that depend on five dimensionless couplings and two mass parameters after spontaneous symmetry breaking, and highlight the implications for the Higgs phenomenology. In particular, we determine (i) the complete set of tree-level unitarity constraints on the couplings of the potential and (ii) the exact tree-level boundedness from below constraints on these couplings, valid for all directions. When combined, these constraints delineate precisely the theoretically allowed parameter space domain within our perturbative approximation. Among the seven physical Higgs states of this model, the mass of the lighter (heavier) CP{sub even} state h{sup 0} (H{sup 0}) will always satisfy a theoretical upper (lower) bound that is reached for a critical value {mu}{sub c} of {mu} (the mass parameter controlling triple couplings among the doublet/triplet Higgses). Saturating the unitarity bounds, we find an upper bound m{sub h}{sup 0} or approx. {mu}{sub c} and {mu} < or approx. {mu}{sub c}. In the first regime the Higgs sector is typically very heavy, and only h{sup 0} that becomes SM-like could be accessible to the LHC. In contrast, in the second regime, somewhat overlooked in the literature, most of the Higgs sector is light. In particular, the heaviest state H{sup 0} becomes SM-like, the lighter states being the CP{sub odd} Higgs, the (doubly) charged Higgses, and a decoupled h{sup 0}, possibly

  5. Prevalence and temporal pattern of hospital readmissions for patients with type I and type II diabetes

    PubMed Central

    Liu, Xiaoqian; Liu, Yuanyuan; Lv, Yuanjun; Li, Changping; Cui, Zhuang; Ma, Jun

    2015-01-01

    Objective Repeated hospitalisation for patients is common and costly, yet partly preventable. However, we know little about readmissions for patients with diabetes in China. The current study aims to assess the frequency and temporal pattern of and risk factors for all-cause readmission among hospitalised patients with diabetes in Tianjin, China. Method This retrospective, cohort analysis used the Tianjin Basic Medical Insurance Register System data of 2011. The patterns of and the reasons for all-cause readmissions for patients with diabetes were described. The differences of readmission-free survival (RFS) between newly and previously diagnosed patients were compared. Time-dependent Cox models were established to identify the risk factors for readmission at different time intervals after discharge. Results Readmission rates were approximately 30%, with the most common diagnoses of cerebral infarction (for type I) or diabetes (for type II) for patients with diabetes. The majority of patients were readmitted to the hospital after more than 90 days, followed by 8–30 days (all p=0.002). Approximately 37.2% and 42.8% of readmitted patients with type I and type II diabetes were diagnosed previously, and the RFS rates for previously diagnosed patients were significantly lower than for newly diagnosed patients at any time interval after discharge. Prior history of diabetes (all p<0.05), length of stay (all p<0.01) and reimbursement ratio (90% vs >92%, all p<0.0002) were consistently associated with the RFS for patients readmitted to the hospital at <7, 8–30, 31–60 and 61–90 days. Conclusions Hospital readmissions among patients with diabetes were affected by the diagnosis status. Patient characteristics and the quality of healthcare might regulate short-interval and long-interval hospital readmission, respectively, after discharge. PMID:26525716

  6. Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents

    PubMed Central

    Schrader, Florian C.; Glinca, Serghei; Sattler, Julia M.; Dahse, Hans-Martin; Afanador, Gustavo A.; Prigge, Sean T.; Lanzer, Michael; Mueller, Ann-Kristin; Klebe, Gerhard; Schlitzer, Martin

    2013-01-01

    Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood- and pre-erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood-stage parasite growth with IC50 values of 1.7 and 3.0 µm and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine. PMID:23341167

  7. Investigation of resistive losses in type II superconductors

    NASA Astrophysics Data System (ADS)

    Benapfl, Brendan W.

    For low-TC materials, the superconducting transition temperature (TC) is depressed by the application of a magnetic field. In contrast, one of the remarkable features of cuprate high-TC materials is that the superconducting transition is broadened by the application of a magnetic field. Tinkham presented a model for the field-dependent resistive transition of high-T C materials, arising from "phase slippage at a complicated network of channels." Coffey & Clem did not include this field-broadening effect in their sophisticated model for the field and temperature dependence of the surface resistance in type-II superconductors. From the model by Lee & Stroud, treating Josephson Junction-coupled superconducting segments, it is concluded that doped, layered superconductors are certain to have a field-broadened superconducting transition. This effect can be identified by measurements of the resistivity as a function of temperature, magnetic field strength, angle of field with respect to the crystal axis as well as with respect to an induced current density. The iron pnictide materials such as Ba0.6K0.4Fe2As2 (BaK122) have chemical layers with different compositions, differentiating them from elemental type-II superconductors such as niobium, and also from cuprates, by the absence of copper. Experimental data on BaK122 indicate a field-broadened transition in conjunction with a field-depressed superconducting transition temperature. In this work, techniques associated with Electron Spin Resonance (ESR) spectroscopy were used to measure the temperature and field-induced changes in the surface resistance of single-crystal BaK122 samples. In addition, polycrystalline foils of niobium and a NbTi (70/30) alloy were measured using the same techniques to provide comparison. Measurements were taken as a function of applied magnetic field, temperature, rf field intensity, and angle of the applied field with respect to the rf-induced current. BaK122 sample field-dependent surface

  8. Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer-Saldino).

    PubMed

    Dertinger, Susanne; Söeder, Stephan; Bösch, Hubert; Aigner, Thomas

    2005-01-01

    Skeletal dysplasias represent in vivo models of genetic defects. Achondrogenesis type II (Langer-Saldino), caused by a genetic defect in the major cartilage matrix protein, collagen type II, is a rare and severe skeletal dysplasia. It comprises a severe derangement of the fetal growth plate cartilage with subsequent ossification defects. In this study, we analyzed the matrix composition and cell differentiation pattern in 3 relatives with achondrogenesis type II. Most strikingly we found a strongly reduced collagen type II and moderately reduced aggrecan proteoglycan content in the dysplastic cartilage matrix. Type II collagen is, at least to some extent, replaced by collagens type I III, and VI. Ultrastructural analysis of the dysplastic cartilage matrix demonstrated a distended rER (rough endoplasmic reticulum), which is typical for this condition and most likely related to improper processing and retention of genetically altered type II collagen. Immunostaining for type IIA and X collagens suggest a severe delay in chondrocyte maturation. Thus, the genetic defect in the present cases leads most likely to a severe retention of collagen type II in the rER and, therefore, a strongly reduced collagen deposition and replacement by other interstitial collagens. However, the latter are less efficient in binding aggrecan proteoglycans in the dysplastic cartilage matrix. Additionally, a delay in chondrocyte maturation appears to be important in achondrogenesis type II. PMID:15574381

  9. Non-insulin-dependent (type II) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that

  10. The Three-Dimensional Structural Basis of Type II Hyperprolinemia

    SciTech Connect

    Srivastava, Dhiraj; Singh, Ranjan K.; Moxley, Michael A.; Henzl, Michael T.; Becker, Donald F.; Tanner, John J.

    2012-08-31

    Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in {Delta}{sup 1}-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-{angstrom}-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 {angstrom}) and S352L (2.85 {angstrom}) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 {angstrom} resolution), glutamate (1.5 {angstrom}), and NAD{sup +} (1.5 {angstrom}) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD{sup +} binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-{angstrom} rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD{sup +}, and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.

  11. Screening of three Usher syndrome type II candidate genes

    SciTech Connect

    Bloemker, B.K.; Swaroop, A.; Kimberling, W.J.

    1994-09-01

    Usher syndrome type II (US2) is an autosomal recessive disorder that results in blindness due to retinitis pigmentosa and congenital hearing loss. The disease affects approximately 1 in 20,000 individuals in the general population and is responsible for over 50% of all cases of deafness with blindness. The underlying US2 defect is unknown. The US2 gene has been localized to the 1q41 region of chromosome 1 by linkage studies. Three genes previously localized to 1q were analyzed to assess their candidacy as the US2 gene. These were evaluated by PCR assays using DNA from a YAC contig spanning the US2 region on chromosome 1. The first gene evaluated was the human choroideremia-like gene (hCHML), which had been mapped to chromosome 1q. The sequence on 1q is a homologue of the human choroideremia gene on chromosome X. Choroideremia is a degenerative disorder causing ocular pathology similar to that observed in US2 patients. Therefore, hCHML is a candidate for the US2 gene. Two cDNAs (A and B) from an enriched human retinal pigment epithelium library have been mapped to 1q41 by in situ hybridization. Both cDNAs are considered good candidates. The hCHML and cDNA A were ruled out as candidates for the US2 gene based on negative results from PCR assays performed on YACs spanning the US2 region. cDNA B could not be ruled out as a candidate for the US2 gene by these assays. Answers to many clinical questions regarding US2 will only be resolved after the gene is identified and characterized. Eventually, understanding the function and expression of the US2 gene will provide a basis for the development of therapy.

  12. OPTICAL AND INFRARED ANALYSIS OF TYPE II SN 2006bc

    SciTech Connect

    Gallagher, Joseph S.; Sugerman, B. E. K.; Clayton, Geoffrey C.; Andrews, J. E.; Clem, J. E-mail: ben.sugerman@goucher.edu E-mail: jandrews@phys.lsu.edu; and others

    2012-07-10

    We present nebular phase optical imaging and spectroscopy and near/mid-IR imaging of the Type II SN 2006bc. Observations reveal the central wavelength of the symmetric H{alpha} line profile to be redshifted with respect to the host galaxy H{alpha} emission by day 325. Such a phenomenon has been argued to result from an asymmetric explosion in the iron-peak elements resulting in a larger mass of {sup 56}Ni and higher excitation of hydrogen on the far side of the supernova (SN) explosion. We also observe a gradual blueshifting of this H{alpha} peak which is indicative of dust formation in the ejecta. Although showing a normal peak brightness, V {approx} -17.2, for a core-collapse SN, 2006bc fades by {approx}6 mag during the first 400 days suggesting either a relatively low {sup 56}Ni yield, an increase in extinction due to new dust, or both. A short-duration flattening of the light curve is observed from day 416 to day 541 suggesting an optical light echo. Based on the narrow time window of this echo, we discuss implications on the location and geometry of the reflecting interstellar medium. With our radiative transfer models, we find an upper limit of 2 Multiplication-Sign 10{sup -3} M{sub Sun} of dust around SN 2006bc. In the event that all of this dust were formed during the SN explosion, this quantity of dust is still several orders of magnitude lower than that needed to explain the large quantities of dust observed in the early universe.

  13. Temperature factor for magnetic instability conditions of type - II superconductors

    NASA Astrophysics Data System (ADS)

    Romanovskii, V.

    2014-10-01

    The macroscopic development of interrelated electrodynamics and thermal states taking place both before and after instability onset in type-II superconductors are studied using the critical state and the flux creep concepts. The physical mechanisms of the non-isothermal formation of the critical state are discussed solving the set of unsteady thermo-electrodynamics equations taking into consideration the unknown moving penetration boundary of the magnetic flux. To make it, the numerical method, which allows to study diffusion phenomena with unknown moving phase-two boundary, is developed. The corresponding non-isothermal flux jump criteria are written. It is proved for the first time that, first, the diffusion phenomena in superconductors have the fission-chain-reaction nature, second, the stability conditions, losses in superconductor and its stable overheating before instability onset are mutually dependent. The results are compared with those following from the existing magnetic instability theory, which does not take into consideration the stable temperature increase of superconductor before the instability onset. It is shown that errors of isothermal approximation are significant for modes closed to adiabatic ones. Therefore, the well-known adiabatic flux jump criterion limits the range of possible stable superconducting states since a correct determination of their stability states must take into account the thermal prehistory of the stable magnetic flux penetration. As a result, the calculation errors in the isothermal approximation will rise when the sweep rate of an external magnetic field or the size of the superconductor’s cross-sectional area increase. The basic conclusions formulated in the framework of the critical state model are verified comparing the experimental results and the numerical analysis of the stability conditions and the temperature dynamics of the helicoid-type superconducting current-carrying element having real voltage

  14. TYPE II-P SUPERNOVAE FROM THE SDSS-II SUPERNOVA SURVEY AND THE STANDARDIZED CANDLE METHOD

    SciTech Connect

    D'Andrea, Chris B.; Sako, Masao; Dilday, Benjamin; Jha, Saurabh; Frieman, Joshua A.; Kessler, Richard; Holtzman, Jon; Konishi, Kohki; Yasuda, Naoki; Schneider, D. P.; Sollerman, Jesper; Wheeler, J. Craig; Cinabro, David; Nichol, Robert C.; Lampeitl, Hubert; Smith, Mathew; Atlee, David W.; Bassett, Bruce; Castander, Francisco J.; Goobar, Ariel

    2010-01-01

    We apply the Standardized Candle Method (SCM) for Type II Plateau supernovae (SNe II-P), which relates the velocity of the ejecta of a SN to its luminosity during the plateau, to 15 SNe II-P discovered over the three season run of the Sloan Digital Sky Survey-II Supernova Survey. The redshifts of these SNe-0.027 < z < 0.144-cover a range hitherto sparsely sampled in the literature; in particular, our SNe II-P sample contains nearly as many SNe in the Hubble flow (z > 0.01) as all of the current literature on the SCM combined. We find that the SDSS SNe have a very small intrinsic I-band dispersion (0.22 mag), which can be attributed to selection effects. When the SCM is applied to the combined SDSS-plus-literature set of SNe II-P, the dispersion increases to 0.29 mag, larger than the scatter for either set of SNe separately. We show that the standardization cannot be further improved by eliminating SNe with positive plateau decline rates, as proposed in Poznanski et al. We thoroughly examine all potential systematic effects and conclude that for the SCM to be useful for cosmology, the methods currently used to determine the Fe II velocity at day 50 must be improved, and spectral templates able to encompass the intrinsic variations of Type II-P SNe will be needed.

  15. Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer

    PubMed Central

    Uccella, S; Mariani, A; Wang, A H; Vierkant, R A; Cliby, W A; Robien, K; Anderson, K E; Cerhan, J R

    2013-01-01

    Background: Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. Methods: Prospective cohort of 23 356 postmenopausal women with 471 Type I and 71 Type II EC cases. Results: Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ⩽1 cup per month: 95% confidence interval (CI): 0.47–0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50–1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m−2 (RR=0.56; 95% CI: 0.36–0.89). Conclusion: Coffee may protect against Type I EC in obese postmenopausal women. PMID:24022184

  16. Type I and II Endometrial Cancers: Have They Different Risk Factors?

    PubMed Central

    Setiawan, Veronica Wendy; Yang, Hannah P.; Pike, Malcolm C.; McCann, Susan E.; Yu, Herbert; Xiang, Yong-Bing; Wolk, Alicja; Wentzensen, Nicolas; Weiss, Noel S.; Webb, Penelope M.; van den Brandt, Piet A.; van de Vijver, Koen; Thompson, Pamela J.; Strom, Brian L.; Spurdle, Amanda B.; Soslow, Robert A.; Shu, Xiao-ou; Schairer, Catherine; Sacerdote, Carlotta; Rohan, Thomas E.; Robien, Kim; Risch, Harvey A.; Ricceri, Fulvio; Rebbeck, Timothy R.; Rastogi, Radhai; Prescott, Jennifer; Polidoro, Silvia; Park, Yikyung; Olson, Sara H.; Moysich, Kirsten B.; Miller, Anthony B.; McCullough, Marjorie L.; Matsuno, Rayna K.; Magliocco, Anthony M.; Lurie, Galina; Lu, Lingeng; Lissowska, Jolanta; Liang, Xiaolin; Lacey, James V.; Kolonel, Laurence N.; Henderson, Brian E.; Hankinson, Susan E.; Håkansson, Niclas; Goodman, Marc T.; Gaudet, Mia M.; Garcia-Closas, Montserrat; Friedenreich, Christine M.; Freudenheim, Jo L.; Doherty, Jennifer; De Vivo, Immaculata; Courneya, Kerry S.; Cook, Linda S.; Chen, Chu; Cerhan, James R.; Cai, Hui; Brinton, Louise A.; Bernstein, Leslie; Anderson, Kristin E.; Anton-Culver, Hoda; Schouten, Leo J.; Horn-Ross, Pamela L.

    2013-01-01

    Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. PMID:23733771

  17. Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones.

    PubMed Central

    Yakushiji, T.; Shirasaki, T.; Munakata, M.; Hirata, A.; Akaike, N.

    1993-01-01

    1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8395299

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

    PubMed Central

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

    2015-01-01

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

  19. Geranylgeranyl transferase type II inhibition prevents myeloma bone disease.

    PubMed

    Lawson, Michelle A; Coulton, Les; Ebetino, Frank H; Vanderkerken, Karin; Croucher, Peter I

    2008-12-12

    Geranylgeranyl transferase II (GGTase II) is an enzyme that plays a key role in the isoprenylation of proteins. 3-PEHPC, a novel GGTase II inhibitor, blocks bone resorption and induces myeloma cell apoptosis in vitro. Its effect on bone resorption and tumor growth in vivo is unknown. We investigated the effect of 3-PEHPC on tumor burden and bone disease in the 5T2MM model of multiple myeloma in vivo. 3-PEHPC significantly reduced osteoclast numbers and osteoclast surface. 3-PEHPC prevented the bone loss and the development of osteolytic bone lesions induced by 5T2MM myeloma cells. Treatment with 3-PEHPC also significantly reduced myeloma burden in bone. The magnitude of response was similar to that seen with the bisphosphonate, risedronate. These data show that targeting GGTase II with 3-PEHPC can prevent osteolytic bone disease and reduce tumor burden in vivo, and represents a novel approach to treating tumors that grow in bone.

  20. 1α,25-dihydroxyvitamin D3 stimulates activin A production to fine-tune osteoblast-induced mineralization.

    PubMed

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

    2013-11-01

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

  1. Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women

    PubMed Central

    Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R.; Anderson, Kristin E.

    2013-01-01

    Background: Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. Methods: We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women’s Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the SEER Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. Results: From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for BMI and other cofounders (ptrend=0.0005). Compared to non-drinkers of SSB, the risk was 78% higher (95% CI=1.32-2.40) among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Conclusion: Higher intake of SSB and sugars were associated with an increased risk of type I, but not type II, endometrial cancer. Impact: SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. PMID:24273064

  2. Stimulation of DNA synthesis in cultured rat alveolar type II cells

    SciTech Connect

    Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

    1985-01-01

    Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated /sup 3/H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of /sup 3/H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture.

  3. 46 CFR 171.073 - Treatment of stepped and recessed bulkheads in Type II subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Treatment of stepped and recessed bulkheads in Type II... Treatment of stepped and recessed bulkheads in Type II subdivision. (a) A main transverse watertight bulkhead may not be stepped unless additional watertight bulkheads are located as shown in Figure...

  4. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... suspended solids in accordance with 40 CFR part 136. The arithmetic mean of the total suspended solids in 38... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent...

  5. 46 CFR 171.072 - Calculation of permeability for Type II subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Calculation of permeability for Type II subdivision. 171... permeability for Type II subdivision. When doing calcualtions to show compliance with § 171.070, the following uniform average permeabilities must be assumed: (a) 85 percent in the machinery space. (b) 60 percent...

  6. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  7. Relationship Between a Coronal Mass Ejection-Driven Shock and a Coronal Metric Type II Burst

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Luhmann, J. G.; Bale, S. D.; Lin, R. P.

    2009-02-01

    It has been an intense matter of debate whether coronal metric type II bursts are generated by coronal mass ejection (CME)-driven shocks or flare blast waves. Using unprecedented high-cadence observations from STEREO/SECCHI, we investigate the relationship between a metric type II event and a shock driven by the 2007 December 31 CME. The existence of the CME-driven shock is indicated by the remote deflection of coronal structures, which is in good timing with the metric type II burst. The CME speed is about 600 km s-1 when the metric type II burst occurs, much larger than the Alfvén speed of 419-489 km s-1 determined from band splitting of the type II burst. A causal relationship is well established between the metric and decametric-hectometric type II bursts. The shock height-time curve determined from the type II bands is also consistent with the shock propagation obtained from the streamer deflection. These results provide unambiguous evidence that the metric type II burst is caused by the CME-driven shock.

  8. 46 CFR 171.073 - Treatment of stepped and recessed bulkheads in Type II subdivision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Treatment of stepped and recessed bulkheads in Type II... Stability § 171.073 Treatment of stepped and recessed bulkheads in Type II subdivision. (a) A main transverse watertight bulkhead may not be stepped unless additional watertight bulkheads are located as...

  9. Interband cascade light emitting devices based on type-II quantum wells

    SciTech Connect

    Yang, Rui Q.; Lin, C.H.; Murry, S.J.

    1997-06-01

    The authors discuss physical processes in the newly developed type-II interband cascade light emitting devices, and review their recent progress in the demonstration of the first type-II interband cascade lasers and the observation of interband cascade electroluminescence up to room temperature in a broad mid-infrared wavelength region (extended to 9 {mu}m).

  10. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in 38... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent...

  11. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in 38... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent...

  12. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in 38... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent...

  13. KRAS and MAPK1 Gene Amplification in Type II Ovarian Carcinomas

    PubMed Central

    Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Ishikawa, Masako; Sato, Emi; Iida, Kouji; Nakayama, Naomi; Ishikawa, Noriyuki; Miyazaki, Kohji

    2013-01-01

    In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2%) and 5 (7.4%) of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2%) out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications. PMID:23820584

  14. Isolated corneal pseudodendrites as the initial manifestation of tyrosinemia type II in monozygotic twins.

    PubMed

    Kymionis, George D; Kankariya, Vardhaman P; Kontadakis, Georgios A; Ziakas, Nikolas G

    2012-05-08

    Fifteen-month-old twins presented with photophobia and bilateral corneal pseudodendrites, and tyrosinemia type II was suspected. Plasma tyrosine levels were elevated. After therapy with tyrosine-restricted diet, corneal lesions resolved. Bilateral pseudodendritic keratitis may be the initial or only manifestation of tyrosinemia type II.

  15. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in 38... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent...

  16. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    SciTech Connect

    Veith, G.D.; Broderius, S.J. )

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  17. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes.

    PubMed

    Veith, G D; Broderius, S J

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed. PMID:2269227

  18. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes.

    PubMed

    Veith, G D; Broderius, S J

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  19. Serum Activin A and Follistatin Levels in Gestational Diabetes and the Association of the Activin A-Follistatin System with Anthropometric Parameters in Offspring

    PubMed Central

    Näf, Silvia; Escote, Xavier; Ballesteros, Mónica; Yañez, Rosa Elena; Simón-Muela, Inmaculada; Gil, Pilar; Albaiges, Gerard

    2014-01-01

    Context The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth. Objective To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity. Design and methods A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity. Results Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = −0.199, P = 0.008) and the diagnosis of gestational diabetes (β = −0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively). Conclusions Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin

  20. Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis imperfecta type II.

    PubMed

    Holappa, Heidi; Nieminen, Pekka; Tolva, Liisa; Lukinmaa, Pirjo-Liisa; Alaluusua, Satu

    2006-10-01

    Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. To date, several mutations have been described in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP in seven Finnish families with DGI type II. We report two mutations and five single nucleotide polymorphisms. In one family we found a mutation that has been described earlier in families with different ethnicity, while in six families we found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known DSPP mutations suggests that DGI type II is usually caused by aberration of normal splicing.

  1. Treatment of Type II Endoleaks After Endovascular Repair of Abdominal Aortic Aneurysms: Transcaval Approach

    SciTech Connect

    Mansueto, Giancarlo Cenzi, Daniela; D'Onofrio, Mirko; Petrella, Enrico; Gumbs, Andrew A.; Mucelli, Roberto Pozzi

    2005-06-15

    The purpose of the note is to describe a new technique for type II endoleak treatment, using an alternative approach through femoral venous access. Three patients who developed type II endoleak after endovascular repair of abdominal aortic aneurysm were treated with direct transcaval puncture and embolization inside the aneurysm sac. The detailed technique is described. All patients were treated without any complications and discharged 48 hours after the treatment. At 1 month follow-up the computed tomograph scan did not show a recurrence of a type II endoleak. The management of patients with type II endoleak is a controversial issue and different techniques have been proposed. We suggest an alternative technique for type II endoleak treatment. The feasibility and the advantages of this approach can offer new possibilities for the diagnosis as well as for the treatment of this complication.

  2. The discrimination of type I and type II collagen and the label-free imaging of engineered cartilage tissue.

    PubMed

    Su, Ping-Jung; Chen, Wei-Liang; Li, Tsung-Hsien; Chou, Chen-Kuan; Chen, Te-Hsuen; Ho, Yi-Yun; Huang, Chi-Hsiu; Chang, Shwu-Jen; Huang, Yi-You; Lee, Hsuan-Shu; Dong, Chen-Yuan

    2010-12-01

    Using excitation polarization-resolved second harmonic generation (SHG) microscopy, we measured SHG intensity as a function of the excitation polarization angle for type I and type II collagens. We determined the second order susceptibility (χ((2))) tensor ratios of type I and II collagens at each pixel, and displayed the results as images. We found that the χ((2)) tensor ratios can be used to distinguish the two types of collagen. In particular, we obtained χ(zzz)/χ(zxx) = 1.40 ± 0.04 and χ(xzx)/χ(zxx) = 0.53 ± 0.10 for type I collagen from rat tail tendon, and χ(zzz)/χ(zxx) = 1.14 ± 0.09 and χ(xzx)/χ(zxx) = 0.29 ± 0.11 for type II collagen from rat trachea cartilage. We also applied this methodology on the label-free imaging of engineered cartilage tissue which produces type I and II collagen simultaneously. By displaying the χ((2)) tensor ratios in the image format, the variation in the χ((2)) tensor ratios can be used as a contrast mechanism for distinguishing type I and II collagens. PMID:20875682

  3. The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A.

    PubMed

    Escribese, María M; Sierra-Filardi, Elena; Nieto, Concha; Samaniego, Rafael; Sánchez-Torres, Carmen; Matsuyama, Takami; Calderon-Gómez, Elisabeth; Vega, Miguel A; Salas, Azucena; Sánchez-Mateos, Paloma; Corbí, Angel L

    2012-08-15

    Modulation of macrophage polarization underlies the onset and resolution of inflammatory processes, with polarization-specific molecules being actively sought as potential diagnostic and therapeutic tools. Based on their cytokine profile upon exposure to pathogenic stimuli, human monocyte-derived macrophages generated in the presence of GM-CSF or M-CSF are considered as proinflammatory (M1) or anti-inflammatory (M2) macrophages, respectively. We report in this study that the prolyl hydroxylase PHD3-encoding EGLN3 gene is specifically expressed by in vitro-generated proinflammatory M1(GM-CSF) human macrophages at the mRNA and protein level. Immunohistochemical analysis revealed the expression of PHD3 in CD163(+) lung macrophages under basal homeostatic conditions, whereas PHD3(+) macrophages were abundantly found in tissues undergoing inflammatory responses (e.g., Crohn's disease and ulcerative colitis) and in tumors. In the case of melanoma, PHD3 expression marked a subset of tumor-associated macrophages that exhibit a weak (e.g., CD163) or absent (e.g., FOLR2) expression of typical M2-polarization markers. EGLN3 gene expression in proinflammatory M1(GM-CSF) macrophages was found to be activin A dependent and could be prevented in the presence of an anti-activin A-blocking Ab or inhibitors of activin receptor-like kinase receptors. Moreover, EGLN3 gene expression was upregulated in response to hypoxia only in M2(M-CSF) macrophages, and the hypoxia-mediated upregulation of EGLN3 expression was significantly impaired by activin A neutralization. These results indicate that EGLN3 gene expression in macrophages is dependent on activin A both under basal and hypoxic conditions and that the expression of the EGLN3-encoded PHD3 prolyl hydroxylase identifies proinflammatory macrophages in vivo and in vitro. PMID:22778395

  4. FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model.

    PubMed

    Gustin, Sonja E; Stringer, Jessica M; Hogg, Kirsten; Sinclair, Andrew H; Western, Patrick S

    2016-11-01

    Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFβs, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFβ to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFβ to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFβ were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing β-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFβ can induce testicular characteristics in XX gonads.

  5. FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model.

    PubMed

    Gustin, Sonja E; Stringer, Jessica M; Hogg, Kirsten; Sinclair, Andrew H; Western, Patrick S

    2016-11-01

    Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFβs, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFβ to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFβ to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFβ were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing β-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFβ can induce testicular characteristics in XX gonads. PMID:27495231

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-09-01

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

  8. Patterns of autoreactivity to collagen type II in autoimmune MRL/l mice.

    PubMed Central

    Tarkowski, A; Holmdahl, R; Rubin, K; Klareskog, L; Nilsson, L A; Gunnarsson, K

    1986-01-01

    The kinetics and mechanisms for secretion of antibodies against native and denatured collagen type II have been studied in spontaneously arthritic MRL/l mice. Circulating antibodies were quantified by an ELISA assay and frequencies of specific antibody secreting spleen cells by an ELISPOT assay. The degree of humoral immunity to collagen type II increased at late stages of the disease (6 months of age) whereas severe synovitis was seen earlier (5 months of age). Both the appearance of anti-collagen II producing cells and development of synovitis was preceded by and not correlated with a general state of polyclonal B cell activation. In MRL/l mice, collagen II specific antibodies appeared spontaneously and titres were largely unaffected by collagen II immunization. The levels of circulating anti-collagen II antibodies in MRL/l mice were lower, and the antibodies displayed lower avidities and different specificities as compared with the antibodies generated in collagen II high responder DBA/l mice after immunization with collagen II. It is suggested that the antibody response in MRL/l mice against collagen type II does not need MHC-restricted T cell help and that induction of antibody production to collagen II in MRL/l mice is triggered by joint cartilage destruction and subsequent collagen II release. PMID:3516469

  9. Differential brain angiotensin-II type I receptor expression in hypertensive rats.

    PubMed

    Braga, Valdir A

    2011-09-01

    Blood-borne angiotensin-II (Ang-II) has profound effects in the brain. We tested the hypothesis that Ang-II-dependent hypertension involves differential Ang-II type I (AT(1)) receptors expression in the subfornical organ (SFO) and the rostral ventrolateral medulla (RVLM). Male Wistar rats were implanted with 14-day osmotic minipump filled with Ang-II (150 ng/kg/min) or saline. AT(1) receptor mRNA levels were detected in the SFO and RVLM by reverse transcription-polymerase chain reaction (RT-PCR). Ang-II caused hypertension (134 ± 10 mmHg vs. 98 ± 9 mmHg, n = 9, p < 0.05). RT-PCR revealed that Ang-II infusion induced increased AT(1) receptor mRNA levels in RVLM and decreased in SFO. Our data suggest that Ang-II-induced hypertension involves differential expression of brain AT(1) receptors. PMID:21897104

  10. Semi-Meissner state and neither type-I nor type-II superconductivity in multicomponent superconductors

    SciTech Connect

    Babaev, Egor; Speight, Martin

    2005-11-01

    Traditionally, superconductors are categorized as type I or type II. Type-I superconductors support only Meissner and normal states, while type-II superconductors form magnetic vortices in sufficiently strong applied magnetic fields. Recently there has been much interest in superconducting systems with several species of condensates, in fields ranging from condensed matter to high energy physics. Here we show that the classification into types I and II is insufficient for such multicomponent superconductors. We obtain solutions representing thermodynamically stable vortices with properties falling outside the usual type-I/type-II dichotomy, in that they have the following features: (i) Pippard electrodynamics, (ii) interaction potential with long-range attractive and short-range repulsive parts, (iii) for an n-quantum vortex, a nonmonotonic ratio E(n)/n where E(n) is the energy per unit length, (iv) energetic preference for nonaxisymmetric vortex states, 'vortex molecules'. Consequently, these superconductors exhibit an emerging first order transition into a 'semi-Meissner' state, an inhomogeneous state comprising a mixture of domains of two-component Meissner state and vortex clusters.

  11. Uterine type II estrogen-binding sites are not of eosinophil origin

    SciTech Connect

    Not Available

    1986-01-05

    A recent report suggested that nuclear type II sites in the rat uterus are of eosinophil origin and may represent (/sup 3/H)estradiol binding to eosinophil peroxidase. To further evaluate this hypothesis the authors examined the response of nuclear type II sites to estrogen under conditions where eosinophils are not present. Results of the experiments show that physiological levels of estradiol-17..beta.. (10 nM for 72 h) will stimulate nuclear type II sites in highly purified cultures of rat uterine stromal and myometrial cells. The magnitude of the response of type II sites to estradiol in these stromal (4-fold) and myometrial (80-fold) cell cultures was essentially identical to that observed in the uterine cell types following in vivo estrogen treatment. Since these highly purified cultures of uterine cells were prepared from the uterus of a 21-day ovariectomized rat which is devoid of eosinophils, it was concluded that estradiol stimulation of nuclear type II sites is a direct intracellular response to estrogen which occurs independent of eosinophil accumulation. Furthermore, it was found that type II sites in the rat uterus are not peroxidase. Stimulation of cytosol and nuclear type II sites by estrogen in the rat uterus is a direct intracellular response to the hormone unrelated to eosinophil accumulation and/or peroxidase activity.

  12. Controlling the type I and type II errors in mapping quantitative trait loci

    SciTech Connect

    Jansen, R.C.

    1994-11-01

    Although the interval mapping method is widely used for mapping quantitative trait loci (QTLs), it is not very well suited for mapping multiple QTLs. The authors present the results of a computer simulation to study the application of exact and approximate models for multiple QTLs. In particular, the authors focus on an automatic two-stage procedure in which in the first stage {open_quotes}important{close_quotes} markers are selected in multiple regression on markers. In the second stage a QTL is moved along the chromosomes by using the preselected markers as cofactors, except for the markers flanking the interval under study. A refined procedure for cases with large numbers of marker cofactors is described. This approach will be called MQM mapping, where MQM is an acronym for {open_quotes}multiple-QTL models{close_quotes} as well as for {open_quotes}marker-QTL-marker{close_quotes}. This simulation work demonstrates the great advantage of MQM mapping compared to interval mapping in reducing the chance of a type I error (i.e., a QTL is indicated at a location where actually no QTL is present) and in reducing the chance of a type II error (i.e., a QTL is not detected). 17 refs., 9 figs.

  13. Interfacial strain effect on type-I and type-II core/shell quantum dots

    NASA Astrophysics Data System (ADS)

    Gheshlaghi, Negar; Pisheh, Hadi Sedaghat; Karim, M. Rezaul; Malkoc, Derya; Ünlü, Hilmi

    2016-09-01

    A comparative experimental and theoretical study on the calculation of capped core diameter in ZnSe/ZnS, CdSe/Cd(Zn)S type-I and ZnSe/CdS type-II core/shell nanocrystals is presented. The lattice mismatch induced interface strain between core and shell was calculated from continuum elastic theory and applied in effective mass approximation method to obtain the corresponding capped core diameter. The calculated results were compared with diameter of bare cores (CdSe and ZnSe) from transmission electron microscopy images to obtain the amount of the stretched or squeezed core after deposition of tensile or compressive shells. The result of the study showed that the core is squeezed in ZnSe/ZnS and CdSe/Cd(Zn)S after compressive shell and stretched in ZnSe/CdS after tensile shell deposition. The stretched and squeezed amount of the capped core found to be in proportion with lattice mismatch amount in the core/shell structure.

  14. Receptor for detection of a Type II sex pheromone in the winter moth Operophtera brumata.

    PubMed

    Zhang, Dan-Dan; Wang, Hong-Lei; Schultze, Anna; Froß, Heidrun; Francke, Wittko; Krieger, Jürgen; Löfstedt, Christer

    2016-01-01

    How signal diversity evolves under stabilizing selection in a pheromone-based mate recognition system is a conundrum. Female moths produce two major types of sex pheromones, i.e., long-chain acetates, alcohols and aldehydes (Type I) and polyenic hydrocarbons and epoxides (Type II), along different biosynthetic pathways. Little is known on how male pheromone receptor (PR) genes evolved to perceive the different pheromones. We report the identification of the first PR tuned to Type II pheromones, namely ObruOR1 from the winter moth, Operophtera brumata (Geometridae). ObruOR1 clusters together with previously ligand-unknown orthologues in the PR subfamily for the ancestral Type I pheromones, suggesting that O. brumata did not evolve a new type of PR to match the novel Type II signal but recruited receptors within an existing PR subfamily. AsegOR3, the ObruOR1 orthologue previously cloned from the noctuid Agrotis segetum that has Type I acetate pheromone components, responded significantly to another Type II hydrocarbon, suggesting that a common ancestor with Type I pheromones had receptors for both types of pheromones, a preadaptation for detection of Type II sex pheromone. PMID:26729427

  15. Receptor for detection of a Type II sex pheromone in the winter moth Operophtera brumata

    PubMed Central

    Zhang, Dan-Dan; Wang, Hong-Lei; Schultze, Anna; Froß, Heidrun; Francke, Wittko; Krieger, Jürgen; Löfstedt, Christer

    2016-01-01

    How signal diversity evolves under stabilizing selection in a pheromone-based mate recognition system is a conundrum. Female moths produce two major types of sex pheromones, i.e., long-chain acetates, alcohols and aldehydes (Type I) and polyenic hydrocarbons and epoxides (Type II), along different biosynthetic pathways. Little is known on how male pheromone receptor (PR) genes evolved to perceive the different pheromones. We report the identification of the first PR tuned to Type II pheromones, namely ObruOR1 from the winter moth, Operophtera brumata (Geometridae). ObruOR1 clusters together with previously ligand-unknown orthologues in the PR subfamily for the ancestral Type I pheromones, suggesting that O. brumata did not evolve a new type of PR to match the novel Type II signal but recruited receptors within an existing PR subfamily. AsegOR3, the ObruOR1 orthologue previously cloned from the noctuid Agrotis segetum that has Type I acetate pheromone components, responded significantly to another Type II hydrocarbon, suggesting that a common ancestor with Type I pheromones had receptors for both types of pheromones, a preadaptation for detection of Type II sex pheromone. PMID:26729427

  16. Ruptured Aortic Aneurysm From Late Type II Endoleak Treated by Transarterial Embolization

    SciTech Connect

    Gunasekaran, Senthil; Funaki, Brian Lorenz, Jonathan

    2013-02-15

    Endoleak is the most common complication after endovascular aneurysm repair. The most common type of endoleak, a type II endoleak, typically follows a benign course and is only treated when associated with increasing aneurysm size. In this case report, we describe a ruptured abdominal aortic aneurysm due to a late, type II endoleak occurring 10 years after endovascular aneurysm repair that was successfully treated by transarterial embolization.

  17. Achondrogenesis: a review with special consideration of achondrogenesis type II (Langer-Saldino).

    PubMed

    Chen, H; Liu, C T; Yang, S S

    1981-01-01

    We describe two dwarfed infants with large head, short neck and chest, prominent abdomen, and short limbs. Both died neonatally. Radiographic and morphologic characteristics identified the Langer-Saldino form of achondrogenesis (type II). Review of type II achondrogenesis documented distinctive clinical and anthropometric manifestations (fewer stillbirths, longer survival time and gestation period, larger size of the baby, longer limbs, and characteristic craniofacial features) as compared with type I achondrogenesis (Parenti-Fraccaro). PMID:7036745

  18. Type II protein secretion and its relationship to bacterial type IV pili and archaeal flagella.

    PubMed

    Peabody, Christopher R; Chung, Yong Joon; Yen, Ming-Ren; Vidal-Ingigliardi, Dominique; Pugsley, Anthony P; Saier, Milton H

    2003-11-01

    Homologues of the protein constituents of the Klebsiella pneumoniae (Klebsiella oxytoca) type II secreton (T2S), the Pseudomonas aeruginosa type IV pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum biogenesis machinery (Fla) have been identified. Known constituents of these systems include (1). a major prepilin (preflagellin), (2). several minor prepilins (preflagellins), (3). a prepilin (preflagellin) peptidase/methylase, (4). an ATPase, (5). a multispanning transmembrane (TM) protein, (6). an outer-membrane secretin (lacking in Fla) and (7). several functionally uncharacterized envelope proteins. Sequence and phylogenetic analyses led to the conclusion that, although many of the protein constituents are probably homologous, extensive sequence divergence during evolution clouds this homology so that a common ancestry can be established for all three types of systems for only two constituents, the ATPase and the TM protein. Sequence divergence of the individual T2S constituents has occurred at characteristic rates, apparently without shuffling of constituents between systems. The same is probably also true for the T4P and Fla systems. The family of ATPases is much larger than the family of TM proteins, and many ATPase homologues function in capacities unrelated to those considered here. Many phylogenetic clusters of the ATPases probably exhibit uniform function. Some of these have a corresponding TM protein homologue although others probably function without one. It is further shown that proteins that compose the different phylogenetic clusters in both the ATPase and the TM protein families exhibit unique structural characteristics that are of probable functional significance. The TM proteins are shown to have arisen by at least two dissimilar intragenic duplication events, one in the bacterial kingdom and one in the archaeal kingdom. The archaeal TM proteins are twice as large as the bacterial TM proteins, suggesting an oligomeric

  19. ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation

    PubMed Central

    Ripoche, Doriane; Charbord, Jérémie; Hennino, Ana; Teinturier, Romain; Bonnavion, Rémy; Jaafar, Rami; Goehrig, Delphine; Cordier-Bussat, Martine; Ritvos, Olli; Zhang, Chang X.; Andersson, Olov

    2015-01-01

    Loss of pancreatic β-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote β-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor β (TGF-β)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and β-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed β-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor β-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of β-cell maturity, islet plasticity, and progression of insulinoma through its participation in β-cell dedifferentiation. PMID:26711255

  20. THE CONNECTIONS BETWEEN THE UV AND OPTICAL Fe ii EMISSION LINES IN TYPE 1 AGNs

    SciTech Connect

    Kovacević-Dojcinović, Jelena; Popović, Luka Č. E-mail: lpopovic@aob.bg.ac.rs

    2015-12-15

    We investigate the spectral properties of the UV (λλ2650–3050 Å) and optical (λλ4000–5500 Å) Fe ii emission features in a sample of 293 Type 1 active galactic nuclei (AGNs) from the Sloan Digital Sky Survey database. We explore different correlations between their emission line properties, as well as the correlations with other emission lines from the spectral range. We find several interesting correlations and outline the most interesting results as follows. (i) There is a kinematical connection between the UV and optical Fe ii lines, indicating that the UV and optical Fe ii lines originate from the outer part of the broad line region, the so-called intermediate line region. (ii) The unexplained anticorrelations of the optical Fe ii equivalent width (EW Fe ii{sub opt}) versus EW [O iii] 5007 Å and EW Fe ii{sub opt} versus FWHM Hβ have not been detected for the UV Fe ii lines. (iii) The significant averaged redshift in the UV Fe ii lines, which is not present in optical Fe ii, indicates an inflow in the UV Fe ii emitting clouds, and probably their asymmetric distribution. (iv) Also, we confirm the anticorrelation between the intensity ratio of the optical and UV Fe ii lines and the FWHM of Hβ, and we find the anticorrelations of this ratio with the widths of Mg ii 2800 Å, optical Fe ii, and UV Fe ii. This indicates a very important role for the column density and microturbulence in the emitting gas. We discuss the starburst activity in high-density regions of young AGNs as a possible explanation of the detected optical Fe ii correlations and intensity line ratios of the UV and optical Fe ii lines.

  1. Availability of type II diabetic families for detection of diabetes susceptibility genes.

    PubMed

    Cook, J T; Page, R C; O'Rahilly, S; Levy, J; Holman, R; Barrow, B; Hattersley, A T; Shaw, A G; Wainscoat, J S; Turner, R C

    1993-10-01

    Type II diabetes is a familial disorder, as evidenced by the increased prevalence in monozygotic cotwins and first-degree relatives of affected subjects; however, its genetic etiology is largely unknown. Well-characterized pedigrees are an essential resource for the study of susceptibility genes for type II diabetes. This study describes a 5-yr search for type II diabetic families in Oxfordshire, U.K. We interviewed 950 type II diabetic subjects concerning the availability of first-degree relatives; 127 Caucasian families ascertained through a proband with type II diabetes were studied, and 589 first-degree relatives were characterized. Three large pedigrees with maturity-onset diabetes of the young, and 8 multiplex multigenerational type II diabetic pedigrees were identified. We identified 12 sib-pairs in which both siblings had type II diabetes; however, only 7 sib-pairs had both parents alive, and 2 of these had both parents affected. If one also considers one sib having diabetes and one sib having glucose intolerance as being an affected sib-pair, we identified 30 sib-pairs of which 7 had both parents affected and probably had bilineal inheritance. We identified 76 complete nuclear families with both parents and offspring available for study, but only 6 were of optimal structure for linkage analysis. In conclusion, multiplex pedigrees and type II diabetic sib-pairs with living parents are uncommon, and their ascertainment requires a substantial investment of resources. Large-scale collaborative multicenter initiatives would be needed to collect a large resource of family material for the study of susceptibility genes for type II diabetes.

  2. Type II pneumocytes in mixed cell culture of human lung: a light and electron microscopic study.

    PubMed Central

    Bingle, L; Bull, T B; Fox, B; Guz, A; Richards, R J; Tetley, T D

    1990-01-01

    Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro. Images FIGURE 1. a FIGURE 1. b FIGURE 1. c FIGURE 1. d FIGURE 1. e FIGURE 1. f FIGURE 2. a FIGURE 2. b FIGURE 2. c FIGURE 2. d FIGURE 2. e FIGURE 2. f FIGURE 2. g FIGURE 3. PMID:2384069

  3. Cytogenetic evidence that DNA topoisomerase II is not involved in radiation induced chromsome-type aberrations.

    PubMed

    Mosesso, P; Pepe, G; Ottavianelli, A; Schinoppi, A; Cinelli, S

    2015-11-01

    ICRF-187 (Cardioxane™, Chiron) is a catalytic inhibitor of DNA topoisomerase II (Topo II), proposed to act by blocking Topo II-mediated DNA cleavage without stabilizing DNA-Topo II-"cleavable complexes". In this study ICRF-187 was used to evaluate the potential involvement of DNA topoisomerase II in the formation of the radiation-induced chromosome-type aberrations in the G0 phase of the cell cycle in human lymphocytes from three healthy male donors. This is based on many evidences that DNA topoisomerases are involved in DNA recombination, mainly of illegitimate type (non-homologous) both in vitro and in vivo. The results obtained clearly indicated that ICRF-187 did not induce per se any chromosomal damage. When challenged with the non-catalytic Topo II poison VP-16 (etoposide), which acts by stabilizing the "cleavable complex" generating "protein concealed" DSB's and thus chromosomal aberrations, it completely abolished the significant induction of chromosome-type aberrations and formation of dicentric chromosomes. This indicates that ICRF-187 acts effectively as catalytic inhibitor of Topo II. On the other hand, when X-ray treatments were challenged with ICRF-187 using experimental conditions as for VP-16 treatments, no modification of the incidence of chromosome-type aberrations and dicentric chromosomes was observed. On this basis, we conclude that Topo II is not involved in the formation of X-ray-induced chromosome-type aberrations and dicentric chromosomes in human lymphocytes in the G0 phase of the cell cycle. PMID:26520368

  4. Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II.

    PubMed

    Kim, Jung-Wook; Hu, Jan C-C; Lee, Jae-Il; Moon, Sung-Kwon; Kim, Young-Jae; Jang, Ki-Taeg; Lee, Sang-Hoon; Kim, Chong-Chul; Hahn, Se-Hyun; Simmer, James P

    2005-02-01

    The current system for the classification of hereditary defects of tooth dentin is based upon clinical and radiographic findings and consists of two types of dentin dysplasia (DD) and three types of dentinogenesis imperfecta (DGI). However, whether DGI type III should be considered a distinct phenotype or a variation of DGI type II is debatable. In the 30 years since the classification system was first proposed, significant advances have been made regarding the genetic etiologies of inherited dentin defects. DGI type II is recognized as an autosomal dominant disorder with almost complete penetrance and a low frequency of de novo mutations. We have identified a mutation (c.52G-->T, p.V18F) at the first nucleotide of exon 3 of the DSPP (dentin sialophosphoprotein) gene in a Korean family (de novo) and a Caucasian family. This mutation has previously been reported as causing DGI type II in a Chinese family. These findings suggest that this mutation site represents a mutational "hot spot" in the DSPP gene. The clinical and radiographic features of these two families include the classic phenotypes associated with both DGI type II and type III. Finding that a single mutation causes both phenotypic patterns strongly supports the conclusion that DGI type II and DGI type III are not separate diseases but rather the phenotypic variation of a single disease. We propose a modification of the current classification system such that the designation "hereditary opalescent dentin" or "DGI type II" should be used to describe both the DGI type II and type III phenotypes.

  5. Quantum cascade light emitting diodes based on type-II quantum wells

    SciTech Connect

    Lin, C.H.; Yang, R.Q.; Zhang, D.; Murry, S.J.; Pei, S.S.; Allerman, A.A.; Kurtz, S.R.

    1997-01-21

    The authors have demonstrated room-temperature CW operation of type-II quantum cascade (QC) light emitting diodes at 4.2 {micro}m using InAs/InGaSb/InAlSb type-II quantum wells. The type-II QC configuration utilizes sequential multiple photon emissions in a staircase of coupled type-II quantum wells. The device was grown by molecular beam epitaxy on a p-type GaSb substrate and was compared of 20 periods of active regions separated by digitally graded quantum well injection regions. The maximum average output power is about 250 {micro}W at 80 K, and 140 {micro}W at 300 K at a repetition rate of 1 kHz with a duty cycle of 50%.

  6. Oligomeric state regulated trafficking of human platelet-activating factor acetylhydrolase type-II.

    PubMed

    Monillas, Elizabeth S; Caplan, Jeffrey L; Thévenin, Anastasia F; Bahnson, Brian J

    2015-05-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response.

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

    PubMed

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

    2005-03-01

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

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

    PubMed

    Miyanaga, Y; Shiurba, R; Asashima, M

    1999-02-01

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

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

    PubMed

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

    2005-03-01

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

  10. A ladder type iron(II) coordination polymer with cooperative spin transition.

    PubMed

    Bauer, Wolfgang; Schlamp, Stephan; Weber, Birgit

    2012-10-21

    Ladder type 1D coordination polymers were synthesised with the aim to improve the spin crossover properties of the iron(II) complexes following the concepts of crystal engineering. A wide hysteresis loop (34 K) was observed if rigid linkers were used. The first X-ray structure for a 1D iron(II) ladder is reported.

  11. Type-II Dirac fermions in the PtSe2 class of transition metal dichalcogenides

    NASA Astrophysics Data System (ADS)

    Huang, Huaqing; Zhou, Shuyun; Duan, Wenhui

    2016-09-01

    Recently, a new "type-II" Weyl fermion, which exhibits exotic phenomena, such as an angle-dependent chiral anomaly, was discovered in a new phase of matter where electron and hole pockets contact at isolated Weyl points [Nature (London) 527, 495 (2015), 10.1038/nature15768]. This raises an interesting question about whether its counterpart, i.e., a type-II Dirac fermion, exists in real materials. Here, we predict the existence of symmetry-protected type-II Dirac fermions in a class of transition metal dichalcogenide materials. Our first-principles calculations on PtSe2 reveal its bulk type-II Dirac fermions which are characterized by strongly tilted Dirac cones, novel surface states, and exotic doping-driven Lifshitz transition. Our results show that the existence of type-II Dirac fermions in PtSe2-type materials is closely related to its structural P 3 ¯m 1 symmetry, which provides useful guidance for the experimental realization of type-II Dirac fermions and intriguing physical properties distinct from those of the standard Dirac fermions known before.

  12. Helicobacter pylori hopQ alleles (type I and II) in gastric cancer

    PubMed Central

    LEYLABADLO, HAMED EBRAHIMZADEH; YEKANI, MINA; GHOTASLOU, REZA

    2016-01-01

    The Helicobacter pylori (H. pylori) outer membrane protein (HopQ) of is one of the proteins involved in bacterial adherence to gastric mucosa and has been suggested to have a role in the virulence of H. pylori. The aim of the present study was to determine the association between H. pylori virulence types I and II hopQ genotypes and patients with different gastrointestinal diseases. A polymerase chain reaction-based assay was used to determine the presence of type I and type II hopQ genes in 88 H. pylori strains isolated from H. pylori-infected patients. Of the total 88 H. pylori isolates, type I and type II hopQ alleles were detected in 52 (59.1%) and 36 (40.9%), respectively. A significant association was found between type I hopQ gene and gastric cancer [odds ratio, 2.3; 95% confidence interval (CI), 1.3–4.1] and gastric ulcers (odds ratio, 2.5; 95% CI, 1.4–4.3). A significant association was also identified between the type II hopQ gene and gastric cancer (odds ratio, 2.4; 95% CI, 1.1–3.0). The association between hopQ type I and hopQ type II genotypes and clinical status suggest that these genes may be helpful in the universal prediction of specific disease risks. PMID:27123254

  13. Quantitative prediction of type II solar radio emission from the Sun to 1 AU

    NASA Astrophysics Data System (ADS)

    Schmidt, J. M.; Cairns, Iver H.

    2016-01-01

    Coronal mass ejections (CMEs) are frequently associated with shocks and type II solar radio bursts. Despite involving fundamental plasma physics and being the archetype for collective radio emission from shocks, type II bursts have resisted detailed explanation for over 60 years. Between 29 November and 1 December 2013 the two widely separated spacecraft STEREO A and B observed a long lasting, intermittent, type II radio burst from ≈4 MHz to 30 kHz (harmonic), including an intensification when the CME-driven shock reached STEREO A. We demonstrate the first accurate and quantitative simulation of a type II burst from the high corona (near 11 solar radii) to 1 AU for this event with a combination of a data-driven three-dimensional magnetohydrodynamic simulation for the CME and plasma background and an analytic quantitative kinetic model for the radio emission.

  14. Enhanced proliferation of primary rat type II pneumocytes by Jaagsiekte sheep retrovirus envelope protein

    SciTech Connect

    Johnson, Chassidy; Jahid, Sohail; Voelker, Dennis R.; Fan Hung

    2011-04-10

    Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a contagious lung cancer in sheep. The envelope protein (Env) is the oncogene, as it can transform cell lines in culture and induce tumors in animals, although the mechanisms for transformation are not yet clear because a system to perform transformation assays in differentiated type II pneumocytes does not exist. In this study we report culture of primary rat type II pneumocytes in conditions that favor prolonged expression of markers for type II pneumocytes. Env-expressing cultures formed more colonies that were larger in size and were viable for longer periods of time compared to vector control samples. The cells that remained in culture longer were confirmed to be derived from type II pneumocytes because they expressed surfactant protein C, cytokeratin, displayed alkaline phosphatase activity and were positive for Nile red. This system will be useful to study JSRV Env in the targets of transformation.

  15. Chromosomal localization and structure of the human type II IMP dehydrogenase gene

    SciTech Connect

    Glesne, D.; Huberman, E. |; Collart, F.; Varkony, T.; Drabkin, H.

    1994-05-01

    We determined the chromosomal localization and structure of the gene encoding human type II inosine 5{prime}-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205), an enzyme associated with cellular proliferation, malignant transformation, and differentiation. Using polymerase chain reaction (PCR) primers specific for type II IMPDH, we screened a panel of human-Chinese hamster cell somatic hybrids and a separate deletion panel of chromosome 3 hybrids and localized the gene to 3p21.1{yields}p24.2. Two overlapping yeast artificial chromosome clones containing the full gene for type II IMPDH were isolated and a physical map of 117 kb of human genomic DNA in this region of chromosome 3 was constructed. The gene for type II IMPDH was localized and oriented on this map and found to span no more than 12.5 kb.

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

    PubMed Central

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

    2015-01-01

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

  17. The types II and III transforming growth factor-beta receptors form homo-oligomers

    PubMed Central

    1994-01-01

    Affinity-labeling experiments have detected hetero-oligomers of the types I, II, and III transforming growth factor beta (TGF-beta) receptors which mediate intracellular signaling by TGF-beta, but the oligomeric state of the individual receptor types remains unknown. Here we use two types of experiments to show that a major portion of the receptor types II and III forms homo-oligomers both in the absence and presence of TGF-beta. Both experiments used COS-7 cells co-transfected with combinations of these receptors carrying different epitope tags at their extracellular termini. In immunoprecipitation experiments, radiolabeled TGF-beta was bound and cross-linked to cells co-expressing two differently tagged type II receptors. Sequential immunoprecipitations using anti-epitope monoclonal antibodies showed that type II TGF-beta receptors form homo-oligomers. In cells co- expressing epitope-tagged types II and III receptors, a low level of co- precipitation of the ligand-labeled receptors was observed, indicating that some hetero-oligomers of the types II and III receptors exist in the presence of ligand. Antibody-mediated cross-linking studies based on double-labeling immunofluorescence explored co-patching of the receptors at the cell surface on live cells. In cells co-expressing two differently tagged type II receptors or two differently tagged type III receptors, forcing one receptor into micropatches by IgG induced co- patching of the receptor carrying the other tag, labeled by noncross- linking monovalent Fab'. These studies showed that homo-oligomers of the types II and III receptors exist on the cell surface in the absence or presence of TGF-beta 1 or -beta 2. In cells co-expressing types II and III receptors, the amount of heterocomplexes at the cell surface was too low to be detected in the immunofluorescence co-patching experiments, confirming that hetero-oligomers of the types II and III receptors are minor and probably transient species. PMID:8027173

  18. The Connections Between the UV and Optical Fe ii Emission Lines in Type 1 AGNs

    NASA Astrophysics Data System (ADS)

    Kovačević-Dojčinović, Jelena; Popović, Luka Č.

    2015-12-01

    We investigate the spectral properties of the UV (λλ2650-3050 Å) and optical (λλ4000-5500 Å) Fe ii emission features in a sample of 293 Type 1 active galactic nuclei (AGNs) from the Sloan Digital Sky Survey database. We explore different correlations between their emission line properties, as well as the correlations with other emission lines from the spectral range. We find several interesting correlations and outline the most interesting results as follows. (i) There is a kinematical connection between the UV and optical Fe ii lines, indicating that the UV and optical Fe ii lines originate from the outer part of the broad line region, the so-called intermediate line region. (ii) The unexplained anticorrelations of the optical Fe ii equivalent width (EW Fe iiopt) versus EW [O iii] 5007 Å and EW Fe iiopt versus FWHM Hβ have not been detected for the UV Fe ii lines. (iii) The significant averaged redshift in the UV Fe ii lines, which is not present in optical Fe ii, indicates an inflow in the UV Fe ii emitting clouds, and probably their asymmetric distribution. (iv) Also, we confirm the anticorrelation between the intensity ratio of the optical and UV Fe ii lines and the FWHM of Hβ, and we find the anticorrelations of this ratio with the widths of Mg ii 2800 Å, optical Fe ii, and UV Fe ii. This indicates a very important role for the column density and microturbulence in the emitting gas. We discuss the starburst activity in high-density regions of young AGNs as a possible explanation of the detected optical Fe ii correlations and intensity line ratios of the UV and optical Fe ii lines.

  19. Relationship between a CME-driven shock and a coronal metric type II burst

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Luhmann, J.; Bale, S.; Lin, R.

    2008-12-01

    It has been a long-standing controversy whether coronal metric type II bursts are generated by CME-driven shocks or flare blast waves. Using unprecedented high-cadence observations from STEREO/SECCHI, we investigate the relationship between a metric type II event and a shock driven by the 2007 December 31 CME. The CME occurs at the east limb and its evolution is observed from about 1.1 to several tens of solar radii. The existence of the CME-driven shock is indicated by the deflection of coronal structures before the CME impinges on them, the best evidence for shocks in imaging observations. The earliest deflection of distant coronal structures occurs at 00:51:22 UT, about 2.6 min before the metric type II onset. The CME- driven shock emerges from the corona and produces a break point in the streamer north of the CME, which allows us to follow the shock propagation in imaging observations for the first time. We also have a continuous frequency coverage of the radio dynamic spectrum by combining observations from STEREO/SWAVES, BIRS and Learmonth, which successfully establishes the connection between the metric and decametric-hectometric (DH) type II bursts. The CME speed is about 600 km/s at the time of the metric type II onset, larger than the Alfven speed 420 - 490 km/s determined from the band splitting of the metric type II burst. The shock height-time curve determined from the metric and DH type II bands is consistent with the shock propagation obtained from the streamer deflection. These results provide unambiguous evidence that the metric type II burst is caused by the CME-driven shock. Implications are also discussed for particle acceleration and space weather forecasting.

  20. Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review.

    PubMed

    al-Hemidan, A I; al-Hazzaa, S A

    1995-03-01

    Richner-Hanhart syndrome (Tyrosinemia Type II) is an autosomal recessive disorder of amino acid metabolism characterized by ocular changes, painful palmoplantar hyperkeratosis, and mental retardation. Serum tyrosine increases due to tyrosine aminotransferase deficiency resulting in the deposition of tyrosine crystals in the cornea and in corneal inflammation. Patients are often misdiagnosed as having herpes simplex keratitis. We report on a child who presented with bilateral keratitis secondary to Tyrosinemia Type II diagnosed as herpes simplex keratitis.

  1. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms

    PubMed Central

    Meyer, Sara C.; Keller, Matthew D.; Chiu, Sophia; Koppikar, Priya; Guryanova, Olga A.; Rapaport, Franck; Xu, Ke; Manova, Katia; Pankov, Dmitry; O’Reilly, Richard J.; Kleppe, Maria; McKenney, Anna Sophia; Shih, Alan H.; Shank, Kaitlyn; Ahn, Jihae; Papalexi, Eftymia; Spitzer, Barbara; Socci, Nick; Viale, Agnes; Mandon, Emeline; Ebel, Nicolas; Andraos, Rita; Rubert, Joëlle; Dammassa, Ernesta; Romanet, Vincent; Dölemeyer, Arno; Zender, Michael; Heinlein, Melanie; Rampal, Rajit; Weinberg, Rona Singer; Hoffman, Ron; Sellers, William R.; Hofmann, Francesco; Murakami, Masato; Baffert, Fabienne; Gaul, Christoph; Radimerski, Thomas; Levine, Ross L.

    2015-01-01

    Summary Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasms (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated if CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2- and MPL-mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients. PMID:26175413

  2. Metabolic response in type I and type II muscle fibers during a 30-s cycle sprint in men and women.

    PubMed

    Esbjörnsson-Liljedahl, M; Sundberg, C J; Norman, B; Jansson, E

    1999-10-01

    The acute metabolic response to sprint exercise was studied in 20 male and 19 female students. We hypothesized that the reduction of muscle glycogen content during sprint exercise would be smaller in women than in men and that a possible gender difference in glycogen reduction would be higher in type II than in type I fibers. The exercise-induced increase in blood lactate concentration was 22% smaller in women than in men. A considerable reduction of ATP (50%), phosphocreatine (83%), and glycogen (35%) was found in type II muscle fibers, and it did not differ between the genders. A smaller reduction of ATP (17%) and phosphocreatine (78%) was found in type I fibers, and it did not differ between the genders. However, the exercise-induced reduction in glycogen content in type I fibers was 50% smaller in women than in men. The hypothesis was indeed partly confirmed: the exercise-induced glycogen reduction was attenuated in women compared with men, but the gender difference was in type I rather than in type II fibers. Fiber-type-specific and gender-related differences in the metabolic response to sprint exercise might have implications for the design of training programs for men and women.

  3. Immunohistochemical findings type I and type II collagen in prenatal mouse mandibular condylar cartilage compared with the tibial anlage.

    PubMed

    Ishii, M; Suda, N; Tengan, T; Suzuki, S; Kuroda, T

    1998-07-01

    In growing animals the mandibular condylar cartilage serves not only as an articular but also as a growth cartilage, yet, condylar cartilage has some characteristic features that are not found in growth cartilage. For example, some reports suggest that type I collagen, which is not seen in the growth plate cartilage of long bones, is present in the extracellular matrix of condylar cartilage postnatally. Here, the condylar and limb bud cartilage of fetal mice was examined. The distribution of type I and type II collagen in condylar cartilage was already different from that in the limb bud at the first appearance of the cartilage. Type I collagen was demonstrated in the extracellular matrix of the condylar cartilage that first appeared on day 15 of gestation. However, the reaction for type II collagen was much weaker than that for type I collagen. On day 18 of gestation, type I collagen was still found throughout the cell layers but became gradually weaker with depth. Type II collagen was limited exclusively to the deeper layers at this stage. These findings are different from those in the limb bud cartilage, indicating a characteristic feature of the cells in the condylar cartilage present from the prenatal period.

  4. L-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytes.

    PubMed

    Hermosilla, Tamara; Moreno, Cristian; Itfinca, Mircea; Altier, Christophe; Armisén, Ricardo; Stutzin, Andres; Zamponi, Gerald W; Varela, Diego

    2011-01-01

    Angiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the underlying signaling events are not completely understood. Moreover, the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has not yet been explored. In this work we study the role of Ca(v)β subunits and the intracellular signaling responsible for L-type calcium current modulation by Angiotensin II. In cardiomyocytes, Angiotensin II exposure induces rapid inhibition of L-type current with a magnitude that is correlated with the rate of current inactivation. Semi-quantitative PCR of cardiomyocytes at different days of culture reveals changes in the Ca(v)β subunits expression pattern that are correlated with the rate of current inactivation and with Angiotensin II effect. Over-expression of individual b subunits in heterologous systems reveals that the magnitude of Angiotensin II inhibition is dependent on the Ca(v)β subunit isoform, with Ca(v)β(1b) containing channels being more strongly regulated. Ca(v)β(2a) containing channels were insensitive to modulation and this effect was partially due to the N-terminal palmitoylation sites of this subunit. Moreover, PLC or diacylglycerol lipase inhibition prevents the Angiotensin II effect on L-type calcium channels, while PKC inhibition with chelerythrine does not, suggesting a role of arachidonic acid in this process. Finally, we show that in intact cardiomyocytes the magnitude of calcium transients on spontaneous beating cells is modulated by Angiotensin II in a Ca(v)β subunit-dependent manner. These data demonstrate that Ca(v)β subunits alter the magnitude of inhibition of L-type current by Angiotensin II. PMID:21525790

  5. Shock-associated kilometric radio emission and solar metric type II bursts

    SciTech Connect

    Kahler, S.W.; Cliver, E.W.; Cane, H.V.

    1989-09-06

    Statistics are presented relating shock-associated (SA) kilometric bursts (Cane et al, 1981) to solar metric type bursts. An SA burst is defined here to be any 1980-kHz emission temporally associated with a reported metric type II burst and not temporally associated with a reported metric type III burst. This extends to lower flux densities and shorter durations the original SA concept of Cane et al. About one quarter of 316 metric type II bursts were not accompanied by any 1980 kHz emission, another quarter were accompanied by emission attributable to preceding or simultaneous type III bursts, and nearly half were associated with SA bursts. Time profiles of 32 SA bursts were compared with Culgoora Observatory dynamic spectral records of metric type II bursts, finding that the SA emission is associated with the most intense and structured part of the metric type II burst. On the other hand, the generally poor correlation found between SA burst profiles and Sagamore Hill Observatory 606- and 2695-MHz flux density profiles suggests that most SA emission is not due to energetic electrons escaping from the microwave-emission region. These results support the interpretation that SA bursts are the long-wavelength extension of type II burst herringbone emission, which is presumed due to the shock acceleration of electrons.

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

    PubMed Central

    2013-01-01

    Introduction 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members of the Transforming Growth Factor β family of proteins, and their binding protein, follistatin, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. Our objectives were to evaluate whether the serum levels of activin A, B and follistatin are elevated in 518 patients with ARF from the FINNALI study compared the concentrations in 138 normal subjects that form a reference range. Methods Specific assays for activin A, B and follistatin were used and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months from the onset of the ARF. Results Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95% CI 1.28-2.12, P = 0.00013]; both activin A and B above reference maximum: LR + 2.78 [95% CI 1.96-3.95, P < 0.00001]. The predictive model at 12 months had an overall accuracy of 80.2% [95% CI 76.6-83.3%]. Conclusions The measurement of activin A and B levels in these patients with ARF would have assisted in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate

  7. Personal Educational Tools (PETs) for Type II Learning

    ERIC Educational Resources Information Center

    Christensen, Rhonda; Overall, Theresa; Knezek, Gerald

    2006-01-01

    This article introduces the concept of Personal Educational Tools (PETs) and places these tools within the context of existing rationales for using technology for teaching, learning, and instruction. An identification of the distinguishing characteristics of these devices is followed by the conjecture that these types of classifying…

  8. Human Blood Typing: A Forensic Science Approach: Part II. Experiments.

    ERIC Educational Resources Information Center

    Kobilinsky, Lawrence; Sheehan, Francis X.

    1988-01-01

    Describes several experiments that explore the methodology available to the forensic serologist for typing a human bloodstain in the ABH grouping system. Presents ABO blood group of wet blood, Lattes Crust test procedure, and the absorption-elution procedure. Uses outdated blood; equipment requirements are minimal. (ML)

  9. Self-consistent calculations of optical properties of type I and type II quantum heterostructures

    NASA Astrophysics Data System (ADS)

    Shuvayev, Vladimir A.

    In this Thesis the self-consistent computational methods are applied to the study of the optical properties of semiconductor nanostructures with one- and two-dimensional quantum confinements. At first, the self-consistent Schrodinger-Poisson system of equations is applied to the cylindrical core-shell structure with type II band alignment without direct Coulomb interaction between carriers. The electron and hole states and confining potential are obtained from a numerical solution of this system. The photoluminescence kinetics is theoretically analyzed, with the nanostructure size dispersion taken into account. The results are applied to the radiative recombination in the system of ZnTe/ZnSe stacked quantum dots. A good agreement with both continuous wave and time-resolved experimental observations is found. It is shown that size distribution results in the photoluminescence decay that has essentially non-exponential behavior even at the tail of the decay where the carrier lifetime is almost the same due to slowly changing overlap of the electron and hole wavefunctions. Also, a model situation applicable to colloidal core-shell nanowires is investigated and discussed. With respect to the excitons in type I quantum wells, a new computationally efficient and flexible approach of calculating the characteristics of excitons, based on a self-consistent variational treatment of the electron-hole Coulomb interaction, is developed. In this approach, a system of self-consistent equations describing the motion of an electron-hole pair is derived. The motion in the growth direction of the quantum well is separated from the in-plane motion, but each of them occurs in modified potentials found self-consistently. This approach is applied to a shallow quantum well with the delta-potential profile, for which analytical expressions for the exciton binding energy and the ground state eigenfunctions are obtained, and to the quantum well with the square potential profile with several

  10. Distributions of types I, II and III collagen by region in the human supraspinatus tendon.

    PubMed

    Buckley, Mark R; Evans, Elisabeth B; Matuszewski, Paul E; Chen, Yi-Ling; Satchel, Lauren N; Elliott, Dawn M; Soslowsky, Louis J; Dodge, George R

    2013-01-01

    The mechanical properties of the human supraspinatus tendon (SST) are highly heterogeneous and may reflect an important adaptive response to its complex, multiaxial loading environment. However, these functional properties are associated with a location-dependent structure and composition that have not been fully elucidated. Therefore, the objective of this study was to determine the concentrations of types I, II and III collagen in six distinct regions of the SST and compare changes in collagen concentration across regions with local changes in mechanical properties. We hypothesized that type I collagen content would be high throughout the tendon, type II collagen would be restricted to regions of compressive loading and type III collagen content would be high in regions associated with damage. We further hypothesized that regions of high type III collagen content would correspond to regions with low tensile modulus and a low degree of collagen alignment. Although type III collagen content was not significantly higher in regions that are frequently damaged, all other hypotheses were supported by our results. In particular, type II collagen content was highest near the insertion while type III collagen was inversely correlated with tendon modulus and collagen alignment. The measured increase in type II collagen under the coracoacromial arch provides evidence of adaptation to compressive loading in the SST. Moreover, the structure-function relationship between type III collagen content and tendon mechanics established in this study demonstrates a mechanism for altered mechanical properties in pathological tendons and provides a guideline for identifying therapeutic targets and pathology-specific biomarkers.

  11. Observations of the Flux Density of Some Interplanetary Type II and Type III Radio Bursts and Initial Comparisons With Theory

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Mohamed, A. A. A.; Hillan, D.; Robinson, P. A.

    2015-12-01

    The measured intensity of a radio signal depends on the effective antenna length, which may vary with (at least) the plasma properties and radiation frequency. Here the effective antenna lengths are estimated as a function of frequency for the RAD1 and RAD2 instruments on the WIND spacecraft when in SUM mode. This is done by calibrating against the known galactic background radiation spectrum after removal of receiver noise and thermal plasma noise where possible. Flux density spectra and lower limits to the maximum brightness temperature are determined for three type II and three type III radio bursts based on two calibration methods, one of which uses the effective antenna lengths as a function of frequency. The second calibration method uses Wind data for the relative flux in dB to equate the minimum flux observed with the galactic background and receiver noise. The results emphasize that the second method is more successful in obtaining calibrated type II and III fluxes. Calibrated flux densities obtained show that The type IIs have similar maximum flux densities to the type III events in this sample, but the type IIs are much more variable in frequency and time. Theoretical predictions are obtained for shocks moving with a suitable range of initial speeds and accelerations. Dynamic spectra are then predicted for the three selected type II events using the theory of Knock et al. [2001] and a simple, unstructured, solar wind model. Because of the continuous emission of 24-26 August 1998 that is present in a wide range from 100 MHz to 21 kHz, albeit with strongly varying intensity, a comparison between its observed and predicted dynamic spectra is presented. The agreement between theory and data is discussed and the implications described for future modeling.

  12. Activin A accelerates the progression of fetal oocytes throughout meiosis and early oogenesis in the mouse.

    PubMed

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

    2015-10-15

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

  13. Angiotensin II-induced angiotensin II type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

    NASA Astrophysics Data System (ADS)

    Li, Hewang; Yu, Peiying; Felder, Robin A.; Periasamy, Ammasi; Jose, Pedro A.

    2009-02-01

    Upon activation, the angiotensin (Ang) II type 1 receptor (AT1Rs) rapidly undergoes endocytosis. After a series of intracellular processes, the internalized AT1Rs recycle back to the plasma membrane or are trafficked to proteasomes or lysosomes for degradation. We recently reported that AT1Rs degrades in proteasomes upon stimulation of the D5 dopamine receptor (D5R) in human renal proximal tubule and HEK-293 cells. This is in contrast to the degradation of AT1R in lysosomes upon binding Ang II. However, the dynamic regulation of the AT1Rs in lysosomes is not well understood. Here we investigated the AT1Rs lysosomal degradation using FRET-FLIM in HEK 293 cells heterologously expressing the human AT1R tagged with EGFP as the donor fluorophore. Compared to its basal state, the lifetime of AT1Rs decreased after a 5-minute treatment with Ang II treatment and colocalized with Rab5 but not Rab7 and LAMP1. With longer Ang II treatment (30 min), the AT1Rs lifetime decreased and co-localized with Rab5, as well as Rab7 and LAMP1. The FLIM data are corroborated with morphological and biochemical co-immunoprecipitation studies. These data demonstrate that Ang II induces the internalization of AT1Rs into early sorting endosomes prior to trafficking to late endosomes and subsequent degradation in lysosomes.

  14. Topological Odd-Parity Superconductivity Close to Type-II 2D Van Hove Singularities

    NASA Astrophysics Data System (ADS)

    Yao, Hong; Yang, Fan

    2014-03-01

    We study unconventional superconductivity induced by weak repulsive interactions in 2D electronic systems at Van Hove singularity (VHS) where electronic density of states is logarithmically divergent. We define two types of VH saddle points. For type-I VH systems, weak repulsive interactions generically induce unconventional singlet pairing. However and more interestingly, for type-II VH systems renormalization group treatment shows that weak repulsive interactions favor triplet pairing (e.g. p-wave) when the Fermi surface has no good nesting. When such type-II VH systems respecting tetragonal or hexagonal point group symmetry, topological superconductivity (chiral p +ip or time reversal invariant Z2 p +ip pairing) will generally occur. We shall also discuss implications of this study to recently discovered BiS2-based superconductors and other superconducting materials that host type-II VH singularities in their Fermi surfaces.

  15. Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats.

    PubMed

    Eldridge, J C; Fleenor, D G; Kerr, D S; Landfield, P W

    1989-01-30

    Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.

  16. PULSATING REVERSE DETONATION MODELS OF TYPE Ia SUPERNOVAE. II. EXPLOSION

    SciTech Connect

    Bravo, Eduardo; Garcia-Senz, Domingo; Cabezon, Ruben M.; DomInguez, Inmaculada E-mail: domingo.garcia@upc.edu E-mail: inma@ugr.es

    2009-04-20

    Observational evidences point to a common explosion mechanism of Type Ia supernovae based on a delayed detonation of a white dwarf (WD). However, all attempts to find a convincing ignition mechanism based on a delayed detonation in a destabilized, expanding, white dwarf have been elusive so far. One of the possibilities that has been invoked is that an inefficient deflagration leads to pulsation of a Chandrasekhar-mass WD, followed by formation of an accretion shock that confines a carbon-oxygen rich core, while transforming the kinetic energy of the collapsing halo into thermal energy of the core, until an inward moving detonation is formed. This chain of events has been termed Pulsating Reverse Detonation (PRD). In this work, we present three-dimensional numerical simulations of PRD models from the time of detonation initiation up to homologous expansion. Different models characterized by the amount of mass burned during the deflagration phase, M {sub defl}, give explosions spanning a range of kinetic energies, K {approx} (1.0-1.2) x 10{sup 51} erg, and {sup 56}Ni masses, M({sup 56}Ni) {approx} 0.6-0.8 M {sub sun}, which are compatible with what is expected for typical Type Ia supernovae. Spectra and light curves of angle-averaged spherically symmetric versions of the PRD models are discussed. Type Ia supernova spectra pose the most stringent requirements on PRD models.

  17. Type-II second-harmonic-generation properties of YCOB and GdCOB single crystals.

    PubMed

    Liu, Yanqing; Qi, Hongwei; Lu, Qingming; Yu, Fapeng; Wang, Zhengping; Xu, Xinguang; Zhao, Xian

    2015-02-01

    As excellent nonlinear optical (NLO) crystals, YCa(4)O(BO(3))(3) (YCOB) and GdCa(4)O(BO(3))(3) (GdCOB) have been paid much attention since their first appearance in 1990's. From that time to now, almost all of related researches and applications have focused on their type-I phase-matching (PM) configurations which possess large effective NLO coefficient (d(eff)). In this paper, type-II second-harmonic-generation (SHG) properties of these two crystals are reported, including PM curve, d(eff), angular acceptance and walk-off angle. Both of the type-II SHG experiments for 1064 and 1320 nm have indicated that the optimum directions which have maximum d(eff) locate in the second octant, i.e. (90° < θ< 180°, 0° < ϕ < 90°). For a (112°, 81.3°)-cut, 24 mm long YCOB crystal, the largest type-II SHG conversion efficiency of a 1064 nm Nd:YAG pico-second laser is 55%, which reaches the same level of the optimum type-I sample. To our knowledge this is the first time that type-II SHG performance of YCOB and GdCOB crystals is investigated intensively. Our research has shown that the smaller d(eff) of type-II PM can be compensated by its larger angular acceptance and less beam walk-off. The same level SHG conversion efficiency implies for such type crystals the type-II components have the potential to replace type-I ones and obtain important NLO applications in the future.

  18. Type-II second-harmonic-generation properties of YCOB and GdCOB single crystals.

    PubMed

    Liu, Yanqing; Qi, Hongwei; Lu, Qingming; Yu, Fapeng; Wang, Zhengping; Xu, Xinguang; Zhao, Xian

    2015-02-01

    As excellent nonlinear optical (NLO) crystals, YCa(4)O(BO(3))(3) (YCOB) and GdCa(4)O(BO(3))(3) (GdCOB) have been paid much attention since their first appearance in 1990's. From that time to now, almost all of related researches and applications have focused on their type-I phase-matching (PM) configurations which possess large effective NLO coefficient (d(eff)). In this paper, type-II second-harmonic-generation (SHG) properties of these two crystals are reported, including PM curve, d(eff), angular acceptance and walk-off angle. Both of the type-II SHG experiments for 1064 and 1320 nm have indicated that the optimum directions which have maximum d(eff) locate in the second octant, i.e. (90° < θ< 180°, 0° < ϕ < 90°). For a (112°, 81.3°)-cut, 24 mm long YCOB crystal, the largest type-II SHG conversion efficiency of a 1064 nm Nd:YAG pico-second laser is 55%, which reaches the same level of the optimum type-I sample. To our knowledge this is the first time that type-II SHG performance of YCOB and GdCOB crystals is investigated intensively. Our research has shown that the smaller d(eff) of type-II PM can be compensated by its larger angular acceptance and less beam walk-off. The same level SHG conversion efficiency implies for such type crystals the type-II components have the potential to replace type-I ones and obtain important NLO applications in the future. PMID:25836087

  19. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

    PubMed

    Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

    1995-09-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

  20. Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats

    PubMed Central

    Soni, Hardik; Patel, Sejal; Patel, Ghanshyam; Paranjape, Archana

    2014-01-01

    Background: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. Objective: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. Materials and Methods: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg). Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg) along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg) treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by ‘analysis of variance’ test followed by post hoc Tukey's test, with significant level of P < 0.05. Results and Discussion: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. Conclusion: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property. PMID:24948860

  1. Dominant mutations in the type II collagen gene, COL2A1, produce spondyloepimetaphyseal dysplasia, Strudwick type.

    PubMed

    Tiller, G E; Polumbo, P A; Weis, M A; Bogaert, R; Lachman, R S; Cohn, D H; Rimoin, D L; Eyre, D R

    1995-09-01

    The chondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth or development of cartilage. Current classification is based on mode of inheritance as well as clinical, histologic, and/or radiographic features. A clinical spectrum of chondrodysplasia phenotypes, ranging from mild to perinatal lethal, is due to defects in the gene for type II collagen, COL2A1. This spectrum includes Stickler syndrome, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), achondrogenesis type II, and hypochondrogenesis. Individuals affected with these disorders exhibit abnormalities of the growth plate, nucleus pulposus, and vitreous humor, which are tissues that contain type II collagen. The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which are not seen in SEDC). The phenotype was first described by Murdoch and Walker in 1969, and a series of 14 patients was later reported by Anderson et al. The observation of two affected sibs born to unaffected parents led to the classification of SEMD Strudwick as an autosomal recessive disorder. We now describe the biochemical characterization of defects in alpha 1(II) collagen in three unrelated individuals with SEMD Strudwick, each of which is due to heterozygosity for a unique mutation in COL2A1. Our data support the hypothesis that some cases, if not all cases, of this distinctive chondrodysplasia result from dominant mutations in COL2A1, thus expanding the clinical spectrum of phenotypes associated with this gene. PMID:7550321

  2. Dominant mutations in the type II collagen gene, COL2A1, produce spondyloepimetaphyseal dysplasia, Strudwick type.

    PubMed

    Tiller, G E; Polumbo, P A; Weis, M A; Bogaert, R; Lachman, R S; Cohn, D H; Rimoin, D L; Eyre, D R

    1995-09-01

    The chondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth or development of cartilage. Current classification is based on mode of inheritance as well as clinical, histologic, and/or radiographic features. A clinical spectrum of chondrodysplasia phenotypes, ranging from mild to perinatal lethal, is due to defects in the gene for type II collagen, COL2A1. This spectrum includes Stickler syndrome, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), achondrogenesis type II, and hypochondrogenesis. Individuals affected with these disorders exhibit abnormalities of the growth plate, nucleus pulposus, and vitreous humor, which are tissues that contain type II collagen. The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which are not seen in SEDC). The phenotype was first described by Murdoch and Walker in 1969, and a series of 14 patients was later reported by Anderson et al. The observation of two affected sibs born to unaffected parents led to the classification of SEMD Strudwick as an autosomal recessive disorder. We now describe the biochemical characterization of defects in alpha 1(II) collagen in three unrelated individuals with SEMD Strudwick, each of which is due to heterozygosity for a unique mutation in COL2A1. Our data support the hypothesis that some cases, if not all cases, of this distinctive chondrodysplasia result from dominant mutations in COL2A1, thus expanding the clinical spectrum of phenotypes associated with this gene.

  3. Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans

    PubMed Central

    Pais, Ramona; Rievaj, Juraj; Larraufie, Pierre

    2016-01-01

    Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan. Ang II raised intracellular calcium levels in L cells in primary cultures, recorded by live-cell imaging of L cells specifically expressing the fluorescent calcium sensor GCaMP3. In Ussing chamber recordings, Ang II reduced short circuit currents in mouse distal colon preparations, which was antagonized by candesartan or a specific neuropeptide Y1 receptor inhibitor but insensitive to amiloride. We conclude that Ang II stimulates PYY secretion, in turn inhibiting epithelial anion fluxes, thereby reducing net fluid secretion into the colonic lumen. Our findings highlight an important role of colonic L cells in whole-body fluid homeostasis by controlling water loss through the intestine. PMID:27447725

  4. [Extraction, purification and identification of type II collagen from Agkistrodon acutus].

    PubMed

    Gu, Heng-Cun; Hu, Jin-Bo; Ding, Zhi-Shan; Fan, Yong-Sheng; Ding, Xing-Hong

    2013-11-01

    The object of the research was to extract, purify and identify the type II collagen of Agkistrodon acutus. Type II collagen of A. acutus was extracted by enzyme decomposition method, and purified by ion exchange column chromatography. It was characterized by SDS-PAGE gel electrophoresis, ultraviolet spectrophotometry, infrared absorption spectroscopy and mass spectroscopy. The results showed that the size of C II was about 130 kDa. It absorbed at 223 nm. IR spectrum obtained showed that the triple helical domains of amino-acid sequences were characterized by the repetition of triplets Gly-X-Y. The MS spectrum graphically stated that C II extracted from cow and A. acutus have the similar peptides. The C II of A. acutus was obtained by extraction and purification. Appraisal analysis by SDS-PAGE, UV, IR and MS, C II of A. acutus was consistent with the standard C II of cow. It was proved that the extracted protein was C II. PMID:24494552

  5. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.

    PubMed

    Carta, Q; Meriggi, E; Trossarelli, G F; Catella, G; Dal Molin, V; Menato, G; Gagliardi, L; Massobrio, M; Vitelli, A

    1986-06-01

    Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.

  6. Alternative gene expression in type I and type II cells may enable further nuclear changes during conjugation of Blepharisma japonicum.

    PubMed

    Sugiura, Mayumi; Tanaka, Yuri; Suzaki, Toshinobu; Harumoto, Terue

    2012-03-01

    In contrast to most ciliates, meiosis and successive nuclear changes during conjugation occur only in heterotypic pairs in Blepharisma. It has been suggested that homotypic pairs are ready for conjugation, but lack a trigger to initiate the nuclear changes, and the conjugation process is arrested before the onset of meiosis. To explore the possible nature of the trigger, we previously identified the genes BjCdk1 (homologous to cdk1/cdc2), Bj4HPPD (4-hydroxy-phenylpyruvate dioxygenase) and BjCks (cyclin dependent kinase regulatory subunit) whose expression is up-regulated in gamone1-treated type II cells. In this study, we investigated the molecular structures of these three genes, and compared their expression patterns in homotypic and heterotypic pairs, finding remarkable differences. BjCdk1, Bj4HPPD and BjCks were expressed specifically in gamone1-treated type II cells, but not in gamone2-treated type I cells. In heterotypic pairs, the expression of these genes stayed at the same level or gradually decreased throughout the entire process of conjugation, but it rapidly decreased and ceased after 10hours in homotypic pairs. These results indicate that some genes are expressed in a mating-type specific manner. Alternative gene expression in mating type I and type II cells and merging of individual factors in a heterotypic pair may induce nuclear changes including meiosis.

  7. Ulysses observations of wave activity at interplanetary shocks and implications for type II radio bursts

    SciTech Connect

    Lengyel-Frey, D. |; Thejappa, G.; MacDowall, R.J.; Stone, R.G.; Phillips, J.L. |

    1997-02-01

    We present the first quantitative investigation of interplanetary type II radio emission in which in situ waves measured at interplanetary shocks are used to compute radio wave intensities for comparison with type II observations. This study is based on in situ measurements of 42 in-ecliptic forward shocks as well as 10 intervals of type II emission observed by the Ulysses spacecraft between 1 AU and 5 AU. The analysis involves comparisons of statistical properties of type II bursts and in situ waves. Most of the 42 shocks are associated with the occurrence of electrostatic waves near the time of shock passage at Ulysses. These waves, which are identified as electron plasma waves and ion acoustic-like waves, are typically most intense several minutes before shock passage. This suggests that wave-wave interactions might be of importance in electromagnetic wave generation and that type II source regions are located immediately upstream of the shocks. We use the in situ wave measurements to compute type II brightness temperatures, assuming that emission at the fundamental of the electron plasma frequency is generated by the merging of electron plasma waves and ion acoustic waves or the decay of electron plasma waves into ion acoustic and transverse waves. Second harmonic emission is assumed to be produced by the merging of electron plasma waves. The latter mechanism requires that a portion of the electron plasma wave distribution is backscattered, presumably by density inhomogeneities in regions of observed ion acoustic wave activity. The computed type II brightness temperatures are found to be consistent with observed values for both fundamental and second harmonic emission, assuming that strong ({approx_equal}10{sup {minus}4}V/m) electron plasma waves and ion acoustic waves are coincident and that the electron plasma waves have phase velocities less than about 10 times the electron thermal velocity. (Abstract Truncated)

  8. Prediction of Type II Radio Bursts Associated with Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, Iver; Schmidt, Joachim

    Type II radio bursts are associated with shocks in the corona and solar wind, either driven by CMEs or else by blast waves. Recently we coupled the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our kinetic ``bolt-on'' theory for type II emission. Initialising the simulation code with event specific coronal and CME data, the combined code can be used to predict the dynamic spectrum of type II emission for a specific radio event. We demonstrate very good agreement with Wind spacecraft observations for three type II bursts, one on 15 February 2011 and two on 7 March 2012 (associated with successive CMEs from different sides of the same active region). The intensities, frequencies, and times of fundamental and harmonic type II emission are predicted very well from the high corona to 1 AU (frequencies ~ 20 MHz - 30 kHz). The islands of increased emission correspond to different regions of the shock interacting with coronal structures, with streamers typically corresponding to reduced emission. The results provide strong evidence that both the type II theory and the BATS-R-US (driven with event-specific data) are accurate. They also provide strong evidence that the observation and detailed theoretical modelling of type II bursts can in principle provide warnings with lead-times of over a day for large and fast CMEs that might produce space weather at Earth. The MHD code can also predict whether the CME will hit Earth's magnetopause and the magnetic field direction at the magnetopause as the shock, sheath, and CME, vital quantities for predicting space weather at Earth.

  9. Synaptic Transfer from Outer Hair Cells to Type II Afferent Fibers in the Rat Cochlea

    PubMed Central

    Weisz, Catherine J.C.; Lehar, Mohamed; Hiel, Hakim; Glowatzki, Elisabeth; Fuchs, Paul Albert

    2012-01-01

    Type II cochlear afferents receive glutamatergic synaptic excitation from outer hair cells (OHCs) in the rat cochlea. However, it remains uncertain whether this connection is capable of providing auditory information to the brain. The functional efficacy of this connection depends in part on the number of presynaptic OHCs, their probability of transmitter release, and the effective electrical distance for spatial summation in the Type II fiber. The present work addresses these questions using whole-cell recordings from the spiral process of type II afferents that run below OHCs in the apical turn of young (5–9 days postnatal) rat cochlea. A ‘high potassium puffer’ was used to elicit calcium action potentials from individual OHCs and thereby show that the average probability of transmitter release was 0.26 (range 0.02 to 0.73). Electron microscopy showed relatively few vesicles tethered to ribbons in equivalent OHCs. A ‘receptive field’ map for individual type II fibers was constructed by successively puffing onto OHCs along the cochlear spiral, up to 180 µm from the recording pipette. These revealed a conservative estimate of 7 presynaptic OHCs per type II fiber (range 1–11). EPSCs evoked from presynaptic OHCs separated by more than 100 µm did not differ in amplitude or waveform, implying that the type II fiber’s length constant exceeded the length of the synaptic input zone. Taken together these data suggest that type II fibers could communicate centrally by maximal activation of their entire pool of presynaptic OHCs. PMID:22787038

  10. In Situ D-periodic Molecular Structure of Type II Collagen

    SciTech Connect

    Antipova, Olga; Orgel, Joseph P.R.O.

    2010-05-06

    Collagens are essential components of extracellular matrices in multicellular animals. Fibrillar type II collagen is the most prominent component of articular cartilage and other cartilage-like tissues such as notochord. Its in situ macromolecular and packing structures have not been fully characterized, but an understanding of these attributes may help reveal mechanisms of tissue assembly and degradation (as in osteo- and rheumatoid arthritis). In some tissues such as lamprey notochord, the collagen fibrillar organization is naturally crystalline and may be studied by x-ray diffraction. We used diffraction data from native and derivative notochord tissue samples to solve the axial, D-periodic structure of type II collagen via multiple isomorphous replacement. The electron density maps and heavy atom data revealed the conformation of the nonhelical telopeptides and the overall D-periodic structure of collagen type II in native tissues, data that were further supported by structure prediction and transmission electron microscopy. These results help to explain the observed differences in collagen type I and type II fibrillar architecture and indicate the collagen type II cross-link organization, which is crucial for fibrillogenesis. Transmission electron microscopy data show the close relationship between lamprey and mammalian collagen fibrils, even though the respective larger scale tissue architecture differs.

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

    SciTech Connect

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

    2015-03-01

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

  12. Pectic type II arabinogalactans from starfruit (Averrhoa carambola L.).

    PubMed

    Leivas, Carolina Lopes; Iacomini, Marcello; Cordeiro, Lucimara M C

    2016-05-15

    A structural characterization of polysaccharides from edible tropical fruit named starfruit (Averrhoa carambola L.) was carried out. After the purification steps, two homogeneous fractions were obtained. Fraction 50R was composed of rhamnose, arabinose, galactose and uronic acid in 4.3:56.2:37.4:2M ratio, respectively and fraction 10R was composed of rhamnose, arabinose, galactose and uronic acid in 2.8:65.8:28.5:3M ratio, respectively. Methylation and NMR spectroscopy analyses showed that these fractions are formed by pectic arabinogalactans, which contain (1→3), (1→6) and (1→3,6)-linked Galp units. The side chains have 3-O-, 5-O- and 3,5-di-O-linked α-Araf and nonreducing end-units of α-Araf, Arap, β-Galp and α-GlcpA. These arabinogalactans were linked to type I rhamnogalacturonans.

  13. Rad: A member of the Ras family overexpressed in muscle of type II diabetic humans

    SciTech Connect

    Reynet, C.; Kahn, C.R. )

    1993-11-26

    To identify the gene or genes associated with insulin resistance in Type II (non-insulin-dependent) diabetes mellitus, subtraction libraries were prepared from skeletal muscle of normal and diabetic humans and screened with subtracted probes. Only one clone out of 4000 was selectively overexpressed in Type II diabetic muscle as compared to muscle of non-diabetic or Type I diabetic individuals. This clone encoded a new 290 kilodalton member of the Ras-guanosine triphosphatase superfamily and was termed Rad (Ras associated with diabetes). Messenger ribonucleic acid of Rad was expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II diabetics as compared to normal individuals.

  14. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    PubMed Central

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Martina; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-01-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit. PMID:25996248

  15. Mg II Spectra of Late Type Stars Used to Probe the LISM

    NASA Technical Reports Server (NTRS)

    Beckman, J. E.; Crivellari, L.; Franco, M.; Molaro, P.; Vladilo, G.

    1984-01-01

    IUE spectra of Mg II h and k in late type dwarfs and giants were used to detect and measure absorption components due to the LISM. This technique gives a method of probing the awkward range from d = 3 pc to d = 80 pc from the Sun. In spite of interpretational uncertainties the HI component of the LISM can be plotted well enough to confirm it as a cloud some 20 to 30 pc in extent, peaking sharply in density towards l(II)-25 deg., moving towards the Sun from l(II)-25 deg, b(II) = + 10 deg., at 28 Km/sec. The hole towards l(II) = 150 deg is confirmed, suggesting a solar position close to the cloud's edge in this direction.

  16. Type Ia supernova rate studies from the SDSS-II Supernova Study

    SciTech Connect

    Dilday, Benjamin

    2008-08-01

    The author presents new measurements of the type Ia SN rate from the SDSS-II Supernova Survey. The SDSS-II Supernova Survey was carried out during the Fall months (Sept.-Nov.) of 2005-2007 and discovered ~ 500 spectroscopically confirmed SNe Ia with densely sampled (once every ~ 4 days), multi-color light curves. Additionally, the SDSS-II Supernova Survey has discovered several hundred SNe Ia candidates with well-measured light curves, but without spectroscopic confirmation of type. This total, achieved in 9 months of observing, represents ~ 15-20% of the total SNe Ia discovered worldwide since 1885. The author describes some technical details of the SN Survey observations and SN search algorithms that contributed to the extremely high-yield of discovered SNe and that are important as context for the SDSS-II Supernova Survey SN Ia rate measurements.

  17. Type Ia and II Supernovae Contributions to Metal Enrichment in the Intracluster Medium Observed with Suzaku

    NASA Astrophysics Data System (ADS)

    Sato, Kosuke; Tokoi, Kazuyo; Matsushita, Kyoko; Ishisaki, Yoshitaka; Yamasaki, Noriko Y.; Ishida, Manabu; Ohashi, Takaya

    2007-09-01

    We studied the properties of the intracluster medium (ICM) in two clusters of galaxies (AWM 7 and Abell 1060) and two groups (HCG 62 and NGC 507) with the X-ray observatory Suzaku. Based on spatially resolved energy spectra, we measured for the first time precise cumulative ICM metal masses within 0.1 and ~0.3r180. Comparing our results with supernova nucleosynthesis models, the number ratio of Type II (SNe II) to Type Ia (SNe Ia) is estimated to be ~3.5, assuming the metal mass in the ICM is represented by the sum of products synthesized in SNe Ia and SNe II. Normalized by the K-band luminosities of present galaxies, and including the metals in stars, the integrated number of past SN II explosions is estimated to be close to or somewhat higher than the star formation rate determined from Hubble Deep Field observations.

  18. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases.

    PubMed

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases. Materials and methods. A total of 30 type II diabetic patients, 30 patients with periodontal diseases, 30 type II diabetic patients with periodontal disease and 30 age- and BMI-matched controls were studied. The periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary melatonin levels were determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results. The mean of salivary melatonin level was significantly lower in patients with either periodontitis or diabetes compared to healthy subjects (P < 0.05). Salivary melatonin concentration decreased in type II diabetic patients and periodontitis patients, and then decreased reaching the lowest levels in type II diabetic patients with periodontal disease. Conclusion. Based on the results of this study, it can probably be concluded that salivary level of melatonin has an important role in the pathogenesis of diabetes and periodontal diseases. It is also worth noting that this factor could probably be used as a pivotal biological marker in the diagnosis and possible treatment of these diseases, although further research is required to validate this hypothesis. PMID:25346835

  19. Trypsin-mediated enzymatic degradation of type II collagen in the human vitreous

    PubMed Central

    van Deemter, Mariëlle; Kuijer, Roel; Harm Pas, Hendri; Jacoba van der Worp, Roelofje; Hooymans, Johanna Martina Maria

    2013-01-01

    Purpose Aging of the vitreous body can result in sight-threatening pathology. One aspect of vitreous aging is liquefaction, which results from the vanishing of collagen fibrils. We investigated the possibility that trypsins are involved in vitreous type II collagen degradation. Methods Immunohistochemistry and western blotting were used for detecting and locating trypsin isoforms in the vitreous and retina of human donor eyes. The capability of the retina to produce these trypsins was analyzed with polymerase chain reaction. Whether the different trypsins degraded type II collagen was tested in vitro. The sizes of the in vitro induced type II collagen degradation products were compared to those present in the vitreous of human eyes of different ages. Results Trypsin-1 and trypsin-2 were detected in the vitreous. In the retina, messenger ribonucleic acid (mRNA) coding for trypsin-2, -3, and -4 was present. Using immunohistochemistry, trypsin-2 was detected in microglial cells located in the vitreous and the retina. All trypsin isoforms degraded type II collagen and produced degradation products of similar sizes as those present in the vitreous. Conclusions Trypsin-1 and trypsin-2 appear to have a function in the degradation of vitreous type II collagen. They could therefore have a role in the development of vitreous liquefaction. PMID:23882137

  20. Vitamin E alters alveolar type II cell phospholipid synthesis in oxygen and air

    SciTech Connect

    Kennedy, K.A.; Snyder, J.M.; Stenzel, W.; Saito, K.; Warshaw, J.B. )

    1990-11-01

    Newborn rats were injected with vitamin E or placebo daily until 6 days after birth. The effect of vitamin E pretreatment on in vitro surfactant phospholipid synthesis was examined in isolated type II cells exposed to oxygen or air form 24 h in vitro. Type II cells were also isolated from untreated 6-day-old rats and cultured for 24 h in oxygen or air with control medium or vitamin E supplemented medium. These cells were used to examine the effect of vitamin E exposure in vitro on type II cell phospholipid synthesis and ultrastructure. Phosphatidylcholine (PC) synthesis was reduced in cells cultured in oxygen as compared with air. This decrease was not prevented by in vivo pretreatment or in vitro supplementation with vitamin E. Vitamin E pretreatment increased the ratio of disaturated PC to total PC and increased phosphatidylglycerol synthesis. The volume density of lamellar bodies in type II cells was increased in cells maintained in oxygen. Vitamin E did not affect the volume density of lamellar bodies. We conclude that in vitro hyperoxia inhibits alveolar type II cell phosphatidylcholine synthesis without decreasing lamellar body volume density and that supplemental vitamin E does not prevent hyperoxia-induced decrease in phosphatidylcholine synthesis.

  1. Reduction of Melatonin Level in Patients with Type II Diabetes and Periodontal Diseases

    PubMed Central

    Abdolsamadi, Hamidreza; Goodarzi, Mohammad Taghi; Ahmadi Motemayel, Fatemeh; Jazaeri, Mina; Feradmal, Javad; Zarabadi, Mahdiyeh; Hoseyni, Mostafa; Torkzaban, Parviz

    2014-01-01

    Background and aims. Melatonin is a circulating hormone that is mainly released from the pineal gland. It possesses antioxidant, free-radical scavenging, and immune-enhancing properties. A growing number of studies reveal a complex role for melatonin in influencing various diseases, including diabetes and periodontal diseases. The aim of this study was to examine the possible links between salivary melatonin levels and type II diabetes and periodontal diseases. Materials and methods. A total of 30 type II diabetic patients, 30 patients with periodontal diseases, 30 type II diabetic patients with periodontal disease and 30 age- and BMI-matched controls were studied. The periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary melatonin levels were determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results. The mean of salivary melatonin level was significantly lower in patients with either periodontitis or diabetes compared to healthy subjects (P < 0.05). Salivary melatonin concentration decreased in type II diabetic patients and periodontitis patients, and then decreased reaching the lowest levels in type II diabetic patients with periodontal disease. Conclusion. Based on the results of this study, it can probably be concluded that salivary level of melatonin has an important role in the pathogenesis of diabetes and periodontal diseases. It is also worth noting that this factor could probably be used as a pivotal biological marker in the diagnosis and possible treatment of these diseases, although further research is required to validate this hypothesis. PMID:25346835

  2. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD. PMID:27082868

  3. DIAGNOSTICS ON THE SOURCE PROPERTIES OF A TYPE II RADIO BURST WITH SPECTRAL BUMPS

    SciTech Connect

    Feng, S. W.; Chen, Y.; Kong, X. L.; Li, G.; Song, H. Q.; Feng, X. S.; Guo, Fan

    2013-04-10

    In recent studies, we proposed that source properties of type II radio bursts can be inferred through a causal relationship between the special shape of the type II dynamic spectrum (e.g., bump or break) and simultaneous extreme ultraviolet (EUV)/white light imaging observations (e.g., CME-shock crossing streamer structures). As a further extension of these studies, in this paper we examine the coronal mass ejection (CME) event on 2007 December 31 associated with a multiple type II radio burst. We identify the presence of two spectral bump features on the observed dynamic spectrum. By combining observational analyses of the radio spectral observations and the EUV-white light imaging data, we conclude that the two spectral bumps result from a CME-shock propagating across dense streamers on the southern and northern sides of the CME. It is inferred that the corresponding two type II emissions originate separately from the two CME-shock flanks where the shock geometries are likely quasi-perpendicular or oblique. Since the emission lanes are bumped as a whole within a relatively short time, it suggests that the type II radio bursts with bumps of this study are emitted from spatially confined sources (with a projected lateral dimension smaller than 0.05-0.1 R{sub Sun} at a fundamental frequency level of 20-30 MHz).

  4. Erythrocyte Membrane Antigen Frequencies in Patients with Type II Congenital Smell Loss

    PubMed Central

    Stateman, William A.; Henkin, Robert I.; Knöppel, Alexandra; Flegel, Willy A.

    2014-01-01

    OBJECTIVE The objective of this study was to determine whether there are genetic factors associated with Type II congenital smell loss. STUDY DESIGN The expression frequencies of 16 erythrocyte antigens among patients with Type II congenital smell loss were determined and compared to those of a large control group. METHODS Blood samples were obtained from 99 patients with Type II congenital smell loss. Presence of the erythrocyte surface antigens A, B, M, N, S, s, Fya, Fyb, D, C, c, E, e, K, Jka, and Jkb was analyzed by blood group serology. Comparisons of expression frequencies of these antigens were made between the patients and a large control group. RESULTS Patients tested for the Duffy b antigen (Fyb haplotype) exhibited a statistically significant 11% decrease in expression frequency compared to the controls. There were no significant differences between patients and controls in the expression frequencies for all other erythrocyte antigens (A, B, M, N, S, s, Fya, D, C, c, E, e, K, Jka, or Jkb). CONCLUSIONS These findings describe the presence of a previously unrevealed genetic tendency among patients with Type II congenital smell loss related to erythrocyte surface antigen expression. The deviation in expression rate of Duffy b suggests a target gene and chromosome region in which future research into this form of congenital smell loss may reveal a more specific genetic basis for Type II congenital smell loss. PMID:25456515

  5. Topology of Type II REases revisited; structural classes and the common conserved core.

    PubMed

    Niv, Masha Y; Ripoll, Daniel R; Vila, Jorge A; Liwo, Adam; Vanamee, Eva S; Aggarwal, Aneel K; Weinstein, Harel; Scheraga, Harold A

    2007-01-01

    Type II restriction endonucleases (REases) are deoxyribonucleases that cleave DNA sequences with remarkable specificity. Type II REases are highly divergent in sequence as well as in topology, i.e. the connectivity of secondary structure elements. A widely held assumption is that a structural core of five beta-strands flanked by two alpha-helices is common to these enzymes. We introduce a systematic procedure to enumerate secondary structure elements in an unambiguous and reproducible way, and use it to analyze the currently available X-ray structures of Type II REases. Based on this analysis, we propose an alternative definition of the core, which we term the alphabetaalpha-core. The alphabetaalpha-core includes the most frequently observed secondary structure elements and is not a sandwich, as it consists of a five-strand beta-sheet and two alpha-helices on the same face of the beta-sheet. We use the alphabetaalpha-core connectivity as a basis for grouping the Type II REases into distinct structural classes. In these new structural classes, the connectivity correlates with the angles between the secondary structure elements and with the cleavage patterns of the REases. We show that there exists a substructure of the alphabetaalpha-core, namely a common conserved core, ccc, defined here as one alpha-helix and four beta-strands common to all Type II REase of known structure.

  6. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD.

  7. The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages

    PubMed Central

    Koe, Chwee Tat; Li, Song; Rossi, Fabrizio; Wong, Jack Jing Lin; Wang, Yan; Zhang, Zhizhuo; Chen, Keng; Aw, Sherry Shiying; Richardson, Helena E; Robson, Paul; Sung, Wing-Kin; Yu, Fengwei; Gonzalez, Cayetano; Wang, Hongyan

    2014-01-01

    The control of self-renewal and differentiation of neural stem and progenitor cells is a crucial issue in stem cell and cancer biology. Drosophila type II neuroblast lineages are prone to developing impaired neuroblast homeostasis if the limited self-renewing potential of intermediate neural progenitors (INPs) is unrestrained. Here, we demonstrate that Drosophila SWI/SNF chromatin remodeling Brahma (Brm) complex functions cooperatively with another chromatin remodeling factor, Histone deacetylase 3 (HDAC3) to suppress the formation of ectopic type II neuroblasts. We show that multiple components of the Brm complex and HDAC3 physically associate with Earmuff (Erm), a type II-specific transcription factor that prevents dedifferentiation of INPs into neuroblasts. Consistently, the predicted Erm-binding motif is present in most of known binding loci of Brm. Furthermore, brm and hdac3 genetically interact with erm to prevent type II neuroblast overgrowth. Thus, the Brm-HDAC3-Erm repressor complex suppresses dedifferentiation of INPs back into type II neuroblasts. DOI: http://dx.doi.org/10.7554/eLife.01906.001 PMID:24618901

  8. Activin Regulates Self-renewal and Differentiation of Trophoblast Stem Cells by Down-regulating the X Chromosome Gene Bcor*

    PubMed Central

    Zhu, Gaoyang; Fei, Teng; Li, Zhongwei; Yan, Xiaohua; Chen, Ye-Guang

    2015-01-01

    The development of a functional placenta is largely dependent upon proper proliferation and differentiation of trophoblast stem cells (TSCs). Activin signaling has long been regarded to play important roles during this process, but the exact mechanism is largely unknown. Here, we demonstrate that the X chromosome gene BCL-6 corepressor (Bcor) is a critical downstream effector of activin to fine-tune mouse TSC fate decision. Bcor was specifically down-regulated by activin A in TSCs in a dose-dependent manner, and immediately up-regulated upon TSC differentiation. Knockdown of Bcor partially compensated for the absence of activin A in maintaining the self-renewal of TSCs together with FGF4, while promoting syncytiotrophoblast differentiation in the absence of FGF4. Moreover, the impaired trophoblast giant cell and spongiotrophoblast differentiation upon Bcor knockdown also resembled the function of activin. Reporter analysis showed that BCOR inhibited the expression of the key trophoblast regulator genes Eomes and Cebpa by binding to their promoter regions. Our findings provide us with a better understanding of placental development and placenta-related diseases. PMID:26221038

  9. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    NASA Astrophysics Data System (ADS)

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S. P.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-06-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.Inhaled nanoparticles have a high deposition rate in

  10. WebCT and Its Growth as a Type II Application

    ERIC Educational Resources Information Center

    Chen, Irene; Willis, Jerry; Mahoney, Sue

    2005-01-01

    Maddux, Johnson, and Willis mentioned in 1992 some "yet to be developed types" that "have the potential to be Type II software if they are used in such a way that the user is given the ability to learn in new and better ways." The authors of this paper will frame the discussion of learning management systems (LMS) around the concept of Type I and…

  11. Excitonic transitions in highly efficient (GaIn)As/Ga(AsSb) type-II quantum-well structures

    SciTech Connect

    Gies, S.; Kruska, C.; Berger, C.; Hens, P.; Fuchs, C.; Rosemann, N. W.; Veletas, J.; Stolz, W.; Koch, S. W.; Heimbrodt, W.; Ruiz Perez, A.; Hader, J.; Moloney, J. V.

    2015-11-02

    The excitonic transitions of the type-II (GaIn)As/Ga(AsSb) gain medium of a “W”-laser structure are characterized experimentally by modulation spectroscopy and analyzed using microscopic quantum theory. On the basis of the very good agreement between the measured and calculated photoreflectivity, the type-I or type-II character of the observable excitonic transitions is identified. Whereas the energetically lowest three transitions exhibit type-II character, the subsequent energetically higher transitions possess type-I character with much stronger dipole moments. Despite the type-II character, the quantum-well structure exhibits a bright luminescence.

  12. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate.

    PubMed

    Green, J B; Smith, J C

    1990-09-27

    The protein XTC-MIF, a Xenopus homologue of activin A and a potent mesoderm-inducing factor, can induce responding animal pole explants to form several different cell types in a dose-dependent manner, higher doses eliciting more dorso-anterior tissues. This graded response, characteristic of classically postulated morphogens, may underlie pattern formation, but the response of intact animal caps to XTC-MIF provides only a crude indication of trends. Here we report the effects of XTC-MIF on dispersed blastomeres rather than intact animal caps. Under these conditions, responding cells distinguish sharply between doses of pure XTC-MIF differing by less than 1.5-fold. Two different response thresholds have been found, defining three cell states. This suggests that XTC-MIF has an instructive effect. Notochord and muscle are both induced in the same narrow dose-range. Mixing treated with untreated cells does not seem to shift the dose thresholds, showing that at least some cells can stably record the received dose of inducing factor.

  13. Molecular cloning, expression, and evolution analysis of type II CHI gene from peanut (Arachis hypogaea L.).

    PubMed

    Liu, Yu; Zhao, Shuzhen; Wang, Jiangshan; Zhao, Chuanzhi; Guan, Hongshan; Hou, Lei; Li, Changsheng; Xia, Han; Wang, Xingjun

    2015-01-01

    Chalcone isomerase (CHI) plays critical roles in plant secondary metabolism, which is important for the interaction between plants and the environment. CHI genes are widely studied in various higher plants. However, little information about CHI genes is available in peanut. Based on conservation of CHI gene family, we cloned the peanut type II CHI gene (AhCHI II) cDNA and genome sequence. The amino acid sequence of peanut CHI II was highly homologous to type II CHI from other plant species. qRT-PCR results showed that peanut CHI II is mainly expressed in roots; however, peanut CHI I is mainly expressed in tissues with high content of anthocyanin. Gene duplication and gene cluster analysis indicated that CHI II was derived from CHI I 65 million years ago approximately. Our gene structure analysis results are not in agreement with the previous hypothesis that CHI II was derived from CHI I by the insertion of an intron into the first exon. Moreover, no positive selection pressure was found in CHIs, while, 32.1 % of sites were under neutral selection, which may lead to mutation accumulation and fixation during great changes of environment.

  14. Assessment of Whole-Genome Regression for Type II Diabetes

    PubMed Central

    Vazquez, Ana I.; Klimentidis, Yann C.; Dhurandhar, Emily J.; Veturi, Yogasudha C.; Paérez-Rodríguez, Paulino

    2015-01-01

    Lifestyle and genetic factors play a large role in the development of Type 2 Diabetes (T2D). Despite the important role of genetic factors, genetic information is not incorporated into the clinical assessment of T2D risk. We assessed and compared Whole Genome Regression methods to predict the T2D status of 5,245 subjects from the Framingham Heart Study. For evaluating each method we constructed the following set of regression models: A clinical baseline model (CBM) which included non-genetic covariates only. CBM was extended by adding the first two marker-derived principal components and 65 SNPs identified by a recent GWAS consortium for T2D (M-65SNPs). Subsequently, it was further extended by adding 249,798 genome-wide SNPs from a high-density array. The Bayesian models used to incorporate genome-wide marker information as predictors were: Bayes A, Bayes Cπ, Bayesian LASSO (BL), and the Genomic Best Linear Unbiased Prediction (G-BLUP). Results included estimates of the genetic variance and heritability, genetic scores for T2D, and predictive ability evaluated in a 10-fold cross-validation. The predictive AUC estimates for CBM and M-65SNPs were: 0.668 and 0.684, respectively. We found evidence of contribution of genetic effects in T2D, as reflected in the genomic heritability estimates (0.492±0.066). The highest predictive AUC among the genome-wide marker Bayesian models was 0.681 for the Bayesian LASSO. Overall, the improvement in predictive ability was moderate and did not differ greatly among models that included genetic information. Approximately 58% of the total number of genetic variants was found to contribute to the overall genetic variation, indicating a complex genetic architecture for T2D. Our results suggest that the Bayes Cπ and the G-BLUP models with a large set of genome-wide markers could be used for predicting risk to T2D, as an alternative to using high-density arrays when selected markers from large consortiums for a given complex trait or

  15. Optical anisotropy in type-II quantum wells on high-index substrates

    SciTech Connect

    Kawazu, Takuya

    2014-02-07

    Optical anisotropy in type-II quantum wells (QWs) on high-index (11n) substrates is studied theoretically. By solving 6 × 6 Luttinger-Kohn Hamiltonian, we analyze GaSb{sub x}As{sub 1-x}/In{sub x}Ga{sub 1-x}As type-II QWs and calculate the degree ρ of polarization at various compositions X. With increasing X, the preferential direction of the polarization is changed from [11-2/n] ([-110]) to [-110] ([11-2/n]) directions for n > 1 (n < 1). The optical anisotropy can be vanished even on high-index (11n) substrates by adjusting the composition X. These curious polarization properties are originated from the spatial separation of electrons and holes in the type-II QWs, where the overlap integral of their wave functions is strongly affected by the composition X.

  16. A specific collagen type II gene (COL2A1) mutation presenting as spondyloperipheral dysplasia

    SciTech Connect

    Zabel, B.; Hilbert, K.; Spranger, J.; Winterpacht, A.; Stoeb, H.; Superti-Furga, A.

    1996-05-03

    We report on a patient with a skeletal dysplasia characterized by short stature, spondylo-epiphyseal involvement, and brachydactyly E-like changes. This condition has been described as spondyloperipheral dysplasia and the few published cases suggest autosomal dominant inheritance with considerable clinical variability. We found our sporadic case to be due to a collagen type II defect resulting from a specific COL2A1 mutation. This mutation is the first to be located at the C-terminal outside the helical domain of COL2A1. A frameshift as consequence of a 5 bp duplication in exon 51 leads to a stop codon. The resulting truncated C-propeptide region seems to affect helix formation and produces changes of chondrocyte morphology, collagen type II fibril structure and cartilage matrix composition. Our case with its distinct phenotype adds another chondrodysplasia to the clinical spectrum of type II collagenopathies. 16 refs., 4 figs.

  17. TYPE II CEPHEID CANDIDATES. IV. OBJECTS FROM THE NORTHERN SKY VARIABILITY SURVEY

    SciTech Connect

    Schmidt, Edward G.

    2013-09-15

    We have obtained VR photometry of 447 Cepheid variable star candidates with declinations north of -14 Degree-Sign 30', most of which were identified using the Northern Sky Variability Survey (NSVS) data archive. Periods and other photometric properties were derived from the combination of our data with the NSVS data. Atmospheric parameters were determined for 81 of these stars from low-resolution spectra. The identification of type II Cepheids based on the data presented in all four papers in this series is discussed. On the basis of spectra, 30 type II Cepheids were identified while 53 variables were identified as cool, main sequence stars and 283 as red giants following the definitions in Paper III. An additional 30 type II Cepheids were identified on the basis of light curves. The present classifications are compared with those from the Machine-learned All Sky Automated Survey Classification Catalog for 174 stars in common.

  18. Effects of sodium diethyldithiocarbamate on type II pulmonary epithelial cells in vitro.

    PubMed

    Tátrai, E; Kováciková, Z; Karácsony, G; Hudák, A; Adamis, Z; Ungváry, G

    2001-02-01

    Dithiocarbamates (DDTC) are chemicals widely used in the form of pesticides, therapeutic and chelating agents, and scavengers. Since DDTC interfere with SH, Cu, and Zn enzymes due to chelating properties, it was of interest to clarify, in primary culture of type II alveolar pneumocytes, the effect of this compound upon enzymes of glutathione cycle, Cu, Zn-superoxide dismutase, and the membrane structure of cells. DDTC significantly inhibited the activity of superoxide dismutase and the activity of gamma-glutamyl transpeptidase, glutathione reductase, and alkaline phosphatase, whereas an increase in the activity of glutathione peroxidase was found. The membranes of pneumocytes type II were injured. Data show that DDTC adversely affected type II pneumocyte function and structure. PMID:11212946

  19. A Copernicus survey of Mg II emission in late-type stars

    NASA Technical Reports Server (NTRS)

    Weiler, E. J.; Oegerle, W. R.

    1979-01-01

    The behavior of Mg II emission in late-type stars is examined using scan data obtained with the Copernicus satellite. The luminosity in the Mg II k emission line was found to be closely related to stellar absolute magnitude, leading to the suggestion that such correlation may be very useful for future UV observations. The stellar surface flux in the k line was observed to be roughly constant or to decrease slowly with later spectral type, a finding which is then used to show that the pressure at the top of the chromosphere decreases with later spectral type, in agreement with the conclusions by McClintock et al. (1975). An asymmetry in the Mg II k line was noticed to be present in the available data for the stars later than K2-K5.

  20. Glycogen accumulation in alveolar type II cells in 3-methylindole--induced pulmonary edema in goats.

    PubMed Central

    Atwal, O. S.; Bray, T. M.

    1981-01-01

    The present study shows that intravenous infusion of 3-methylindole (3MI) induced acute pulmonary edema in goats. Edematous changes were seen in the alveoli and the interalveolar interstitium. At 72 hours after treatment, an accumulation of glycogen that had a pathognomonic appearance of alpha particles was observed in the alveolar Type II cells. A rich accumulation of glycogen particles and defective lamellar bodies containing triglycerides were the significant morphologic changes in the alveolar Type II cells. These findings suggest that massive glycogen deposition in the alveolar Type II cells is a defect that might interfere with surfactant production, further complicating the disease process. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6274198

  1. [The benefits of L-carnitine therapy in essential arterial hypertension with diabetes mellitus type II].

    PubMed

    Digiesi, V; Palchetti, R; Cantini, F

    1989-03-01

    Carnitine is a natural substance essential for the mitochondrial oxidation of long-chain fatty acids and therefore regulates the energy metabolism of the cells. Tissue carnitine levels are altered under diabetes mellitus or hypertension. The aim of this study was to evaluate the efficacy and tolerability of L-carnitine therapy in essential hypertension with diabetes mellitus type II. A clinical trial was performed in two homogeneous groups with essential hypertension and diabetes mellitus type II. L-carnitine was given orally, 2 g twice daily, for 45 weeks. In the group of patients treated with L-carnitine in comparison with control group cardiac arrhythmias, chiefly extrasystoles, some disorders of A-V conduction and some electrocardiographic signs of ischaemia stopped or diminished and symptoms, chiefly asthenia, significantly improved. No side effects were observed during the treatment. These results show that treatment with L-carnitine is useful and well tolerated in patients with essential hypertension and diabetes mellitus type II.

  2. TEMPORAL SPECTRAL SHIFT AND POLARIZATION OF A BAND-SPLITTING SOLAR TYPE II RADIO BURST

    SciTech Connect

    Du, Guohui; Chen, Yao; Lv, Maoshui; Kong, Xiangliang; Feng, Shiwei; Guo, Fan; Li, Gang

    2014-10-01

    In many type II solar radio bursts, the fundamental and/or the harmonic branches of the bursts can split into two almost parallel bands with similar spectral shapes and frequency drifts. However, the mechanisms accounting for this intriguing phenomenon remain elusive. In this study, we report a special band-splitting type II event in which spectral features appear systematically earlier on the upper band (with higher frequencies) than on the lower band (with lower frequencies) by several seconds. Furthermore, the emissions carried by the splitting band are moderately polarized with the left-hand polarized signals stronger than the right-hand ones. The polarization degree varies in a range of –0.3 to –0.6. These novel observational findings provide important constraints on the underlying physical mechanisms of band-splitting of type II radio bursts.

  3. Understanding the source: The nitrogen isotope composition of Type II mantle diamonds

    NASA Astrophysics Data System (ADS)

    Mikhail, Sami; Howell, Dan; Jones, Adrian; Milledge, Judith; Verchovsky, Sasha

    2010-05-01

    Diamonds can be broadly subdivided into 2 groups based on their nitrogen content; type I with > 10ppm nitrogen and type II with < 10ppm (1). Roughly 98 % of upper mantle diamonds are classified as type I, interestingly nearly all lower mantle diamonds are of type II (2). This study aims to identify the processes involved or source of type II diamonds from several localities by measuring their carbon and nitrogen stable isotope compositions simultaneously for the first time. Samples have been categorised as type II using Fourier transform infra-red (FTIR) analysis. The carbon and nitrogen isotopes as well as additional nitrogen content data have been acquired using a custom made a hi-sensitivity gas sourced mass spectrometer built and housed at the Open University, UK. There are two ways in which we can model the petrogenesis of type II diamonds. 1- During diamond growth nitrogen can be incorporated into diamond as a compatible element in a closed system and therefore the N/C ratio in the source can be depleted by Rayleigh fractionation as the first diamonds to crystallise will partition nitrogen atoms into their lattice as a 1:1 substitution for carbon atoms (type I diamonds). However nitrogen may behave as an incompatible element in diamond (and be a compatible element in the metasomatic fluid), this coupled with an open system would lead to the removal of nitrogen by the metasomatic fluids, thus causing the source to progressively become depleted in nitrogen. Continued diamond crystallization in either system will produce diamonds with ever decreasing nitrogen concentrations with time, possibly to the point of them being almost nitrogen free. 2- It is conceivable that type I & II diamonds found in the same deposit and sharing a common paragenesis (eclogitic or peridotitic) may have formed from different metasomatic fluids in separate diamond forming events. The latter has been proposed for samples from the Cullinan mine (South Africa) based on their carbon

  4. Between types I and II: Intertype flux exotic states in thin superconductors

    NASA Astrophysics Data System (ADS)

    Córdoba-Camacho, W. Y.; da Silva, R. M.; Vagov, A.; Shanenko, A. A.; Aguiar, J. Albino

    2016-08-01

    The Bogomolnyi point separates superconductivity types I and II while itself hiding infinitely degenerate magnetic flux configurations, including very exotic states (referred to here as flux "monsters"). When the degeneracy is removed, the Bogomolnyi point unfolds into a finite, intertype domain in the phase diagram between types I and II. One can expect that in this case the flux monsters can escape their "prison" at the Bogomolnyi point, occupying the intertype domain and shaping its internal structure. Our calculations reveal that such exotic flux distributions are indeed stable in the intertype regime of thin superconductors made of a type-I material, where the Bogomolnyi degeneracy is removed by stray magnetic fields. They can be classified into three typical patterns that are qualitatively different from those in types I and II: superconducting islands separated by vortex chains; stripes/worms/labyrinths patterns; and mixtures of giant vortices and vortex clusters. Our findings shed light on the problem of the interchange between types I and II, raising important questions on the completeness of the textbook classification of the superconductivity types.

  5. Evaluation of Coronal Shock Wave Velocities from the II Type Radio Bursts Parameters

    NASA Astrophysics Data System (ADS)

    Galanin, V. V.; Isaeva, E. A.; Kravetz, R. O.

    The work presents the results of research of connection between the coronal shock waves and the parameters of type II (mII) meter-decameter bursts in 25-180 MHz band for 66 solar proton events. The velocities of coronal shock waves for this two cases where determined. In the first case the velocities of the shock waves was evaluated according to the Newkirck model and in the second case - directly from the type II radio burst parameters. The calculated values of shock waves velocity was compared with the same velocity values that is published on NGDC site. The comparative analysis showed that precision of coronal shock waves velocity estimation which gets directly from type II radio bursts parameters was higher than the same one which used the Newkirck model. Research showed that there is exist the sufficiently strong connection between the shock wave velocity and the delay of type II burst intensity maximum on the second harmonica. Correlation coefficient between the studied parameters was equal to ≍ 0.65.

  6. Recurrence of achondrogenesis type II within the same family: evidence for germline mosaicism.

    PubMed

    Faivre, Laurence; Le Merrer, Martine; Douvier, Serges; Laurent, Nicole; Thauvin-Robinet, Christel; Rousseau, Thierry; Vereecke, Inge; Sagot, Paul; Delezoide, Anne-Lise; Coucke, Paul; Mortier, Geert

    2004-04-30

    Achondrogenesis type II is a lethal skeletal dysplasia caused by new dominant mutations within the type II collagen gene (COL2A1). Here we report on two pregnancies of a healthy, nonconsanguineous young couple. In the first pregnancy, severe micromelia and generalized edema were noted on ultrasound at 21 weeks' gestation. Clinical, radiological, and histological evaluation of the fetus after termination of the pregnancy showed typical findings of achondrogenesis type II. In the second pregnancy, fetal hygroma was noted at 11 weeks' gestation. Similar clinical, radiographic, and histologic findings were observed in the second fetus, suggesting the recurrence of achondrogenesis II within this family. Molecular analysis of genomic DNA extracted from amniotic cells of the second fetus revealed heterozygosity for a 1340G > A missense mutation (G316D) in the COL2A1 gene. This mutation was not found in the parents. Although, we could not evaluate the presence of this mutation in the first fetus, we strongly believe that our data are in favor of germline mosaicism as the most likely explanation for the recurrence of type II achondrogenesis in both sibs. PMID:15054848

  7. Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury

    SciTech Connect

    Skillrud, D.M.; Martin, W.J.

    1984-06-01

    Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggest the alveolar epithelial cells (types I and II) are specific targets of paraquat toxicity. This study used /sup 51/Cr-labeled type II cells to demonstrate that paraquat (10-5 M) resulted in type II cell injury in vitro, independent of interacting immune effector agents. With /sup 51/Cr release expressed as the cytotoxic index (Cl), type II cell injury was found to accelerate with increasing paraquat concentrations (10(-5) M, 10(-4) M, and 10(-3) M, resulting in a Cl of 12.5 +/- 2.2, 22.8 +/- 1.8, and 35.1 +/- 1.9, respectively). Paraquat-induced cytotoxicity (10(-4) M, with a Cl of 22.8 +/- 1.8) was effectively reduced by catalase 1,100 U/ml (Cl 8.0 +/- 3.2, p less than 0.001), superoxide dismutase, 300 U/ml (Cl 17.4 +/- 1.7, p less than 0.05), alpha tocopherol, 10 micrograms/ml (Cl 17.8 +/- 1.6, p less than 0.05). Paraquat toxicity (10(-3) M) was potentiated in the presence of 95% O2 with an increase in Cl from 31.1 +/- 1.7 to 36.4 +/- 2.3 (p less than 0.05). Paraquat-induced type II cell injury was noted as early as 4 h incubation by electron microscopic evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. Thus, this in vitro model indicates that paraquat-induced type II cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants, and potentiated by hyperoxia.

  8. Investigating the Conditions of the Formation of a Type II Radio Burst on 2014 January 8

    NASA Astrophysics Data System (ADS)

    Su, W.; Cheng, X.; Ding, M. D.; Chen, P. F.; Ning, Z. J.; Ji, H. S.

    2016-10-01

    It is believed that type II radio bursts are generated by shock waves. In order to understand the generation conditions of type II radio bursts, we analyze the physical parameters of a shock front. The type II radio burst we selected was observed by the Siberian Solar Radio Telescope (SSRT) and Learmonth radio station and was associated with a limb coronal mass ejection (CME) occurring on 2014 January 8 observed by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. The evolution of the CME in the inner corona presents a double-layered structure that propagates outward. We fit the outer layer (OL) of the structure with a partial circle and divide it into seven directions from ‑45° to 45° with an angular separation of 15°. We measure the OL speed along the seven directions and find that the speed in the direction of ‑15° with respect to the central direction is the fastest. We use the differential emission measure method to calculate the physical parameters at the OL at the moment when the type II radio burst was initiated, including the temperature (T), emission measure (EM), temperature ratio ({T}d/{T}{{u}}), compression ratio (X), and Alfvén Mach number (M A). We compare the quantities X and M A to those obtained from band-splitting in the radio spectrum, and find that this type II radio burst is generated at a small region of the OL that is located at the sector in the 45° direction. The results suggest that the generation of type II radio bursts (shocks) requires larger values of X and M A rather than simply a higher speed of the disturbance.

  9. Newton’s second law, radiation reaction and type II Einstein-Maxwell fields

    NASA Astrophysics Data System (ADS)

    Newman, Ezra T.

    2011-12-01

    Considering perturbations of the Reissner-Nordström metric while keeping the perturbations in the class of type II Einstein-Maxwell metrics, we perform a spherical harmonic expansion of all the variables up to the quadrupole term. This leads to rather surprising results. Referring to the source of the metric as a type II particle (analogous to referring to a Schwarzschild-Reissner-Nordström or Kerr-Newman particle), we see immediately that the Bondi momentum of the particle takes the classical form of mass times velocity plus an electromagnetic radiation reaction term, while the Bondi mass loss equation becomes the classical gravitational and electromagnetic (electric and magnetic) dipole and quadrupole radiation. The Bondi momentum loss equation turns into Newton’s second law of motion containing the Abraham-Lorentz-Dirac radiation reaction force plus a momentum recoil (rocket) force, while the reality condition on the Bondi mass aspect yields the conservation of angular momentum. Two things must be pointed out: (1) these results, (equations of motion, etc) take place, not in the spacetime of the type II metric but in an auxiliary space referred to as {H}-space, whose physical meaning is rather obscure and (2) this analysis of the type II field equations is a very special case of a similar analysis of the general asymptotically flat Einstein-Maxwell equations. Although the final results are similar (though not the same), the analysis uses different equations (specifically, the type II field equations) and is vastly simpler than the general case. Without a great deal of the technical structures needed in the general case, one can see rather easily where the basic results reside in the type II field equations.

  10. Exciton binding energies and the valence-band offset in mixed type-I--type-II strained-layer superlattices

    SciTech Connect

    Peyla, P.; Merle d'Aubigne, Y.; Wasiela, A.; Romestain, R.; Mariette, H. ); Sturge, M.D. ); Magnea, N.; Tuffigo, H. )

    1992-07-15

    Strained CdTe-Cd{sub 1{minus}{ital x}}Zn{sub {ital x}}Te superlattices are of mixed type: electrons and heavy holes are confined to the CdTe layers (type I) while light holes are confined to the Cd{sub 1{minus}{ital x}}Zn{sub {ital x}}Te layers (type II). In this paper we calculate the exciton binding energy (EBE) as a function of superlattice period for both type-I (spatially direct) and type-II (spatially indirect) excitons. For the heavy-hole (type-I) exciton the binding energy is larger than the bulk value, and varies only slowly with the period down to small periods, where the exciton acquires a three-dimensional character and our calculation breaks down. For the light-hole (type-II) exciton the binding energy at large period is much smaller, due to the spatial separation of electron and hole. As the period decreases, the binding energy increases steadily to reach its bulk value for vanishingly small period. Given the EBE's, we can fit the already published data on the exciton transition energies with a single adjustable parameter, the average valence-band offset'' (averaged over the heavy and light holes). This is the algebraic sum of the chemical-offset and the hydrostatic-strain contribution, and is found to be (2{plus minus}4)% of the difference in band gap between the barrier and well. This value lies in the range predicted theoretically.

  11. Type II Activation of Macrophages and Microglia by Immune Complexes Enhances Th17 Biasing in an IL-6-Independent Manner

    PubMed Central

    Stone, Sarrabeth; La Flamme, Anne Camille

    2016-01-01

    Macrophages can be activated into several distinct activation states. One of these states, type II activation, has a regulatory phenotype characterized by decreased IL-12 and increased IL-10, and has been shown to bias naïve CD4+ T cells to a Th2 response. Microglia, the resident macrophage-like cells in the central nervous system (CNS), are important contributors to neuroinflammation and, thus, we investigated if type II activated microglia could bias CD4+ T cell responses in a similar manner as type II activated macrophages. Using immune complex ligation in the presence of LPS to induce type II activation, we found that both type II macrophages and type II microglia biased CD4+ T cell responses in vitro to express increased levels of IL-17A and CD124. The enhanced IL-17A production occurred independently of IL-6, and IL-10 and IL-12, which were key regulators of IFN-γ production, but were not involved in the increased IL-17A. Finally, we found that another type II-activating compound, glatiramer acetate, did not bias CD4+ T cells to produce enhanced IL-17A. Taken together, this study demonstrates that microglia can be type II activated and, similarly to type II macrophages, can bias CD4+ T cell responses; however, depending on the type II stimulus, the effect on CD4+ T cell subset differentiation may vary. PMID:27732670

  12. Orocardiodigital syndrome: an oral-facial-digital type II variant associated with atrioventricular canal.

    PubMed Central

    Digilio, M C; Marino, B; Giannotti, A; Dallapiccola, B

    1996-01-01

    We report on a patient with a constellation of anomalies including hamartomas of the tongue, polysyndactyly, and atrioventricular canal. A similar association has been previously described by Orstavik et al in two sibs. The clinical spectrum of the oralfacial-digital syndrome (OFDS) type II includes all these features. In particular, congenital heart defect, mainly atrioventricular canal, has been described in a few cases. It has been previously suggested that these latter patients may be affected by a variant of OFDS type II. We propose to distinguish this orocardiodigital variant and point out the association of the syndrome with atrioventricular canal. Images PMID:8733055

  13. Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

    PubMed

    Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

    2004-12-01

    Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

  14. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

    PubMed

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  15. Relation Between Type II Bursts and CMEs Inferred from STEREO Observations

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Thompson, W.; Davila, J.; Kaiser, M.; Yashiro, S.; Maelekae, P.; Michalek, G.; Bougret, J.-L.; Howard, R. A.

    2009-01-01

    The inner coronagraph (COR1) of the Solar Terrestrial Relations Observatory (STEREO) mission has made it possible to observe CMEs in the spatial domain overlapping with that of the metric type II radio bursts. The type II bursts were associated with generally weak flares (mostly B and C class soft X-ray flares), but the CMEs were quite energetic. Using CME data for a set of type II bursts during the declining phase of solar cycle 23, we determine the CME height when the type II bursts start, thus giving an estimate of the heliocentric distance at which CME-driven shocks form. This distance has been determined to be approx. 1.5Rs (solar radii), which coincides with the distance at which the Alfven speed profile has a minimum value.We also use type II radio observations from STEREO/WAVES and Wind/WAVES observations to show that CMEs with moderate speed drive either weak shocks or no shock at all when they attain a height where the Alfven speed peaks (approx. 3Rs - 4Rs). Thus the shocks seem to be most efficient in accelerating electrons in the heliocentric distance range of 1.5Rs to 4Rs. By combining the radial variation of the CME speed in the inner corona (CME speed increase) and interplanetary medium (speed decrease) we were able to correctly account for the deviations from the universal drift-rate spectrum of type II bursts, thus confirming the close physical connection between type II bursts and CMEs. The average height (approx 1.5Rs) of STEREO CMEs at the time of type II bursts is smaller than that (2.2Rs) obtained for SOHO (Solar and Heliospheric Observatory) CMEs. We suggest that this may indicate, at least partly, the density reduction in the corona between the maximum and declining phases, so a given plasma level occurs closer to the Sun in the latter phase. In two cases, there was a diffuse shock-like feature ahead of the main body of the CME, indicating a standoff distance of 1Rs - 2Rs by the time the CME left the LASCO field of view.

  16. Relation Between Type II Bursts and CMEs Inferred from STEREO Observations

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Thompson, W.; Davila, J.; Kaiser, M. L.; Yashiro, S.; Maekelae, P.; Michalek, G.; Bougeret, J.-L.; Hoawrd, R. A.

    2010-01-01

    The inner coronagraph (COR1) of the Solar Terrestrial Relations Observatory (STEREO) mission has made it possible to observe coronal mass ejections (CMEs) a in the spatial domain overlapping with that of the metric type II radio bursts. The type II bursts were associated with generally weak flares (mostly B and C class soft X-ray flares), but the CMEs were quite energetic. Using CME data for a set of type II bursts during the declining phase of solar cycle 23, we determine the CME height when the type II bursts start, thus giving an estimate of the heliocentric distance at which CME-driven shocks form. This distance has been determined to be approximately 1.5Rs (solar radii), which coincides with the distance at which the Alfv?n speed profile has a minimum value. We also use type II radio observations from STEREO/WAVES and Wind/WAVES observations to show that CMEs with moderate speed drive either weak shocks or no shock at all when they attain a height where the Alfv?n speed peaks (?3Rs ? 4Rs). Thus the shocks seem to be most efficient in accelerating electrons in the heliocentric distance range of 1.5Rs to 4Rs. By combining the radial variation of the CME speed in the inner corona (CME speed increase) and interplanetary medium (speed decrease) we were able to correctly account for the deviations from the universal drift-rate spectrum of type II bursts, thus confirming the close physical connection between type II bursts and CMEs. The average height (approximately 1.5 Rs) of STEREO CMEs at the time of type II bursts is smaller than that (2.2 Rs) obtained for SOHO (Solar and Heliospheric Observatory) CMEs. We suggest that this may indicate, at least partly, the density reduction in the corona between the maximum and declining phases, so a given plasma level occurs closer to the Sun in the latter phase. In two cases, there was a diffuse shock-like feature ahead of the main body of the CME, indicating a standoff distance of 1Rs - 2Rs by the time the CME left the LASCO

  17. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

    PubMed

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  18. Erythrocyte membrane analysis for type II diabetes detection using Raman spectroscopy in high-wavenumber region

    NASA Astrophysics Data System (ADS)

    Lin, Jinyong; Zeng, Yongyi; Lin, Juqiang; Wang, Jing; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

    2014-03-01

    Raman spectroscopy was employed to detect lipid variation occurring in type II diabetic erythrocyte membrane (EM) without using exogenous reagents. In high-wavenumber (HW) region, significant Raman spectral differences between diabetic and normal EM are observed at 2850, 2873, 2885, 2935, and 2965 cm-1, which are mainly related to lipid in EM. Based on principal component analysis, the diagnostic accuracy of HW region for diabetes detection is 98.8%, which is much higher than that of low-wavenumber region (82.9%). The results suggest that EM HW Raman region has great promise for the reagent-free and non-invasive detection of type II diabetes.

  19. Antimicrobial activity of pantothenol against staphylococci possessing a prokaryotic type II pantothenate kinase.

    PubMed

    Chohnan, Shigeru; Murase, Misa; Kurikawa, Kota; Higashi, Kodai; Ogata, Yuta

    2014-01-01

    Pantothenol is a provitamin of pantothenic acid (vitamin B5) that is widely used in healthcare and cosmetic products. This analog of pantothenate has been shown to markedly inhibit the phosphorylation activity of the prokaryotic type II pantothenate kinase of Staphylococcus aureus, which catalyzes the first step of the coenzyme A biosynthetic pathway. Since type II enzymes are found exclusively in staphylococci, pantothenol suppresses the growth of S. aureus, S. epidermidis, and S. saprophyticus, which inhabit the skin of humans. Therefore, the addition of this provitamin to ointment and skincare products may be highly effective in preventing infections by opportunistic pathogens. PMID:24759689

  20. Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase

    PubMed Central

    2014-01-01

    A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein–ligand X-ray crystallography and incorporation of a slender linkage capable of bypassing a large gate-keeper residue, thus enabling design of molecules accessing both hinge and induced pocket regions. Optimization of an initial hit led to the identification of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK. PMID:25589926

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

    PubMed

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

    2013-01-01

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

  2. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns.

    PubMed

    Altman, R; Harrich, D; Garcia, J A; Gaynor, R B

    1988-04-01

    Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, we performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.

  3. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    PubMed Central

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  4. Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells

    SciTech Connect

    Dobbs, L.G.; Wright, J.R.; Hawgood, S.; Gonzalez, R.; Venstrom, K.; Nellenbogen, J.

    1987-02-01

    Pulmonary surfactant is synthesized and secreted by alveolar type II cells. Radioactive phosphatidylcholine has been used as a marker for surfactant secretion. The authors report findings that suggest that surfactant inhibits secretion of /sup 3/H-labeled phosphatidylcholine by cultured rat type II cells. The lipid components and the surfactant protein group of M/sub r/ 26,000-36,000 (SP 26-36) inhibit secretion to different extents. Surfactant lipids do not completely inhibit release; in concentrations of 100 ..mu..g/ml, lipids inhibit stimulated secretion by 40%. SP 26-36 inhibits release with an EC/sub 50/ of 0.1 ..mu..g/ml. At concentrations of 1.0 ..mu..g/ml, SP 26-36 inhibits basal secretion and reduces to basal levels secretion stimulated by terbutaline, phorbol 12-myristate 13-acetate, and the ionophore A23187. The inhibitory effect of SP 26-36 can be blocked by washing type II cells after adding SP 26-36, by heating the proteins to 100/sup 0/C for 10 min, by adding antiserum specific to SP 26-36, or by incubating cells in the presence of 0.2 mM EGTA. SP 26-36 isolated from canine and human sources also inhibits phosphatidylcholine release from rat type II cells. Neither type I collagen nor serum apolipoprotein A-1 inhibits secretion. These findings are compatible with the hypothesis that surfactant secretion is under feedback regulatory control.

  5. Altered lipid synthesis in type II pneumonocytes exposed to lung surfactant

    SciTech Connect

    Bleasdale, J.E.; Thakur, N.R.

    1986-05-01

    Uptake of lung surfactant by isolated type II cells was accompanied by decreased incorporation of (/sup 3/H)choline, (/sup 14/C)-palmitate and (/sup 14/C)acetate into phospholipids. Inhibition of incorporation of radiolabeled precursors, like uptake of surfactant, was half-maximal at approximately 0.1 ..mu..mol surfactant lipid P/ml, and was not due to altered specific radioactivities of intracellular precursor pools. Activity of DHAP acyltransferase, but not G-3-P acyltransferase, was decreased in type II cells exposed to surfactant. This was reflected in a decreased /sup 14/C//sup 3/H ratio in total lipids synthesized when cells incubated with (U-/sup 14/C)glycerol and (2-/sup 3/H)glycerol were exposed to surfactant. Disaturated phosphatidylcholine, disaturated phosphatidylglycerol and cholesterol (individually or mixed) did not mimic the inhibition of precursor incorporation observed with whole surfactant. In contrast, an apoprotein fraction isolated from surfactant inhibited the incorporation of (/sup 3/H)choline into lipids by type II cells. Inhibitory activity of the apoprotein fraction (either alone or mixed with lipids) was half-maximal at approximately 0.5 ..mu..g protein/ml, and was labile to heat and to trypsin. Lipid synthesis in some other cell types (but not all) was also influenced by extracellular surfactant. These data support the proposition that synthesis of surfactant lipids is inhibited in type II cells that are taking up extracellular surfactant.

  6. β-Hemolytic Streptococci with Group A and Type II Carbohydrate Antigens1

    PubMed Central

    Jablon, James M.; Brust, Betty; Saslaw, Milton S.

    1965-01-01

    Jablon, James M. (National Children's Cardiac Hospital, Miami, Fla.), Betty Brust, and Milton S. Saslaw. β-Hemolytic streptococci with group A and type II carbohydrate antigens. J. Bacteriol. 89:529–534. 1965.—Ten strains of β-hemolytic streptococci with unusual somatic antigens were isolated from excised tonsils or throat cultures or both. Acid extracts of these strains reacted with commercial group A and group F antisera, but gave no reaction when tested with 35 type-specific group A antisera. Serum cross-absorption and agar-gel diffusion studies established the identity of the reactive antigens as the specific carbohydrates of group A and of type II. The latter antigen has been found in many strains of group F streptococci. The organisms do not possess the group-specific carbohydrate of group F, and the reaction with the commercial group F antiserum is due to the presence of type II antibody in the antiserum. The organisms give a stronger reaction to fluorescein-conjugated type II antiserum than to group A. However, the organisms have only one group-specific carbohydrate, that of group A, and, tentatively, should be classified as such. Images PMID:14255723

  7. Angiotensin II centrally induces frequent detrusor contractility of the bladder by acting on brain angiotensin II type 1 receptors in rats

    PubMed Central

    Kawamoto, Bunya; Shimizu, Shogo; Shimizu, Takahiro; Higashi, Youichirou; Honda, Masashi; Sejima, Takehiro; Saito, Motoaki; Takenaka, Atsushi

    2016-01-01

    Angiotensin (Ang) II plays an important role in the brain as a neurotransmitter and is involved in psychological stress reactions, for example through activation of the sympatho-adrenomedullary system. We investigated the effects of centrally administered Ang II on the micturition reflex, which is potentially affected by the sympatho-adrenomedullary system, and brain Ang II receptors in urethane-anesthetized (1.0 g/kg, intraperitoneally) male rats. Central administration of Ang II (0.01, 0.02, and 0.07 nmol per rat, intracerebroventricularly, icv) but not vehicle rapidly and dose-dependently decreased the urinary bladder intercontraction interval, without altering the bladder detrusor pressure. Central administration of antagonists of Ang II type 1 but not type 2 receptors inhibited the Ang II-induced shortening of intercontraction intervals. Administration of the highest dose of Ang II (0.07 nmol per rat, icv) but not lower doses (0.01 and 0.02 nmol per rat, icv) elevated the plasma concentration of adrenaline. Bilateral adrenalectomy reduced Ang II-induced elevation in adrenaline, but had no effect on the Ang II-induced shortening of the intercontraction interval. These data suggest that central administration of Ang II increases urinary frequency by acting on brain Ang II type 1 receptors, independent of activation of the sympatho-adrenomedullary system. PMID:26908391

  8. Intersection of RNA Processing and the Type II Fatty Acid Synthesis Pathway in Yeast Mitochondria▿

    PubMed Central

    Schonauer, Melissa S.; Kastaniotis, Alexander J.; Hiltunen, J. Kalervo; Dieckmann, Carol L.

    2008-01-01

    Distinct metabolic pathways can intersect in ways that allow hierarchical or reciprocal regulation. In a screen of respiration-deficient Saccharomyces cerevisiae gene deletion strains for defects in mitochondrial RNA processing, we found that lack of any enzyme in the mitochondrial fatty acid type II biosynthetic pathway (FAS II) led to inefficient 5′ processing of mitochondrial precursor tRNAs by RNase P. In particular, the precursor containing both RNase P RNA (RPM1) and tRNAPro accumulated dramatically. Subsequent Pet127-driven 5′ processing of RPM1 was blocked. The FAS II pathway defects resulted in the loss of lipoic acid attachment to subunits of three key mitochondrial enzymes, which suggests that the octanoic acid produced by the pathway is the sole precursor for lipoic acid synthesis and attachment. The protein component of yeast mitochondrial RNase P, Rpm2, is not modified by lipoic acid in the wild-type strain, and it is imported in FAS II mutant strains. Thus, a product of the FAS II pathway is required for RNase P RNA maturation, which positively affects RNase P activity. In addition, a product is required for lipoic acid production, which is needed for the activity of pyruvate dehydrogenase, which feeds acetyl-coenzyme A into the FAS II pathway. These two positive feedback cycles may provide switch-like control of mitochondrial gene expression in response to the metabolic state of the cell. PMID:18779316

  9. A novel splicing mutation alters DSPP transcription and leads to dentinogenesis imperfecta type II.

    PubMed

    Zhang, Jun; Wang, Jiucun; Ma, Yanyun; Du, Wenqi; Zhao, Siyang; Zhang, Zuowei; Zhang, Xiaojiao; Liu, Yue; Xiao, Huasheng; Wang, Hongyan; Jin, Li; Liu, Jie

    2011-01-01

    Dentinogenesis imperfecta (DGI) type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP) gene were revealed to be the causation of DGI type II (DGI-II). In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C) lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases.

  10. VizieR Online Data Catalog: UBVRIz light curves of 51 Type II supernovae (Galbany+, 2016)

    NASA Astrophysics Data System (ADS)

    Galbany, L.; Hamuy, M.; Phillips, M. M.; Suntzeff, N. B.; Maza, J.; de Jaeger, T.; Moraga, T.; Gonzalez-Gaitan, S.; Krisciunas, K.; Morrell, N. I.; Thomas-Osip, J.; Krzeminski, W.; Gonzalez, L.; Antezana, R.; Wishnjewski, M.; McCarthy, P.; Anderson, J. P.; Gutierrez, C. P.; Stritzinger, M.; Folatelli, G.; Anguita, C.; Galaz, G.; Green, E. M.; Impey, C.; Kim, Y.-C.; Kirhakos, S.; Malkan, M. A.; Mulchaey, J. S.; Phillips, A. C.; Pizzella, A.; Prosser, C. F.; Schmidt, B. P.; Schommer, R. A.; Sherry, W.; Strolger, L.-G.; Wells, L. A.; Williger, G. M.

    2016-08-01

    This paper presents a sample of multi-band, visual-wavelength light curves of 51 type II supernovae (SNe II) observed from 1986 to 2003 in the course of four different surveys: the Cerro Tololo Supernova Survey, the Calan Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernovae Survey (CATS). Near-infrared photometry and optical spectroscopy of this set of SNe II will be published in two companion papers. A list of the SNe II used in this study is presented in Table1. The first object in our list is SN 1986L and it is the only SN observed with photoelectric techniques (by M.M.P and S.K., using the Cerro Tololo Inter-American Observatory (CTIO) 0.9m equipped with a photometer and B and V filters). The remaining SNe were observed using a variety of telescopes equipped with CCD detectors and UBV(RI)KCz filters (see Table5). The magnitudes for the photometric sequences of the 51 SNe II are listed in Table4. In every case, these sequences were derived from observations of Landolt standards (see Appendix D in Hamuy et al. 2001ApJ...558..615H for the definition of the z band and Stritzinger et al. 2002AJ....124.2100S for the description of the z-band standards). Table5 lists the resulting UBVRIz magnitudes for the 51 SNe. (3 data files).

  11. Spatial modelling of type II diabetes outcomes: a systematic review of approaches used

    PubMed Central

    Baker, Jannah; White, Nicole; Mengersen, Kerrie

    2015-01-01

    With the rising incidence of type II diabetes mellitus (DM II) worldwide, methods to identify high-risk geographical areas have become increasingly important. In this comprehensive review following Cochrane Collaboration guidelines, we outline spatial methods, outcomes and covariates used in all spatial studies involving outcomes of DM II. A total of 1894 potentially relevant citations were identified. Studies were included if spatial methods were used to explore outcomes of DM II or type I and 2 diabetes combined. Descriptive tables were used to summarize information from included studies. Ten spatial studies conducted in the USA, UK and Europe met selection criteria. Three studies used Bayesian generalized linear mixed modelling (GLMM), three used classic generalized linear modelling, one used classic GLMM, two used geographic information systems mapping tools and one compared case:provider ratios across regions. Spatial studies have been effective in identifying high-risk areas and spatial factors associated with DM II outcomes in the USA, UK and Europe, and would be useful in other parts of the world for allocation of additional services to detect and manage DM II early. PMID:26543572

  12. Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules

    PubMed Central

    Park, Yoon-Kyung; Jung, Sundo; Park, Se-Ho

    2016-01-01

    In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-Aq in a murine CIA model. We found that recombinant I-Aq/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-Aq/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis. [BMB Reports 2016; 49(6): 331-336 PMID:26779996

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

    PubMed

    Lengil, Tamar; Gancz, Dana; Gilboa, Lilach

    2015-03-01

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

  14. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development

    PubMed Central

    Vaughan, Ashley M; O'Neill, Matthew T; Tarun, Alice S; Camargo, Nelly; Phuong, Thuan M; Aly, Ahmed S I; Cowman, Alan F; Kappe, Stefan H I

    2009-01-01

    Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of FabB/F, a critical enzyme in fatty acid synthesis, did not affect parasite blood stage replication, mosquito stage development and initial infection in the liver. This was confirmed by knockout of FabZ, another critical FAS II enzyme. However, FAS II-deficient Plasmodium yoelii liver stages failed to form exo-erythrocytic merozoites, the invasive stage that first initiates blood stage infection. Furthermore, deletion of FabI in the human malaria parasite Plasmodium falciparum did not show a reduction in asexual blood stage replication in vitro. Malaria parasites therefore depend on the intrinsic FAS II pathway only at one specific life cycle transition point, from liver to blood. PMID:19068099

  15. A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation

    PubMed Central

    Mitani, Marie; Furuichi, Munehiro; Narumi, Satoshi; Hasegawa, Tomonobu; Chiga, Motoko; Uchida, Shinichi; Sato, Seiji

    2016-01-01

    Abstract. Pseudohypoaldosteronism type II (PHA II) is a renal tubular disease that causes hyperkalemia, hypertension, and metabolic acidosis. Mutations in four genes (WNK4, WNK1, KLHL3, and CUL3) are known to cause PHA II. We report a patient with PHA II carrying a KLHL3 mutation, who also had congenital hypopituitarism. The patient, a 3-yr-old boy, experienced loss of consciousness at age 10 mo. He exhibited growth failure, hypertension, hyperkalemia, and metabolic acidosis. We diagnosed him as having PHA II because he had low plasma renin activity with normal plasma aldosterone level and a low transtubular potassium gradient. Further investigations revealed defective secretion of GH and gonadotropins and anterior pituitary gland hypoplasia. Genetic analyses revealed a previously known heterozygous KLHL3 mutation (p.Leu387Pro), but no mutation was detected in 27 genes associated with congenital hypopituitarism. He was treated with sodium restriction and recombinant human GH, which normalized growth velocity. This is the first report of a molecularly confirmed patient with PHA II complicated by congenital hypopituitarism. We speculate that both GH deficiency and metabolic acidosis contributed to growth failure. Endocrinological investigations will help to individualize the treatment of patients with PHA II presenting with growth failure. PMID:27780982

  16. Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families.

    PubMed

    Acevedo, A C; Santos, L J S; Paula, L M; Dong, J; MacDougall, M

    2009-01-01

    The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II (DGI-II) attending the Dental Anomalies Clinic in Brasilia, Brazil. Physical and oral examinations, as well as radiographic and histopathological analyses, were performed on 28 affected and unaffected individuals. Clinical, radiographic and histopathological analyses confirmed the diagnosis of DGI-II in 19 individuals. Pulp stones were observed in ground sections of several teeth in 2 families, suggesting that obliteration of pulp chambers and root canals results from the growth of these nodular structures. Mutational DSPP gene analysis of representative affected family members revealed 7 various non-disease-causing alterations in exons 1-4 within the dentin sialoprotein domain. Further longitudinal studies are necessary to elucidate the progression of pulpal obliteration in the DGI-II patients studied as well as the molecular basis of their disease.

  17. Central nervous system disorders and possible brain type carnitine palmitoyltransferase II deficiency.

    PubMed

    Ohtani, Y; Tomoda, A; Miike, T; Matsukura, M; Miyatake, M; Narazaki, O

    1994-01-01

    We describe two male infants with central nervous system disorders, i.e. infantile spasms in one and athetotic quadriplegia in the other, and with recurrent attacks of high plasma creatine kinase levels induced by viral infections. Although carnitine palmitoyltransferase I (CPT I) activity in biopsied muscle was normal in both cases, that of carnitine palmitoyltransferase II (CPT II) was decreased to 37% and 25% of the control value, respectively. Meanwhile, to determine whether or not and how CPT exists in the central nervous system (CNS), we studied animal brain tissues. CPT activity was demonstrated in almost all regions, especially in the brainstem, cerebellum and spinal cord. Although CPT deficiency can be classified into hepatic (CPT I) and muscular (CPT II) presentations, these data suggest that another symptomatology of CPT II deficiency with CNS involvement (brain type?) might exist. PMID:8048703

  18. Novel π-type vortex in a nanoscale extreme type-II superconductor: Induced by quantum-size effect

    NASA Astrophysics Data System (ADS)

    Huang, Haiyan; Liu, Qing; Zhang, Wenhui; Chen, Yajiang

    2016-11-01

    By numerically solving the Bogoliubov-de Gennes equations, we report a novel π-type vortex state whose order parameter near the core undergoes an extraordinary π-phase change for a quantum-confined extreme type-II s-wave superconductor. Its supercurrent behaves as the cube of the radial coordinate near the core, and its local density of states spectrum exhibits a significant negative-shifted zero-bias peak. Such π-type vortex state is induced by quantum-size effect, and can survive thermal smearing at temperatures up to a critical value Tτ. The Anderson's approximation indicates that the π-type vortex may remain stable under sufficiently week magnetic field in the case less deep in the type-II limit. Moreover, we find that its appearance is governed by the sample size and kFξ0 with kF the Fermi wave number and ξ0 the zero-temperature coherence length. Similar effects may be expected in quantum-confined ultracold superfluid Fermi gasses, or even high-Tc superconductors with proper kFξ0 value.

  19. TaIrTe4: A ternary type-II Weyl semimetal

    NASA Astrophysics Data System (ADS)

    Koepernik, K.; Kasinathan, D.; Efremov, D. V.; Khim, Seunghyun; Borisenko, Sergey; Büchner, Bernd; van den Brink, Jeroen

    2016-05-01

    In metallic condensed matter systems two different types of Weyl fermions can in principle emerge, with either a vanishing (type-I) or with a finite (type-II) density of states at the Weyl node energy. So far only WTe2 and MoTe2 were predicted to be type-II Weyl semimetals. Here we identify TaIrTe4 as a third member of this family of topological semimetals. TaIrTe4 has the attractive feature that it hosts only four well-separated Weyl points, the minimum imposed by symmetry. Moreover, the resulting topological surface states—Fermi arcs connecting Weyl nodes of opposite chirality—extend to about 1/3 of the surface Brillouin zone. This large momentum-space separation is very favorable for detecting the Fermi arcs spectroscopically and in transport experiments.

  20. Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier.

    PubMed

    Froud, Kristina E; Wong, Ann Chi Yan; Cederholm, Jennie M E; Klugmann, Matthias; Sandow, Shaun L; Julien, Jean-Pierre; Ryan, Allen F; Housley, Gary D

    2015-01-01

    The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses the gain of the 'cochlear amplifier' in each ear. Such efferent feedback is important for promoting discrimination of sounds in background noise, sound localization and protecting the cochleae from acoustic overstimulation. However, the sensory driver for the olivocochlear reflex is unknown. Here, we resolve this longstanding question using a mouse model null for the gene encoding the type III intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral ganglion neuron innervation of the outer hair cells, whereas innervation of the inner hair cells by type I spiral ganglion neurons was normal. Compared with Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent-mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice, demonstrating that outer hair cells and their type II afferents constitute the sensory drive for the olivocochlear efferent reflex.

  1. INTEGRAL FIELD SPECTROSCOPY OF SUPERNOVA EXPLOSION SITES: CONSTRAINING THE MASS AND METALLICITY OF THE PROGENITORS. II. TYPE II-P AND II-L SUPERNOVAE

    SciTech Connect

    Kuncarayakti, Hanindyo; Maeda, Keiichi; Doi, Mamoru; Morokuma, Tomoki; Hashiba, Yasuhito; Aldering, Greg; Arimoto, Nobuo; Pereira, Rui

    2013-08-01

    Thirteen explosion sites of Type II-P and II-L supernovae (SNe) in nearby galaxies have been observed using integral field spectroscopy, enabling both spatial and spectral study of the explosion sites. We used the properties of the parent stellar population of the coeval SN progenitor star to derive its metallicity and initial mass. The spectrum of the parent stellar population yields estimates of metallicity via the strong-line method and age via a comparison with simple stellar population models. These metallicity and age parameters are adopted for the progenitor star. Age, or lifetime of the star, was used to derive the initial (zero-age main sequence) mass of the star using comparisons with stellar evolution models. With this technique, we were able to determine the metallicities and initial masses of the SN progenitors in our sample. Our results indicate that some Type II SN progenitors may have been stars with masses comparable to those of SN Ib/c progenitors.

  2. Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis

    PubMed Central

    Zainudin, Sueziani Binte; Kaushik, Manish; Khor, Li Yan; Chng, Chiaw Ling

    2016-01-01

    Summary Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. Learning points Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment. Prompt diagnosis and therapy are important, as patients may deteriorate rapidly. Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy. This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h. Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery. PMID:27398220

  3. Bright but slow - Type II supernovae from OGLE-IV - implications for magnitude-limited surveys

    NASA Astrophysics Data System (ADS)

    Poznanski, D.; Kostrzewa-Rutkowska, Z.; Wyrzykowski, L.; Blagorodnova, N.

    2015-05-01

    We study a sample of 11 Type II supernovae (SNe) discovered by the OGLE-IV survey. All objects have well-sampled I-band light curves, and at least one spectrum. We find that two or three of the 11 SNe have a declining light curve, and spectra consistent with other SNe II-L, while the rest have plateaus that can be as short as 70 d, unlike the 100 d typically found in nearby galaxies. The OGLE SNe are also brighter, and show that magnitude-limited surveys find SNe that are different than usually found in nearby galaxies. We discuss this sample in the context of understanding Type II SNe as a class and their suggested use as standard candles.

  4. Electromyographic analysis of physical examination tests for type II superior labrum anterior-posterior lesions.

    PubMed

    Swaringen, Jennifer C; Mell, Amy G; Langenderfer, Joseph; LaScalza, Suzanne; Hughes, Richard E; Kuhn, John E

    2006-01-01

    Physical examination tests that place tension on the long head of the biceps may best reproduce symptoms in patients with type II superior labrum anterior-posterior (SLAP) lesions. The objective of this study is to compare the normalized electromyographic signal of the long head of the biceps for SLAP lesion physical examination tests. The active compression test, anterior-superior SLAP test, biceps load test II, biceps tension test, and pain provocation test were performed on 13 subjects while biceps electromyographic data were recorded. The active compression test and biceps tension test had significantly higher electromyographic signals than the other tests. We found no significant differences when comparing forearm supination and pronation within individual tests. Because the active compression and biceps tension tests maximize muscle activation on the long head of the biceps, they may be the best physical examination tests by which to identify type II SLAP lesions.

  5. Growth and Characteristics of Type-II InAs/GaSb Superlattice-Based Detectors

    NASA Technical Reports Server (NTRS)

    Khoshakhlagh, A.; Soibel, A.; Ting, D. Z.; Hoglund, L.; Nguyen, J.; Keo, S. A.; Liao, A.; Gunapala, S. D.

    2011-01-01

    We report on growth and device performance of infrared photodetectors based on type II InAs/Ga(In)Sb strain layer superlattices (SLs) using the complementary barrier infrared detector (CBIRD) design. The unipolar barriers on either side of the absorber in the CBIRD design in combination with the type-II InAs/GaSb superlattice material system are expected to outperform traditional III-V LWIR imaging technologies and offer significant advantages over the conventional II-VI material based FPAs. The innovative design of CBIRDS, low defect density material growth, and robust fabrication processes have resulted in the development of high performance long wave infrared (LWIR) focal plane arrays at JPL.

  6. ANESTHESIA MANAGEMENT IN AN INFANT WITH GLYCOGEN STORAGE DISEASE TYPE II (POMPE DISEASE).

    PubMed

    Al Atassi, Abdulaleem; Al Zughaibi, Nezar; Naeim, Anas; Al Basha, Abdulatif; Dimitriou, Vassilios

    2015-10-01

    Pompe or Glycogen Storage Disease type II (GSD-II) is a genetic disorder affecting both cardiac and skeletal muscle. Historically, patients with the infantile form usually die within the first year of life due to cardiac and respiratory failure. Recently a promising enzyme replacement therapy has resulted in improved clinical outcomes and a resurgence of elective anesthesia for these patients. Understanding the unique cardiac physiology in patients with GSD-II is essential to providing safe general anesthesia. Additional care in maximizing coronary perfusion pressure and minimizing arrhythmia risk must be given. For these reasons, it is recommended that anesthesia for infantile Pompe patients should specifically avoid propofol or high concentrations of sevoflurane and, instead, use an agent such as ketamine as the cornerstone for induction in order to better support coronary perfusion pressure and to avoid decreasing diastolic blood pressure (DBP) with vasodilatory agents. We present the anesthetic technique in a case of infantile type Pompe disease. PMID:26860026

  7. Pulmonary Alveolar Type II Epithelial Cells and Adult Respiratory Distress Syndrome

    PubMed Central

    Mason, Robert J.

    1985-01-01

    During the past ten years, functions of alveolar type II cells have been well characterized with isolated cells in vitro. Some of the functions were well known from studies in vivo, but others such as transepithelial sodium transport were unsuspected. A better understanding of this important pulmonary cell type improves our knowledge of the pathophysiology of adult respiratory distress syndrome and may in time lead to new therapeutic strategies. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:3909639

  8. Novel type-II material system for laser applications in the near-infrared regime

    SciTech Connect

    Berger, C. Möller, C.; Hens, P.; Fuchs, C.; Stolz, W.; Koch, S. W.; Ruiz Perez, A.

    2015-04-15

    The design and experimental realization of a type-II “W”-multiple quantum well heterostructure for emission in the λ > 1.2 μm range is presented. The experimental photoluminescence spectra for different excitation intensities are analyzed using microscopic quantum theory. On the basis of the good theory–experiment agreement,