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Sample records for factor-beta type iii

  1. Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

    NASA Technical Reports Server (NTRS)

    Ji, C.; Chen, Y.; McCarthy, T. L.; Centrella, M.

    1999-01-01

    Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

  2. The type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis

    PubMed Central

    Hill, Cynthia R.; Jacobs, Britni H.; Brown, Christopher B.; Barnett, Joey V.; Goudy, Steven L.

    2015-01-01

    Background Cleft palate occurs in up to 1:1000 live births and is associated with mutations in multiple genes. Palatogenesis involves a complex choreography of palatal shelf elongation, elevation, and fusion. Transforming growth factor β (TGFβ) and bone morphogenetic protein 2 (BMP2) canonical signaling is required during each stage of palate development. The type III TGFβ receptor (TGFβR3) binds all three TGFβ ligands and BMP2, but its contribution to palatogenesis is unknown. Results The role of TGFβR3 during palate formation was found to be during palatal shelf elongation and elevation. Tgfbr3-/- embryos displayed reduced palatal shelf width and height, changes in proliferation and apoptosis, and reduced vascular and osteoblast differentiation. Abnormal vascular plexus organization as well as aberrant expression of arterial (Notch1, Alk1), venous (EphB4), and lymphatic (Lyve1) markers was also observed. Decreased osteoblast differentiation factors (Runx2, alk phos, osteocalcin, col1A1, and col1A2) demonstrated poor mesenchymal cell commitment to the osteoblast lineage within the maxilla and palatal shelves in Tgfbr3-/- embryos. Additionally, in vitro bone mineralization induced by osteogenic medium (OM+BMP2) was insufficient in Tgfbr3-/- palatal mesenchyme, but mineralization was rescued by overexpression of TGFβR3. Conclusions These data reveal a critical, previously unrecognized role for TGFβR3 in vascular and osteoblast development during palatogenesis. PMID:25382630

  3. Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer

    PubMed Central

    2014-01-01

    Introduction There is a major need to better understand the molecular basis of triple negative breast cancer (TNBC) in order to develop effective therapeutic strategies. Using gene expression data from 587 TNBC patients we previously identified six subtypes of the disease, among which a mesenchymal-stem like (MSL) subtype. The MSL subtype has significantly higher expression of the transforming growth factor beta (TGF-β) pathway-associated genes relative to other subtypes, including the TGF-β receptor type III (TβRIII). We hypothesize that TβRIII is tumor promoter in mesenchymal-stem like TNBC cells. Methods Representative MSL cell lines SUM159, MDA-MB-231 and MDA-MB-157 were used to study the roles of TβRIII in the MSL subtype. We stably expressed short hairpin RNAs specific to TβRIII (TβRIII-KD). These cells were then used for xenograft tumor studies in vivo; and migration, invasion, proliferation and three dimensional culture studies in vitro. Furthermore, we utilized human gene expression datasets to examine TβRIII expression patterns across all TNBC subtypes. Results TβRIII was the most differentially expressed TGF-β signaling gene in the MSL subtype. Silencing TβRIII expression in MSL cell lines significantly decreased cell motility and invasion. In addition, when TβRIII-KD cells were grown in a three dimensional (3D) culture system or nude mice, there was a loss of invasive protrusions and a significant decrease in xenograft tumor growth, respectively. In pursuit of the mechanistic underpinnings for the observed TβRIII-dependent phenotypes, we discovered that integrin-α2 was expressed at higher level in MSL cells after TβRIII-KD. Stable knockdown of integrin-α2 in TβRIII-KD MSL cells rescued the ability of the MSL cells to migrate and invade at the same level as MSL control cells. Conclusions We have found that TβRIII is required for migration and invasion in vitro and xenograft growth in vivo. We also show that TβRIII-KD elevates

  4. Assignment of human transforming growth factor-{beta} type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively

    SciTech Connect

    Johnson, D.W.; Qumsiyeh, M.; Marchuk, D.A.; Benkhalifa, M.

    1995-07-20

    Transforming growth factor-{Beta} (TGF-{beta}) is a multifunctional cytokine, known to modulate several tissue development and repair processes, including cell differentiation, cell cycle progression, cellular migration, adhesion, and extracellular matrix production. The TGF-{beta} receptors and cell surface binding proteins mediate the diverse effects of TGF-{beta}. An endothelial cell-specific TGF-{beta} binding protein, endoglin, is mutated in hereditary hemorrhagic telangiectasia type 1, an autosomal dominant disorder of vascular dysplasia. Mutations in other TGF-{beta} binding protein genes may also lead to disease. We have used PCR with a cell hybrid DNA panel, and fluorescence in situ chromosomal hybridization (FISH), to localize two other TGF-{beta} receptor genes. These are the TGF-{beta} type I and type II receptors (also known as ALK-5 and betaglycan, respectively). The corresponding gene loci are designated TGFBR1 and TGFBR3. 10 refs., 1 fig., 1 tab.

  5. Regulation of type II transforming-growth-factor-beta receptors by protein kinase C iota.

    PubMed Central

    Chuang, Lea-Yea; Guh, Jinn-Yuh; Liu, Shu-Fen; Hung, Min-Yuan; Liao, Tung-Nan; Chiang, Tai-An; Huang, Jau-Shyang; Huang, Yu-Lun; Lin, Chi-Fong; Yang, Yu-Lin

    2003-01-01

    TGF-beta (transforming growth factor-beta) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-beta receptor (TbetaRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. We have elucidated the mechanism by using cultured Madin-Darby canine kidney cells. Enhancer assay and electrophoretic-mobility-shift assay were used to estimate the involvement of transcription factors. Western blotting and an in vitro kinase assay were used to evaluate the level and activity of protein kinase. We showed that glucose (100-900 mg/dl) induced an increase in mRNA level and promoter activity of TbetaRII (note: 'mg/dl' are the units commonly used in diabetes studies). The promoter region -209 to -177 appeared to contribute to positive transactivation of TbetaRII promoter by comparing five TbetaRII-promoter-CAT (chloramphenicol acetyl-transferase) plasmids. Moreover, the transcription factor AP-1 (activator protein 1) was significantly activated and specifically binds to TbetaRII promoter (-209 to -177). More importantly, we found that atypical PKC iota might be pivotal for high glucose-induced increase in both AP-1 binding and TbetaRII promoter activity. First, high glucose induced cytosolic translocation, activation and autophosphorylation of PKC iota. Secondly, antisense PKC iota expression plasmids attenuated high-glucose-induced increase in AP-1 binding and TbetaRII promoter activity; moreover, sense PKC iota expression plasmids enhanced these instead. Finally, we showed that antisense PKC iota expression plasmids might partly attenuate a high-glucose/TGF-beta1-induced increase in fibronectin. We conclude that PKC iota might mediate high-glucose-induced increase in TbetaRII promoter activity. In addition, antisense PKC iota expression plasmid effectively suppressed up-regulation of TbetaRII and

  6. The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

    PubMed Central

    Bhushan, A; Lin, H Y; Lodish, H F; Kintner, C R

    1994-01-01

    The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells. Images PMID:8196664

  7. Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5).

    PubMed

    Callahan, James F; Burgess, Joelle L; Fornwald, James A; Gaster, Laramie M; Harling, John D; Harrington, Frank P; Heer, Jag; Kwon, Chet; Lehr, Ruth; Mathur, A; Olson, Barbara A; Weinstock, Joseph; Laping, Nicholas J

    2002-02-28

    Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay. PMID:11855979

  8. Oncogenic Ki-ras confers a more aggressive colon cancer phenotype through modification of transforming growth factor-beta receptor III.

    PubMed

    Yan, Z; Deng, X; Friedman, E

    2001-01-12

    Transforming growth factor-beta1 (TGF-beta1) can act as a tumor suppressor or a tumor promoter depending on the characteristics of the malignant cell. Each of three Ki-ras(G12V) transfectants of HD6-4 colon cancer cells had been shown to be more aggressive in vivo than controls in earlier studies (Yan, Z., Chen, M., Perucho, M., and Friedman, E. (1997) J. Biol. Chem. 272, 30928-30936). We now show that stable expression of oncogenic Ki-ras(G12V) converts the HD6-4 colon cancer cell line from insensitive to TGF-beta1 to growth-promoted by TGF-beta1. Each of three Ki-ras(G12V) transfectants responded to TGF-beta1 by an increase in proliferation and by decreasing the abundance of the Cdk inhibitor p21 and the tumor suppressor PTEN, whereas each of three wild-type Ki-ras transfectants remained unresponsive to TGF-beta1. The wild-type Ki-ras transfectants lack functional TGF-beta receptors, whereas all three Ki-ras(G12V) transfectants expressed functional TGF-beta receptors that bound (125)I-TGF-beta1. The previous studies showed that in cells with wild-type Ki-ras, TGF-beta receptors were not mutated, and receptor proteins were transported to the cell surface, but post-translational modification of TGF-beta receptor III (TbetaRIII) was incomplete. We now show that the betaglycan form of TbetaRIII is highly modified following translation when transiently expressed in Ki-ras(G12V) cells, whereas no such post-translational modification of TbetaRIII occurs in control cells. Antisense oligonucleotides directed to Ki-Ras decreased both TbetaRIII post-translational modification in Ki-ras(G12V) cells and TGF-beta1 down-regulation of p21, demonstrating the direct effect of mutant Ras. Therefore, one mechanism by which mutant Ki-Ras confers a more aggressive tumor phenotype is by enhancing TbetaRIII post-translational modification. PMID:11029459

  9. Microsatellite mutation of type II transforming growth factor-beta receptor is rare in atherosclerotic plaques.

    PubMed

    Clark, K J; Cary, N R; Grace, A A; Metcalfe, J C

    2001-04-01

    A somatic mutation within a microsatellite polyA tract in the coding region of the type II transforming growth factor (TGF)-beta receptor gene was reported to occur in human atherosclerotic and restenotic lesions. This mutation occurs frequently in colorectal cancer with the replication error repair phenotype and results in loss of sensitivity to the growth inhibitory effects of TGF-beta in cells from the tumors. The mutation was proposed to account for the clonal expansion of vascular smooth muscle cells observed in atherosclerotic plaques, through loss of the growth inhibitory effect of TGF-beta. The frequency of the mutation and the extent of clonal expansion of the mutated cells have major implications for the mechanism of atherogenesis and therapeutic strategies. We analyzed a set of 22 coronary arterial and 9 aortic samples containing early to advanced atherosclerotic lesions for the mutation in the type II TGF-beta receptor polyA tract. Only 1 coronary arterial sample from an advanced lesion showed detectable amounts of the mutation, present at a low level (8% of the DNA sample). The data imply that the mutation occurs only at low frequency and is not a major mechanistic contributor to the development of atherosclerosis. PMID:11304472

  10. Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

    PubMed Central

    Santibanez, Juan F.

    2013-01-01

    Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer. PMID:23984088

  11. Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase.

    PubMed Central

    Marti, H. P.; Lee, L.; Kashgarian, M.; Lovett, D. H.

    1994-01-01

    Transforming growth factor-beta 1 (TGF-beta 1) is generally considered to exert positive effects on the accumulation of extracellular matrices. These occur as the net result of enhanced matrix protein synthesis, diminished matrix metalloproteinase (MMP) synthesis, and augmented production of specific inhibitors, including the tissue inhibitor of metalloproteinases (TIMP-1). Given that glomerular TGF-beta 1 synthesis is induced by inflammation, the effects of this cytokine on synthesis of the 72-kd type IV collagenase and TIMP-1 by cultured human mesangial cells were evaluated. Concentrations of TGF-beta 1 of 5 ng/ml and above specifically stimulated the synthesis of the 72-kd type IV collagenase. This effect was independent of the stimulatory effect of TGF-beta 1 on TIMP-1 synthesis, which was maximal in a lower concentration range (0.1 to 1 ng/ml). Most significantly, the net effect at the higher concentrations of TGF-beta 1 was an excess of enzyme over the TIMP-1 inhibitor. Northern blot analysis of TGF-beta 1-stimulated human mesangial cells demonstrated a specific increase in the abundance of the 3.1 kb mRNA transcript encoding the 72-kd type IV collagenase, presumably mediated by a direct stimulation of 72-kd type IV collagenase mRNA transcription observed as early as 3 hours after exposure to TGF-beta 1. These studies were extended to an analysis of the expression of TGF-beta 1 and 72-kd type IV collagenase mRNAs in normal and nephritic rats. In normal animals, basal TGF-beta 1 and 72-kd type IV collagenase mRNA expression was observed in a strictly mesangial distribution. After induction of acute immune complex-mediated glomerulonephritis, there was a major increase in TGF-beta 1 and 72-kd type IV collagenase mRNA expression, which was strictly limited to the expanded, hypercellular mesangial compartment. Enhanced synthesis of the mesangial type IV collagenase in response to TGF-beta 1 released during glomerular inflammatory processes could have an important

  12. Migration Type III

    NASA Astrophysics Data System (ADS)

    Artymowicz, Pawel

    2004-03-01

    Migration type IIIMigration of objects embedded in disks (and the accompanying eccentricity evolution) is becoming a major theme in planetary system formation.The underlying physics can be distilled into the notion of disk-planet coupling via Lindblad resonances, which launch waves, sometimes spectacular spiral shock waves in gas disks. The wave pattern exchanges angular momentum with the planet. That causes (i) migration, (ii) eccentricity evolution, and (iii) gap opening by sufficiently massive planets.A competing source of disk-planet interaction, the corotationaltorques, are much less conspicuous (corotation does not produce easilydetectable waves, as galaxy observers can attest) and have often been missed in the analysis of planet migration. If spiral waves are like waves at Goleta beach, then the corotation acts more like a stealthy riptide. Corotationalflows lie at the basis of a new, surprisingly rapid, mode of migration (type III),superseding the standard type II migration (with a gap), and revising the speed of type I migration (without a gap). The talk will contain results obtained at KITP, e.g., an analytical derivation of da/dt in type III motion. It will be illustrated by videos of high-resolution numerical simulations obtained with different implementations of the Piecewise Parabolic Method hydrodynamics.

  13. Fueling type III secretion

    PubMed Central

    Lee, Pei-Chung

    2015-01-01

    Type III secretion systems are complex nanomachines that export proteins from the bacterial cytoplasm across the cell envelope in a single step. They are at the core of the machinery used to assemble the bacterial flagellum, and the needle complex many Gram-negative pathogens use to inject effector proteins into host cells and cause disease. Several models have been put forward to explain how this export is energized, and the mechanism has been the subject of considerable debate. Here we present an overview of these models and discuss their relative merits. Recent evidence suggests that the proton motive force is the primary energy source for type III secretion, although contribution from refolding of secreted proteins has not been ruled out. The mechanism, by which the proton motive force is converted to protein export, remains enigmatic. PMID:25701111

  14. Cranial mononeuropathy III - diabetic type

    MedlinePlus

    ... gov/ency/article/000692.htm Cranial mononeuropathy III - diabetic type To use the sharing features on this page, please enable JavaScript. Cranial mononeuropathy III -- diabetic type -- is usually a complication of diabetes that causes ...

  15. Localization of type I procollagen gene expression in silica-induced granulomatous lung disease and implication of transforming growth factor-beta as a mediator of fibrosis.

    PubMed Central

    Mariani, T. J.; Roby, J. D.; Mecham, R. P.; Parks, W. C.; Crouch, E.; Pierce, R. A.

    1996-01-01

    We have used the silica-induced model of pulmonary injury in the rat to study the pattern of collagen expression in granulomatous lung inflammation. A single intratracheal instillation of silica into adult rats resulted in granulomatous inflammation leading to fibrosis and alveolar proteinosis. The development of disease in these animals was characterized over a 27-day period after treatment by means of histological, biochemical, and molecular analyses. Biochemical analyses indicated that significant increases in the weights of silicotic lungs were due to elevated amounts of DNA and total protein. Analysis of hydroxyproline content showed a 15-fold increase in this amino acid in silicotic lungs, confirming the development of a fibrotic reaction. In situ hybridization for type I procollagen mRNA displayed increased gene expression in the parenchyma, conducting airways, and vasculature of silicotic rats. Within the parenchyma, type I procollagen was expressed uniquely within granulomatous lesions. Immunohistochemistry indicated type I procollagen was being expressed by an alpha-smooth muscle actin-negative population of cells. Immunolocalization of extra-cellular transforming growth factor-beta showed coincident temporal and spatial overlap with type I procollagen expression, implicating this cytokine as a mediator of collagen gene expression in this model. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8546202

  16. Type I (RI) and type II (RII) receptors for transforming growth factor-beta isoforms are expressed subsequent to transforming growth factor-beta ligands during excisional wound repair.

    PubMed Central

    Gold, L. I.; Sung, J. J.; Siebert, J. W.; Longaker, M. T.

    1997-01-01

    Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulate cell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling. Signal transduction for TGF-beta function is transmitted by a heteromeric complex of receptors consisting of two serine/threonine kinase transmembrane proteins (RI and RII). We have previously shown that each TGF-beta isoform is widely expressed in a distinct spatial and temporal pattern throughout the processes of excisional and incisional wound repair. As the presence of TGF-beta receptors determines cellular responsiveness, we have currently examined, by immunohistochemistry, the localization of RI (ALK-1, ALK-5) and RII throughout repair of full-thickness excisional wounds up to 21 days after wounding. The expression of RI (ALK-5) and RII co-localized in both the unwounded and wounded skin and was present in the same cell types as TGF-beta ligands. However, immunoreactivity for TGF-beta receptors, throughout repair, occurred 1 to 5 days later than TGF-beta isoform immunostaining. This implies that the presence of TGF-beta ligands may up-regulate TGF-beta receptors for function and/or may reflect a lag due to local processing of latent TGF-beta. As observed for the immunohistochemical localization of TGF-beta isoforms in unwounded skin, RI and RII were expressed throughout the four layers of the epidermis, showing a wavy pattern of slight to moderate immunostaining, and hair follicles, sweat glands, and sebaceous glands were moderately immunoreactive. The extracellular matrix, fibroblasts, and blood vessels in the dermis were not immunoreactive. After injury, as observed for TGF-beta ligands, RI and RII expression was increased in the epidermis adjacent to the wound and the epithelium migrating over the wound was completely devoid of TGF-beta receptor immunoreactivity until re-epithelialization was completed by day 7 after wounding. The dermis was only

  17. Endogenous interleukin-22 protects against inflammatory bowel disease but not autoimmune cholangitis in dominant negative form of transforming growth factor beta receptor type II mice.

    PubMed

    Yang, G-X; Sun, Y; Tsuneyama, K; Zhang, W; Leung, P S C; He, X-S; Ansari, A A; Bowlus, C; Ridgway, W M; Gershwin, M E

    2016-08-01

    During chronic inflammation, interleukin (IL)-22 expression is up-regulated in both CD4 and CD8 T cells, exerting a protective role in infections. However, in autoimmunity, IL-22 appears to have either a protective or a pathogenic role in a variety of murine models of autoimmunity and, by extrapolation, in humans. It is not clear whether IL-22 itself mediates inflammation or is a by-product of inflammation. We have taken advantage of the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice that develop both inflammatory bowel disease and autoimmune cholangitis and studied the role and the biological function of IL-22 by generating IL-22(-/-) dnTGF-βRII mice. Our data suggest that the influence of IL-22 on autoimmunity is determined in part by the local microenvironment. In particular, IL-22 deficiency exacerbates tissue injury in inflammatory bowel disease, but has no influence on either the hepatocytes or cholangiocytes in the same model. These data take on particular significance in the previously defined effects of IL-17A, IL-12p40 and IL-23p19 deficiency and emphasize that, in colitis, there is a dominant role of IL-23/T helper type 17 (Th17) signalling. Furthermore, the levels of IL-22 are IL-23-dependent. The use of cytokine therapy in patients with autoimmune disease has significant potential, but must take into account the overlapping and often promiscuous effects that can theoretically exacerbate inflammation. PMID:27148790

  18. Rat testicular germ cells and sertoli cells release different types of bioactive transforming growth factor beta in vitro

    PubMed Central

    Haagmans, Bart L; Hoogerbrugge, Jos W; Themmen, Axel PN; Teerds, Katja J

    2003-01-01

    Several in vivo studies have reported the presence of immunoreactive transforming growth factor-β's (TGF-β's) in testicular cells at defined stages of their differentiation. The most pronounced changes in TGF-β1 and TGF-β2 immunoreactivity occurred during spermatogenesis. In the present study we have investigated whether germ cells and Sertoli cells are able to secrete bioactive TGF-β's in vitro, using the CCl64 mink lung epithelial cell line as bioassay for the measurement of TGF-β. In cellular lysates, TGF-β bioactivity was only observed following heat-treatment, indicating that within these cells TGF-β is present in a latent form. To our surprise, active TGF-β could be detected in the culture supernatant of germ cells and Sertoli cells without prior heat-treatment. This suggests that these cells not only produce and release TGF-β in a latent form, but that they also release a factor which can convert latent TGF-β into its active form. Following heat-activation of these culture supernatant's, total TGF-β bioactivity increased 6- to 9-fold. Spermatocytes are the cell type that releases most bioactive TGF-β during a 24 h culture period, although round and elongated spermatids and Sertoli cells also secrete significant amounts of TGF-β. The biological activity of TGF-β could be inhibited by neutralizing antibodies against TGF-β1 (spermatocytes and round spermatids) and TGF-β2 (round and elongating spermatids). TGF-β activity in the Sertoli cell culture supernatant was inhibited slightly by either the TGF-β1 and TGF-β2 neutralizing antibody. These in vitro data suggest that germ cells and Sertoli cells release latent TGF-β's. Following secretion, the TGF-β's are converted to a biological active form that can interact with specific TGF-β receptors. These results strengthen the hypothesis that TGF-β's may play a physiological role in germ cell proliferation/differentiation and Sertoli cell function. PMID:12646048

  19. Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes

    PubMed Central

    Paine, Suman Kalyan; Basu, Analabha; Mondal, Lakshmi Kanta; Sen, Aditi; Choudhuri, Subhadip; Chowdhury, Imran Hussain; Saha, Avijit; Bhadhuri, Gautam; Mukherjee, Ankur

    2012-01-01

    Purpose Chronic hyperglycemia and hypoxemia are believed to be causal factors in the development of proliferative diabetic retinopathy (PDR) among individuals with type 2 diabetes. It is hypothesized that formation of new blood vessels in the retina due to prolonged hypoxia is associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we investigated the association of genetic polymorphisms in vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and interferon γ (IFN-γ) genes, which may be responsible for the hypoxia-induced VEGF-mediated neovascularization pathway for the pathogenesis of PDR. Methods Our case-control association study composed of 493 ethnically matched volunteers (253 with PDR [cases] and 240 diabetic controls [DC]). Gene polymorphisms were determined with Taqman-based real-time PCR and amplification refractory mutation analysis system PCR. Results The VEGF-460C (rs833061C; p=0.0043) and IFN-γ +874T (rs2430561T; p=0.0011) alleles were significantly associated with PDR. Conclusions Genetic variations at VEGF-460C and IFN-γ +874T might accelerate the pathogenesis of retinal neovascularization in PDR. PMID:23213275

  20. LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp).

    PubMed

    Poulsen, Ebbe Toftgaard; Nielsen, Nadia Sukusu; Jensen, Morten M; Nielsen, Esben; Hjortdal, Jesper; Kim, Eung Kweon; Enghild, Jan J

    2016-02-01

    More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals. PMID:26864644

  1. Neovascularization in aged mice: delayed angiogenesis is coincident with decreased levels of transforming growth factor beta1 and type I collagen.

    PubMed Central

    Reed, M. J.; Corsa, A.; Pendergrass, W.; Penn, P.; Sage, E. H.; Abrass, I. B.

    1998-01-01

    Angiogenesis, the growth of new vessels from existing microvasculature, is delayed in aged animals. In this study we asked whether this impairment might be due, in part, to changes in the expression of a growth factor, transforming growth factor-beta1 (TGF-beta1), and a matrix protein, type I collagen, which have been shown to regulate angiogenesis in vivo. We implanted polyvinyl alcohol sponges subcutaneously in the dorsa of young and aged mice and examined the sponges 7 to 21 days later for the presence of invasive fibrovascular bundles. Blood vessel ingrowth and proliferative activity were assessed by immunostain for von Willebrand factor and Ki-67, respectively. The fibrovascular bundles were also analyzed for TGF-beta1 and type I collagen. Relative to young mice, angiogenic invasion of sponges in aged mice was similar at 7 days, was diminished significantly (70%) at 14 days, but was again similar by 21 days after implantation. The expression of TGF-beta1 and type I collagen mRNA and protein in fibrovascular bundles was coincident but was also delayed (42 to 47%) at 14 days in the aged mice. Moreover, levels of active TGF-beta1 were decreased (48%) in the sera of aged relative to young mice. The delay in angiogenesis in aged mice was thus associated with decreased expression of TGF-beta1 and type I collagen by neovascular bundles. We conclude that changes in the levels of growth factors and proteins in the extracellular matrix contribute to impaired angiogenesis in aging. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 7 Figure 8 PMID:9422529

  2. Cranial mononeuropathy III - diabetic type

    MedlinePlus

    Diabetic third nerve palsy; Pupil-sparing third cranial nerve palsy ... Cranial mononeuropathy III - diabetic type -- is a mononeuropathy . This means that only one nerve is damaged. The condition affects the third cranial (oculomotor) ...

  3. An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy.

    PubMed

    Ohsawa, Yutaka; Okada, Tadashi; Nishimatsu, Shin-Ichiro; Ishizaki, Masatoshi; Suga, Tomohiro; Fujino, Masahiro; Murakami, Tatsufumi; Uchino, Makoto; Tsuchida, Kunihiro; Noji, Sumihare; Hinohara, Atsushi; Shimizu, Toshiyuki; Shimizu, Kiyoshi; Sunada, Yoshihide

    2012-08-01

    Skeletal muscle expressing Pro104Leu mutant caveolin 3 (CAV3(P104L)) in mouse becomes atrophied and serves as a model of autosomal dominant limb-girdle muscular dystrophy 1C. We previously found that caveolin 3-deficient muscles showed activated intramuscular transforming growth factor beta (TGF-β) signals. However, the cellular mechanism by which loss of caveolin 3 leads to muscle atrophy is unknown. Recently, several small-molecule inhibitors of TGF-β type I receptor (TβRI) kinase have been developed as molecular-targeting drugs for cancer therapy by suppressing intracellular TGF-β1, -β2, and -β3 signaling. Here, we show that a TβRI kinase inhibitor, Ki26894, restores impaired myoblast differentiation in vitro caused by activin, myostatin, and TGF-β1, as well as CAV3(P104L). Oral administration of Ki26894 increased muscle mass and strength in vivo in wild-type mice, and improved muscle atrophy and weakness in the CAV3(P104L) mice. The inhibitor restored the number of satellite cells, the resident stem cells of adult skeletal muscle, with suppression of the increased phosphorylation of Smad2, an effector, and the upregulation of p21 (also known as Cdkn1a), a target gene of the TGF-β family members in muscle. These data indicate that both TGF-β-dependent reduction in satellite cells and impairment of myoblast differentiation contribute to the cellular mechanism underlying caveolin 3-deficient muscle atrophy. TβRI kinase inhibitors could antagonize the activation of intramuscular anti-myogenic TGF-β signals, thereby providing a novel therapeutic rationale for the alternative use of this type of anticancer drug in reversing muscle atrophy in various clinical settings. PMID:22584670

  4. Role of Flightless-I (Drosophila) homolog in the transcription activation of type I collagen gene mediated by transforming growth factor beta

    SciTech Connect

    Lim, Mi-Sun; Jeong, Kwang Won

    2014-11-21

    Highlights: • FLII activates TGFβ-mediated expression of COL1A2 gene. • TGFβ induces the association of FLII with SMAD3 and BRG1 in A549 cells. • FLII is required for the recruitment of SWI/SNF complex and chromatin accessibility to COL1A2 promoter. - Abstract: Flightless-I (Drosophila) homolog (FLII) is a nuclear receptor coactivator that is known to interact with other transcriptional regulators such as the SWI/SNF complex, an ATP-dependent chromatin-remodeling complex, at the promoter or enhancer region of estrogen receptor (ER)-α target genes. However, little is known about the role of FLII during transcription initiation in the transforming growth factor beta (TGFβ)/SMAD-dependent signaling pathway. Here, we demonstrate that FLII functions as a coactivator in the expression of type I collagen gene induced by TGFβ in A549 cells. FLII activates the reporter gene driven by COL1A2 promoter in a dose-dependent manner. Co-expression of GRIP1, CARM1, or p300 did not show any synergistic activation of transcription. Furthermore, the level of COL1A2 expression correlated with the endogenous level of FLII mRNA level. Depletion of FLII resulted in a reduction of TGFβ-induced expression of COL1A2 gene. In contrast, over-expression of FLII caused an increase in the endogenous expression of COL1A2. We also showed that FLII is associated with Brahma-related gene 1 (BRG1) as well as SMAD in A549 cells. Notably, the recruitment of BRG1 to the COL1A2 promoter region was decreased in FLII-depleted A549 cells, suggesting that FLII is required for TGFβ-induced chromatin remodeling, which is carried out by the SWI/SNF complex. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments revealed that depletion of FLII caused a reduction in chromatin accessibility at the COL1A2 promoter. These results suggest that FLII plays a critical role in TGFβ/SMAD-mediated transcription of the COL1A2 gene

  5. Glycosaminoglycans and mucopolysaccharidosis type III.

    PubMed

    Jakobkiewicz-Banecka, Joanna; Gabig-Ciminska, Magdalena; Kloska, Anna; Malinowska, Marcelina; Piotrowska, Ewa; Banecka-Majkutewicz, Zyta; Banecki, Bogdan; Wegrzyn, Alicja; Wegrzyn, Grzegorz

    2016-01-01

    Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is a lysosomal storage disease in which heparan sulfate is accumulated in lysosomes, as well as outside of cells, as the primary storage material. This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) - causing MPS IIIA, NAGLU (coding for alpha-N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA alpha-glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) - causing MPS IIID. The primary storage is responsible for some disease symptoms, but other arise as a result of secondary storage, including glycosphingolipids, and subsequent processes, like oxidative stress and neuroinflammation. Central nervous system is predominantly affected in all subtypes of MPS III. Heparan sulfate and its derivatives are the most commonly used biomarkers for diagnosis and prediction procedures. Currently, there is no therapy for Sanfilippo syndrome, however, clinical trials are ongoing for enzyme replacement therapy, gene therapy and substrate reduction therapy (particularly gene expression-targeted isoflavone therapy). PMID:27100513

  6. Dens invaginatus (Type III B)

    PubMed Central

    Kallianpur, Shreenivas; Sudheendra, US; Kasetty, Sowmya; Joshi, Prathamesh

    2012-01-01

    Dens invaginatus or ‘dens in dente’ is a developmental malformation of the tooth resulting from infolding of the dental papilla before calcification. This article presents a case of dens invaginatus occurring in maxillary right lateral incisor of a 45-year-old male patient. The patient presented with pain and clinically missing maxillary right canine. The tooth was found to be non-vital. Radiographic examination revealed the tooth-in-tooth appearance of lateral incisor with a dilated pulp chamber. The crown of impacted canine was found within the pulp chamber of lateral incisor. Owing to this unique clinical presentation, both the lateral incisor and the impacted canine were extracted. Histopathologic examination confirmed the diagnosis of Dens invaginatus Type III B. A brief review on etiopathogenesis, radiographic features and treatment of dens invaginatus has also been included. PMID:22923901

  7. Time Course, Distribution and Cell Types of Induction of Transforming Growth Factor Betas following Middle Cerebral Artery Occlusion in the Rat Brain

    PubMed Central

    Pál, Gabriella; Vincze, Csilla; Renner, Éva; Wappler, Edina A.; Nagy, Zoltán; Lovas, Gábor; Dobolyi, Arpád

    2012-01-01

    Transforming growth factor-βs (TGF-β1–3) are cytokines that regulate the proliferation, differentiation, and survival of various cell types. The present study describes the induction of TGF-β1–3 in the rat after focal ischemia at 3 h, 24 h, 72 h and 1 month after transient (1 h) or permanent (24 h) middle cerebral artery occlusion (MCAO) using in situ hybridization histochemistry and quantitative analysis. Double labeling with different markers was used to identify the localization of TGF-β mRNA relative to the penumbra and glial scar, and the types of cells expressing TGF-βs. TGF-β1 expression increased 3 h after MCAO in the penumbra and was further elevated 24 h after MCAO. TGF-β1 was present mostly in microglial cells but also in some astrocytes. By 72 h and 1 month after the occlusion, TGF-β1 mRNA-expressing cells also appeared in microglia within the ischemic core and in the glial scar. In contrast, TGF-β2 mRNA level was increased in neurons but not in astrocytes or microglial cells in layers II, III, and V of the ipsilateral cerebral cortex 24 h after MCAO. TGF-β3 was not induced in cells around the penumbra. Its expression increased in only a few cells in layer II of the cerebral cortex 24 h after MCAO. The levels of TGF-β2 and -β3 decreased at subsequent time points. Permanent MCAO further elevated the levels of all 3 subtypes of TGF-βs suggesting that reperfusion is not a major factor in their induction. TGF-β1 did not co-localize with either Fos or ATF-3, while the co-localization of TGF-β2 with Fos but not with ATF-3 suggests that cortical spreading depolarization, but not damage to neural processes, might be the mechanism of induction for TGF-β2. The results imply that endogenous TGF-βs are induced by different mechanisms following an ischemic attack in the brain suggesting that they are involved in distinct spatially and temporally regulated inflammatory and neuroprotective processes. PMID:23056426

  8. Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

    PubMed Central

    Estes, D M; Tuo, W; Brown, W C; Goin, J

    1998-01-01

    In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons. PMID:9893052

  9. Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties.

    PubMed

    Narushima, Yuta; Kozuka-Hata, Hiroko; Koyama-Nasu, Ryo; Tsumoto, Kouhei; Inoue, Jun-ichiro; Akiyama, Tetsu; Oyama, Masaaki

    2016-03-01

    Glioblastoma is one of the most malignant brain tumors with poor prognosis and their development and progression are known to be driven by glioblastoma stem cells. Although glioblastoma stem cells lose their cancer stem cell properties during cultivation in serum-containing medium, little is known about the molecular mechanisms regulating signaling alteration in relation to reduction of stem cell-like characteristics. To elucidate the global phosphorylation-related signaling events, we performed a SILAC-based quantitative phosphoproteome analysis of serum-induced dynamics in glioblastoma stem cells established from the tumor tissues of the patient. Among a total of 2876 phosphorylation sites on 1584 proteins identified in our analysis, 732 phosphorylation sites on 419 proteins were regulated through the alteration of stem cell-like characteristics. The integrative computational analyses based on the quantified phosphoproteome data revealed the relevant changes of phosphorylation levels regarding the proteins associated with cytoskeleton reorganization such as Rho family GTPase and Intermediate filament signaling, in addition to transforming growth factor-β receptor type-2 (TGFBR2) as a prominent upstream regulator involved in the serum-induced phosphoproteome regulation. The functional association of transforming growth factor-β receptor type-2 with stem cell-like properties was experimentally validated through signaling perturbation using the corresponding inhibitors, which indicated that transforming growth factor-β receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. PMID:26670566

  10. Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes.

    PubMed

    Alyanakian, Marie-Alexandra; Grela, Françoise; Aumeunier, Aude; Chiavaroli, Carlo; Gouarin, Christine; Bardel, Emilie; Normier, Gérard; Chatenoud, Lucienne; Thieblemont, Nathalie; Bach, Jean-François

    2006-01-01

    The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-beta. Natural killer T-cells also participate in the therapeutic effect because CD1d(-/-) NOD mice are partially resistant to the protective effect of OM-85. The question remains of the specificity of the protective effect of OM-85, which may include proinflammatory components. It will thus be important to further characterize the molecular components that afford protection from type 1 diabetes. Lipopolysaccharide is excluded, but other Toll-like receptor (TLR) agonists could be involved because OM-85 stimulated dendritic cells and induced TGF-beta production by splenocytes in a TLR-2-, TLR-4-, and MyD88-dependent fashion. PMID:16380491

  11. Adipose-derived mesenchymal stem cells from the sand rat: transforming growth factor beta and 3D co-culture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix

    PubMed Central

    Tapp, Hazel; Deepe, Ray; Ingram, Jane A; Kuremsky, Marshall; Hanley, Edward N; Gruber, Helen E

    2008-01-01

    Introduction Adult mesenchymal stem cell therapy has a potential application in the biological treatment of disc degeneration. Our objectives were: to direct adipose-derived mesenchymal stem cells (AD-MSC) from the sand rat to produce a proteoglycan and collagen type I extracellular matrix (ECM) rich in known ECM components of the annulus fibrosis of disc; and to stimulate proteoglycan production by co-culture of human annulus cells with AD-MSC. Methods AD-MSC were isolated and characterised by adherence to plastic, appropriate expression of cluster of differentiation (CD) markers, and differentiation to osteoblasts and chondrocytes in vitro. AD-MSC were grown in three-dimensional (3D) culture and treated with or without transforming growth factor beta (TGFβ) to direct them to produce annulus-like ECM as determined by proteoglycan content and collagen expression. AD-MSC were co-cultured with human annulus cells and grown in 3D culture. Results AD-MSC produced a proteoglycan and collagen type I rich ECM after treatment with TGFβ in 3D culture as confirmed by a 48% increase in proteoglycan content assayed by 1,9-dimethylmethylene blue (DMB), and by immunohistochemical identification of ECM components. Co-culture of human annulus and sand rat AD-MSC in 3D culture resulted in a 20% increase in proteoglycan production compared with the predicted value of the sum of the individual cultures. Conclusion Results support the hypothesis that AD-MSC have potential in cell-based therapy for disc degeneration. PMID:18691412

  12. Type III functional response in Daphnia.

    PubMed

    Sarnelle, Orlando; Wilson, Alan E

    2008-06-01

    The functional response of Daphnia, a common pelagic herbivore in lakes, was assessed with a combination of secondary and meta-analyses of published data and new data from an experiment conducted using very low food levels. Secondary analyses of literature data (28 studies, n = 239-393) revealed a significant positive influence of food concentration on Daphnia clearance rate at low food levels, i.e., evidence of an overall Type III functional response. This result was not an artifact of including data from Daphnia that were exhausted from prolonged food deprivation (more than three hours at very low food). Meta-analysis of Daphnia clearance rate vs. food concentration across a range of low food concentrations (eight studies) showed a significantly positive slope across studies, which also supports the presence of a Type III response. Congruent with these analyses of published data, the feeding experiment showed clear evidence of a Type III functional response for D. pulicaria feeding on Ankistrodesmus falcatus. Food levels at which Daphnia clearance rate declined with decreasing food were near the minimum resource requirement for Daphnia population maintenance at steady state (R*). We suggest that Type III responses are more common than previously believed, perhaps because of the relative paucity of observations at low food levels, and that reduced prey mortality at low phytoplankton densities could be a stabilizing mechanism for Daphnia-phytoplankton systems under resource scarcity. PMID:18589536

  13. Transforming growth factor-beta and transforming growth factor beta-receptor expression in human meningioma cells.

    PubMed Central

    Johnson, M. D.; Federspiel, C. F.; Gold, L. I.; Moses, H. L.

    1992-01-01

    The transforming growth factor-beta (TGF beta) family in mammals includes three closely related peptides that influence proliferation and numerous physiologic processes in most mesenchymal cells. In this study, Northern blots, immunohistochemistry, TGF beta radioreceptor assays, TGF beta receptor affinity labeling and [3H] thymidine incorporation were used to evaluate whether primary cell cultures of human meningiomas synthesize the three TGF beta isoforms, bear TGF beta receptors, and respond to TGF beta. Transcripts for TGF beta 1 and 2 were detected in the three cases analyzed. Transforming growth factor-beta 1 immunoreactivity was detected in three of six cases, and TGF beta 2 and 3 immunoreactivity were detected in each case analyzed. Media conditioned by cells cultured from six meningiomas also contained latent TGF beta-like activity. Transforming growth factor-beta receptor cross-linking studies identified TGF beta binding sites corresponding to the type 1, type 2, and type 3 receptors on meningioma cells. Treatment with active TGF beta 1 produced a statistically significant reduction in [3H] thymidine incorporation after stimulation with 10% fetal calf serum and epidermal growth factor in all six cases studied. Images Figure 1 Figure 2 Figure 4 PMID:1325741

  14. Mucolipidosis Type III α/β

    PubMed Central

    Kerr, Darcy A.; Memoli, Vincent A.; Cathey, Sara S.; Harris, Brent T.

    2014-01-01

    We report findings from an autopsy of a 45-year-old woman with the rare lysosomal storage disease mucolipidosis type III α/β. Her disease manifested most notably as multiple bone and cartilage problems with tracheal and bronchial malacia. Principal autopsy findings included gross abnormalities in bone and cartilage with corresponding microscopic cytoplasmic lysosomal granules. These cytoplasmic granules were also seen in histologic preparations of the brain, myocardium, heart valves, and fibroblasts of the liver and skin by light and electron microscopy. By electron microscopy there were scattered, diffuse vesicular cytoplasmic granules in neurons and glia and an increase in lysosomal structures with fine electron lucent granularity in the above tissue types. Our findings help elaborate current understanding of this disease and differentiate it from the mucopolysaccharidoses and related disorders. To our knowledge, this is the first report to document pathologic findings in a patient with mucolipidosis type III α/β by autopsy. PMID:21466370

  15. Energy source of flagellar type III secretion.

    PubMed

    Paul, Koushik; Erhardt, Marc; Hirano, Takanori; Blair, David F; Hughes, Kelly T

    2008-01-24

    Bacterial flagella contain a specialized secretion apparatus that functions to deliver the protein subunits that form the filament and other structures to outside the membrane. This apparatus is related to the injectisome used by many gram-negative pathogens and symbionts to transfer effector proteins into host cells; in both systems this export mechanism is termed 'type III' secretion. The flagellar secretion apparatus comprises a membrane-embedded complex of about five proteins, and soluble factors, which include export-dedicated chaperones and an ATPase, FliI, that was thought to provide the energy for export. Here we show that flagellar secretion in Salmonella enterica requires the proton motive force (PMF) and does not require ATP hydrolysis by FliI. The export of several flagellar export substrates was prevented by treatment with the protonophore CCCP, with no accompanying decrease in cellular ATP levels. Weak swarming motility and rare flagella were observed in a mutant deleted for FliI and for the non-flagellar type-III secretion ATPases InvJ and SsaN. These findings show that the flagellar secretion apparatus functions as a proton-driven protein exporter and that ATP hydrolysis is not essential for type III secretion. PMID:18216859

  16. Arthroscopic fixation of type III acromioclavicular dislocations.

    PubMed

    Somers, Jan F A; Van der Linden, Dietert

    2007-10-01

    Type III Acromio-Clavicular Joint dislocations can be treated successfully by surgical stabilisation in situ, with or without reconstruction of the coracoclavicular ligaments. The authors describe a simple and reliable mode of fixation, performed arthroscopically. The technique can be used for in situ fixation, or as part of an arthroscopically assisted Weaver and Dunn procedure. Using a metallic anchor loaded with a braided polyfilament suture, a strong and reliable fixation of the clavicle to the coracoid process is obtained. No hardware removal is necessary. Concomitant glenohumeral pathology can be treated simultaneously. PMID:18019910

  17. Sources of type III solar microwave bursts

    NASA Astrophysics Data System (ADS)

    Zhdanov, Dmitriy; Lesovoi, Sergey; Tokhchukova, Susanna

    2016-06-01

    Microwave fine structures allow us to study plasma evolution in an energy release region. The Siberian Solar Radio Telescope (SSRT) is a unique instrument designed to examine fine structures at 5.7 GHz. A complex analysis of data from RATAN-600, 4-8 GHz spectropolarimeter, and SSRT, simultaneously with extreme UV data, made it possible to localize sources of III type microwave drift bursts in August 10, 2011 event within the entire frequency band of burst occurrences, as well as to determine the most probable region of primary energy release. To localize sources of III type bursts from RATAN-600 data, an original method for data processing has been worked out. At 5.7 GHz, the source of bursts was determined along two coordinates whereas at 4.5, 4.7, 4.9, 5.1, 5.3, 5.5 and 6.0 GHz, their locations were identified along one coordinate. The size of the burst source at 5.1 GHz was found to be maximum as compared to source sizes at other frequencies.

  18. DECIMETRIC TYPE III BURSTS: GENERATION AND PROPAGATION

    SciTech Connect

    Li, B.; Cairns, Iver H.; Robinson, P. A.; Yan, Y. H.

    2011-09-01

    Simulations are presented for decimetric type III radio bursts at 2f{sub p} , where f{sub p} is the local electron plasma frequency. The simulations show that 2f{sub p} radiation can be observed at Earth in two scenarios for the radiation's generation and propagation. In Scenario A, radiation is produced and propagates in warm plasmas in the lower corona that are caused by previous magnetic reconnection outflows and/or chromospheric evaporation. In Scenario B radiation is generated in normal plasmas, then due to its natural directivity pattern and refraction, radiation partly propagates into nearby regions, which are hot because of previous reconnection/evaporation. The profiles of plasma density n{sub e} (r) and electron temperature T{sub e} (r) in the lower corona (r - R{sub sun} {approx}< 100 Mm) are found to be crucial to whether radiation can be produced and escape at observable levels against the effects of free-free absorption, where r is the heliocentric distance. Significantly, the observed wide ranges of radiation properties (e.g., drift rates) require n{sub e} (r) with a large range of scale heights h{sub s} , consistent nonetheless for Scenario B with short observed EUV loops. This is relevant to problems with large h{sub s} inferred from tall EUV loops. The simulations suggest: (1) n{sub e} (r) with small h{sub s} , such as n{sub e} (r){proportional_to}(r - R{sub sun}){sup -2.38} for flaring regions, are unexpectedly common deep in the corona. This result is consistent with recent work on n{sub e} (r) for r {approx} (1.05-2)R{sub sun} extracted from observed metric type IIIs. (2) The dominance of reverse-slope bursts over normal bursts sometimes observed may originate from asymmetric reconnection/acceleration, which favors downgoing beams.

  19. Type III Radio Bursts and Microflares

    NASA Astrophysics Data System (ADS)

    Christe, S.; Krucker, S.; Arzner, K.; Lin, R. P.

    2003-05-01

    We present recent observations of microflares observed simultaneously in EUV (TRACE), radio (Nancay, Phoenix-2), and X-rays (RHESSI). During a period of 15 min on 19 July 2002 14:23-14:35 UT, RHESSI observed microflares approximately every 2 minutes. Each microflare was accompagnied by a radio Type III burst. The largest flare (14:29:25 UT) was also accompagnied by a cluster of decimetric radio spikes in the frequency range 1 to 2 GHz. In addition, FeXII (195 Å) images provided by TRACE show two jets-like emissions originating from a complex double arche structure. The centroid of the jets were found to travel at apparent speeds of ˜ 100 km s-1, consistent with observations by Shimojo et al. (1996). X-ray images show non-thermal emission (9-30 keV) from the footpoints of the TRACE arches. Strong correlation in flux amplitude is found between emissions in the radio ( ˜1340 MHz) and non-thermal X-ray (9-30 keV integrated). The event is interpreted as an anemone-jet in the model by Shibata et al. (1994). This research is supported by NASA contract NAS 5-98033.

  20. Type III TGFβ receptor and Src direct hyaluronan-mediated invasive cell motility.

    PubMed

    Allison, Patrick; Espiritu, Daniella; Barnett, Joey V; Camenisch, Todd D

    2015-03-01

    During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. This process requires epithelial to mesenchymal transition (EMT) and directed cellular invasion. The Type III Transforming Growth Factor-beta Receptor (TGFβR3) is required for epicardial cell invasion and coronary vessel development. Using primary epicardial cells derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, high-molecular weight hyaluronan (HMWHA) stimulated cellular invasion and filamentous (f-actin) polymerization are detected in Tgfbr3(+/+) cells, but not in Tgfbr3(-/-) cells. Furthermore, HMWHA-stimulated cellular invasion and f-actin polymerization in Tgfbr3(+/+) epicardial cells are dependent on Src kinase. Src activation in HMWHA-stimulated Tgfbr3(-/-) epicardial cells is not detected in response to HMWHA. RhoA and Rac1 also fail to activate in response to HMWHA in Tgfbr3(-/-) cells. These events coincide with defective f-actin formation and deficient cellular invasion. Finally, a T841A activating substitution in TGFβR3 drives ligand-independent Src activation. Collectively, these data define a TGFβR3-Src-RhoA/Rac1 pathway that is essential for hyaluronan-directed cell invasion in epicardial cells. PMID:25499979

  1. Extrapyramidal Symptoms and Medication Use in Mucopolysaccharidosis Type III

    ERIC Educational Resources Information Center

    Tchan, Michel C.; Sillence, David

    2009-01-01

    Background: We report the case of a 16-year-old male with Mucopolysaccharidosis III type A (Sanfilippo syndrome) who was commenced on risperidone for behaviour management. He rapidly developed extrapyramidal symptoms that have not resolved. Method: The medication histories of 20 patients with Mucopolysaccharidosis III seen at a Lysosomal Storage…

  2. Cardiac fibroblasts are predisposed to convert into myocyte phenotype: Specific effect of transforming growth factor. beta

    SciTech Connect

    Eghbali, M.; Tomek, R.; Woods, C.; Bhambi, B. )

    1991-02-01

    Cardiac fibroblasts are mainly responsible for the synthesis of major extracellular matrix proteins in the heart, including fibrillar collagen types I and III and fibronectin. In this report we show that these cells, when stimulated by transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 1}), acquire certain myocyte-specific properties. Cultured cardiac fibroblasts from adult rabbit heart were treated with TGF-{beta}{sub 1}, (10-15 ng/ml) for different periods of time. Northern hybridization analysis of total RNA showed that cells treated with TGF-{beta}{sub 1} became stained with a monoclonal antibody to muscle-specific actin. After treatment of quiescent cells with TGF-{beta}{sub 1}, cell proliferation (as measured by ({sup 3}H)thymidine incorporation) was moderately increased. Cultured cardiac fibroblasts at the subconfluent stage, when exposed to TGF-{beta}{sub 1} in the presence of 10% fetal bovine serum, gave rise to a second generation of slowly growing cells that expressed muscle-specific actin filaments. The findings demonstrate that cardiac fibroblasts can be made to differentiate into cells that display many characteristics of cardiac myocytes. TGF-{beta}{sub 1} seems to be a specific inducer of such conversion.

  3. Decametric and hectometric Solar Type III bursts at Saturn's orbit

    NASA Astrophysics Data System (ADS)

    Boudjada, Mohammed Y.; Sawas, Sami; Galopeau, Patrick H. M.; Maksimovic, Milan

    2015-04-01

    We report on solar radio bursts observed by RPWS experiment onboard Cassini spacecraft. We consider Type III solar bursts observed in the frequency range from 1 MHz to 16 MHz. Those bursts are probably generated in the solar corona and the interplanetary medium. We show that the Type III burst occurrence is depending on the solar activity. We attempt to localize the regions where the Type III burst is probably emitted. We consider that the electrons at the origin of the Solar Type III bursts follow the interplanetary magnetic field. The trajectory is an Archimedean spiral contained in the ecliptic plane. We discuss our results taking into consideration on the one hand the spacecraft positions with regards to the source location, and on the other hand the temporal and spectral radio beam variation when combining Cassini and Wind observations.

  4. Heterogeneity of collagens in rabbit cornea: type III collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.; Covington, H.I.; Macarak, E.J.

    1988-05-01

    Whole neonate rabbit corneas and adult corneas containing 2-week-old scars were incubated in the presence of (/sup 14/C) glycine. Radiolabeled collagen extracted from the corneas and scar tissue were analyzed by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography to determine the types and relative quantity of collagen polypeptides present and synthesized by these tissues. In addition to other collagen types, type III was found in both neonate cornea and scar tissue from adult cornea, albeit in relatively small quantities. Type III collagen in normal cornea was associated with the residue after pepsin digestion and formic acid extraction of the tissue, and the same type of collagen was extracted from scar tissue after similar treatment. Type III collagen-specific monoclonal antibody bound to developing normal corneas and healing adult tissue sections, as determined by immunofluorescence. Antibody binding was localized to the endothelium and growing Descemet's membrane in fetal and neonate corneas, and restricted to the most posterior region of the corneal scar tissue. Although monoclonal antibody to keratan sulfate, used as a marker for stromal fibroblasts, bound to most of the scar tissue, the antibody failed to bind to the posterior scar tissue positive for type III collagen. We conclude that endothelial cells from fetal and neonate rabbit cornea and endothelium-derived fibroblasts from healing wounds of adult cornea synthesize and deposit type III collagen. Moreover, this collagen appears to be incorporated into the growing Descemet's membrane of normal corneas and narrow posterior portion of the scar tissue.

  5. Novel chitosan/collagen scaffold containing transforming growth factor-{beta}1 DNA for periodontal tissue engineering

    SciTech Connect

    Zhang Yufeng; Cheng Xiangrong . E-mail: Xiangrongcheng@hotmail.com; Wang Jiawei; Wang Yining; Shi Bin; Huang Cui; Yang Xuechao; Liu Tongjun

    2006-05-26

    The current rapid progression in tissue engineering and local gene delivery system has enhanced our applications to periodontal tissue engineering. In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with plasmid and adenoviral vector encoding human transforming growth factor-{beta}1 (TGF-{beta}1). These scaffolds were evaluated in vitro by analysis of microscopic structure, porosity, and cytocompatibility. Human periodontal ligament cells (HPLCs) were seeded in this scaffold, and gene transfection could be traced by green fluorescent protein (GFP). The expression of type I and type III collagen was detected with RT-PCR, and then these scaffolds were implanted subcutaneously into athymic mice. Results indicated that the pore diameter of the gene-combined scaffolds was lower than that of pure chitosan/collagen scaffold. The scaffold containing Ad-TGF-{beta}1 exhibited the highest proliferation rate, and the expression of type I and type III collagen up-regulated in Ad-TGF-{beta}1 scaffold. After implanted in vivo, EGFP-transfected HPLCs not only proliferated but also recruited surrounding tissue to grow in the scaffold. This study demonstrated the potential of chitosan/collagen scaffold combined Ad-TGF-{beta}1 as a good substrate candidate in periodontal tissue engineering.

  6. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

    PubMed Central

    Dobolyi, Arpád; Vincze, Csilla; Pál, Gabriella; Lovas, Gábor

    2012-01-01

    Transforming growth factor beta (TGF-β) proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed. PMID:22942700

  7. Auroral Kilometric Radiation and Type III Solar Radio Bursts

    NASA Astrophysics Data System (ADS)

    Romantsova, T. V.; Mogilevsky, M. M.; Skalsky, A. A.; Hanasz, J.

    2009-04-01

    Simultaneous wave observations onboard the ISEE-1 and ISEE-3 spacecraft show that onsets of the Auroral Kilometric Radiation frequently coincide with an arrival of type III solar burst (Calvert, 1981). It was supposed that solar burst stimulates maser instability in auroral region and AKR consequently . We present statistical and case studies of events when both type III solar radio bursts and Auroral Kilometric Radiation are recorded simultaneously. AKR was observed onboard the INTERBALL-2 spacecraft orbiting around the Earth by the POLRAD experiment. Wave measurements carried out onboard the Wind, INTEBALL-TAIL and Geotail spacecraft are used to identify unambiguously the type III solar radio bursts. The origin of close relation between onsets of both solar radiation and AKR is discussed and interpreted. Acknowledgements. This work is supported by grant RFBR 06-02-72560.

  8. Assessment of Sleep in Children with Mucopolysaccharidosis Type III

    PubMed Central

    Mahon, Louise Victoria; Lomax, Michelle; Grant, Sheena; Cross, Elaine; Hare, Dougal Julian; Wraith, James Ed; Jones, Simon; Bigger, Brian; Langford-Smith, Kia; Canal, Maria

    2014-01-01

    Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7–10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice. PMID:24504123

  9. Transforming growth factor-betas and vascular disorders.

    PubMed

    Bobik, Alex

    2006-08-01

    Transforming growth factor-beta (TGF-beta) superfamily members, TGF-beta and bone morphogenetic proteins (BMPs), are potent regulatory cytokines with diverse functions on vascular cells. They signal through heteromeric type I and II receptor complexes activating Smad-dependent and Smad-independent signals, which regulate proliferation, differentiation, and survival. They are potent regulators of vascular development and vessel remodeling and play key roles in atherosclerosis and restenosis, regulating endothelial, smooth muscle cell, macrophage, T cell, and probably vascular calcifying cell responses. In atherosclerosis, TGF-beta regulates lesion phenotype by controlling T-cell responses and stimulating smooth muscle cells to produce collagen. It contributes to restenosis by augmenting neointimal cell proliferation and collagen accumulation. Defective TGF-beta signaling in endothelial cells attributable to mutations in endoglin or the type I receptor ALK-1 leads to hereditary hemorrhagic telangiectasia, whereas defective BMP signaling attributable to mutations in the BMP receptor II has been associated with development of primary pulmonary hypertension. The development of mouse models with either cell type-specific or general inactivation of TGF-beta/BMP signaling has started to reveal the importance of the regulatory network of TGF-beta/BMP pathways in vivo and their significance for atherosclerosis, hereditary hemorrhagic telangiectasia, and primary pulmonary hypertension. This review highlights recent findings that have advanced our understanding of the roles of TGF-beta superfamily members in regulating vascular cell responses and provides likely avenues for future research that may lead to novel pharmacological therapies for the treatment or prevention of vascular disorders. PMID:16675726

  10. The general solution of Bianchi type III vacuum cosmology

    NASA Astrophysics Data System (ADS)

    Christodoulakis, T.; Terzis, Petros A.

    2007-02-01

    The second-order ordinary differential equation which describes the unknown part of the solution space of some vacuum Bianchi cosmologies is completely integrated for type III, thus obtaining the general solution to Einstein's field equations for this case, with the aid of the sixth Painlevé transcendent PVI. For particular representations of PVI we obtain the known Kinnersley two-parameter spacetime and a solution of Euclidean signature. The imposition of the spacetime generalization of a 'hidden' symmetry of the generic type III spatial slice enables us to retrieve the two-parameter subfamily without considering the Painlevé transcendent.

  11. Exploiting the Biosynthetic Potential of Type III Polyketide Synthases.

    PubMed

    Lim, Yan Ping; Go, Maybelle K; Yew, Wen Shan

    2016-01-01

    Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development. PMID:27338328

  12. Type III restriction-modification enzymes: a historical perspective

    PubMed Central

    Rao, Desirazu N.; Dryden, David T. F.; Bheemanaik, Shivakumara

    2014-01-01

    Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction–modification (R–M) systems are classified into four groups. Type III R–M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25–27 bp downstream of one of the recognition sites). Like the Type I R–M enzymes, Type III R–M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R–M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R–M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis. PMID:23863841

  13. Microwave Type III Pair Bursts in Solar Flares

    NASA Astrophysics Data System (ADS)

    Tan, Baolin; Mészárosová, Hana; Karlický, Marian; Huang, Guangli; Tan, Chengming

    2016-03-01

    A solar microwave type III pair burst is composed of normal and reverse-sloped (RS) burst branches with oppositely fast frequency drifts. It is the most sensitive signature of the primary energy release and electron accelerations in flares. This work reports 11 microwave type III pair events in 9 flares observed by radio spectrometers in China and the Czech Republic at a frequency of 0.80-7.60 GHz during 1994-2014. These type III pairs occurred in flare impulsive and postflare phases with separate frequencies in the range of 1.08-3.42 GHz and a frequency gap of 10-1700 MHz. The frequency drift increases with the separate frequency (fx), the lifetime of each burst is anti-correlated to fx, while the frequency gap is independent of fx. In most events, the normal branches are drifting obviously faster than the RS branches. The type III pairs occurring in flare impulsive phase have lower separate frequencies, longer lifetimes, wider frequency gaps, and slower frequency drifts than that occurring in postflare phase. Also, the latter always has strong circular polarization. Further analysis indicates that near the flare energy release sites the plasma density is about {10}10{--}{10}11 cm-3 and the temperature is higher than 107 K. These results provide new constraints to the acceleration mechanism in solar flares.

  14. Interplanetary density models as inferred from solar Type III bursts

    NASA Astrophysics Data System (ADS)

    Oppeneiger, Lucas; Boudjada, Mohammed Y.; Lammer, Helmut; Lichtenegger, Herbert

    2016-04-01

    We report on the density models derived from spectral features of solar Type III bursts. They are generated by beams of electrons travelling outward from the Sun along open magnetic field lines. Electrons generate Langmuir waves at the plasma frequency along their ray paths through the corona and the interplanetary medium. A large frequency band is covered by the Type III bursts from several MHz down to few kHz. In this analysis, we consider the previous empirical density models proposed to describe the electron density in the interplanetary medium. We show that those models are mainly based on the analysis of Type III bursts generated in the interplanetary medium and observed by satellites (e.g. RAE, HELIOS, VOYAGER, ULYSSES,WIND). Those models are confronted to stereoscopic observations of Type III bursts recorded by WIND, ULYSSES and CASSINI spacecraft. We discuss the spatial evolution of the electron beam along the interplanetary medium where the trajectory is an Archimedean spiral. We show that the electron beams and the source locations are depending on the choose of the empirical density models.

  15. The position and polarization of Type III solar bursts

    NASA Technical Reports Server (NTRS)

    Dulk, G. A.; Suzuki, S.

    1980-01-01

    The position and polarization of Type III solar bursts in the range of 24-220 MHz are studied, with emphasis on the bursts continuing to frequencies lower than 24 MHz. Consideration is given to the statistics of burst polarization, the relation between polarization and source position, and brightness temperature, flux densities, and source sizes.

  16. Severe inflammatory bowel disease associated with congenital alteration of transforming growth factor beta signaling.

    PubMed

    Naviglio, Samuele; Arrigo, Serena; Martelossi, Stefano; Villanacci, Vincenzo; Tommasini, Alberto; Loganes, Claudia; Fabretto, Antonella; Vignola, Silvia; Lonardi, Silvia; Ventura, Alessandro

    2014-08-01

    Transforming growth factor beta is a pleiotropic cytokine which plays a central role in the homeostasis of the immune system. A complex dysregulation of its signaling occurs in Loeys-Dietz syndrome, a monogenic disorder caused by mutations of transforming growth factor beta receptors type 1 or type 2, characterized by skeletal involvement, craniofacial abnormalities, and arterial tortuosity with a strong predisposition for aneurysm and dissection. In addition, several immunologic abnormalities have been described in these patients, including an increased risk of allergic disorders as well as eosinophilic gastrointestinal disorders. The occurrence of inflammatory bowel disorders has been also reported, but it is poorly documented. We describe two unrelated children with Loeys-Dietz syndrome affected by severe chronic inflammatory colitis appearing at an early age. The intestinal disease presented similar features in both patients, including a histopathological picture of non-eosinophilic chronic ulcerative colitis, striking elevation of inflammatory markers, and a distinctly severe clinical course leading to failure to thrive, with resistance to multiple immunosuppressive treatments. One of the patients also presented autoimmune thyroiditis. Our report confirms that chronic ulcerative colitis may be associated with Loeys-Dietz syndrome. This finding suggests that an alteration of transforming growth factor beta signaling may by itself predispose to inflammatory colitis in humans, and represent an invaluable model to understand inflammatory bowel diseases. PMID:24486179

  17. Structural Analysis of H2-Db Class I Molecules Containing Two Different Allelic Forms of the type 1 Diabetes Susceptibility Factor beta-2 Microglobulin: Implications for the Mechanism Underlying Viriations in Antigen Presentation

    SciTech Connect

    Roden,M.; Brims, D.; Fedorov, A.; DiLorenzo, T.; Almo, S.; Nathenson, s.; Anovitz, L.; Wesolowski, D.

    2006-01-01

    Beta-2 microglobulin ({beta}2m) is a member of the immunoglobulin-like domain superfamily that is an essential structural subunit of the MHC class I (MHC-I) molecule. {beta}2m was previously identified as a susceptibility factor for the development of type 1 diabetes (T1D) in NOD mice, whereby transgenic expression of the {beta}2m{sup a} variant, but not the {beta}2mb variant, restored diabetes susceptibility to normally resistant NOD.{beta}2m{sup null} mice. Here we report the crystal structures and thermodynamic stabilities of the NOD MHC-I molecule H2-D{sup b} containing these two variants. Our results reveal subtle differences in the structures of the {beta}2m variants, namely in minor loop shifts and in variations in the hydrogen bonding networks at the interfaces between the components of the ternary complex. We also demonstrate that the thermodynamic stabilities of the {beta}2m variants in isolation differ. However, the conformation of the peptide in the MHC cleft is unchanged in {beta}2m allelic Db complexes, as are the TCR recognition surfaces. Thus, despite modest structural differences between allelic complexes, the evidence indicates that D{sup b} peptide presentation of the representative peptide is unchanged in the context of either {beta}2m allelic variant. These data suggest that other mechanisms, such as differential association of MHC-I in multiprotein complexes, are likely responsible for the effect of {beta}2m on T1D development.

  18. A tiny event producing an interplanetary type III burst

    NASA Astrophysics Data System (ADS)

    Alissandrakis, C. E.; Nindos, A.; Patsourakos, S.; Kontogeorgos, A.; Tsitsipis, P.

    2015-10-01

    Aims: We investigate the conditions under which small-scale energy release events in the low corona gave rise to strong interplanetary (IP) type III bursts. Methods: We analyzed observations of three tiny events, detected by the Nançay Radio Heliograph (NRH), two of which produced IP type III bursts. We took advantage of the NRH positioning information and of the high cadence of AIA/SDO data to identify the associated extreme-UV (EUV) emissions. We measured positions and time profiles of the metric and EUV sources. Results: We found that the EUV events that produced IP type III bursts were located near a coronal hole boundary, while the one that did not was located in a closed magnetic field region. In all three cases tiny flaring loops were involved, without any associated mass eruption. In the best observed case, the radio emission at the highest frequency (435 MHz) was displaced by ~55'' with respect to the small flaring loop. The metric type III emission shows a complex structure in space and in time, indicative of multiple electron beams, despite the low intensity of the events. From the combined analysis of dynamic spectra and NRH images, we derived the electron beam velocity as well as the height, ambient plasma temperature, and density at the level of formation of the 160 MHz emission. From the analysis of the differential emission measure derived from the AIA images, we found that the first evidence of energy release was at the footpoints, and this was followed by the development of flaring loops and subsequent cooling. Conclusions: Even small energy release events can accelerate enough electrons to give rise to powerful IP type III bursts. The proximity of the electron acceleration site to open magnetic field lines facilitates the escape of the electrons into the interplanetary space. The offset between the site of energy release and the metric type III location warrants further investigation. The movie is available in electronic form at http://www.aanda.org

  19. 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.

  20. TYPE III EXCITABILITY, SLOPE SENSITIVITY AND COINCIDENCE DETECTION.

    PubMed

    Meng, Xiangying; Huguet, Gemma; Rinzel, John

    2012-08-01

    Some neurons in the nervous system do not show repetitive firing for steady currents. For time-varying inputs, they fire once if the input rise is fast enough. This property of phasic firing is known as Type III excitability. Type III excitability has been observed in neurons in the auditory brainstem (MSO), which show strong phase-locking and accurate coincidence detection. In this paper, we consider a Hodgkin-Huxley type model (RM03) that is widely-used for phasic MSO neurons and we compare it with a modification of it, showing tonic behavior. We provide insight into the temporal processing of these neuron models by means of developing and analyzing two reduced models that reproduce qualitatively the properties of the exemplar ones. The geometric and mathematical analysis of the reduced models allows us to detect and quantify relevant features for the temporal computation such as nearness to threshold and a temporal integration window. Our results underscore the importance of Type III excitability for precise coincidence detection. PMID:23667306

  1. 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

  2. Transforming growth factor-betas and their signaling receptors are coexpressed in Crohn's disease.

    PubMed Central

    di Mola, F F; Friess, H; Scheuren, A; Di Sebastiano, P; Graber, H; Egger, B; Zimmermann, A; Korc, M; Büchler, M W

    1999-01-01

    OBJECTIVE: To evaluate mechanisms that contribute to tissue repair and tissue remodeling in Crohn's disease (CD). SUMMARY BACKGROUND DATA: Transforming growth factor-betas (TGF-betas) are involved in different chronic inflammatory disorders. They function by binding to two receptors, type I (TbetaR-I) subtype ALK5 and type II (TbetaR-II), which are concomitantly required for signal transduction. METHODS: Tissues were obtained from 18 patients with CD (10 female patients, 8 male patients, median age 38.7 years [range 16 to 58 years]) undergoing surgery because of CD-related complications. Tissue samples of 18 healthy organ donors (10 female subjects, 8 male subjects, median age 50.3 years [range 15 to 65 years]) served as controls. The expression and localization of TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-IALK5, TbetaR-II, and TbetaR-III were studied by Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS: On Northern blot analysis, 94% of the CD samples exhibited enhanced TGF-beta1, TGF-beta3, and TbetaR-II mRNA expression compared with controls. TGF-beta2 was increased in 72%, TbetaR-IALK5 in 72%, and TbetaR-III in 82% of the patients with CD. On in situ hybridization and immunohistochemical analysis, TGF-beta1, TbetaR-IALK5, and TbetaR-II were seen to be colocalized in the lamina propria cells and in the lymphocytes closest to the luminal surface, but also in the remaining epithelial cells, and in fibroblasts of CD tissue samples. CONCLUSIONS: The concomitant overexpression of TGF-betas and their signaling receptors in CD points to a potential role of these regulatory molecules in the pathophysiology of CD. Activation of TGF-beta-mediated pathways might promote the repair of mucosal injury by enhancing the process of reepithelization, but might also contribute to extracellular matrix generation and subsequently to intramural fibrosis and intestinal obstruction. Images Figure 1. Figure 3. Figure 4. Figure 5. PMID:9923802

  3. Spatial trends in Pearson Type III statistical parameters

    USGS Publications Warehouse

    Lichty, R.W.; Karlinger, M.R.

    1995-01-01

    Spatial trends in the statistical parameters (mean, standard deviation, and skewness coefficient) of a Pearson Type III distribution of the logarithms of annual flood peaks for small rural basins (less than 90 km2) are delineated using a climate factor CT, (T=2-, 25-, and 100-yr recurrence intervals), which quantifies the effects of long-term climatic data (rainfall and pan evaporation) on observed T-yr floods. Maps showing trends in average parameter values demonstrate the geographically varying influence of climate on the magnitude of Pearson Type III statistical parameters. The spatial trends in variability of the parameter values characterize the sensitivity of statistical parameters to the interaction of basin-runoff characteristics (hydrology) and climate. -from Authors

  4. EMISSION PATTERNS OF SOLAR TYPE III RADIO BURSTS: STEREOSCOPIC OBSERVATIONS

    SciTech Connect

    Thejappa, G.; Bergamo, M.; MacDowall, R. J. E-mail: mbergamo@umd.edu

    2012-02-01

    Simultaneous observations of solar type III radio bursts obtained by the STEREO A, B, and WIND spacecraft at low frequencies from different vantage points in the ecliptic plane are used to determine their directivity. The heliolongitudes of the sources of these bursts, estimated at different frequencies by assuming that they are located on the Parker spiral magnetic field lines emerging from the associated active regions into the spherically symmetric solar atmosphere, and the heliolongitudes of the spacecraft are used to estimate the viewing angle, which is the angle between the direction of the magnetic field at the source and the line connecting the source to the spacecraft. The normalized peak intensities at each spacecraft R{sub j} = I{sub j} /{Sigma}I{sub j} (the subscript j corresponds to the spacecraft STEREO A, B, and WIND), which are defined as the directivity factors are determined using the time profiles of the type III bursts. It is shown that the distribution of the viewing angles divides the type III bursts into: (1) bursts emitting into a very narrow cone centered around the tangent to the magnetic field with angular width of {approx}2 Degree-Sign and (2) bursts emitting into a wider cone with angular width spanning from {approx} - 100 Degree-Sign to {approx}100 Degree-Sign . The plots of the directivity factors versus the viewing angles of the sources from all three spacecraft indicate that the type III emissions are very intense along the tangent to the spiral magnetic field lines at the source, and steadily fall as the viewing angles increase to higher values. The comparison of these emission patterns with the computed distributions of the ray trajectories indicate that the intense bursts visible in a narrow range of angles around the magnetic field directions probably are emitted in the fundamental mode, whereas the relatively weaker bursts visible to a wide range of angles are probably emitted in the harmonic mode.

  5. Assembly and function of type III secretory systems.

    PubMed

    Cornelis, G R; Van Gijsegem, F

    2000-01-01

    Type III secretion systems allow Yersinia spp., Salmonella spp., Shigella spp., Bordetella spp., and Pseudomonas aeruginosa and enteropathogenic Escherichia coli adhering at the surface of a eukaryotic cell to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane to destroy or subvert the target cell. These systems consist of a secretion apparatus, made of approximately 25 proteins, and an array of proteins released by this apparatus. Some of these released proteins are "effectors," which are delivered into the cytosol of the target cell, whereas the others are "translocators," which help the effectors to cross the membrane of the eukaryotic cell. Most of the effectors act on the cytoskeleton or on intracellular-signaling cascades. A protein injected by the enteropathogenic E. coli serves as a membrane receptor for the docking of the bacterium itself at the surface of the cell. Type III secretion systems also occur in plant pathogens where they are involved both in causing disease in susceptible hosts and in eliciting the so-called hypersensitive response in resistant or nonhost plants. They consist of 15-20 Hrp proteins building a secretion apparatus and two groups of effectors: harpins and avirulence proteins. Harpins are presumably secreted in the extracellular compartment, whereas avirulence proteins are thought to be targeted into plant cells. Although a coherent picture is clearly emerging, basic questions remain to be answered. In particular, little is known about how the type III apparatus fits together to deliver proteins in animal cells. It is even more mysterious for plant cells where a thick wall has to be crossed. In spite of these haunting questions, type III secretion appears as a fascinating trans-kingdom communication device. PMID:11018143

  6. Arthroscopic-Assisted Fixation of Ideberg Type III Glenoid Fractures

    PubMed Central

    Tao, Matthew A.; Garrigues, Grant E.

    2015-01-01

    Operative treatment of scapular fractures with extension into the glenoid can be a challenging clinical scenario. Though traditionally addressed in an open fashion, the morbidity of this approach, complemented by advancements in arthroscopic technique and instrumentation, has led to increasing use of arthroscopic-assisted fixation. We describe our technique, including pearls and pitfalls, for minimally invasive fixation of Ideberg type III glenoid fractures. This approach minimizes morbidity, allows optimal visualization and reduction, and provides good functional results. PMID:26052487

  7. Murine gammaherpesvirus targets type I IFN receptor but not type III IFN receptor early in infection.

    PubMed

    Lopušná, Katarína; Benkóczka, Tímea; Lupták, Jakub; Matúšková, Radka; Lukáčiková, Ľubomíra; Ovečková, Ingrid; Režuchová, Ingeborg

    2016-07-01

    The innate immune response represents a primary line of defense against invading viral pathogens. Since epithelial cells are the primary site of gammaherpesvirus replication during infection in vivo and there are no information on activity of IFN-III signaling against gammaherpesviruses in this cell type, in present study, we evaluated the expression profile and virus-host interactions in mouse mammary epithelial cell (NMuMG) infected with three strains of murine gammaherpesvirus, MHV-68, MHV-72 and MHV-4556. Studying three strains of murine gammaherpesvirus, which differ in nucleotide sequence of some structural and non-structural genes, allowed us to compare the strain-dependent interactions with host organism. Our results clearly demonstrate that: (i) MHV-68, MHV-72 and MHV-4556 differentially interact with intracellular signaling and dysregulate IFN signal transduction; (ii) MHV-68, MHV-72 and MHV-4556 degrade type I IFN receptor in very early stages of infection (2-4hpi), but not type III IFN receptor; (iii) type III IFN signaling might play a key role in antiviral defense of epithelial cells in early stages of murine gammaherpesvirus replication; (iv) NMuMG cells are an appropriate model for study of not only type I IFN signaling, but also type III IFN signaling pathway. These findings are important for better understanding of individual virus-host interactions in lytic as well as in persistent gammaherpesvirus replication and help us to elucidate IFN-III function in early events of virus infection. PMID:27152708

  8. A Qualitative Study of Recovery from Type III-B and III-C Tibial Fractures

    PubMed Central

    Shauver, Melissa S.; Aravind, Maya S.; Chung, Kevin C.

    2011-01-01

    The literature has shown that long-term outcomes for both below-knee amputation and reconstruction following type III-B and III-C tibial fracture are poor. Yet, patients often report satisfaction with their treatment and/or outcomes. The aim of this study is to explore the relationship between patient outcomes and satisfaction after open tibial fractures via qualitative methodology. Twenty patients who were treated for open tibial fractures at one institution were selected using purposeful sampling and interviewed in-person in a semi-structured manner. Data were analyzed using grounded theory methodology. Despite reporting marked physical and psychosocial deficits, participants relayed high satisfaction. We hypothesize that the use adaptive coping techniques successfully reduces stress, which leads to an increase in coping self-efficacy that results in the further use of adaptive coping strategies, culminating in personal growth. This stress reduction and personal growth leads to satisfaction despite poor functional and emotional outcomes. PMID:20948418

  9. Effective Identification of Bacterial Type III Secretion Signals Using Joint Element Features

    PubMed Central

    Wang, Yejun; Sun, Ming’an; Bao, Hongxia; Zhang, Qing; Guo, Dianjing

    2013-01-01

    Type III secretion system (T3SS) plays important roles in bacteria and host cell interactions by specifically translocating type III effectors into the cytoplasm of the host cells. The N-terminal amino acid sequences of the bacterial type III effectors determine their specific secretion via type III secretion conduits. It is still unclear as to how the N-terminal sequences guide this specificity. In this work, the amino acid composition, secondary structure, and solvent accessibility in the N-termini of type III and non-type III secreted proteins were compared and contrasted. A high-efficacy mathematical model based on these joint features was developed to distinguish the type III proteins from the non-type III ones. The results indicate that secondary structure and solvent accessibility may make important contribution to the specific recognition of type III secretion signals. Analysis also showed that the joint feature of the N-terminal 6th–10th amino acids are especially important for guiding specific type III secretion. Furthermore, a genome-wide screening was performed to predict Salmonella type III secreted proteins, and 8 new candidates were experimentally validated. Interestingly, type III secretion signals were also predicted in gram-positive bacteria and yeasts. Experimental validation showed that two candidates from yeast can indeed be secreted through Salmonella type III secretion conduit. This research provides the first line of direct evidence that secondary structure and solvent accessibility contain important features for guiding specific type III secretion. The new software based on these joint features ensures a high accuracy (general cross-validation sensitivity of ∼96% at a specificity of ∼98%) in silico identification of new type III secreted proteins, which may facilitate our understanding about the specificity of type III secretion and the evolution of type III secreted proteins. PMID:23593149

  10. Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator.

    PubMed

    Imada, Katsumi; Minamino, Tohru; Uchida, Yumiko; Kinoshita, Miki; Namba, Keiichi

    2016-03-29

    FliI and FliJ form the FliI6FliJ ATPase complex of the bacterial flagellar export apparatus, a member of the type III secretion system. The FliI6FliJ complex is structurally similar to the α3β3γ complex of F1-ATPase. The FliH homodimer binds to FliI to connect the ATPase complex to the flagellar base, but the details are unknown. Here we report the structure of the homodimer of a C-terminal fragment of FliH (FliHC2) in complex with FliI. FliHC2 shows an unusually asymmetric homodimeric structure that markedly resembles the peripheral stalk of the A/V-type ATPases. The FliHC2-FliI hexamer model reveals that the C-terminal domains of the FliI ATPase face the cell membrane in a way similar to the F/A/V-type ATPases. We discuss the mechanism of flagellar ATPase complex formation and a common origin shared by the type III secretion system and the F/A/V-type ATPases. PMID:26984495

  11. A clinical study of canine collagen type III glomerulopathy

    PubMed Central

    2013-01-01

    Background Collagen type III glomerulopathy (Col3GP), also known as collagenofibrotic glomerulonephropathy, is a rare renal disease with unknown pathogenesis that occurs in animals and humans. We recently described a naturally occurring canine autosomal recessive model of Col3GP, and the aim of the present work was to study the clinical features of canine Col3GP and compare with the human phenotype. In humans two different clinical syndromes with different age at onset (child- or adulthood) have been observed. In children a more aggressive course with familial occurrence is described, characterized by progressively increasing proteinuria, nephrotic syndrome, hypertension and chronic renal failure. A markedly increased serum level of the aminoterminal propeptide of type III procollagen (PIIINP) is considered a useful marker for the disease. Since Col3GP and concurrent hypocomplementemia have been observed in humans, we also aimed to investigate if hypocomplementemia was present in Col3GP affected dogs. A litter consisting of seven puppies, four Col3GP affected and three healthy unaffected, was observed from the day of birth until the affected puppies developed a mild or moderate renal azotemia. Results During the period of observation growth retardation, increasing blood pressure, progressive proteinuria, azotemia, hypoalbuminemia, hypercholesterolemia and increased serum PIIINP were observed in all the affected dogs. Hypocomplementemia was not detected. Affected dogs were euthanized between 109 and 144 days of age, and pathological examinations revealed ascites and massive glomerular accumulations of collagen type III, consistent with Col3GP. Conclusions Dogs with Col3GP develop juvenile chronic renal failure, preceded by nephrotic syndrome, elevated serum PIIINP and hypertension, thus have similar clinical features as the juvenile Col3GP in humans. Further studies of this naturally occurring canine phenotype may provide more information on the pathogenesis and

  12. Modified Radical Mastoidectomy with Type III Tympanoplasty: Revisited.

    PubMed

    Goyal, Rashmi; Mourya, Ashish; Qureshi, Sadat; Sharma, Sandeep

    2016-03-01

    Chronic suppurative otitis media with cholesteatoma is a fairly common condition presenting in any ENT clinic and its surgery remains one of the most challenging surgeries in otology. The primary goal of cholesteatoma surgery is to clear the disease and produce a safe and stable ear but there is still debate on whether these goals are best achieved by canal wall down or canal wall up procedures. A retrospective study was done to access benefits of modified radical mastoidectomy (MRM) with type III tympanoplasty in terms of eradication of disease and hearing improvement. It consisted of 140 patients of chronic otitis media (attico-antral) who underwent MRM with type III tympanoplasty in 156 ears in a tertiary care centre. Temporalis fascia graft was used for tympanoplasty. Results were analyzed in terms of condition of cavity, condition of graft and gain in hearing. The study showed significant improvement in gain in air conduction (21.24 dB) and closure of AB gap (15.62 dB). In the Indian population with low socio-economic status and poor follow up, single stage canal wall down procedure (MRM) provides maximum benefit to patients in terms of eradication of disease and hearing improvement. PMID:27066411

  13. Wave-wave interactions in solar type III radio bursts

    SciTech Connect

    Thejappa, G.; MacDowall, R. J.

    2014-02-11

    The high time resolution observations from the STEREO/WAVES experiment show that in type III radio bursts, the Langmuir waves often occur as localized magnetic field aligned coherent wave packets with durations of a few ms and with peak intensities well exceeding the strong turbulence thresholds. Some of these wave packets show spectral signatures of beam-resonant Langmuir waves, down- and up-shifted sidebands, and ion sound waves, with frequencies, wave numbers, and tricoherences satisfying the resonance conditions of the oscillating two stream instability (four wave interaction). The spectra of a few of these wave packets also contain peaks at f{sub pe}, 2f{sub pe} and 3 f{sub pe} (f{sub pe} is the electron plasma frequency), with frequencies, wave numbers and bicoherences (computed using the wavelet based bispectral analysis techniques) satisfying the resonance conditions of three wave interactions: (1) excitation of second harmonic electromagnetic waves as a result of coalescence of two oppositely propagating Langmuir waves, and (2) excitation of third harmonic electromagnetic waves as a result of coalescence of Langmuir waves with second harmonic electromagnetic waves. The implication of these findings is that the strong turbulence processes play major roles in beam stabilization as well as conversion of Langmuir waves into escaping radiation in type III radio bursts.

  14. 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

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

    PubMed Central

    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

  16. Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Segarini, P.; Tsang, M. L.; Carroll, A. G.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1997-01-01

    The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the

  17. Inhibition of Type III Interferon Activity by Orthopoxvirus Immunomodulatory Proteins

    PubMed Central

    2010-01-01

    The type III interferon (IFN) family elicits an antiviral response that is nearly identical to that evoked by IFN-α/β. However, these cytokines (known as IFN-λ1, 2, and 3) signal through a distinct receptor, and thus may be resistant to the evasion strategies used by some viruses to avoid the IFN-α/β response. Orthopoxviruses are highly resistant to IFN-α/β because they encode well-characterized immunomodulatory proteins that inhibit IFN activity. These include a secreted receptor (B18R) that neutralizes IFN-α/β, and a cytoplasmic protein (E3L) that blocks IFN-α/β effector functions in infected cells. We therefore determined the ability of these immunomodulators to abrogate the IFN-λ–induced antiviral response. We found that (i) vaccinia virus (VACV) replication is resistant to IFN-λ antiviral activity; (ii) neither VACV B18R nor the variola virus homolog B20R neutralizes IFN-λ; (iii) VACV E3L inhibits the IFN-λ–mediated antiviral response through a PKR-dependent pathway; (iv) VACV infection inhibits IFN-λR–mediated signal transduction and gene expression. These results demonstrate differential sensitivity of IFN-λ to multiple distinct evasion mechanisms employed by a single virus. PMID:20038204

  18. Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons

    PubMed Central

    Rauch, Isabella; Rosebrock, Felix; Hainzl, Eva; Heider, Susanne; Majoros, Andrea; Wienerroither, Sebastian; Strobl, Birgit; Stockinger, Silvia; Kenner, Lukas; Müller, Mathias

    2015-01-01

    The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription factor with its Stat1, Stat2, and interferon regulatory factor 9 (IRF9) subunits is employed for transcriptional responses downstream of receptors for type I interferons (IFN-I) that include IFN-α and IFN-β and type III interferons (IFN-III), also called IFN-λ. Here, we show in a murine model of dextran sodium sulfate (DSS)-induced colitis that IRF9 deficiency protects animals, whereas the combined loss of IFN-I and IFN-III receptors worsens their condition. We explain the different phenotypes by demonstrating a function of IRF9 in a noncanonical transcriptional complex with Stat1, apart from IFN-I and IFN-III signaling. Together, Stat1 and IRF9 produce a proinflammatory activity that overrides the benefits of the IFN-III response on intestinal epithelial cells. Our results further suggest that the CXCL10 chemokine gene is an important mediator of this proinflammatory activity. We thus establish IFN-λ as a potentially anticolitogenic cytokine and propose an important role for IRF9 as a component of noncanonical Stat complexes in the development of colitis. PMID:25918247

  19. Clark Lake microbursts - On a lower limit to type III burst brightness temperatures

    NASA Technical Reports Server (NTRS)

    White, S. M.; Kundu, M. R.; Szabo, A.

    1987-01-01

    Further observations of solar microbursts by the Clark Lake radioheliograph are reported. The microbursts have properties consistent with weak type III bursts, with the implication that type III's can have brightness temperatures as low as 1 million K. The importance of this result is explored. A single model to explain the stronger type III bursts and the weaker microbursts is sought. It is shown that none of the models for stabilizing the strongest type III electron streams can explain the observed microbursts: these models have threshold levels of Langmuir waves which imply emission (due to spontaneous scattering off ions) with brightness temperatures in excess of those observed. It appears that either some vital physics is still missing from models for type III bursts, or that microbursts should have properties significantly different from those of type III bursts. In the latter case further observations should allow important tests of type III models.

  20. Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production.

    PubMed Central

    Davis, B H; Kramer, R T; Davidson, N O

    1990-01-01

    Recent studies suggest that vitamin A plays an inhibitory role with respect to "activation" of the hepatic Ito cell, a likely effector of hepatic fibrogenesis. Ito cell "activation" during fibrogenesis is characterized by a decrease in intracellular vitamin A and an increase in cellular proliferation and collagen production. To explore the hypothesis that retinoids have the capacity to diminish Ito cell activation, cultured Ito cells were exposed to retinoic acid and its effects assessed on three key features: cell proliferation, collagen protein production and mRNA abundance, and transforming growth factor beta protein production. Retinoic acid was 100-1,000X more potent than retinol with respect to inhibition of Ito cell proliferation. Interstitial collagen and transforming growth factor beta production were also reduced by 10(-6) M retinoic acid. The relative abundance of type I collagen mRNA however, was not significantly altered. By contrast, retinoic acid administration to rats caused a marked reduction in the abundance of type I collagen mRNA in both total hepatic and purified Ito cell RNA. The relative abundance of rat hepatic fibronectin or apolipoprotein E mRNA was not significantly altered. These studies demonstrate that retinoic acid can differentially modulate several key features of hepatic fibrogenesis in vitro and in vivo. Images PMID:2254460

  1. High-Frequency Cutoff in Type III Bursts

    NASA Astrophysics Data System (ADS)

    Stanislavsky, A. A.; Konovalenko, A. A.; Volvach, Ya. S.; Koval, A. A.

    In this article we report about a group of solar bursts with high-frequency cutoff, observed on 19 August of 2012 near 8:23 UT, simultaneously by three different radio telescopes: the Ukrainian decameter radio telescope (8-33 MHz), the French Nancay Decametric Array (10-70 MHz) and the Italian San Vito Solar Observatory of RSTN (25-180 MHz). Morphologically the bursts are very similar to the type III bursts. The solar activity is connected with the emergency of a new group of solar spots on the far side of the Sun with respect to observers on Earth. The solar bursts accompany many moderate flares over eastern limb. The refraction of the behind-limb radio bursts towards the Earth is favorable, if CMEs generate low-density cavities in solar corona.

  2. Yersinia Type III Secretion System Master Regulator LcrF

    PubMed Central

    Schwiesow, Leah; Lam, Hanh

    2015-01-01

    Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters. PMID:26644429

  3. Type III radio source located by Ulysses/Wind triangulation

    NASA Astrophysics Data System (ADS)

    Reiner, M. J.; Fainberg, J.; Kaiser, M. L.; Stone, R. G.

    1998-02-01

    Radio triangulation from the widely separated Ulysses and Wind spacecraft is used to reconstruct the trajectory of a type III radio burst in the 3D heliosphere. The derived radio trajectory follows a (Parker) spiral path corresponding to a solar wind speed of about 200 km/s and progresses to the south of the ecliptic plane. These remote radio observations also measure the interplanetary plasma density along the path of the radio source. The derived average density-distance scale is very similar to the previously derived RAE density scale, which was determined in a different way. The results of the radio triangulation, combined with a drift rate analysis, give an average electron exciter speed of about 0.3 c. The radio source size and the brightness temperature as viewed from Ulysses and Wind are determined and compared as a function of observing frequency.

  4. Surgical management of Mason type III radial head fractures

    PubMed Central

    Miller, George; Humadi, Ali; Unni, Raghavan; Hau, Raphael

    2013-01-01

    The evidence for optimal management of Mason type III fracture of radial head is unclear hence a systematic review of the published literature was performed in April 2012. This review includes 5 prospective studies (including 2 randomized trials), 4 retrospective studies and 9 case series. No study can be interpreted as level 1 evidence. Level 2 and 3 evidence provides some insight into the success of each modality through subjective and objective measurements of function and complication rates. Radial head replacement, open reduction internal fixation (ORIF) and radial head resection all provide satisfactory outcomes for patients in most cases. One treatment modality cannot be recommended over any other due to the small number of clinical trials and cases included in each study. Further randomized control trials are needed to evaluate the full benefits and shortcomings of each of the different surgical treatment modalities. PMID:23960274

  5. Yersinia Type III Secretion System Master Regulator LcrF.

    PubMed

    Schwiesow, Leah; Lam, Hanh; Dersch, Petra; Auerbuch, Victoria

    2016-02-01

    Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters. PMID:26644429

  6. Near-Relativistic Solar Electrons and Type III Radio Bursts

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    2003-01-01

    Recently it has been found that the inferred injection times of greater than 25 keV electrons are up to 30 minutes later than the start times of the associated type III radio bursts at the Sun. Thus it has been suggested that the electrons that produce type III bursts do not belong to the same population as those observed above 25 keV. This paper examines the characteristics and circumstances of 79 solar electron beam events measured on the ACE spacecraft. Particular attention is paid to the very low frequency emissions of the associated radio bursts and the ambient conditions at the arrival times of the electrons at the spacecraft. It is found that the inferred greater than 25 keV electron injection delays are correlated with the times required for the associated radio bursts to drift to the lowest frequencies. This suggests that the electrons responsible for the radio emission and those observed above 25 keV are part of a single population, and that the electrons both above and below 25 keV are delayed in the interplanetary medium. Further evidence for a single population is the general correspondence between electron and local radio intensities and temporal profiles. It is found that the delays increase with the ambient solar wind density consistent with the propagation times of the electrons being determined by the characteristics of the interplanetary medium. However it is known that particle arrival times at 1 AU are a linear function of inverse particle speed. Conventionally such a relationship is taken to indicate scatter-free propagation when inferred path lengths lie close to 1.2 AU, as they do for the electron events studied here. These conflicting interpretations require further investigation.

  7. Response of a Type III waste tank to hydrogen deflagration

    SciTech Connect

    Gong, Chung; Jerrell, J.W.; Pelfrey, J.R.; Yau, W.W.F.

    1992-01-01

    The type III waste tank is built with ASTM A516 Grade 70 steel shells in the shape of a torus with a central concrete core. The tank is buried underground and covered with a four foot thick reinforced concrete slab. The tank is enriched by 2.5 foot thick reinforced concrete wall. Between the tank surface and the wall there is a 2.5 foot annular space. The tank itself is called the primary liner.'' The interior surface of the concrete wall is line with steel plates, called the secondary liner.'' The base of the tank rests on a concrete mat. Underneath the mat the secondary liner extends from the wall to the central column surfaces. The bottom liner is attached to the reinforced concrete foundation. Based on the conditions that the tank is filled with liquid wastes to 50% of the design capacity, and that the accumulation of hydrogen becomes 20% inside its free board, the resulting deflagration would cause an overpressure of 100 psig in the tank (Wallace and Yau, 1986). The task of this analysis is to simulate the hydrogen deflagration'' scenario in the Type III Waste Tank complex. During the deflagration, the stresses in the steel tank would be expected to exceed the elastic limit of the steel and the tank would then undergo large deformation. The concrete roof slab could be fractured by the expansion of the tank. The central concrete column would start to exhibit large deformation first. All the structural members in the system are expected to interact drastically during the deflagration.

  8. Response of a Type III waste tank to hydrogen deflagration

    SciTech Connect

    Gong, Chung; Jerrell, J.W.; Pelfrey, J.R.; Yau, W.W.F.

    1992-05-01

    The type III waste tank is built with ASTM A516 Grade 70 steel shells in the shape of a torus with a central concrete core. The tank is buried underground and covered with a four foot thick reinforced concrete slab. The tank is enriched by 2.5 foot thick reinforced concrete wall. Between the tank surface and the wall there is a 2.5 foot annular space. The tank itself is called the ``primary liner.`` The interior surface of the concrete wall is line with steel plates, called the ``secondary liner.`` The base of the tank rests on a concrete mat. Underneath the mat the secondary liner extends from the wall to the central column surfaces. The bottom liner is attached to the reinforced concrete foundation. Based on the conditions that the tank is filled with liquid wastes to 50% of the design capacity, and that the accumulation of hydrogen becomes 20% inside its free board, the resulting deflagration would cause an overpressure of 100 psig in the tank [Wallace and Yau, 1986]. The task of this analysis is to simulate the ``hydrogen deflagration`` scenario in the Type III Waste Tank complex. During the deflagration, the stresses in the steel tank would be expected to exceed the elastic limit of the steel and the tank would then undergo large deformation. The concrete roof slab could be fractured by the expansion of the tank. The central concrete column would start to exhibit large deformation first. All the structural members in the system are expected to interact drastically during the deflagration.

  9. Hereditary angioedema with normal C1-INH (HAE type III).

    PubMed

    Riedl, Marc A

    2013-01-01

    Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency. PMID:24565612

  10. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    PubMed Central

    Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

    2013-01-01

    The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway. PMID:23503326

  11. Thermal stability of type I and type III procollagens from normal human fibroblasts and from a patient with osteogenesis imperfecta.

    PubMed

    Peltonen, L; Palotie, A; Hayashi, T; Prockop, D J

    1980-01-01

    Type I and type III procollagens were isolated from the medium of human fibroblast cultures in amounts adequate for examination by circular dichroism. Type I procollagen had a spectrum similar to that of type I procollagen and collagen from chicken embryos. The human type III procollagen showed a red shift not seen in type III collagen from calf skin. The midpoint (tm) for the helix-to-coil transition for both human procollagens was 40 degrees C. the same tm values were obtained with type I and type III procollagens synthesized by fibroblasts from a patient with osteogenesis imperfecta. Type I procollagen synthesized by the patient's fibroblasts, however, tended to aggregate more readily than type I procollagen from normal human fibroblasts, apparently because of a structural alteration of the protein. PMID:6928611

  12. Adsorptive separation of rhodium(III) using Fe(III)-templated oxine type of chemically modified chitosan

    SciTech Connect

    Alam, M.S.; Inoue, Katsutoshi; Yoshizuka, Kazuharu; Ishibashi, Hideaki

    1998-03-01

    The oxine type of chemically modified chitosan was prepared by the template crosslinking method using Fe(III) as a template ion. Batchwise adsorption of rhodium(III) on this chemically modified chitosan was examined from chloride media in the absence and presence of a large amount of tin(II). It was observed that the Fe(III)-templated oxine type of chemically modified chitosan shows better performance for rhodium adsorption than that of the original chitosan. When Sn(II) is absent from the solution, Rh(III) is hardly adsorbed on the modified chitosan and the order of selectivity of the adsorption of Rh(III), Pt(IV), and Cu(II) was found to be Pt(IV) > Cu(II) {approx} Rh(III). On the other hand, adsorption of rhodium is significantly increased in the presence of Sn(II) and the selectivity order of the adsorption was drastically changed to Rh(III) > Pt(IV) {much_gt} Cu(II), which ensures selective separation of Rh(III) from their mixture. Adsorption of Rh(III) increases with an increase in the concentration of Sn(II) in the aqueous solution, and maximum adsorption is achieved at a molar ratio, [Sn]/[Rh], of >6. The adsorption of Rh(III) decreases at a high concentration of hydrochloric acid. The maximum adsorption capacity was evaluated to be 0.92 mol/kg-dry adsorbent. Stripping tests of rhodium from the loaded chemically modified chitosan were carried out using different kinds of stripping agents containing some oxidizing agent. The maximum stripping of rhodium under these experimental conditions was found to be 72.5% by a single contact with 0.5 M HCl + 8 M HNO{sub 3}.

  13. Solar Flares, Type III Radio Bursts, CMEs, and Energetic Particles

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    2004-01-01

    Despite the fact that it has been well known since the earliest observations that solar energetic particle events are well associated with solar flares it is often considered that the association is not physically significant. Instead, in large events, the particles are considered to be only accelerated at a shock driven by the coronal mass ejection (CME) that is also always present. If particles are accelerated in the associated flare, it is claimed that such particles do not find access to open field lines and therefore do not escape from the low corona. However recent work has established that long lasting type III radio bursts extending to low frequencies are associated with all prompt solar particle events. Such bursts establish the presence of open field lines. Furthermore, tracing the radio bursts to the lowest frequencies, generated near the observer, shows that the radio producing electrons gain access to a region of large angular extent. It is likely that the electrons undergo cross field transport and it seems reasonable that ions do also. Such observations indicate that particle propagation in the inner heliosphere is not yet fully understood. They also imply that the contribution of flare particles in major particle events needs to be properly addressed.

  14. The Structure and Function of Type III Secretion Systems

    PubMed Central

    Notti, Ryan Q.; Stebbins, C. Erec

    2015-01-01

    ARTICLE SUMMARY Type III secretion systems (T3SS) afford gram-negative bacteria a most intimate means of altering the biology of their eukaryotic hosts — the direct delivery of effector proteins from the bacterial cytoplasm to that of the eukaryote. This incredible biophysical feat is accomplished by nanosyringe “injectisomes,” which form a conduit across the three plasma membranes, peptidoglycan layer and extracellular space that form a barrier to the direct delivery of proteins from bacterium to host. The focus of this chapter is T3SS function at the structural level; we will summarize the core findings that have shaped our understanding of the structure and function of these systems and highlight recent developments in the field. In turn, we describe the T3SS secretory apparatus, consider its engagement with secretion substrates, and discuss the post-translational regulation of secretory function. Lastly, we close with a discussion of the future prospects for the interrogation of structure-function relationships in the T3SS. PMID:26999392

  15. Functional Activation of the Flagellar Type III Secretion Export Apparatus

    PubMed Central

    Phillips, Andrew M.; Calvo, Rebecca A.; Kearns, Daniel B.

    2015-01-01

    Flagella are assembled sequentially from the inside-out with morphogenetic checkpoints that enforce the temporal order of subunit addition. Here we show that flagellar basal bodies fail to proceed to hook assembly at high frequency in the absence of the monotopic protein SwrB of Bacillus subtilis. Genetic suppressor analysis indicates that SwrB activates the flagellar type III secretion export apparatus by the membrane protein FliP. Furthermore, mutants defective in the flagellar C-ring phenocopy the absence of SwrB for reduced hook frequency and C-ring defects may be bypassed either by SwrB overexpression or by a gain-of-function allele in the polymerization domain of FliG. We conclude that SwrB enhances the probability that the flagellar basal body adopts a conformation proficient for secretion to ensure that rod and hook subunits are not secreted in the absence of a suitable platform on which to polymerize. PMID:26244495

  16. The Type III Secretion Translocation Pore Senses Host Cell Contact

    PubMed Central

    Armentrout, Erin I.; Rietsch, Arne

    2016-01-01

    Type III secretion systems (T3SS) are nano-syringes used by a wide range of Gram-negative pathogens to promote infection by directly injecting effector proteins into targeted host cells. Translocation of effectors is triggered by host-cell contact and requires assembly of a pore in the host-cell plasma membrane, which consists of two translocator proteins. Our understanding of the translocation pore, how it is assembled in the host cell membrane and its precise role in effector translocation, is extremely limited. Here we use a genetic technique to identify protein-protein contacts between pore-forming translocator proteins, as well as the T3SS needle-tip, that are critical for translocon function. The data help establish the orientation of the translocator proteins in the host cell membrane. Analysis of translocon function in mutants that break these contacts demonstrates that an interaction between the pore-forming translocator PopD and the needle-tip is required for sensing host cell contact. Moreover, tethering PopD at a dimer interface also specifically prevents host-cell sensing, arguing that the translocation pore is actively involved in detecting host cell contact. The work presented here therefore establishes a signal transduction pathway for sensing host cell contact that is initiated by a conformational change in the translocation pore, and is subsequently transmitted to the base of the apparatus via a specific contact between the pore and the T3SS needle-tip. PMID:27022930

  17. Transgenic silkworms produce recombinant human type III procollagen in cocoons.

    PubMed

    Tomita, Masahiro; Munetsuna, Hiroto; Sato, Tsutomu; Adachi, Takahiro; Hino, Rika; Hayashi, Masahiro; Shimizu, Katsuhiko; Nakamura, Namiko; Tamura, Toshiki; Yoshizato, Katsutoshi

    2003-01-01

    We describe the generation of transgenic silkworms that produce cocoons containing recombinant human collagen. A fusion cDNA was constructed encoding a protein that incorporated a human type III procollagen mini-chain with C-propeptide deleted, a fibroin light chain (L-chain), and an enhanced green fluorescent protein (EGFP). This cDNA was ligated downstream of the fibroin L-chain promoter and inserted into a piggyBac vector. Silkworm eggs were injected with the vectors, producing worms displaying EGFP fluorescence in their silk glands. The cocoons emitted EGFP fluorescence, indicating that the promoter and fibroin L-chain cDNAs directed the synthesized products to be secreted into cocoons. The presence of fusion proteins in cocoons was demonstrated by immunoblotting, collagenase-sensitivity tests, and amino acid sequencing. The fusion proteins from cocoons were purified to a single electrophoretic band. This study demonstrates the viability of transgenic silkworms as a tool for producing useful proteins in bulk. PMID:12483223

  18. GOES Type III Loop Heat Pipe Life Test Results

    NASA Technical Reports Server (NTRS)

    Ottenstein, Laura

    2011-01-01

    The GOES Type III Loop Heat Pipe (LHP) was built as a life test unit for the loop heat pipes on the GOES N-Q series satellites. This propylene LHP was built by Dynatherm Corporation in 2000 and tested continuously for approximately 14 months. It was then put into storage for 3 years. Following the storage period, the LHP was tested at Swales Aerospace to verify that the loop performance hadn t changed. Most test results were consistent with earlier results. At the conclusion of testing at Swales, the LHP was transferred to NASA/GSFC for continued periodic testing. The LHP has been set up for testing in the Thermal Lab at GSFC since 2006. A group of tests consisting of start-ups, power cycles, and a heat transport limit test have been performed every six to nine months since March 2006. Tests results have shown no change in the loop performance over the five years of testing. This presentation will discuss the test hardware, test set-up, and tests performed. Test results to be presented include sample plots from individual tests, along with conductance measurements for all tests performed.

  19. Polarization and position measurements of Type III bursts

    NASA Technical Reports Server (NTRS)

    Suzuki, S.; Sheridan, K. V.; Dulk, G. A.

    1980-01-01

    The positional and polarization characteristics of Type III bursts in the range 24-220 MHz as measured by the Culgoora radioheliograph, spectrograph and spectropolarimeter are reported. The study includes 997 bursts which are of two classes: fundamental-harmonic (F-H) pairs and 'structureless' bursts with no visible F-H structure, and concentrates on the polarization of the bursts and the variation of polarization from centre to limb. The observed centre-to-limb decrease in polarization approximately follows a cosine law. This decrease is not as predicted by simple theory but is consistent with other observations which imply that open field lines from an active region diverge strongly. The observed o-mode polarization of harmonic radiation implies that the wave vectors of Langmuir waves are always parallel, within about 20 deg, to the magnetic field, while the constancy of H polarization with frequency implies that the ratio of gyromagnetic to plasma frequency, the Alfven speed and the plasma beta are constant with height on the open field lines above an active region. Finally, it is inferred that some factor, in addition to the magnetic field strength, controls the polarization of F radiation.

  20. RIEGER-TYPE PERIODICITY IN THE OCCURRENCE OF SOLAR TYPE III RADIO BURSTS

    SciTech Connect

    Lobzin, V. V.; Cairns, Iver H.; Robinson, P. A.

    2012-08-01

    This Letter presents the first observations of a Rieger-type periodicity with the period of 156{sub -9}{sup +19} days in the occurrence rate of solar coronal type III radio bursts. The periodicity was detected during the time interval from 2000 June 22 to 2003 December 31. This interval partially contains the maximum and the declining phase of solar cycle 23. The radio spectra were provided by the Learmonth Solar Radio Observatory in Western Australia, part of the USAF Radio Solar Telescope Network.

  1. Rieger-type Periodicity in the Occurrence of Solar Type III Radio Bursts

    NASA Astrophysics Data System (ADS)

    Lobzin, V. V.; Cairns, Iver H.; Robinson, P. A.

    2012-08-01

    This Letter presents the first observations of a Rieger-type periodicity with the period of 156{+19\\atop -9} days in the occurrence rate of solar coronal type III radio bursts. The periodicity was detected during the time interval from 2000 June 22 to 2003 December 31. This interval partially contains the maximum and the declining phase of solar cycle 23. The radio spectra were provided by the Learmonth Solar Radio Observatory in Western Australia, part of the USAF Radio Solar Telescope Network.

  2. A statistical study of solar type III bursts and auroral kilometric radiation onsets

    NASA Astrophysics Data System (ADS)

    Farrell, W. M.; Gurnett, D. A.

    1985-10-01

    Simultaneous occurrences of type III solar radio bursts and auroral kilometric radiation were observed by Calvert (1981) using ISEE 1 spectrograms. Calvert presented evidence suggesting that the incoming type III burst stimulates the onset of auroral kilometric radiation (AKR). This paper presents a statistical study of the correlation between type III bursts and auroral kilometric radiation. A superposed epoch analysis was performed on as many as 186 type III events. The type III bursts were detected by the ISEE 3 spacecraft on the sunward side of the earth. At the same time the IMP 8 spacecraft was used to detect onsets of kilometric radiation on the nightside of the earth. For each event the intensities measured by ISEE 3 (type III intensities) were subtracted from the intensities measured by IMP 8 (type III and possible AKR intensities). The resulting intensities for each event were then added to determine if kilometric radiation was preferentially observed following a type III burst. This analysis was performed at frequencies of 100, 178, and 500 kHz. The results of this study show that a statistically significant correlation exists between incoming type III bursts from the sun and kilometric radiation from the earth.

  3. Yersinia type III effectors perturb host innate immune responses.

    PubMed

    Pha, Khavong; Navarro, Lorena

    2016-02-26

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  4. Protein export through the bacterial flagellar type III export pathway.

    PubMed

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID:24064315

  5. Yersinia type III effectors perturb host innate immune responses

    PubMed Central

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  6. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    PubMed

    Georgy, Gehan S; Nassar, Noha N; Mansour, Hanaa A; Abdallah, Dalaal M

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and

  7. The latent transforming growth factor beta binding protein (LTBP) family.

    PubMed Central

    Oklü, R; Hesketh, R

    2000-01-01

    The transforming growth factor beta (TGFbeta) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFbetas is regulated by their association with latency-associated proteins and latent TGFbeta binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFbeta activity, is associated with a variety of cancers. PMID:11104663

  8. A note on tilted Bianchi type VIh models: the type III bifurcation

    NASA Astrophysics Data System (ADS)

    Coley, A. A.; Hervik, S.

    2008-10-01

    In this note we complete the analysis of Hervik, van den Hoogen, Lim and Coley (2007 Class. Quantum Grav. 24 3859) of the late-time behaviour of tilted perfect fluid Bianchi type III models. We consider models with dust, and perfect fluids stiffer than dust, and eludicate the late-time behaviour by studying the centre manifold which dominates the behaviour of the model at late times. In the dust case, this centre manifold is three-dimensional and can be considered a double bifurcation as the two parameters (h and γ) of the type VIh model are varied. We therefore complete the analysis of the late-time behaviour of tilted ever-expanding Bianchi models of types I VIII.

  9. Transforming Growth Factor {beta} Can Stimulate Smad1 Phosphorylation Independently of Bone Morphogenic Protein Receptors.

    PubMed

    Wrighton, Katharine H; Lin, Xia; Yu, Paul B; Feng, Xin-Hua

    2009-04-10

    Transforming growth factor-beta (TGFbeta) superfamily ligands control a diverse set of cellular processes by activating type I and type II serine-threonine receptor kinases. Canonical TGFbeta signaling is mediated via the TbetaRI/ALK5 type I receptor that phosphorylates Smad2 and Smad3 in their SXS motif to facilitate their activation and subsequent role in transcriptional regulation. Canonical bone morphogenic protein (BMP) signaling is mediated via the ALK1/2/3/6 type I receptors that phosphorylate Smad1, Smad5, and Smad8 in their SXS motif. However, studies in endothelial cells have shown that TGFbeta can also lead to the phosphorylation of Smad1, dependent on ALK1 receptor activity. Here we present data showing that TGFbeta can significantly induce Smad1 phosphorylation in several non-endothelial cell lineages. Additionally, by using chemical inhibitors specific for the TGFbeta/activin/nodal (ALK4/5/7) and BMP (ALK1/2/3/6) type I receptors, we show that in some cell types TGFbeta induces Smad1 phosphorylation independently of the BMP type I receptors. Thus, TGFbeta-mediated Smad1 phosphorylation appears to occur via different receptor complexes in a cell type-specific manner. PMID:19224917

  10. Immunomodulation by the Pseudomonas syringae HopZ Type III Effector Family in Aribidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas syringae employs a type III secretion system to inject 20-30 different type III effector (T3SE) proteins into plant host cells. A major role of T3SEs is to suppress plant immune responses and promote bacterial infection. The YopJ/HopZ acetyltransferases are a superfamily of T3SEs found i...

  11. 77 FR 76382 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

    ...This document contains both final regulations and temporary regulations regarding the requirements to qualify as a Type III supporting organization that is operated in connection with one or more supported organizations. The regulations reflect changes to the law made by the Pension Protection Act of 2006. The regulations will affect Type III supporting organizations and their supported......

  12. ROLE OF TYPE III PROTEIN SECRETION SYSTEM IN SINORHIZOBIUM FREDII USDA257 AND SOYBEAN INTERACTIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant and animal pathogenic bacteria have evolved a specialized protein secretion system called type III to directly inject proteins into their host cells. The Type III secretion system (TTSS) plays an important role in plant-microbe interactions since mutation in TTSS causes a loss of bacterial pa...

  13. Antiviral activity of bovine type III interferon against foot-and-mouth disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interferons (IFN) are the first line of defense against viral infections. Recently a new family of IFNs, type III, has been identified in humans, mice, swine and chickens. Here we report the identification and characterization of a member of the bovine type III IFN family, boIFN-lambda3, also known...

  14. 46 CFR 171.082 - Damage stability standards for vessels with Type III subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Damage stability standards for vessels with Type III...) SUBDIVISION AND STABILITY SPECIAL RULES PERTAINING TO VESSELS CARRYING PASSENGERS Large Vessels § 171.082 Damage stability standards for vessels with Type III subdivision. (a) Each vessel must be shown by...

  15. HCV infection selectively impairs type I but not type III IFN signaling.

    PubMed

    Chandra, Partha K; Bao, Lili; Song, Kyoungsub; Aboulnasr, Fatma M; Baker, Darren P; Shores, Nathan; Wimley, William C; Liu, Shuanghu; Hagedorn, Curt H; Fuchs, Serge Y; Wu, Tong; Balart, Luis A; Dash, Srikanta

    2014-01-01

    A stable and persistent Hepatitis C virus (HCV) replication cell culture model was developed to examine clearance of viral replication during long-term treatment using interferon-α (IFN-α), IFN-λ, and ribavirin (RBV). Persistently HCV-infected cell culture exhibited an impaired antiviral response to IFN-α+RBV combination treatment, whereas IFN-λ treatment produced a strong and sustained antiviral response that cleared HCV replication. HCV replication in persistently infected cells induced chronic endoplasmic reticulum (ER) stress and an autophagy response that selectively down-regulated the functional IFN-α receptor-1 chain of type I, but not type II (IFN-γ) or type III (IFN-λ) IFN receptors. Down-regulation of IFN-α receptor-1 resulted in defective JAK-STAT signaling, impaired STAT phosphorylation, and impaired nuclear translocation of STAT. Furthermore, HCV replication impaired RBV uptake, because of reduced expression of the nucleoside transporters ENT1 and CNT1. Silencing ER stress and the autophagy response using chemical inhibitors or siRNA additively inhibited HCV replication and induced viral clearance by the IFN-α+RBV combination treatment. These results indicate that HCV induces ER stress and that the autophagy response selectively impairs type I (but not type III) IFN signaling, which explains why IFN-λ (but not IFN-α) produced a sustained antiviral response against HCV. The results also indicate that inhibition of ER stress and of the autophagy response overcomes IFN-α+RBV resistance mechanisms associated with HCV infection. PMID:24215913

  16. HCV Infection Selectively Impairs Type I but Not Type III IFN Signaling

    PubMed Central

    Chandra, Partha K.; Bao, Lili; Song, Kyoungsub; Aboulnasr, Fatma M.; Baker, Darren P.; Shores, Nathan; Wimley, William C.; Liu, Shuanghu; Hagedorn, Curt H.; Fuchs, Serge Y.; Wu, Tong; Balart, Luis A.; Dash, Srikanta

    2015-01-01

    A stable and persistent Hepatitis C virus (HCV) replication cell culture model was developed to examine clearance of viral replication during long-term treatment using interferon-α (IFN-α), IFN-λ, and ribavirin (RBV). Persistently HCV-infected cell culture exhibited an impaired antiviral response to IFN-α+RBV combination treatment, whereas IFN-λ treatment produced a strong and sustained antiviral response that cleared HCV replication. HCV replication in persistently infected cells induced chronic endoplasmic reticulum (ER) stress and an autophagy response that selectively down-regulated the functional IFN-α receptor-1 chain of type I, but not type II (IFN-γ) or type III (IFN-λ) IFN receptors. Down-regulation of IFN-α receptor-1 resulted in defective JAK–STAT signaling, impaired STAT phosphorylation, and impaired nuclear translocation of STAT. Furthermore, HCV replication impaired RBV uptake, because of reduced expression of the nucleoside transporters ENT1 and CNT1. Silencing ER stress and the autophagy response using chemical inhibitors or siRNA additively inhibited HCV replication and induced viral clearance by the IFN-α+RBV combination treatment. These results indicate that HCV induces ER stress and that the autophagy response selectively impairs type I (but not type III) IFN signaling, which explains why IFN-λ (but not IFN-α) produced a sustained antiviral response against HCV. The results also indicate that inhibition of ER stress and of the autophagy response overcomes IFN-α+RBV resistance mechanisms associated with HCV infection. PMID:24215913

  17. Transforming growth factor-{beta}-inducible phosphorylation of Smad3.

    PubMed

    Wang, Guannan; Matsuura, Isao; He, Dongming; Liu, Fang

    2009-04-10

    Smad proteins transduce the transforming growth factor-beta (TGF-beta) signal at the cell surface into gene regulation in the nucleus. Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail. Here we show that in addition to the C-tail, three (S/T)-P sites in the Smad3 linker region, Ser(208), Ser(204), and Thr(179) are phosphorylated in response to TGF-beta. The linker phosphorylation peaks at 1 h after TGF-beta treatment, behind the peak of the C-tail phosphorylation. We provide evidence suggesting that the C-tail phosphorylation by the TGF-beta receptor is necessary for the TGF-beta-induced linker phosphorylation. Although the TGF-beta receptor is necessary for the linker phosphorylation, the receptor itself does not phosphorylate these sites. We further show that ERK is not responsible for TGF-beta-dependent phosphorylation of these three sites. We show that GSK3 accounts for TGF-beta-inducible Ser(204) phosphorylation. Flavopiridol, a pan-CDK inhibitor, abolishes TGF-beta-induced phosphorylation of Thr(179) and Ser(208), suggesting that the CDK family is responsible for phosphorylation of Thr(179) and Ser(208) in response to TGF-beta. Mutation of the linker phosphorylation sites to nonphosphorylatable residues increases the ability of Smad3 to activate a TGF-beta/Smad-target gene as well as the growth-inhibitory function of Smad3. Thus, these observations suggest that TGF-beta-induced phosphorylation of Smad3 linker sites inhibits its antiproliferative activity. PMID:19218245

  18. Tumor necrosis factor-beta in human pregnancy and labor.

    PubMed

    Laham, N; Van Dunné, F; Abraham, L J; Farrugia, W; Bendtzen, K; Brennecke, S P; Rice, G E

    1997-04-01

    The aims of this study were to determine tumor necrosis factor-beta (TNF-beta) concentration profiles in peripheral venous plasma and amniotic fluid during pregnancy and at the time of labor and to characterise TNF-beta mRNA expression and TNF-beta release from human gestational tissues. In addition, we investigated the expression of TNF-beta binding protein, lymphotoxin-beta (LT-beta), in human gestational tissues. The mean (+/-S.E.M.) TNF-beta concentrations in maternal plasma (TIL, 78 +/- 12 pg/ml, n = 7 vs. TNIL, 304 +/- 88 pg/ml, n = 7) and amniotic fluid (TIL, 8 +/- 5 pg/ml, n = 6 vs. TNIL, 73 +/- 20 pg/ml, n = 20) were significantly (P < 0.05) decreased in association with term labor-onset (TIL) compared to term not-in-labor (TNIL). TNF-beta concentration in maternal plasma and amniotic fluid did not change significantly either with preterm labor (PIL), or during pregnancy. Group-matched comparison of maternal plasma and amniotic fluid TNF-beta concentrations demonstrated that amniotic fluid TNF-beta concentrations were 6-8 fold lower than maternal plasma TNF-beta concentrations. Furthermore, no detectable TNF-beta was secreted from cultured human amniotic, choriodecidual and placental explants. Although, TNF-beta mRNA was detected in amnion, choriodecidual and placenta, LT-beta was similarly expressed in these tissues, suggesting that TNF-beta may be cell membrane bound. These data demonstrate that TNF-beta is present at low levels within the intrauterine environment and may suggest that TNF-beta is specifically inhibited at the maternal-fetal interface. PMID:9185077

  19. Type III Protein Secretion Systems in Bacterial Pathogens of Animals and Plants

    PubMed Central

    Hueck, Christoph J.

    1998-01-01

    Various gram-negative animal and plant pathogens use a novel, sec-independent protein secretion system as a basic virulence mechanism. It is becoming increasingly clear that these so-called type III secretion systems inject (translocate) proteins into the cytosol of eukaryotic cells, where the translocated proteins facilitate bacterial pathogenesis by specifically interfering with host cell signal transduction and other cellular processes. Accordingly, some type III secretion systems are activated by bacterial contact with host cell surfaces. Individual type III secretion systems direct the secretion and translocation of a variety of unrelated proteins, which account for species-specific pathogenesis phenotypes. In contrast to the secreted virulence factors, most of the 15 to 20 membrane-associated proteins which constitute the type III secretion apparatus are conserved among different pathogens. Most of the inner membrane components of the type III secretion apparatus show additional homologies to flagellar biosynthetic proteins, while a conserved outer membrane factor is similar to secretins from type II and other secretion pathways. Structurally conserved chaperones which specifically bind to individual secreted proteins play an important role in type III protein secretion, apparently by preventing premature interactions of the secreted factors with other proteins. The genes encoding type III secretion systems are clustered, and various pieces of evidence suggest that these systems have been acquired by horizontal genetic transfer during evolution. Expression of type III secretion systems is coordinately regulated in response to host environmental stimuli by networks of transcription factors. This review comprises a comparison of the structure, function, regulation, and impact on host cells of the type III secretion systems in the animal pathogens Yersinia spp., Pseudomonas aeruginosa, Shigella flexneri, Salmonella typhimurium, enteropathogenic Escherichia coli

  20. Low-Frequency Type III Bursts and Solar Energetic Particle Events

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Nat; Makela, Pertti

    2010-01-01

    We analyzed the coronal mass ejections (CMEs), flares, and type 11 radio bursts associated with a set of six low frequency (<14 MHz) extended type III bursts from active region 10588. The durations were measured at 1 and 14 MHz using high resolution data from Wind/WAVES and were within the range (>15 min) normally used to define these bursts. All but one of the type III bursts was not associated with a type 11 burst in the metric or longer wavelength domains. The burst without type 11 burst also lacked a solar energetic particle (SEP) event at energies >25 MeV. The 1-MHz duration of the type III burst (28 min) is near the median value of type III durations found for gradual SEP events and ground level enhancement (GLE) events. Yet, there was no sign of SEP events. On the other hand, two other type III bursts from the same active region had similar duration but accompanied by WAVES type 11 bursts; these bursts were also accompanied by SEP events detected by SOHO/ERNE. The CMEs were of similar speeds and the flares are also of similar size and duration. This study suggests that the type III burst duration may not be a good indicator of an SEP event.

  1. Statistical analysies of the type III bursts and CMEs during the 23rd solar cycle

    NASA Astrophysics Data System (ADS)

    Ma, Yuan; Wang, De-Yu; Yan, Yi-Hua

    2006-12-01

    The statistics analyses of the microwave type III bursts, coronal mass ejections (CMEs), Hα flares and relevant events observed with 5200-7600MHz spectrograph at the National Astronomical Observatory during the 23rd solar cycle are carried out in this article. It is found that the relation between the microwave type III bursts and CMEs is not closer than that between the type II radio bursts and CMEs; the Hα flares corresponding to the CMEs are all gradual flares.

  2. Thioaptamers Targeting Dengue Virus Type-2 Envelope Protein Domain III

    PubMed Central

    Gandham, Sai Hari A.; Volk, David E.; Rao, Lokesh G. L.; Neerathilingam, Muniasamy; Gorenstein, David G.

    2014-01-01

    Thioaptamers targeting the dengue-2 virus (DENV-2) envelope protein domain III (EDIII) were developed. EDIII, which contains epitopes for binding neutralizing antibodies, is the putative host-receptor binding domain and is thus an attractive target for development of vaccines, anti-viral therapeutic and diagnostic agents. Thioaptamer DENTA-1 bound to DENV-2 EDIII adjacent to a known neutralizing antibody binding site with a dissociation constant of 154 nM. PMID:25261724

  3. LONG-DURATION LOW-FREQUENCY TYPE III BURSTS AND SOLAR ENERGETIC PARTICLE EVENTS

    SciTech Connect

    Gopalswamy, Nat; Maekelae, Pertti

    2010-09-20

    We analyzed the coronal mass ejections (CMEs), flares, and type II radio bursts associated with a set of three complex, long-duration, low-frequency (<14 MHz) type III bursts from active region 10588 in 2004 April. The durations were measured at 1 and 14 MHz using data from Wind/WAVES and were well above the threshold value (>15 minutes) normally used to define these bursts. One of the three type III bursts was not associated with a type II burst, which also lacked a solar energetic particle (SEP) event at energies >25 MeV. The 1 MHz duration of the type III burst (28 minutes) for this event was near the median value of type III durations found for gradual SEP events and ground level enhancement events. Yet, there was no sign of an SEP event. On the other hand, the other two type III bursts from the same active region had similar duration but were accompanied by WAVES type II bursts; these bursts were also accompanied by SEP events detected by SOHO/ERNE. The CMEs for the three events had similar speeds, and the flares also had similar size and duration. This study suggests that the occurrence of a complex, long-duration, low-frequency type III burst is not a good indicator of an SEP event.

  4. Laparoscopic treatment of type III and IV hiatal hernia – authors’ experience

    PubMed Central

    Grzesiak-Kuik, Agata; Pędziwiatr, Michał; Budzyński, Andrzej

    2014-01-01

    Introduction There are four types of hiatal hernias, and diagnosis is established on the basis of gastroscopy in the majority of cases. Type III represents a mixed type in which the abdominal esophagus as well as the gastric cardia and fundus protrude into the thorax through the pathologically widened esophageal hiatus. Type IV, the so-called upside down stomach, can be considered an evolutionary form of type III, and refers to herniation of nearly the whole stomach (except for the cardia and pylorus) into the thorax. Types III and IV of hiatal hernias represent a group of rare diaphragmatic defects; thus, most centers do not possess considerable experience in their treatment. Frequently, laparoscopic treatment is implemented, although, according to some authors, conversion to laparotomy, thoracotomy, or thoracolaparotomy is necessary in selected cases. Aim To analyze the outcomes of laparoscopic treatment of the largest hiatal hernias, i.e. type III and IV hernias. Material and methods A total of 25 patients diagnosed with type III and IV hiatal hernia were included in further analysis. Results As many as 19 out of 25 patients (76%) assessed the outcome of the surgery as evidently positive and reported marked improvement in the quality of life. Conclusions The laparoscopic technique constitutes an excellent and safe method of repair of even the most complex defects in the esophageal hiatus. Therefore, the minimally invasive technique combined with an anti-reflux procedure should be the method of choice in patients with type III and IV hernia. PMID:25097681

  5. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    PubMed

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. PMID:24931134

  6. Infection of monocyte/macrophages by human T lymphotropic virus type III.

    PubMed Central

    Ho, D D; Rota, T R; Hirsch, M S

    1986-01-01

    Normal blood-derived monocyte/macrophages were found to be susceptible to infection in vitro by human T lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome. In addition, HTLV-III was recovered from monocyte/macrophages of patients infected with this virus. The above findings raise the possibility that HTLV-III-infected monocyte/macrophages may serve as a vehicle for the dissemination of virus to target organs and as a reservoir for viral persistence, as has been shown for other lentiviruses including visna virus and caprine arthritis encephalitis virus. PMID:2422213

  7. Second harmonic generation microscopy differentiates collagen type I and type III in COPD

    NASA Astrophysics Data System (ADS)

    Suzuki, Masaru; Kayra, Damian; Elliott, W. Mark; Hogg, James C.; Abraham, Thomas

    2012-03-01

    The structural remodeling of extracellular matrix proteins in peripheral lung region is an important feature in chronic obstructive pulmonary disease (COPD). Multiphoton microscopy is capable of inducing specific second harmonic generation (SHG) signal from non-centrosymmetric structural proteins such as fibrillar collagens. In this study, SHG microscopy was used to examine structural remodeling of the fibrillar collagens in human lungs undergoing emphysematous destruction (n=2). The SHG signals originating from these diseased lung thin sections from base to apex (n=16) were captured simultaneously in both forward and backward directions. We found that the SHG images detected in the forward direction showed well-developed and well-structured thick collagen fibers while the SHG images detected in the backward direction showed striking different morphological features which included the diffused pattern of forward detected structures plus other forms of collagen structures. Comparison of these images with the wellestablished immunohistochemical staining indicated that the structures detected in the forward direction are primarily the thick collagen type I fibers and the structures identified in the backward direction are diffusive structures of forward detected collagen type I plus collagen type III. In conclusion, we here demonstrate the feasibility of SHG microscopy in differentiating fibrillar collagen subtypes and understanding their remodeling in diseased lung tissues.

  8. Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma.

    PubMed

    Asakura, S; Colby, T V; Limper, A H

    1996-11-01

    Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma. PMID:8912775

  9. The stimulation of auroral kilometric radiation by type III solar radio bursts

    NASA Technical Reports Server (NTRS)

    Calvert, W.

    1981-01-01

    It has been found that the onset of auroral kilometric radiation (AKR) frequently coincides with the arrival of type III solar radio bursts. Although the AKR onsets are usually abrupt and appear to be spontaneous, they sometimes develop from a discrete frequency near the leading edge of a type III burst or sometimes occur at progressively lower frequencies following that edge. From this, and the absence of the related solar electrons in specific cases, it was concluded that the incoming type III waves were sometimes responsible for stimulating auroral kilometric radiation. It was estimated that intense, isolated type III bursts were capable of stimulating AKR roughly one third of the time, and that at least ten percent of the observed AKR onsets could be attributed to these and weaker bursts, including some barely detectable by the ISEE plasma wave receivers.

  10. A New Look at Type-III Bursts and Their Use as Coronal Diagnostics

    NASA Astrophysics Data System (ADS)

    Tun Beltran, Samuel D.; Cutchin, S.; White, S.

    2015-09-01

    We present meter-wave solar radio spectra of the highest spectro-temporal resolution achieved to date. The observations, obtained with the first station of the Long Wavelength Array (LWA1), show unprecedented detail of solar emissions across a wide bandwidth during a Type-III/IIIb storm. Our flux calibration demonstrates that the LWA1 can detect Type-III bursts much weaker than 1 SFU, much lower than previous observations, and that the distribution of fluxes in these bursts varies with frequency. The high sensitivity and low noise in the data provide strong constraints to models of this type of plasma emission, providing evidence against the idea that Type-IIIb striae are generated from electrons trapped in Langmuir-wave sidebands. The continuous generation of electron beams in the corona revealed by the high density Type-III storm is evidence for ubiquitous magnetic reconnection in the lower corona. Such an abundance of reconnection events not only contributes to the total coronal energy budget, but also provides an engine by which to form the populations of seed particles responsible for proton-rich solar energetic-particle events. An active region (AR) with such levels of reconnection and the accompanying Type-III/IIIb storms is proposed here to be associated with an increase of SEP production if a CME erupts. The data's constraints on existing theories of Type-IIIb production are used to make an association of the observed Type-IIIb storm to specific electron-beam paths with increased inhomogeneities in density, temperature, and/or turbulence. This scenario ties in the observed timing of Type-III and -IIIb storms, constrained theories of Type-III and -IIIb emission, and the ability of the emitting AR to produce a strong SEP event. The result requires but a single observable to cement these ideas, the statistical correlation of Type-III/IIIb activity with SEP-productive AR.

  11. Structural Basis for Substrate Binding and the Catalytic Mechanism of Type III Pantothenate Kinase

    SciTech Connect

    Yang, Kun; Strauss, Erick; Huerta, Carlos; Zhang, Hong

    2008-07-15

    Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exemplified by the Escherichia coli CoaA protein) and the predominantly eukaryotic type II PanK (PanK-II). PanK-III enzymes have an unusually high K{sub m} for ATP, are resistant to feedback inhibition by CoA, and are unable to utilize the N-alkylpantothenamide family of pantothenate analogues as alternative substrates, thus making type III PanK ineffective in generating CoA analogues as antimetabolites in vivo. Previously, we reported the crystal structure of the PanK-III from Thermotoga maritima and identified it as a member of the 'acetate and sugar kinase/heat shock protein 70/actin' (ASKHA) superfamily. Here we report the crystal structures of the same PanK-III in complex with one of its substrates (pantothenate), its product (phosphopantothenate) as well as a ternary complex structure of PanK-III with pantothenate and ADP. These results are combined with isothermal titration calorimetry experiments to present a detailed structural and thermodynamic characterization of the interactions between PanK-III and its substrates ATP and pantothenate. Comparison of substrate binding and catalytic sites of PanK-III with that of eukaryotic PanK-II revealed drastic differences in the binding modes for both ATP and pantothenate substrates, and suggests that these differences may be exploited in the development of new inhibitors specifically targeting PanK-III.

  12. Solar Micro-Type III Burst Storms and Long Dipolar Magnetic Field in the Outer Corona

    NASA Astrophysics Data System (ADS)

    Morioka, A.; Miyoshi, Y.; Iwai, K.; Kasaba, Y.; Masuda, S.; Misawa, H.; Obara, T.

    2015-08-01

    Solar micro-type III radio bursts are elements of the so-called type III storms and are characterized by short-lived, continuous, and weak emissions. Their frequency of occurrence with respect to radiation power is quite different from that of ordinary type III bursts, suggesting that the generation process is not flare-related, but due to some recurrent acceleration processes around the active region. We examine the relationship of micro-type III radio bursts with coronal streamers. We also explore the propagation channel of bursts in the outer corona, the acceleration process, and the escape route of electron beams. It is observationally confirmed that micro-type III bursts occur near the edge of coronal streamers. The magnetic field line of the escaping electron beams is tracked on the basis of the frequency drift rate of micro-type III bursts and the electron density distribution model. The results demonstrate that electron beams are trapped along closed dipolar field lines in the outer coronal region, which arise from the interface region between the active region and the coronal hole. A 22 year statistical study reveals that the apex altitude of the magnetic loop ranges from 15 to 50 RS. The distribution of the apex altitude has a sharp upper limit around 50 RS suggesting that an unknown but universal condition regulates the upper boundary of the streamer dipolar field.

  13. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system.

    PubMed

    Huang, Liang-Liang; Liu, Zhong-Yang; Huang, Jing-Hui; Luo, Zhuo-Jing

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelinating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various developmental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10). PMID:25788922

  14. Solar Flares, Type III Radio Bursts, Coronal Mass Ejections, and Energetic Particles

    NASA Technical Reports Server (NTRS)

    Cane, Hilary V.; Erickson, W. C.; Prestage, N. P.; White, Nicholas E. (Technical Monitor)

    2002-01-01

    In this correlative study between greater than 20 MeV solar proton events, coronal mass ejections (CMEs), flares, and radio bursts it is found that essentially all of the proton events are preceded by groups of type III bursts and all are preceded by CMEs. These type III bursts (that are a flare phenomenon) usually are long-lasting, intense bursts seen in the low-frequency observations made from space. They are caused by streams of electrons traveling from close to the solar surface out to 1 AU. In most events the type III emissions extend into, or originate at, the time when type II and type IV bursts are reported (some 5 to 10 minutes after the start of the associated soft X-ray flare) and have starting frequencies in the 500 to approximately 100 MHz range that often get lower as a function of time. These later type III emissions are often not reported by ground-based observers, probably because of undue attention to type II bursts. It is suggested to call them type III-1. Type III-1 bursts have previously been called shock accelerated (SA) events, but an examination of radio dynamic spectra over an extended frequency range shows that the type III-1 bursts usually start at frequencies above any type II burst that may be present. The bursts sometimes continue beyond the time when type II emission is seen and, furthermore, sometimes occur in the absence of any type II emission. Thus the causative electrons are unlikely to be shock accelerated and probably originate in the reconnection regions below fast CMEs. A search did not find any type III-1 bursts that were not associated with CMEs. The existence of low-frequency type III bursts proves that open field lines extend from within 0.5 radius of the Sun into the interplanetary medium (the bursts start above 100 MHz, and such emission originates within 0.5 solar radius of the solar surface). Thus it is not valid to assume that only closed field lines exist in the flaring regions associated with CMEs and some

  15. Diversity in ABC transporters: Type I, II and III importers

    PubMed Central

    Rice, Austin J.; Park, Aekyung

    2014-01-01

    ATP-binding cassette transporters are multi-subunit membrane pumps that transport substrates across membranes. While significant in the transport process, transporter architecture exhibits a range of diversity that we are only beginning to recognize. This divergence may provide insight into the mechanisms of substrate transport and homeostasis. Until recently, ABC importers have been classified into two types, but with the emergence of energy-coupling factor (ECF) transporters there are potentially three types of ABC importers. In this review, we summarize an expansive body of research on the three types of importers with an emphasis on the basics that underlie ABC importers, such as structure, subunit composition and mechanism. PMID:25155087

  16. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.

    PubMed

    Cichon, Sven; Martin, Ludovic; Hennies, Hans Christian; Müller, Felicitas; Van Driessche, Karen; Karpushova, Anna; Stevens, Wim; Colombo, Roberto; Renné, Thomas; Drouet, Christian; Bork, Konrad; Nöthen, Markus M

    2006-12-01

    Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities. PMID:17186468

  17. Avoiding type III, IV, and V errors through collaborative research.

    PubMed

    Yamatani, Hide; Mann, Aaron; Feit, Marvin

    2013-01-01

    Major types of empirical errors reviewed by a number of leading research textbooks include discussions of Type I and Type II errors. However, applied human service researchers can commit other types of errors that should be avoided. The potential benefits of the applied, collaborative research (in contrast to traditional participatory research) include an assurance that the study begins with the "right" questions that are important for community residents. Such research practice also helps generate useful research findings for decisions regarding redistribution of resources and resolving community issues. The aim of collaborative research is not merely to advance scientific understanding, but also to produce empirical findings that are usable for addressing priority needs and problems of distressed communities. A review of a case example (Garfield Community Assessment Study) illustrates the principles and practices of collaborative research. PMID:23879359

  18. Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases.

    PubMed Central

    Jagirdar, J; Lee, T C; Reibman, J; Gold, L I; Aston, C; Bégin, R; Rom, W N

    1997-01-01

    Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. PMID:9400723

  19. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections

    PubMed Central

    Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Smirnov, Sergey V.; Peng, Jianya; Yasukawa, Linda L.; Durbin, Russell K.; Durbin, Joan E.; Greenberg, Harry B.; Kotenko, Sergei V.

    2016-01-01

    Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets

  20. Type I and III interferon production in response to RNA viruses.

    PubMed

    Reid, Elizabeth; Charleston, Bryan

    2014-09-01

    The biology of RNA viruses is closely linked to the type I and type III interferon (IFN) response of the host. These viruses display a range of molecular patterns that may be detected by host cells resulting in the induction of IFNs. Consequently, there are many examples of mechanisms employed by RNA viruses to block or delay IFN induction and reduce the expression of IFN-stimulated genes (ISGs), a necessary step in the virus lifecycle because of the capacity of IFNs to block virus replication. Efficient transmission of viruses depends, in part, on maintaining a balance between virus replication and host survival; specialized host cells, such as plasmacytoid dendritic cells, can sense viral molecular patterns and produce IFNs to help maintain this balance. There are now many examples of RNA viruses inducing type I and type III IFNs, and although these IFNs act through different receptors, in many systems studied, they induce a similar spectrum of genes. However, there may be a difference in the temporal expression pattern, with more prolonged expression of ISGs in response to type III IFN compared with type I IFN. There are also examples of synergy between type I and type III IFNs to induce antiviral responses. Clearly, it is important to understand the different roles of these IFNs in the antiviral response in vivo. One of the most striking differences between these 2 IFN systems is the distribution of the receptors: type I IFN receptors are expressed on most cells, yet type III receptor expression is restricted primarily to epithelial cells but has also been demonstrated on other cells, including dendritic cells. There is increasing evidence that type III IFNs are a key control mechanism against RNA viruses that infect respiratory and enteric epithelia. PMID:24956361

  1. Solar noise storms - The polarization of storm Type III and related bursts

    NASA Technical Reports Server (NTRS)

    Dulk, G. A.; Suzuki, S.; Sheridan, K. V.

    1984-01-01

    The spectral and polarization characteristics of 19 noise storms that occurred during 1976-1982 are reported. All components of the storms - Type I bursts and continuum, storm Type III bursts, and fine structures such as reverse drift pairs - are found to have the same sense of circular polarization. While the degree of polarization p of Type I bursts and continuum is generally greater than or approximately equal to 0.5, that of storm Type III bursts is almost always less than 0.5. Two set of storm Type III bursts stand out: one with less than or approximately equal to 0.2 and another with greater than or approximately equal to 0.3. Because these sets respectively have degrees of polarization so similar to those of fundamental (F) the harmonic (H) components of non-storm F - H pairs, it is deduced that storm Type III bursts are due sometimes to fundamental plasma radiation and sometimes to harmonic. However, F - H pairs are extremely rare among storm Type III bursts.

  2. Cementogenesis and the induction of periodontal tissue regeneration by the osteogenic proteins of the transforming growth factor-beta superfamily.

    PubMed

    Ripamonti, U; Petit, J-C; Teare, J

    2009-04-01

    The antiquity and severity of periodontal diseases are demonstrated by the hard evidence of alveolar bone loss in gnathic remains of the Pliocene/Pleistocene deposits of the Bloubank Valley at Sterkfontein, Swartkrans and Kromdrai in South Africa. Extant Homo has characterized and cloned a superfamily of proteins which include the bone morphogenetic proteins that regulate tooth morphogenesis at different stages of development as temporally and spatially connected events. The induction of cementogenesis, periodontal ligament and alveolar bone regeneration are regulated by the co-ordinated expression of bone morphogenetic proteins. Naturally derived and recombinant human bone morphogenetic proteins induce periodontal tissue regeneration in mammals. Morphological analyses on undecalcified sections cut at 3-6 mum on a series of mandibular molar Class II and III furcation defects induced in the non-human primate Papio ursinus show the induction of cementogenesis. Sharpey's fibers nucleate as a series of composite collagen bundles within the cementoid matrix in close relation to embedded cementocytes. Osteogenic protein-1 and bone morphogenetic protein-2 possess a structure-activity profile, as shown by the morphology of tissue regeneration, preferentially cementogenic and osteogenic, respectively. In Papio ursinus, transforming growth factor-beta(3) also induces cementogenesis, with Sharpey's fibers inserting into newly formed alveolar bone. Capillary sprouting and invasion determine the sequential insertion and alignment of individual collagenic bundles. The addition of responding stem cells prepared by finely mincing fragments of autogenous rectus abdominis muscle significantly enhances the induction of periodontal tissue regeneration when combined with transforming growth factor-beta(3) implanted in Class II and III furcation defects of Papio ursinus. PMID:18842117

  3. Identification and characterization of a type III Trichomonas vaginalis virus in the protozoan pathogen Trichomonas vaginalis.

    PubMed

    Bessarab, Irina N; Nakajima, Rui; Liu, Hsing-Wei; Tai, Jung-Hsiang

    2011-02-01

    A type III Trichomonas vaginalis virus, which may be involved in transcriptional regulation of the major surface protein gene P270 of the protozoan pathogen Trichomonas vaginalis, was purified and characterized in the present study. The complete 4844-base-pair complementary DNA sequence of the viral genome reveals overlapping cap and pol genes with a putative ribosomal frame-shifting signal within the overlap region. The type III virus is related more closely to the type II virus than to the type I virus in the sequence of its ribosomal frameshift signal and in its capsid protein. Phylogenetic analysis revealed that these viruses could be grouped in the same clade as a genus distantly related to other genera in the family Totiviridae. Virus-induced P270 gene expression was only evident in Trichomonas vaginalis cells infected with either a type II or type III virus, but not with a type I virus. These findings suggest that transcription of the P270 gene is likely regulated by viral factors common to type II and type III viruses and thus provides important information for future investigation of virus-host interactions. PMID:21110050

  4. Arthroscopy Assisted Percutaneous Fixation of Ideberg Type Iii Glenoid Fractures

    PubMed Central

    Acharya, Prashant; Arora, Bakul; Pinto, Nelson

    2015-01-01

    Introduction: Intra-articular glenoid fractures are extremely rare and may be associated with other injuries. Traditionally open reduction and internal fixation has been recommended in displaced intra-articular glenoid fractures. However open reduction is difficult and it may not be possible to address the associated intra-articular soft tissue injuries. A few reports of arthroscopic assisted fixation of these fractures have been recently published. We are reporting a case of Ideberg type 3 glenoid fracture and its treatment. Case Report: We are presenting our case where a 52 year old man presented with Type 3 intra-articular glenoid fracture. The fracture was fixed percutaneously under simultaneous arthroscopic and fluoroscopic guidance. Conclusion: Intra-articular glenoid fractures are uncommon and difficult to treat. Arthroscopy assisted percutaneous fixation technique can be a valuable adjunct for the surgeon in dealing with not only the fracture but also the associated soft-tissue injuries. PMID:27299041

  5. Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium.

    PubMed

    Olivey, Harold E; Mundell, Nathan A; Austin, Anita F; Barnett, Joey V

    2006-01-01

    The proepicardium (PE) migrates over the heart and forms the epicardium. A subset of these PE-derived cells undergoes epithelial-mesenchymal transformation (EMT) and gives rise to cardiac fibroblasts and components of the coronary vasculature. We report that transforming growth factor-beta (TGFbeta) 1 and TGFbeta2 increase EMT in PE explants as measured by invasion into a collagen gel, loss of cytokeratin expression, and redistribution of ZO1. The type I TGFbeta receptors ALK2 and ALK5 are both expressed in the PE. However, only constitutively active (ca) ALK2 stimulates PE-derived epithelial cell activation, the first step in transformation, whereas caALK5 stimulates neither activation nor transformation in PE explants. Overexpression of Smad6, an inhibitor of ALK2 signaling, inhibits epithelial cell activation, whereas BMP7, a known ligand for ALK2, has no effect. These data demonstrate that TGFbeta stimulates transformation in the PE and suggest that ALK2 partially mediates this effect. PMID:16245329

  6. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells.

    PubMed Central

    MacKay, K; Striker, L J; Stauffer, J W; Doi, T; Agodoa, L Y; Striker, G E

    1989-01-01

    Proliferation of resident glomerular cells and the accumulation of mesangial matrix are histologic abnormalities which are observed in the course of many progressive glomerular diseases. We explored the potential regulatory effects of transforming growth factor-beta (TGF-beta) on these processes. We found that cultured mouse glomerular endothelial, mesangial, and epithelial cells as well as isolated intact rat glomeruli possess high-affinity receptors for TGF-beta. We also found that, although TGF-beta consistently inhibited the proliferation of glomerular endothelial and epithelial cells, it acted as a bifunctional regulator of mesangial cell proliferation. TGF-beta significantly increased the production of collagen and fibronectin by glomerular mesangial cells whereas only fibronectin production was augmented in glomerular epithelial cells. The presence of TGF-beta receptors on intact glomeruli and on each glomerular cell type and the demonstrated responsiveness of these cells to TGF-beta combine to suggest that potentially important interactions may occur between resident glomerular cells and TGF-beta in vivo. Images PMID:2539392

  7. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function

    PubMed Central

    Heupel, Katharina; Sargsyan, Vardanush; Plomp, Jaap J; Rickmann, Michael; Varoqueaux, Frédérique; Zhang, Weiqi; Krieglstein, Kerstin

    2008-01-01

    Background The formation of functional synapses is a crucial event in neuronal network formation, and with regard to regulation of breathing it is essential for life. Members of the transforming growth factor-beta (TGF-β) superfamily act as intercellular signaling molecules during synaptogenesis of the neuromuscular junction of Drosophila and are involved in synaptic function of sensory neurons of Aplysia. Results Here we show that while TGF-β2 is not crucial for the morphology and function of the neuromuscular junction of the diaphragm muscle of mice, it is essential for proper synaptic function in the pre-Bötzinger complex, a central rhythm organizer located in the brainstem. Genetic deletion of TGF-β2 in mice strongly impaired both GABA/glycinergic and glutamatergic synaptic transmission in the pre-Bötzinger complex area, while numbers and morphology of central synapses of knock-out animals were indistinguishable from their wild-type littermates at embryonic day 18.5. Conclusion The results demonstrate that TGF-β2 influences synaptic function, rather than synaptogenesis, specifically at central synapses. The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-β2 knock-out mice. PMID:18854036

  8. Generation of Mice With a Conditional Allele for the Transforming Growth Factor Beta3 Gene

    PubMed Central

    Doetschman, Thomas; Georgieva, Teodora; Li, Hongqi; Reed, Thomas D.; Grisham, Christina; Friel, Jacqueline; Estabrook, Mark A.; Gard, Connie; Sanford, L.P.; Azhar, Mohamad

    2013-01-01

    Summary The transforming growth factor beta (TGFβ) pathway is involved in embryonic development and several inherited and acquired human diseases. The gene for TGFβ3 (Tgfb3) encodes one of the three ligands for TGF b receptors. It is widely expressed in the embryo and its mutation or misexpression is found in human diseases. Tgfb3−/− mice die at birth from cleft palate, precluding functional studies in adults. Here, we generated mice in which exon 6 of Tgfb3 was flanked with LoxP sites (Tgfb3flox/flox). The adult mice were normal and fertile. EIIa-Cre-mediated deletion of exon 6 in Tgfb3flox/flox mice efficiently generated Tgfb3 conditional knockout (Tgfb3cko/cko) mice which died at birth from the same cleft palate defect as Tgfb3−/− mice, indicating that the conditional and knockout alleles are functionally equivalent. This Tgfb3cko allele will now enable studies of TGFβ3 function in different cell or tissue types in embryonic development and during adulthood. genesis 50:59-66, 2012. PMID:22223248

  9. In vitro growth characteristics of simian T-lymphotropic virus type III.

    PubMed Central

    Kannagi, M; Yetz, J M; Letvin, N L

    1985-01-01

    The type C retrovirus simian T-lymphotropic virus type III (STLV-III) has been isolated recently from immunodeficient macaque monkeys at the New England Regional Primate Research Center. The present studies were done to define the in vitro growth characteristics of this agent. STLV-III replicates efficiently in interleukin 2-dependent T-cell cultures of macaque peripheral blood lymphocytes (PBL), less efficiently in such cultures of human and gibbon PBL, and inefficiently in baboon PBL. No replication, as assessed by measuring reverse transcriptase activity in these culture supernatants, could be detected in similarly maintained cultures of chimpanzee, squirrel monkey, and cotton-top tamarin PBL. Like the human acquired immunodeficiency syndrome (AIDS) virus, human T-cell lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV), STLV-III replicates in T4+ but not T8+ lymphocytes and its infection of macaque and human lymphocytes can be blocked with monoclonal anti-T4 antibodies. STLV-III differs from the human AIDS virus, however, in its apparent inability to grow in the Epstein-Barr virus-transformed B lymphocytes tested, the differing range of nonhuman primate T-cell populations that support its growth, and its less striking toxicity for T lymphocytes. These studies provide further characterization of an agent that will be extremely important in facilitating the development of vaccines and antiviral therapy for AIDS. PMID:2996002

  10. Solar type III radio bursts modulated by homochromous Alfvén waves

    SciTech Connect

    Zhao, G. Q.; Chen, L.; Wu, D. J.

    2013-12-10

    Solar type III radio bursts and their production mechanisms have been intensively studied in both theory and observation and are believed to be the most important signatures of electron acceleration in active regions. Recently, Wu et al. proposed that the electron-cyclotron maser emission (ECME) driven by an energetic electron beam could be responsible for producing type III bursts and pointed out that turbulent Alfvén waves can greatly influence the basic process of ECME via the oscillation of these electrons in the wave fields. This paper investigates effects of homochromous Alfvén waves (HAWs) on ECME driven by electron beams. Our results show that the growth rate of the O-mode wave will be significantly modulated by HAWs. We also discuss possible application to the formation of fine structures in type III bursts, such as so-called solar type IIIb radio bursts.

  11. III-V-on-silicon anti-colliding pulse-type mode-locked laser.

    PubMed

    Keyvaninia, S; Uvin, S; Tassaert, M; Wang, Z; Fu, X; Latkowski, S; Marien, J; Thomassen, L; Lelarge, F; Duan, G; Lepage, G; Verheyen, P; Van Campenhout, J; Bente, E; Roelkens, G

    2015-07-01

    An anti-colliding pulse-type III-V-on-silicon passively mode-locked laser is presented for the first time based on a III-V-on-silicon distributed Bragg reflector as outcoupling mirror implemented partially underneath the III-V saturable absorber. Passive mode-locking at 4.83 GHz repetition rate generating 3 ps pulses is demonstrated. The generated fundamental RF tone shows a 1.7 kHz 3 dB linewidth. Over 9 mW waveguide coupled output power is demonstrated. PMID:26125366

  12. The [Fe(III)[Fe(III)(L1)2]3] star-type single-molecule magnet.

    PubMed

    Saalfrank, Rolf W; Scheurer, Andreas; Bernt, Ingo; Heinemann, Frank W; Postnikov, Andrei V; Schünemann, Volker; Trautwein, Alfred X; Alam, Mohammad S; Rupp, Holger; Müller, Paul

    2006-06-21

    Star-shaped complex [Fe(III)[Fe(III)(L1)2]3] (3) was synthesized starting from N-methyldiethanolamine H2L1 (1) and ferric chloride in the presence of sodium hydride. For 3, two different high-spin iron(III) ion sites were confirmed by Mössbauer spectroscopy at 77 K. Single-crystal X-ray structure determination revealed that 3 crystallizes with four molecules of chloroform, but, with only three molecules of dichloromethane. The unit cell of 3.4CHCl3 contains the enantiomers (delta)-[(S,S)(R,R)(R,R)] and (lambda)-[(R,R)(S,S)(S,S)], whereas in case of 3.3CH2Cl2 four independent molecules, forming pairs of the enantiomers [lambda-(R,R)(R,R)(R,R)]-3 and [lambda-(S,S)(S,S)(S,S)]-3, were observed in the unit cell. According to SQUID measurements, the antiferromagnetic intramolecular coupling of the iron(III) ions in 3 results in a S = 10/2 ground state multiplet. The anisotropy is of the easy-axis type. EPR measurements enabled an accurate determination of the ligand-field splitting parameters. The ferric star 3 is a single-molecule magnet (SMM) and shows hysteretic magnetization characteristics below a blocking temperature of about 1.2 K. However, weak intermolecular couplings, mediated in a chainlike fashion via solvent molecules, have a strong influence on the magnetic properties. Scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) were used to determine the structural and electronic properties of star-type tetranuclear iron(III) complex 3. The molecules were deposited onto highly ordered pyrolytic graphite (HOPG). Small, regular molecule clusters, two-dimensional monolayers as well as separated single molecules were observed. In our STS measurements we found a rather large contrast at the expected locations of the metal centers of the molecules. This direct addressing of the metal centers was confirmed by DFT calculations. PMID:16751895

  13. Production of fine structures in type III solar radio bursts due to turbulent density profiles

    SciTech Connect

    Loi, Shyeh Tjing; Cairns, Iver H.; Li, Bo

    2014-07-20

    Magnetic reconnection events in the corona release energetic electron beams along open field lines, and the beams generate radio emission at multiples of the electron plasma frequency f{sub p} to produce type III solar radio bursts. Type III bursts often exhibit irregularities in the form of flux modulations with frequency and/or local temporal advances and delays, and a type IIIb burst represents the extreme case where a type III burst is fragmented into a chain of narrowband features called striae. Remote and in situ spacecraft measurements have shown that density turbulence is ubiquitous in the corona and solar wind, and often exhibits a Kolmogorov power spectrum. In this work, we numerically investigate the effects of one-dimensional macroscopic density turbulence (along the beam direction) on the behavior of type III bursts, and find that this turbulence produces stria-like fine structures in the dynamic spectra of both f{sub p} and 2 f{sub p} radiation. Spectral and temporal fine structures in the predicted type III emission are produced by variations in the scattering path lengths and group speeds of radio emission, and in the locations and sizes of emitting volumes. Moderate turbulence levels yield flux enhancements with much broader half-power bandwidths in f{sub p} than 2 f{sub p} emission, possibly explaining the often observed type IIIb-III harmonic pairs as being where intensifications in 2 f{sub p} radiation are not resolved observationally. Larger turbulence levels producing trough-peak regions in the plasma density profile may lead to broader, resolvable intensifications in 2 f{sub p} radiation, which may account for the type IIIb-IIIb pairs that are sometimes observed.

  14. Are type III radio aurorae directly excited by electrostatic ion cyclotron waves

    SciTech Connect

    McDiarmid, D.R.; Watermann, J.; McNamara, A.G. ); Koehler, J.A.; Sofko, G.J. )

    1989-10-01

    In 1981, a network of three 50-MHz radar transmitters and two receivers were operated in the CW mode on the Canadian prairies. The echoes obtained from coherent ionospheric backscatter were divided into segments of 205 ms such that their FFT spectra yielded frequency resolution of 4.9 Hz. The spectra were subsequently averaged over 10 s. Type III spectra (narrow spectra with sub ion-acoustic Doppler shifts) were observed (often simultaneously) on radar links whose wave vector components perpendicular to the geomagnetic field were almost identical while their components parallel to the field were significantly different. From a statistical analysis of more than 300 type III spectra it is inferred that these are in general unlikely to arise from electrostatic ion cyclotron waves directly excited by an essentially linear process. Doppler shifts around 55 Hz were much more frequently observed than around 30 Hz, the occurrence of type III spectra increased with increasing magnetic aspect angle (deviation of the scatter wave vector from perpendicular to the geomagnetic field), and the mean Doppler shifts of type III spectra simultaneously on different radar links went through a minimum for aspect angles between 4{degree} and 7{degree} (depending on the assumed backscatter height). These three results disagree with theoretical expectations. The spectral width the type III echoes decreased linearly with magnetic aspect by about 2 Hz/deg.

  15. Cryptic activity within the Type III1 domain of fibronectin regulates tissue inflammation and angiogenesis

    PubMed Central

    Cho, Christina; Kelsh-Lasher, Rhiannon; Ambesi, Anthony; McKeown-Longo, Paula J.

    2016-01-01

    The fibronectin matrix provides mechanical and biochemical information to regulate homeostatic and pathological processes within tissues. Fibronectin consists of independently-folded modules termed Types I, II and III. In response to cellular contractile force, Type III domains unfold to initiate a series of homophilic binding events which result in the assembly of a complex network of intertwining fibrils. The unfolding of Type III modules provides elasticity to the assembled fibronectin matrix allowing it to function as a dynamic scaffold which provides binding sites for cellular receptors, growth factors and other matrix molecules. Access to bioactive sites within the fibronectin matrix is under complex regulation and controlled through a combination of mechanical and proteolytic activity. Mechanical unfolding of Type III modules and limited proteolysis can alter the topographical display of bioactive sites within the fibronectin fibrils by exposing previously cryptic sites and disrupting functional sites. In this review we will discuss cryptic activity found within the first Type III module of fibronectin and its impact on tissue angiogenesis and inflammation.

  16. Flare fragmentation and type III productivity in the 1980 June 27 flare

    NASA Technical Reports Server (NTRS)

    Aschwanden, M. J.; Schwartz, R. A.; Benz, A. O.; Lin, R. P.; Pelling, R. M.

    1990-01-01

    Observations of the solar flare on June 27, 1980 were presented, 16:14-16:33 UT, which was observed by a balloon-borne 300 sq cm phoswich hard X-ray detector and by the IKARUS radio spectrometer. This flare shows intense hard X-ray (HXR) emission and an extreme productivity of (at least 754) type III bursts at 200-400 MHz. A linear correlation was found between the type III burst rate and the HXR fluence. The occurrence of about 10 type III bursts/second, and also the even higher rate of millisecond spikes, suggests a high degree of fragmentation in the acceleration region. This high quantization of injected beams, assuming the thick-target model, shows up in a linear relationship between hard X-ray fluence and the type III rate, but not as fine structures in the HXR time profile. The generation of a superhot isothermal HXR component in the decay phase of the flare coincides with the fade-out of type III production.

  17. Type III polyketide synthase repertoire in Zingiberaceae: computational insights into the sequence, structure and evolution.

    PubMed

    Mallika, Vijayanathan; Aiswarya, Girija; Gincy, Paily Thottathil; Remakanthan, Appukuttan; Soniya, Eppurathu Vasudevan

    2016-07-01

    Zingiberaceae or 'ginger family' is the largest family in the order 'Zingiberales' with more than 1300 species in 52 genera, which are mostly distributed throughout Asia, tropical Africa and the native regions of America with their maximum diversity in Southeast Asia. Many of the members are important spice, medicinal or ornamental plants including ginger, turmeric, cardamom and kaempferia. These plants are distinguished for the highly valuable metabolic products, which are synthesised through phenylpropanoid pathway, where type III polyketide synthase is the key enzyme. In our present study, we used sequence, structural and evolutionary approaches to scrutinise the type III polyketide synthase (PKS) repertoire encoded in the Zingiberaceae family. Highly conserved amino acid residues in the sequence alignment and phylogram suggested strong relationships between the type III PKS members of Zingiberaceae. Sequence and structural level investigation of type III PKSs showed a small number of variations in the substrate binding pocket, leading to functional divergence among these PKS members. Molecular evolutionary studies indicate that type III PKSs within Zingiberaceae evolved under strong purifying selection pressure, and positive selections were rarely detected in the family. Structural modelling and protein-small molecule interaction studies on Zingiber officinale PKS 'a representative from Zingiberaceae' suggested that the protein is comparatively stable without much disorder and exhibited wide substrate acceptance. PMID:27138283

  18. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics.

    PubMed

    Fujioka, Shinsuke; Sundal, Christina; Wszolek, Zbigniew K

    2013-01-01

    Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments. PMID:23331413

  19. Deficiency of monoclonal non-specific suppressor factor beta (MNSFB) promotes pregnancy loss in mice.

    PubMed

    Gu, Yan; He, Yaping; Zhang, Xuan; Shi, Yan; Yang, Qian; Yu, Lin; Sun, Zhaogui; Zhang, Huiqing; Wang, Jianmei; Gao, Xiang; Wang, Jian

    2015-06-01

    Maternal immune tolerance to the semi-allogenic fetus is required for successful pregnancy in mammals. Monoclonal nonspecific suppressor factor beta (MNSFB) is an immunosuppressive factor present in uterine epithelial and stromal cells, as well as in macrophages and T cells. Although the functional neutralization of MNSFB using specific antibodies against it lead to failed embryo implantation in mice, the exact role of MNSFB at the fetal-maternal interface remains unclear. The present study generated conditional heterozygous Mnsfb-deficient (Mnsfb(+/) (-) ) mice using the LoxP/Cre system. Western-blot analyses showed that uterine MNSFB protein in Mnsfb(+/-) mice was remarkably down-regulated compared to that in the wild-type (Mnsfb(+/+) ) mice. The litter size of female Mnsfb(+/-) mice was significantly reduced, which corresponded to developmental failure of embryos beyond Day 11 of pregnancy. The expression level of MNSFB protein was also lower in the failing compared to the normal embryos. An aberrant interaction between the embryos of Day-4 pregnant wild-type mice and endometrial stromal cells of female Mnsfb(+/-) mice was observed in vitro. The uterine Day-5 abundance of P53, BAX, and BCL-G in pregnant Mnsfb(+/-) mice was significantly decreased compared to that of wild-type mice, whereas the expression of P27 and tumor necrosis factor alpha (TNFA) was elevated. By comparison, the levels of MNSFB and BAX proteins in human decidual tissues obtained from recurrent spontaneous miscarriage patients were significantly reduced compared to those obtained from legal medial abortion, highlighting the involvement of MNSFB in the pathogenesis of recurrent spontaneous miscarriage. Together, these results demonstrated that a deficiency in MNSFb is associated with pregnancy loss, probably through reduced P53 and/or increased TNFA production at the fetal-maternal interface. PMID:26031240

  20. Ulysses-Wind stereoscopic study of type III radiation pattern over a large latitude range.

    NASA Astrophysics Data System (ADS)

    Bonnin, X.; Maksimovic, M.; Hoang, S.

    2006-12-01

    Type III radio bursts are generated by suprathermal electrons, accelerated from solar active region and travelling outwards along open magnetic field lines to lower densities in the interplanetary medium (IPM). Along their path in the IPM, these electrons trigger radio emission at the fundamental (F) and/or harmonic (H) of the local plasma frequency fp. We have selected 278 type III bursts observed simultaneously by Wind and Ulysses spacecraft (s/c) during all the year 2001. Deriving radio sources trajectory by diffrent ways, we have deduced some type III characteristics and derived apparent radiation pattern at low frequencies over a large latitude range. First results confirm that radiation pattern shifts east when frequency decreases (Hoang et al. 1997). It brings new evidence of strong refraction effects in local density gradients.

  1. Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage

    PubMed Central

    Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H. Zafer; Polat, Yılmaz; Osmanoglu, Gokhan; Aygar, Muhittin; Ciftciler, A. Erdinc; Parlak, Omer

    2016-01-01

    Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests. PMID:27293947

  2. Characterization of an ExoS Type III Translocation-Resistant Cell Line

    PubMed Central

    Rucks, Elizabeth A.; Olson, Joan C.

    2005-01-01

    Pseudomonas aeruginosa ExoS is a type III-secreted type III-secreted, bifunctional protein that causes diverse effects on eukaryotic cell function. The coculture of P. aeruginosa strains expressing ExoS with HL-60 myeloid cells revealed the cell line to be resistant to the toxic effects of ExoS. Differentiation of HL-60 cells with phorbol 12-myristate 13-acetate (TPA) rendered the cell line sensitive to ExoS. To understand the cellular basis for the alteration in sensitivity, undifferentiated and TPA-differentiated HL-60 cells were compared for differences in bacterial adherence, type III secretion induction, and ExoS translocation. These comparisons found that ExoS was translocated more efficiently in TPA-differentiated HL-60 cells than in undifferentiated cells. The studies support the ability of eukaryotic cells to influence P. aeruginosa TTS at the level of membrane translocation. PMID:15618208

  3. Real-time imaging of type III secretion: Salmonella SipA injection into host cells.

    PubMed

    Schlumberger, Markus C; Müller, Andreas J; Ehrbar, Kristin; Winnen, Brit; Duss, Iwan; Stecher, Bärbel; Hardt, Wolf-Dietrich

    2005-08-30

    Many pathogenic and symbiotic Gram-negative bacteria employ type III secretion systems to inject "effector" proteins into eukaryotic host cells. These effectors manipulate signaling pathways to initiate symbiosis or disease. By using time-lapse microscopy, we have imaged delivery of the Salmonella type III effector protein SipA/SspA into animal cells in real time. SipA delivery mostly began 10-90 sec after docking and proceeded for 100-600 sec until the bacterial SipA pool (6 +/- 3 x 10(3) molecules) was exhausted. Similar observations were made for the effector protein SopE. This visualization of type III secretion in real time explains the efficiency of host cell manipulation by means of this virulence system. PMID:16107539

  4. Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

    PubMed

    Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

    2011-11-01

    Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia. PMID:22616341

  5. Class III β-Tubulin Is a Component of the Mitotic Spindle in Multiple Cell Types

    PubMed Central

    Jouhilahti, Eeva-Mari; Peltonen, Sirkku; Peltonen, Juha

    2008-01-01

    The findings of this study show that Class III β-tubulin is a component of the mitotic spindle in multiple cell types. Class III β-tubulin has been widely used as a neuron-specific marker, but it has been detected also in association with breast and pancreatic cancers. In this study, we describe a novel finding of Class III β-tubulin in a subpopulation of cells in malignant peripheral nerve sheath tumor. The findings of this study also show that Class III β-tubulin is expressed by normal mesenchymal and epithelial cells (fibroblasts and keratinocytes), two transitional cell carcinoma cell lines, and neurofibroma Schwann cells, as shown by immunolabeling and Western transfer analysis using two different Tuj-1 antibodies that are specific for Class III β-tubulin. The corresponding mRNA was detected using RT-PCR and whole human genome microarrays. Both antibodies localized Class III β-tubulin to the mitotic spindle and showed a colocalization with α-tubulin. The immunoreaction became visible in early prophase, and the most intense immunoreaction was detected during metaphase and anaphase when microtubules were connected to the kinetochores on chromosomes. Class III β-tubulin–specific immunoreaction lasted to the point when the midbody of cytokinesis became detectable. (J Histochem Cytochem 56:1113–1119, 2008) PMID:18796406

  6. Electron Exciter Speeds Associated with Interplanetary Type III Solar Radio Bursts

    NASA Astrophysics Data System (ADS)

    Reiner, M. J.; MacDowall, R. J.

    2015-10-01

    This article provides a comprehensive quantitative investigation of the kinematics of the electron exciters associated with interplanetary type III solar radio bursts. Detailed multispacecraft analyses of the radio and plasma wave data from the widely separated Wind and STEREO spacecraft are provided for five interplanetary type III bursts that illustrate different aspects of the problems involved in establishing the electron exciter speeds. The exciter kinematics are determined from the observed frequency drift and in-situ radiation characteristics for each type III burst. The analysis assumes propagation of the electron exciters along a Parker spiral, with origin at the associated solar active region, and curvature determined by the measured solar wind speed. The analyses take fully into account the appropriate light-propagation-time corrections from the radio source to the observing spacecraft as the exciters propagate along the Parker spiral path. For the five in-situ type III bursts analyzed in detail here, we found that their initial exciter speeds, near the Sun, ranged from 0.2c to 0.38c, where c is the speed of light. This is significantly higher than the exciter speeds derived from other recent analyses. The results presented here further suggest that the type III electron exciters normally decelerate as they propagate through the interplanetary medium. We argue based on the observations by the widely separated spacecraft that the initial part of the type III radiation usually occurs at the fundamental of the plasma frequency. Finally, we compare the results for the exciter speeds to all previous determinations and provide quantitative arguments to explain the differences.

  7. Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases.

    PubMed

    Fleck, Daniel; Voss, Matthias; Brankatschk, Ben; Giudici, Camilla; Hampel, Heike; Schwenk, Benjamin; Edbauer, Dieter; Fukumori, Akio; Steiner, Harald; Kremmer, Elisabeth; Haug-Kröper, Martina; Rossner, Moritz J; Fluhrer, Regina; Willem, Michael; Haass, Christian

    2016-01-01

    Numerous membrane-bound proteins undergo regulated intramembrane proteolysis. Regulated intramembrane proteolysis is initiated by shedding, and the remaining stubs are further processed by intramembrane-cleaving proteases (I-CLiPs). Neuregulin 1 type III (NRG1 type III) is a major physiological substrate of β-secretase (β-site amyloid precursor protein-cleaving enzyme 1 (BACE1)). BACE1-mediated cleavage is required to allow signaling of NRG1 type III. Because of the hairpin nature of NRG1 type III, two membrane-bound stubs with a type 1 and a type 2 orientation are generated by proteolytic processing. We demonstrate that these stubs are substrates for three I-CLiPs. The type 1-oriented stub is further cleaved by γ-secretase at an ϵ-like site five amino acids N-terminal to the C-terminal membrane anchor and at a γ-like site in the middle of the transmembrane domain. The ϵ-cleavage site is only one amino acid N-terminal to a Val/Leu substitution associated with schizophrenia. The mutation reduces generation of the NRG1 type III β-peptide as well as reverses signaling. Moreover, it affects the cleavage precision of γ-secretase at the γ-site similar to certain Alzheimer disease-associated mutations within the amyloid precursor protein. The type 2-oriented membrane-retained stub of NRG1 type III is further processed by signal peptide peptidase-like proteases SPPL2a and SPPL2b. Expression of catalytically inactive aspartate mutations as well as treatment with 2,2'-(2-oxo-1,3-propanediyl)bis[(phenylmethoxy)carbonyl]-l-leucyl-l-leucinamide ketone inhibits formation of N-terminal intracellular domains and the corresponding secreted C-peptide. Thus, NRG1 type III is the first protein substrate that is not only cleaved by multiple sheddases but is also processed by three different I-CLiPs. PMID:26574544

  8. Solar longitude dependence of some characteristics of type III radio bursts from metric to hectometric wavelengths

    NASA Technical Reports Server (NTRS)

    Sakurai, K.

    1974-01-01

    Using the observed data for metric and hectometric type III radio bursts, the dependence of burst characteristics on the solar longitude has been examined over a wide frequency range. It is found that there exists and east-west asymmetry for the extension of metric type III bursts into the hectometric wavelength range. In particular, hectometric bursts are rarely observed for solar flares associated with metric bursts east of 60 E solar longitude. Furthermore, for east longitudes, the low-frequency radio observations show a large dispersion in drift time interval.

  9. Vitamin A-containing lipocytes and formation of type III collagen in liver injury.

    PubMed

    Kent, G; Gay, S; Inouye, T; Bahu, R; Minick, O T; Popper, H

    1976-10-01

    Hepatocellular necrosis in carbon tetracholride-induced injury of rats is associated with an accumulation of lipocytes (perisinusoidal cells or Ito cells) containing fat droplets and giving vitamin A fluorescence. In the subsequent formation of connective tissue septa, transitional cells having morphologic characteristics of lipocytes and fibroblasts are abundant and are associated with the appearance of type III collage-. The features suggest that the lipocyte is the precursor of the fibroblasts responsible for parenchymal fibrillogenesis and under these conditions forms type III collagen. The process is a postulated link between hepatocellular necrosis and fibrosis. PMID:1068482

  10. Crystal structure of the Yersinia type III secretion protein YscE

    SciTech Connect

    Phan, Jason; Austin, Brian P.; Waugh, David S.

    2010-12-06

    The plague-causing bacterium Yersinia pestis utilizes a contact-dependent (type III) secretion system (T3SS) to transport virulence factors from the bacterial cytosol directly into the interior of mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. The type III secretion apparatus is composed of 20-25 different Yersinia secretion (Ysc) proteins. We report here the structure of YscE, the smallest Ysc protein, which is a dimer in solution. The probable mode of oligomerization is discussed.

  11. Solar wind density model from km-wave type III bursts.

    NASA Technical Reports Server (NTRS)

    Alvarez, H.; Haddock, F. T.

    1973-01-01

    The analysis of type III bursts observed from the OGO-5 satellite between 3.5 MHz and 50 kHz gives an empirical expression for the frequency drift rate as a function of frequency that is valid from 75 kHz to 550 MHz. Using this expression and some simplifying assumptions we obtain indirectly an empirical formula for the electron density distribution of the solar wind to 1 AU which is consistent with published values of electron density and with observed type III burst drift rates.

  12. Three cross leg flaps for lower leg reconstruction of Gustilo type III C open fracture

    PubMed Central

    Sano, Kazufumi; Ozeki, Satoru; Sugimoto, Ichiro; Ogawa, Masato

    2016-01-01

    A 60 year old male had Gustilo type III C open fracture of the right lower leg. After radical debridement, the large open defect including certain loss of the bone tissue was successfully augmented and covered, by consecutive three cross-leg flaps, which consisted of the free rectus abdominis musculocutaneous flap, the fibula osteocutaneous flap and the conventional sural flap. Although indication for amputation or preservation is decided with multiple factors in each case, a strategic combination of cross-leg flap, free flap, external fixation and vascular delay could increase the potential of preservation of the lower leg with even disastrous Gustilo type III C. PMID:27293297

  13. Conventional Treatment of Maxillary Incisor Type III Dens Invaginatus with Periapical Lesion: A Case Report

    PubMed Central

    Borges, Álvaro Henrique; Semenoff Segundo, Alex; Nadalin, Michele Regina; Pedro, Fábio Luís Miranda; da Cruz Filho, Antônio Miranda; Sousa-Neto, Manoel Damião

    2011-01-01

    Dens invaginatus is a developmental dental anomaly clinically characterized by a palatine furrow that can be limited to the coronal pulp or may extend to the radicular apex. The purpose of this paper was to present a clinical case of type III dens invaginatus, identified on the maxillary right central incisor in anterior periapical radiographs, in which the tooth was submitted to conventional endodontic treatment. The results obtained after five years of clinical and radiographic followup demonstrated that conventional endodontic treatment is a clinically viable alternative in cases of type III dens invaginatus. PMID:21991460

  14. Inactivation of human T-cell lymphotropic virus, type III by heat, chemicals, and irradiation

    SciTech Connect

    Quinnan, G.V. Jr.; Wells, M.A.; Wittek, A.E.; Phelan, M.A.; Mayner, R.E.; Feinstone, S.; Purcell, R.H.; Epstein, J.S.

    1986-09-01

    Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was inactivated by heat more rapidly if in liquid medium than if lyophilized and more rapidly at 60 than 56/sup 0/C. When HTLV-III was added to factor VIII suspension, then lyophilized and heated at 60/sup 0/C for 2 hours or longer there was elimination of 1 X 10(6) in vitro infectious units (IVIU) of virus. Much of the viral inactivation appeared to result from lyophilization. The application of water-saturated chloroform to the lyophilized material containing virus also resulted in elimination of infectivity. HTLV-III was efficiently inactivated by formalin, beta-propiolactone, ethyl ether, detergent, and ultraviolet light plus psoralen. The results are reassuring regarding the potential safety of various biological products.

  15. Coxsackievirus counters the host innate immune response by blocking type III interferon expression.

    PubMed

    Lind, Katharina; Svedin, Emma; Domsgen, Erna; Kapell, Sebastian; Laitinen, Olli; Moll, Markus; Flodström-Tullberg, Malin

    2016-06-01

    Type I IFNs play an important role in the immune response to enterovirus infections. Their importance is underscored by observations showing that many enteroviruses including coxsackie B viruses (CVBs) have developed strategies to block type I IFN production. Recent studies have highlighted a role for the type III IFNs (also called IFNλs) in reducing permissiveness to infections with enteric viruses including coxsackievirus. However, whether or not CVBs have measures to evade the effects of type III IFNs remains unknown. By combining virus infection studies and different modes of administrating the dsRNA mimic poly I : C, we discovered that CVBs target both TLR3- and MDA5/RIG-I-mediated type III IFN expression. Consistent with this, the cellular protein expression levels of the signal transduction proteins TRIF and IPS1 were reduced and no hyperphosphorylation of IRF-3 was observed following infection with the virus. Notably, decreased expression of full-length TRIF and IPS1 and the appearance of cleavage products was observed upon both CVB3 infection and in cellular protein extracts incubated with recombinant 2Apro, indicating an important role for the viral protease in subverting the cellular immune system. Collectively, our study reveals that CVBs block the expression of type III IFNs, and that this is achieved by a similar mechanism as the virus uses to block type I IFN production. We also demonstrate that the virus blocks several intracellular viral recognition pathways of importance for both type I and III IFN production. The simultaneous targeting of numerous arms of the host immune response may be required for successful viral replication and dissemination. PMID:26935471

  16. Early alterations in extracellular matrix and transforming growth factor [beta] gene expression in mouse lung indicative of late radiation fibrosis

    SciTech Connect

    Finkelstein, J.N.; Johnston, C.J.; Baggs, R.; Rubin, P. )

    1994-02-01

    Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The expression of late radiation injury can be found immediately after irradiation by measuring messenger RNA (mRNA) abundance. To determine if extracellular matrix mRNA and transforming growth factor beta abundance was affected acutely after irradiation, the authors measured mRNA levels of collagen I (CI), collagen III (CIII), collagen IV (CIV), fibronectin (FN), and transforming growth factor [beta] (TGF[beta][sub 1,2 3]) in mouse lungs on day 1 and day 14 after graded doses of radiation. C57BL/6 female mice were irradiated with a single dose to the thorax of 5 or 12.5 Gy. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabelled cDNA probes for CI, CIII, CIV, FN, TGF[beta][sub 1,2 3] and a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Autoradiographic data were quantified by video densitometry and results normalized to GAPDH. Changes in the expression of CI, CIII, CIV, FN and TGF[beta][sub 1,2 3] were observed as early as 1 day after exposure. Through 14 days, changes in mRNA up to 5-fold were seen for any one dose. Dose related changes as high as 10-fold were also evident. The CI:CIII ratio increased gradually for the 5 Gy dose at 14 days postirradiation while the CI:CII ratio for the 12.5 Gy dose decreased by approximately 4-fold as compared to the control. These studies suggest that alterations in expression of extracellular matrix and TGF[beta] mRNA occur very early after radiation injury even at low doses and may play a role in the development of chronic fibrosis. 37 refs., 6 figs.

  17. Transforming growth factor-beta as a differentiating factor for cultured smooth muscle cells.

    PubMed

    Gawaziuk, J P; X; Sheikh, F; Cheng, Z-Q; Cattini, P A; Stephens, N L

    2007-10-01

    The aim of the present study was to determine whether the development of supercontractile smooth muscle cells, contributing to the nonspecific hyperreactivity of airways in asthmatic patients, is due to transforming growth factor (TGF)-beta. In cultured smooth muscle cells starved by removal of 10% foetal bovine serum for 7 days, growth arrest was seen; 30% became elongated and demonstrated super contractility. Study of conditioned medium suggested that the differentiating factor was TGF-beta. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was carried out on conditioned medium from the arrested cells. Two protein bands were identified as matrix metalloproteinase (MMP)-2 and TGF-beta1. To determine second messenger signalling by SMAD2, Western blotting and confocal microscopy were employed. Conditioned medium from arrested cultures showed the presence of MMP-2 and TGF-beta1, as revealed by SDS-PAGE; 68- and 25-kDa bands were seen. Differentiation was confirmed by upregulation of marker proteins, smooth muscle type myosin heavy chain and myosin light chain kinase. Confirmation was obtained by downregulating these proteins with decorin treatment, which reduces the levels of active TGF-beta and an adenoviral dominant-negative vector coding for a mutated type II TGF-beta-receptor. Activation of second messenger signalling was demonstrated immunocytochemically by the presence of phosphorylated SMAD2 and SMAD4. Transforming growth factor-beta is likely to be the differentiating factor responsible for the development of these supercontractile smooth muscle cells. The development of such cells in vivo after cessation of an asthmatic attack could contribute to the nonspecific hyperreactivity of airways seen in patients. PMID:17596270

  18. Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation.

    PubMed Central

    Pertovaara, L; Sistonen, L; Bos, T J; Vogt, P K; Keski-Oja, J; Alitalo, K

    1989-01-01

    Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta. Images PMID:2725496

  19. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

    PubMed

    Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

    2013-02-01

    Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH. PMID:22781098

  20. Plasma ApoC-III Levels, Triglycerides, and Coronary Artery Calcification in Type 2 Diabetics

    PubMed Central

    Qamar, Arman; Khetarpal, Sumeet A.; Khera, Amit V.; Qasim, Atif; Rader, Daniel J.; Reilly, Muredach P.

    2015-01-01

    Objective Triglyceride-rich lipoproteins (TRL) have emerged as causal risk factors for developing coronary heart disease (CHD) independent of low-density lipoprotein cholesterol (LDL-C) levels. Apolipoprotein C-III (ApoC-III) modulates TRL metabolism through inhibition of lipoprotein lipase and hepatic uptake of TRL. Mutations causing loss-of-function of ApoC-III lower TG and reduce CHD risk, suggestive of a causal role for ApoC-III. Little data exist regarding the relationship of ApoC-III, TG, and atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Here, we examined the relationships between plasma ApoC-III, TG and coronary artery calcification (CAC) in T2DM patients. Approach & Results Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest CHD. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), TG (r=0.59), LDL-C (r=0.16), fasting glucose (r=0.16) and glycosylated hemoglobin (r=0.12) (P < 0.0001 for all). In age, gender, and race-adjusted analysis, ApoC-III levels were positively associated with CAC (Tobit regression ratio (TRR) 1.78, 95% CI 1.27–2.50 per SD-increase in ApoC-III, P <0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both TG (TRR 1.43, 95% CI 0.94–2.18, P=0.086) and separately for VLDL-C (TRR 1.14, 95% ci 0.75–1.71, P=0.53). Conclusions In persons with T2DM, increased plasma ApoC-III is associated with higher TG, less favorable cardiometabolic phenotypes, and higher CAC, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma TRLs and cardiovascular risk in T2DM. PMID:26069232

  1. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    PubMed

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species. PMID:26598110

  2. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.

    PubMed

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2006-09-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  3. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

    PubMed Central

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2010-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two ~3,000-residue D. discoideum proteins, termed ‘steely’, as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  4. Direct transfer of starter substrates from type I fatty acid synthase to type III polyketide synthases in phenolic lipid synthesis.

    PubMed

    Miyanaga, Akimasa; Funa, Nobutaka; Awakawa, Takayoshi; Horinouchi, Sueharu

    2008-01-22

    Alkylresorcinols and alkylpyrones, which have a polar aromatic ring and a hydrophobic alkyl chain, are phenolic lipids found in plants, fungi, and bacteria. In the Gram-negative bacterium Azotobacter vinelandii, phenolic lipids in the membrane of dormant cysts are essential for encystment. The aromatic moieties of the phenolic lipids in A. vinelandii are synthesized by two type III polyketide synthases (PKSs), ArsB and ArsC, which are encoded by the ars operon. However, details of the synthesis of hydrophobic acyl chains, which might serve as starter substrates for the type III polyketide synthases (PKSs), were unknown. Here, we show that two type I fatty acid synthases (FASs), ArsA and ArsD, which are members of the ars operon, are responsible for the biosynthesis of C(22)-C(26) fatty acids from malonyl-CoA. In vivo and in vitro reconstitution of phenolic lipid synthesis systems with the Ars enzymes suggested that the C(22)-C(26) fatty acids produced by ArsA and ArsD remained attached to the ACP domain of ArsA and were transferred hand-to-hand to the active-site cysteine residues of ArsB and ArsC. The type III PKSs then used the fatty acids as starter substrates and carried out two or three extensions with malonyl-CoA to yield the phenolic lipids. The phenolic lipids in A. vinelandii were thus found to be synthesized solely from malonyl-CoA by the four members of the ars operon. This is the first demonstration that a type I FAS interacts directly with a type III PKS through substrate transfer. PMID:18199837

  5. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Certification of certain Type III devices. 159.12a Section 159.12a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Certification Procedures § 159.12a...

  6. Evolutionary Implications and Physicochemical Analyses of Selected Proteins of Type III Polyketide Synthase Family

    PubMed Central

    Mallika, V.; Sivakumar, K.C.; Soniya, E.V.

    2011-01-01

    Type III polyketide synthases have a substantial role in the biosynthesis of various polyketides in plants and microorganisms. Comparative proteomic analysis of type III polyketide synthases showed evolutionarily and structurally related positions in a compilation of amino acid sequences from different families. Bacterial and fungal type III polyketide synthase proteins showed <50% similarity but in higher plants, it exhibited >80% among chalcone synthases and >70% in the case of non-chalcone synthases. In a consensus phylogenetic tree based on 1000 replicates; bacterial, fungal and plant proteins were clustered in separate groups. Proteins from bryophytes and pteridophytes grouped immediately near to the fungal cluster, demonstrated how evolutionary lineage has occurred among type III polyketide synthase proteins. Upon physicochemical analysis, it was observed that the proteins localized in the cytoplasm and were hydrophobic in nature. Molecular structural analysis revealed comparatively stable structure comprising of alpha helices and random coils as major structural components. It was found that there was a decline in the structural stability with active site mutation as prophesied by the in silico mutation studies. PMID:21697991

  7. The Chlamydial Type III Secretion Mechanism: Revealing Cracks in a Tough Nut

    PubMed Central

    Betts-Hampikian, Helen Jennifer; Fields, Kenneth A.

    2010-01-01

    Present-day members of the Chlamydiaceae contain parasitic bacteria that have been co-evolving with their eukaryotic hosts over hundreds of millions of years. Likewise, a type III secretion system encoded within all genomes has been refined to complement the unique obligate intracellular niche colonized so successfully by Chlamydia spp. All this adaptation has occurred in the apparent absence of the horizontal gene transfer responsible for creating the wide range of diversity in other Gram-negative, type III-expressing bacteria. The result is a system that is, in many ways, uniquely chlamydial. A critical mass of information has been amassed that sheds significant light on how the chlamydial secretion system functions and contributes to an obligate intracellular lifestyle. Although the overall mechanism is certainly similar to homologous systems, an image has emerged where the chlamydial secretion system is essential for both survival and virulence. Numerous apparent differences, some subtle and some profound, differentiate chlamydial type III secretion from others. Herein, we provide a comprehensive review of the current state of knowledge regarding the Chlamydia type III secretion mechanism. We focus on the aspects that are distinctly chlamydial and comment on how this important system influences chlamydial pathogenesis. Gaining a grasp on this fascinating system has been challenging in the absence of a tractable genetic system. However, the surface of this tough nut has been scored and the future promises to be fruitful and revealing. PMID:21738522

  8. A Bacterial Pathogen uses Distinct Type III Secretion Systems to Alternate between Host Kingdom

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gram-negative bacterial pathogens of eukaryotes often secrete proteins directly into host cells via a needle-like protein channel called a ‘type III secretion system’ (T3SS). Bacteria that are adapted to either animal or plant hosts use phylogenetically distinct T3SSs for secreting proteins. Here, ...

  9. Preliminary Analysis of Soybean Gene Expression Response to a Bradyrhizobium japonicum Type III Secretion System Mutant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant pathogens deliver proteinaceous effector molecules into their host via complex secretion systems, such as the type III secretion system (T3SS). Some of these T3SS effectors have been shown to function as suppressors of host defense responses. The role of the T3SS during plant interactions wit...

  10. A bacterial pathogen uses distinct type III secretion systems to alternate between host kingdoms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (Pnss), the causative agent of Stewart’s bacterial wilt and...

  11. Aquatic Therapy for a Child with Type III Spinal Muscular Atrophy: A Case Report

    ERIC Educational Resources Information Center

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-01-01

    Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons. This case report describes an aquatic therapy program and the outcomes for a 3-year-old girl with type III SMA. Motor skills were examined using the 88-item Gross Motor Function Measure (GMFM), the Peabody Developmental Motor Scales…

  12. Contribution of Bordetella bronchiseptica Type III secretion system to respiratory disease in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The type III secretion system (TTSS) of gram negative bacteria allows injection of effector proteins directly into the cytosol of eukaryotic cells. Previous studies have demonstrated that the B. bronchiseptica TTSS plays a role in the persistent bacterial colonization of the trachea of m...

  13. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue.

    PubMed

    Olczyk, Pawel; Wisowski, Grzegorz; Komosinska-Vassev, Katarzyna; Stojko, Jerzy; Klimek, Katarzyna; Olczyk, Monika; Kozma, Ewa M

    2013-01-01

    Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues. Burn wounds were inflicted on pigs, chosen for the evaluation of wound repair because of many similarities between pig and human skin. Isolated collagen types I and III were estimated by the surface plasmon resonance method with a subsequent collagenous quantification using electrophoretic and densitometric analyses. Propolis burn treatment led to enhanced collagens and its components expression, especially during the initial stage of the study. Less expressed changes were observed after silver sulfadiazine (AgSD) application. AgSD and, with a smaller intensity, propolis stimulated accumulation of collagenous degradation products. The assessed propolis therapeutic efficacy, throughout quantitatively and qualitatively analyses of collagen types I and III expression and degradation in wounds matrix, may indicate that apitherapeutic agent can generate favorable biochemical environment supporting reepithelization. PMID:23781260

  14. Mutualistic Co-evolution of Type III Effector Genes in Sinorhizobium fredii and Bradyrhizobium japonicum

    PubMed Central

    Jiang, Yuan; Creason, Allison L.; Thireault, Caitlin A.; Sachs, Joel L.; Chang, Jeff H.

    2013-01-01

    Two diametric paradigms have been proposed to model the molecular co-evolution of microbial mutualists and their eukaryotic hosts. In one, mutualist and host exhibit an antagonistic arms race and each partner evolves rapidly to maximize their own fitness from the interaction at potential expense of the other. In the opposing model, conflicts between mutualist and host are largely resolved and the interaction is characterized by evolutionary stasis. We tested these opposing frameworks in two lineages of mutualistic rhizobia, Sinorhizobium fredii and Bradyrhizobium japonicum. To examine genes demonstrably important for host-interactions we coupled the mining of genome sequences to a comprehensive functional screen for type III effector genes, which are necessary for many Gram-negative pathogens to infect their hosts. We demonstrate that the rhizobial type III effector genes exhibit a surprisingly high degree of conservation in content and sequence that is in contrast to those of a well characterized plant pathogenic species. This type III effector gene conservation is particularly striking in the context of the relatively high genome-wide diversity of rhizobia. The evolution of rhizobial type III effectors is inconsistent with the molecular arms race paradigm. Instead, our results reveal that these loci are relatively static in rhizobial lineages and suggest that fitness conflicts between rhizobia mutualists and their host plants have been largely resolved. PMID:23468637

  15. Decameter Type III Bursts with Changing Frequency Drift-Rate Signs

    NASA Astrophysics Data System (ADS)

    Melnik, V. N.; Brazhenko, A. I.; Konovalenko, A. A.; Briand, C.; Dorovskyy, V. V.; Zarka, P.; Frantsuzenko, A. V.; Rucker, H. O.; Rutkevych, B. P.; Panchenko, M.; Denis, L.; Zaqarashvili, T.; Shergelashvili, B.

    2015-01-01

    We discuss properties of type III bursts that change the sign of their drift rate from negative to positive and vice versa. Moreover, these bursts may change the sign of their drift rates more than once. These particular type III bursts were observed simultaneously by the radio telescopes UTR-2 ( Ukrainian T-shaped Radio telescope, Kharkov, Ukraine), URAN-2 ( Ukrainian Radio telescope of the Academy of Sciences, Poltava, Ukraine), and by the NDA ( Nançay Decametric Array, Nancay, France) in the frequency range 8 - 41 MHz. The negative drift rates of these bursts are similar to those of previously reported decameter type III bursts and vary from -0.7 MHz s-1 to -1.7 MHz s-1, but their positive drift rates vary in a wider range from 0.44 MHz s-1 to 6 MHz s-1. Unlike inverted U-bursts, the tracks of these type III bursts have C- or inverted C-shapes.

  16. Synthesis and immunological properties of conjugates composed of group B streptococcus type III capsular polysaccharide covalently bound to tetanus toxoid.

    PubMed

    Lagergard, T; Shiloach, J; Robbins, J B; Schneerson, R

    1990-03-01

    A synthetic scheme for covalently binding group B streptococcus type III to tetanus toxoid (TT), using adipic acid dihydrazide as a spacer, is described. Type III alone or as a conjugate with TT was injected subcutaneously into laboratory mice, and the type-specific and TT antibody responses elicited by these immunogens were assayed. Type III-TT elicited significantly higher levels of type-specific antibodies after each immunization than did the type III alone. These levels were related to the dosage of the conjugate, enhanced by Freund adjuvant, and exhibited booster responses. Type III alone elicited only immunoglobulin M (IgM) antibodies in Swiss albino mice and mostly IgM and low levels of IgG antibodies of the IgG3 subclass in BALB/c mice. Type III-TT conjugates, in contrast, elicited mostly IgG antibodies in both strains of mice. IgA type III antibodies were not detected. The first two immunizations with the conjugates elicited type III antibodies in the IgG1 and in the IgG3 subclasses. Low levels of IgG2a type III antibodies were detected after a third injection of type III-TT. Conjugate-induced antibodies facilitated opsonization of group B streptococcus type III organisms and did not react with the structurally related pneumococcus type 14. TT alone or as a component of type III-TT induced mostly antibodies of the IgG class: IgG1 levels were the highest of the four subclasses. No IgA TT antibodies were detected. The conjugation procedure, therefore, enhanced the immunogenicity of and conferred T-cell dependent properties to the type III while preserving the immunogenicity of the TT component. The T-cell dependent properties of the conjugates were responsible for stimulating IgG type III antibodies which could be boosted. Evaluation of type III-TT conjugates in antibody-negative women of child-bearing age is planned. PMID:2407652

  17. Redox-mediated activation of latent transforming growth factor-beta 1

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Dix, T. A.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during

  18. Transforming growth factor-beta during carcinogenesis: the shift from epithelial to mesenchymal signaling.

    PubMed

    Matsuzaki, Koichi; Okazaki, Kazuichi

    2006-04-01

    Transforming growth factor-beta (TGF-beta) activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells, JNK/pSmad3L-mediated signaling is involved in invasion by activated mesenchymal cells. During sporadic human colorectal carcinogenesis, TGF-beta signaling confers a selective advantage on tumor cells by shifting from the TbetaRI/pSmad3C pathway characteristic of mature epithelial cells to the JNK/pSmad3L pathway, which is more characteristic of the state of flux shown by the activated mesenchymal cells. JNK acts as a regulator of TGF-beta signaling by increasing the basal level of pSmad3L available for action in the nuclei of the invasive adenocarcinoma, in the meantime shutting down TGF-beta-dependent nuclear activity of pSmad3C. Loss of epithelial homeostasis and acquisition of a migratory, mesenchymal phenotype are essential for tumor invasion. From the viewpoint of TGF-beta signaling, a key therapeutic aim in cancer would be restoration of the lost tumor suppressor function observed in normal colorectal epithelial cells at the expense of effects promoting aggressive behavior of the adenocarcinoma. Specific inhibitors of the JNK/pSmad3L pathway might prove useful in this respect. In the case of molecularly targeted therapy for human cancer, pSmad3L and pSmad3C could be assessed as biomarkers to evaluate the likely benefit from specific inhibition of the JNK/pSmad3L pathway. PMID:16741607

  19. Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice

    PubMed Central

    Katre, Ashwini; Ballinger, Carol; Akhter, Hasina; Fanucchi, Michelle; Kim, Dae-Kee; Postlethwait, Edward; Liu, Rui-Ming

    2013-01-01

    Ozone (O3), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O3-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O3 exposure protocol consisting of 2 days of filtered air and 5 days of O3 exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O3 exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O3 exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O3 exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O3-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O3 exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O3-induced lung fibrotic responses in vivo. PMID:21689010

  20. Redox-mediated activation of latent transforming growth factor-beta 1.

    PubMed

    Barcellos-Hoff, M H; Dix, T A

    1996-09-01

    Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during

  1. Autocrine and exogenous transforming growth factor beta control cell cycle inhibition through pathways with different sensitivity.

    PubMed

    Wang, Jing; Sergina, Natalia; Ko, Tien C; Gong, Jiangeng; Brattain, Michael G

    2004-09-17

    Human colon carcinoma cells HCT116 that lack transforming growth factor beta (TGF-beta) type II receptor (RII) demonstrated restoration of autocrine TGF-beta activity upon reexpression of RII without restoring inhibitory responses to exogenous TGF-beta treatment. RII transfectants (designated RII Cl 37) had a longer lag phase relative to NEO-transfected control cells (designated NEO pool) before entering exponential growth in tissue culture. The prolonged growth arrest of RII Cl 37 cells was associated with markedly reduced cyclin-dependent kinase (CDK)2 activity. Our results demonstrate that p21 induction by autocrine TGF-beta is responsible for reduced CDK2 activity, which at least partially contributes to prolonged growth arrest and reduced cell proliferation in RII Cl 37 cells. In contrast to RII transfectants, HCT116 cells transfected with chromosome 3 (designated HCT116Ch3), which bears the RII gene, restored the response to exogenous TGF-beta as well as autocrine TGF-beta activity. Autocrine TGF-beta activity in HCT116Ch3 cells induced p21 expression as seen in RII Cl 37 cells; however, in addition to autocrine activity, HCT116Ch3 cells responded to exogenous TGF-beta as decreased CDK4 expression and reduced pRb phosphorylation mediated a TGF-beta inhibitory response in these cells. These results indicate that autocrine TGF-beta regulates the cell cycle through a pathway different from exogenous TGF-beta in the sense that p21 is a more sensitive effector of the TGF-beta signaling pathway, which can be induced and saturated by autocrine TGF-beta, whereas CDK4 inhibition is a less sensitive effector, which can only be activated by high levels of exogenous TGF-beta PMID:15271980

  2. Effect of transforming growth factor beta on synthesis of glycosaminoglycans by human lung fibroblasts

    SciTech Connect

    Dubaybo, B.A.; Thet, L.A. )

    1990-09-01

    The processes of lung growth, injury, and repair are characterized by alterations in fibroblast synthesis and interstitial distribution of extracellular matrix components. Transforming growth factor beta (TGF-beta), which is postulated to play a role in modulating lung repair, alters the distribution of several matrix components such as collagen and fibronectin. We studied the effect of TGF-beta on the synthesis and distribution of the various glycosaminoglycans (GAGs) and whether these effects may explain its role in lung repair. Human diploid lung fibroblasts (IMR-90) were exposed to various concentrations of TGF-beta (0-5 nM) for variable periods of time (0-18 h). Newly synthesized GAGs were labeled with either (3H)glucosamine or (35S)sulfate. Individual GAGs were separated by size exclusion chromatography after serial enzymatic and chemical digestions and quantitated using scintillation counting. There was a dose-dependent increase in total GAG synthesis with maximal levels detected after 6 h of exposure. This increase was noted in all individual GAG types measured and was observed in both the cell associated GAGs (cell-matrix fraction) as well as the GAGs released into the medium (medium fraction). In the cell-matrix fraction, TGF-beta increased the proportion of heparan sulfate that was membrane bound as well as the proportion of dermatan sulfate in the intracellular compartment. In the medium fraction, TGF-beta increased the proportion of hyaluronic acid, chondroitin sulfate and dermatan sulfate released. We conclude that the role of TGF-beta in lung growth and repair may be related to increased synthesis of GAGs by human lung fibroblasts as well as alterations in the distribution of individual GAGs.

  3. Transforming growth factor: beta signaling is essential for limb regeneration in axolotls.

    PubMed

    Lévesque, Mathieu; Gatien, Samuel; Finnson, Kenneth; Desmeules, Sophie; Villiard, Eric; Pilote, Mireille; Philip, Anie; Roy, Stéphane

    2007-01-01

    Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-beta). In the present study, the full length sequence of the axolotl TGF-beta1 cDNA was isolated. The spatio-temporal expression pattern of TGF-beta1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-beta signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-beta type I receptor, SB-431542, we show that TGF-beta signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-beta signaling are down-regulated. These data directly implicate TGF-beta signaling in the

  4. Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4.

    PubMed

    Chou, Wan-Chih; Prokova, Vassiliki; Shiraishi, Keiko; Valcourt, Ulrich; Moustakas, Aristidis; Hadzopoulou-Cladaras, Margarita; Zannis, Vassilis I; Kardassis, Dimitris

    2003-03-01

    We have shown previously that the transforming growth factor-beta (TGFbeta)-regulated Sma-Mad (Smad) protein 3 and Smad4 proteins transactivate the apolipoprotein C-III promoter in hepatic cells via a hormone response element that binds the nuclear receptor hepatocyte nuclear factor 4 (HNF-4). In the present study, we show that Smad3 and Smad4 but not Smad2 physically interact with HNF-4 via their Mad homology 1 domains both in vitro and in vivo. The synergistic transactivation of target promoters by Smads and HNF-4 was shown to depend on the specific promoter context and did not require an intact beta-hairpin/DNA binding domain of the Smads. Using glutathione S-transferase interaction assays, we established that two regions of HNF-4, the N-terminal activation function 1 (AF-1) domain (aa 1-24) and the C-terminal F domain (aa 388-455) can mediate physical Smad3/HNF-4 interactions in vitro. In vivo, Smad3 and Smad4 proteins enhanced the transactivation function of various GAL4-HNF-4 fusion proteins via the AF-1 and the adjacent DNA binding domain, whereas a single tyrosine to alanine substitution in AF-1 abolished coactivation by Smads. The findings suggest that the transcriptional cross talk between the TGFbeta-regulated Smads and HNF-4 is mediated by specific functional domains in the two types of transcription factors. Furthermore, the specificity of this interaction for certain target promoters may play an important role in various hepatocyte functions, which are regulated by TGFbeta and the Smads. PMID:12631740

  5. Structural characterization of CFA/III and Longus type IVb pili from enterotoxigenic Escherichia coli.

    PubMed

    Kolappan, Subramaniapillai; Roos, Justin; Yuen, Alex S W; Pierce, Owen M; Craig, Lisa

    2012-05-01

    The type IV pili are helical filaments found on many Gram-negative pathogenic bacteria, with multiple diverse roles in pathogenesis, including microcolony formation, adhesion, and twitching motility. Many pathogenic enterotoxigenic Escherichia coli (ETEC) isolates express one of two type IV pili belonging to the type IVb subclass: CFA/III or Longus. Here we show a direct correlation between CFA/III expression and ETEC aggregation, suggesting that these pili, like the Vibrio cholerae toxin-coregulated pili (TCP), mediate microcolony formation. We report a 1.26-Å resolution crystal structure of CofA, the major pilin subunit from CFA/III. CofA is very similar in structure to V. cholerae TcpA but possesses a 10-amino-acid insertion that replaces part of the α2-helix with an irregular loop containing a 3(10)-helix. Homology modeling suggests a very similar structure for the Longus LngA pilin. A model for the CFA/III pilus filament was generated using the TCP electron microscopy reconstruction as a template. The unique 3(10)-helix insert fits perfectly within the gap between CofA globular domains. This insert, together with differences in surface-exposed residues, produces a filament that is smoother and more negatively charged than TCP. To explore the specificity of the type IV pilus assembly apparatus, CofA was expressed heterologously in V. cholerae by replacing the tcpA gene with that of cofA within the tcp operon. Although CofA was synthesized and processed by V. cholerae, no CFA/III filaments were detected, suggesting that the components of the type IVb pilus assembly system are highly specific to their pilin substrates. PMID:22447901

  6. Disturbances in affective touch in hereditary sensory & autonomic neuropathy type III.

    PubMed

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Löken, Line; Axelrod, Felicia B; Kaufmann, Horacio

    2014-07-01

    Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1-10 cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity. PMID:24726998

  7. Vascular Ehlers-Danlos syndrome mutations in type III collagen differently stall the triple helical folding.

    PubMed

    Mizuno, Kazunori; Boudko, Sergei; Engel, Jürgen; Bächinger, Hans Peter

    2013-06-28

    Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at a low temperature. At 33 °C, the natural collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at Gly-910 and at the C terminus at Gly-1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue. PMID:23645670

  8. Vascular Ehlers-Danlos Syndrome Mutations in Type III Collagen Differently Stall the Triple Helical Folding*

    PubMed Central

    Mizuno, Kazunori; Boudko, Sergei; Engel, Jürgen; Bächinger, Hans Peter

    2013-01-01

    Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-terminal quarter, 252 residues, of the natural human type III collagen was attached to (GPP)7 with the type XIX collagen trimerization domain (NC2). The natural collagen domain forms a triple helical structure without 4-hydroxylation of proline at a low temperature. At 33 °C, the natural collagenous part is denatured, but the C-terminal (GPP)7-NC2 remains intact. Switching to a low temperature triggers the folding of the type III collagen domain in a zipper-like fashion that resembles the natural process. We used this system for the two known EDS mutations (Gly-to-Val) in the middle at Gly-910 and at the C terminus at Gly-1018. In addition, wild-type and Gly-to-Ala mutants were made. The mutations significantly slow down the overall rate of triple helix formation. The effect of the Gly-to-Val mutation is much more severe compared with Gly-to-Ala. This is the first report on the folding of collagen with EDS mutations, which demonstrates local delays in the triple helix propagation around the mutated residue. PMID:23645670

  9. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

    PubMed

    Bristol, Sarah K; Woodruff, Teresa K

    2004-03-01

    Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2

  10. Osteogenesis imperfecta type III in South Africa: Psychosocial challenges.

    PubMed

    Stephen, L X G; Roberts, T; Van Hayden, E; Chetty, M

    2016-01-01

    Individuals with osteogenesis imperfecta type III (OI III) are severely physically disabled due to frequent fracturing. Their disability poses numerous barriers that challenge their social development. Despite these limitations, several affected persons are able to rise above these problems and achieve success in their personal and professional life. This outcome is directly relevant to their psychosocial development.The achievements of five individuals with OI III living in Cape Town are highlighted in this article, as well as the challenges that they have experienced and continue to experience in their daily lives. The authors intend to promulgate understanding of the psychosocial circumstances of affected persons, thereby facilitating the deployment of appropriate efforts and resources to address these challenges. PMID:27245537

  11. Dietary management in glycogen storage disease type III: what is the evidence?

    PubMed

    Derks, Terry G J; Smit, G Peter A

    2015-05-01

    In childhood, GSD type III causes relatively severe fasting intolerance, classically associated with ketotic hypoglycaemia. During follow up, history of (documented) hypoglycaemia, clinical parameters (growth, liver size, motor development, neuromuscular parameters), laboratory parameters (glucose, lactate, ALAT, cholesterol, triglycerides, creatine kinase and ketones) and cardiac parameters all need to be integrated in order to titrate dietary management, for which age-dependent requirements need to be taken into account. Evidence from case studies and small cohort studies in both children and adults with GSD III demonstrate that prevention of hypoglycaemia and maintenance of euglycemia is not sufficient to prevent complications. Moreover, over-treatment with carbohydrates may even be harmful. The ageing cohort of GSD III patients, including the non-traditional clinical presentations in adulthood, raises ‬‬‬new questions. PMID:25164784

  12. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    SciTech Connect

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. ); Murray, J. ); Crall, M. )

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  13. Economic Impacts of Treatment for Type II or III Thoracoabdominal Aortic Aneurysm in the United States

    PubMed Central

    Vaislic, Mickael; Vaislic, Claude; Alsac, Jean-Marc; Benjelloun, Amira; Chocron, Sidney; Unterseeh, Thierry; Fabiani, Jean-Noel

    2014-01-01

    Background: Current treatment for extensive thoracoabdominal aortic aneurysms (TAAAs) involves high-risk surgical and endovascular repairs, with a hospital mortality exceeding 20%, and a postoperative paraplegia rate beyond 10.5%. Objectives: The aim of this study was to present an estimation of the economic impacts of surgical and endovascular treatments of types II and III TAAAs in the US as well as the economic consequences of the elimination of spinal cord injury and mortality via an endovascular repair of extensive TAAAs (1). Materials and Methods: We compared the current hospital charges of endovascular and surgical repair of extensive TAAAs, also provided a cost analysis of health care charges resulting from paraplegia in the United States, and determined the prevalence of extensive TAAAs found yearly during autopsies in the U.S. Based on the figures gathered and the frequency of Thoracic Aortic Aneurysms per year, we were able to calculate the nationwide inpatient hospital charges, the total average expenses affected by paraplegia during the first 12 months after the repair, the total average expenses after paraplegia for each subsequent year, mortality rate at 30 days and one year, and the number of extensive TAAAs ruptures. Results: The current nationwide inpatient hospital charges for type II or III TAAA repair cost $12484324 and $37612665 for endovascular repair and surgical repair respectively, and the total average expenses for patients affected by paraplegia during the first 12-month were $4882291 and $23179110 after endovascular repair and surgical repair respectively. The nationwide average expense after 10 years for patients undergoing surgical repair and affected by paraplegia is $33421910 and $6,316,183 for patients undergoing endovascular repair. Moreover, 55 patients with a type II or type III TAAA died after 30 days, and 100 after 1 year. The potential risk of type II or III TAAA ruptures is totally 1637 in a year. Conclusions: Major economic

  14. Bianchi type-I, type-III and Kantowski-Sachs solutions in f( T) gravity

    NASA Astrophysics Data System (ADS)

    Rodrigues, M. E.; Kpadonou, A. V.; Rahaman, F.; Oliveira, P. J.; Houndjo, M. J. S.

    2015-06-01

    In the context of modified tele-parallel theory of gravity, we undertake cosmological anisotropic models and search for their solutions. Within a suitable choice of non-diagonal tetrads, the decoupled equations of motion are obtained for Bianchi-I, Bianchi-III and Kantowski-Sachs models, from which we obtain the correspondent solutions. By the way, energy density and pressures are also obtained, showing, as an important result, that our universe may live a quintessence like universe even while anisotropic models are considered.

  15. Type III acromioclavicular separation: results of a recent survey on its management.

    PubMed

    Nissen, Carl W; Chatterjee, Abhishek

    2007-02-01

    The issue of managing type III acromioclavicular (AC) separations remains controversial, and decisions about using operative versus conservative management have undergone many distinct changes over the years. To review current management preferences within the orthopedic community, we sent a mail-in survey to all members of the American Orthopaedic Society for Sports Medicine (AOSSM) and approved Accreditation Council for Graduate Medical Education (ACGME) orthopedic program residency directors. Of the 664 respondents (577 AOSSM members, 87 directors), 81% (71/87 AOSSM members) to 86% (502/577 directors) continue to treat uncomplicated type III AC separations conservatively. Providing a sling for comfort remains the preferred type of conservative management (AOSSM members, 91% [456/502]; directors, 89% [63/71]). For surgical management, respondents recommended resection of the distal clavicle slightly more often than not (AOSSM members, 57% [42/74]; directors, 59% [319/538]) and rigid stabilization of the AC joint during early postoperative rehabilitation (AOSSM members, 80% [444/555]; directors, 82% [61/74]). Finally, most recommended reconstructing either the coracoclavicular ligaments (69% [330/476] and 61% [33/54], respectively) or both the coracoclavicular ligaments and the AC ligaments (27% 130/476] and 33% [18/54]) when addressing this problem. Since the early 1990s, there has been little change in initial conservative management of type III AC separations. Furthermore, the surgical approach to reconstruction, when necessary, has also undergone relatively few changes, with the exception of an increased preference for primary distal clavicle excision. PMID:17405638

  16. Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

    PubMed

    Gripp, K W; Stolle, C A; McDonald-McGinn, D M; Markowitz, R I; Bartlett, S P; Katowitz, J A; Muenke, M; Zackai, E H

    1998-07-24

    We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis. PMID:9714439

  17. Tibial spine fractures: an analysis of outcome in surgically treated type III injuries.

    PubMed

    Mulhall, K J; Dowdall, J; Grannell, M; McCabe, J P

    1999-05-01

    We analysed the outcome of open reduction and internal fixation of type III tibial spine fractures, assessing treatment and determining a treatment protocol. A total of 10 patients presented over 3 years to our institution with a mean age of 15 years (range 10-21), a male-to-female ratio of 8:2. left to right 6:4 and anterior to posterior spine fracture 9:1. Only one patient had associated meniscal injury noted at arthroscopy (no treatment required). The mode of injury was road traffic accidents four, sports injuries three and falls three. The mean follow-up was 9 months. There were seven excellent results and three good results. Those patients with good results exhibited either minimal quadriceps weakness, extensor lag (< 10 degrees) or antero-posterior laxity. This reflects the experience of other authors in dealing with these injuries in younger patients. There is widespread agreement that types I and II should be treated by plaster cast alone and that is also the policy at our institution. We recommend a routine treatment protocol in type III injuries of (1) examination under anaesthesia, (2) arthroscopy (evaluating the fracture, cruciate integrity and other associated injuries), (3) open reduction and screw fixation and (4) vigorous physiotherapy/rehabilitation of all type III fractures, as we feel this provides the best possible outcome in these injuries. PMID:10476299

  18. The Pseudomonas aeruginosa Type III Translocon Is Required for Biofilm Formation at the Epithelial Barrier

    PubMed Central

    Tran, Cindy S.; Rangel, Stephanie M.; Almblad, Henrik; Kierbel, Arlinet; Givskov, Michael; Tolker-Nielsen, Tim; Hauser, Alan R.; Engel, Joanne N.

    2014-01-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates exhibit key characteristics of biofilms, including the presence of extracellular matrix and increased resistance to antibiotics compared to planktonic bacteria. Using isogenic mutants in the type III secretion system, we found that the translocon, but not the effectors themselves, were required for cell-associated aggregation on the surface of polarized epithelial cells and at early time points in a murine model of acute pneumonia. In contrast, the translocon was not required for aggregation on abiotic surfaces, suggesting a novel function for the type III secretion system during cell-associated aggregation. Supernatants from epithelial cells infected with wild-type bacteria or from cells treated with the pore-forming toxin streptolysin O could rescue aggregate formation in a type III secretion mutant, indicating that cell-associated aggregation requires one or more host cell factors. Our results suggest a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection. PMID:25375398

  19. The Pseudomonas aeruginosa type III translocon is required for biofilm formation at the epithelial barrier.

    PubMed

    Tran, Cindy S; Rangel, Stephanie M; Almblad, Henrik; Kierbel, Arlinet; Givskov, Michael; Tolker-Nielsen, Tim; Hauser, Alan R; Engel, Joanne N

    2014-11-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates exhibit key characteristics of biofilms, including the presence of extracellular matrix and increased resistance to antibiotics compared to planktonic bacteria. Using isogenic mutants in the type III secretion system, we found that the translocon, but not the effectors themselves, were required for cell-associated aggregation on the surface of polarized epithelial cells and at early time points in a murine model of acute pneumonia. In contrast, the translocon was not required for aggregation on abiotic surfaces, suggesting a novel function for the type III secretion system during cell-associated aggregation. Supernatants from epithelial cells infected with wild-type bacteria or from cells treated with the pore-forming toxin streptolysin O could rescue aggregate formation in a type III secretion mutant, indicating that cell-associated aggregation requires one or more host cell factors. Our results suggest a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection. PMID:25375398

  20. In Situ Detection of Strong Langmuir Turbulence Processes in Solar Type III Radio Bursts

    NASA Technical Reports Server (NTRS)

    Golla, Thejappa; Macdowall, Robert J.; Bergamo, M.

    2012-01-01

    The high time resolution observations obtained by the WAVES experiment of the STEREO spacecraft in solar type III radio bursts show that Langmuir waves often occur as intense localized wave packets. These wave packets are characterized by short durations of only a few ms and peak intensities, which well exceed the supersonic modulational instability (MI) thresholds. These timescales and peak intensities satisfy the criterion of the solitons collapsed to spatial scales of a few hundred Debye lengths. The spectra of these wave packets consist of primary spectral peaks corresponding to beam-resonant Langmuir waves, two or more sidebands corresponding to down-shifted and up-shifted daughter Langmuir waves, and low frequency enhancements below a few hundred Hz corresponding to daughter ion sound waves. The frequencies and wave numbers of these spectral components satisfy the resonance conditions of the modulational instability (MI). Moreover, the tricoherences, computed using trispectral analysis techniques show that these spectral components are coupled to each other with a high degree of coherency as expected of the MI type of four wave interactions. The high intensities, short scale lengths, sideband spectral structures and low frequency spectral enhancements and, high levels of tricoherences amongst the spectral components of these wave packets provide unambiguous evidence for the supersonic MI and related strong turbulence processes in type III radio bursts. The implication of these observations include: (1) the MI and related strong turbulence processes often occur in type III source regions, (2) the strong turbulence processes probably play very important roles in beam stabilization as well as conversion of Langmuir waves into escaping radiation at the fundamental and second harmonic of the electron plasma frequency, fpe, and (3) the Langmuir collapse probably follows the route of MI in type III radio bursts.

  1. 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

  2. Evidence for nonlinear wave-wave interactions in solar type III radio bursts

    NASA Technical Reports Server (NTRS)

    Lin, R. P.; Levedahl, W. K.; Lotko, W.; Gurnett, D. A.; Scarf, F. L.

    1986-01-01

    Evidence is presented that nonlinear wave-wave interactions occur in type III solar radio bursts. Intense, spiky Langmuir waves are observed to be driven by electron beams associated with type III solar radio bursts in the interplanetary medium. Bursts of 30-300 Hz (in the spacecraft frame) waves are often observed coincident in time with the most intense spikes of the Langmuir waves. These low-frequency waves appear to be long-wavelength ion acoustic waves, with wavenumber approximately equal to the beam resonant Langmuir wavenumber. Three possible interpretations of these observations are considered: modulational instability, parametric decay of the parent Langmuir waves to daughter ion acoustic and Langmuir waves, and decay to daughter electromagnetic waves and ion acoustic waves.

  3. RNA-activated DNA cleavage by the Type III-B CRISPR-Cas effector complex.

    PubMed

    Estrella, Michael A; Kuo, Fang-Ting; Bailey, Scott

    2016-02-15

    The CRISPR (clustered regularly interspaced short palindromic repeat) system is an RNA-guided immune system that protects prokaryotes from invading genetic elements. This system represents an inheritable and adaptable immune system that is mediated by multisubunit effector complexes. In the Type III-B system, the Cmr effector complex has been found to cleave ssRNA in vitro. However, in vivo, it has been implicated in transcription-dependent DNA targeting. We show here that the Cmr complex from Thermotoga maritima can cleave an ssRNA target that is complementary to the CRISPR RNA. We also show that binding of a complementary ssRNA target activates an ssDNA-specific nuclease activity in the histidine-aspartate (HD) domain of the Cmr2 subunit of the complex. These data suggest a mechanism for transcription-coupled DNA targeting by the Cmr complex and provide a unifying mechanism for all Type III systems. PMID:26848046

  4. Structural and functional characterization of a novel type-III dockerin from Ruminococcus flavefaciens.

    PubMed

    Karpol, Alon; Jobby, Maroor K; Slutzki, Michal; Noach, Ilit; Chitayat, Seth; Smith, Steven P; Bayer, Edward A

    2013-01-01

    Phylogenetic analysis of known dockerins in Ruminococcus flavefaciens revealed a novel subtype, type-III, in the scaffoldin proteins, ScaA, ScaB, ScaC and ScaE. In this study, we explored the Ca²⁺-binding properties of the type-III dockerin from the ScaA scaffoldin (ScaADoc) using a battery of structural and biophysical approaches including circular dichroism spectroscopy, isothermal titration calorimetry, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. Despite the lack of a second canonical Ca²⁺-binding loop, the behaviour of ScaADoc is similar with respect to other dockerin protein modules in terms of its responsiveness to Ca²⁺ and affinity for the cohesin from the ScaB scaffoldin. Our results highlight the robustness of dockerin modules and how their Ca²⁺-binding properties can be exploited in the construction of designer cellulosomes. PMID:23195689

  5. Association of flaring X-ray bright points with type III bursts

    NASA Technical Reports Server (NTRS)

    Kundu, M. R.; Gergely, T. E.; Golub, L.

    1980-01-01

    Using the swept-frequency radio observations obtained at the Clark Lake Radio Observatory and the X-ray photographs taken by the S-054 experiment aboard Skylab, a search has been made for type III bursts associated with X-ray bright point (XBP) flares. Using temporal as well as spatial criteria for the association, four such events are found over a period of 43 days. The time period was selected in such a way that the level of flare and radio activity was low in order to minimize the chance coincidences. The detection of type III bursts from the flaring XBPs is of great interest, since it identifies them with the flare process, of which XBP flares are thought to be the simplest form.

  6. Type III Dyson Sphere of Highly Advanced Civilisations around a Super Massive Black Hole

    NASA Astrophysics Data System (ADS)

    Inoue, M.; Yokoo, H.

    We describe a new system for a society of highly advanced civilizations around a super massive black hole (SMBH), as an advanced Type III “Dyson Sphere,” pointing out an efficient usage of energy for the advanced civilizations. SMBH also works as a sink for waste materials. Here we assume that Type III civilisations of Kardashev classification [1] form a galactic club [2] in a galaxy, and the energy from the SMBH will be delivered to the club members, forming an energy control system similar to power grids in our present society. The energy is probably transmitted by a sharp beam with coherent electro-magnetic waves, which provide a new concept for the search for extraterrestrial intelligence (SETI) via detection of such energy transmission signals. This expands the search window for other intelligences within the Universe.

  7. Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes.

    PubMed

    Koska, Juraj; Yassine, Hussein; Trenchevska, Olgica; Sinari, Shripad; Schwenke, Dawn C; Yen, Frances T; Billheimer, Dean; Nelson, Randall W; Nedelkov, Dobrin; Reaven, Peter D

    2016-05-01

    The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma apoC-III proteoforms (by mass spectrometric immunoassay) and plasma lipids were tested in two randomized clinical trials: ACT NOW, a study of pioglitazone in subjects with impaired glucose tolerance (n = 531), and RACED (n = 296), a study of intensive glycemic control and atherosclerosis in type 2 diabetes patients. At baseline, higher relative apoC-III2 and apoC-III2/apoC-III1 ratios were associated with lower triglycerides and total cholesterol in both cohorts, and with lower small dense LDL in the RACED. Longitudinally, changes in apoC-III2/apoC-III1 were inversely associated with changes in triglycerides in both cohorts, and with total and small dense LDL in the RACED. apoC-III2/apoC-III1 was also higher in patients treated with PPAR-γ agonists and was associated with reduced cardiovascular events in the RACED control group. Ex vivo studies of apoC-III complexes with higher apoC-III2/apoC-III1 showed attenuated inhibition of VLDL uptake by HepG2 cells and LPL-mediated lipolysis, providing possible functional explanations for the inverse association between a higher apoC-III2/apoC-III1 and hypertriglyceridemia, proatherogenic plasma lipid profiles, and cardiovascular risk. PMID:26945091

  8. Enhanced jun gene expression is an early genomic response to transforming growth factor. beta. stimulation

    SciTech Connect

    Pertovaara, L.; Sistonen, L.; Keski-Oja, J.; Alitalo, K. ); Bos, T.J.; Vogt, P.K. . Dept. of Microbiology)

    1989-03-01

    Transforming growth factor {beta} (TGF{beta}) is a multifunctional polypeptide4 that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF{beta} signal transduction in cells is unknown. The authors report here that an early effect of TGF{beta} is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF{beta}, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF{beta}, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TFG{beta}. The increase in jun mRNA occurred with picomolar TGF{beta} concentrations within 1 h of TGF{beta} stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-fine levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF{beta}, evidently in a protein synthesis-independent fashion. The junB response to TGF{beta} was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF{beta} may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF{beta}.

  9. A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity

    SciTech Connect

    Schirmer, Markus A.; Brockmoeller, Juergen; Rave-Fraenk, Margret; Virsik, Patricia; Wilken, Barbara; Kuehnle, Elna; Campean, Radu; Hoffmann, Arne O.; Mueller, Katarina; Goetze, Robert G.; Neumann, Michael; Janke, Joerg H.; Nasser, Fatima; Wolff, Hendrik A.; Ghadimi, B. Michael; Schmidberger, Heinz; Hess, Clemens F.; Christiansen, Hans; Hille, Andrea

    2011-03-01

    Purpose: To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-{beta}1 (TGF-{beta}1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods: Transforming growth factor-{beta}1 plasma concentrations (n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations (n = 71) ex vivo before therapy start. Furthermore, TGF-{beta}1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5' region of the TGFB1 gene. Because of high linkage disequilibrium, these five polymorphisms reflect frequent genetic variation in this region. A presumed impact of TGF-{beta}1 on DNA damage or repair was measured as micronucleus formation in 30 lymphoblastoid cell lines. Results: We identified a hypofunctional genetic haplotype termed H3 tagging the 5' region of the TGFB1 gene encoding TGF-{beta}1. H3 was associated with lower TGF-{beta}1 plasma concentrations in patients (p = 0.01) and reduced TGF-{beta}1 secretion in irradiated peripheral blood mononuclear cells (p = 0.003). Furthermore, cells with H3 were less prone to induction of chromosomal aberrations (p = 0.001) and apoptosis (p = 0.003) by irradiation. The hypothesis that high TGF-{beta}1 could sensitize cells to DNA damage was further supported by increased micronuclei formation in 30 lymphoblastoid cell lines when preincubated with TGF-{beta}1 before irradiation (p = 0.04). Conclusions: On the basis of TGF-{beta}1 plasma levels and radiation sensitivity of lymphoid cells, this study revealed a putatively hypofunctional TGFB1 haplotype. The significance of this haplotype and the suggested link between TGF-{beta}1 function and DNA integrity should be further explored in other cell types, as well as other experimental and clinical conditions.

  10. Overactive bladder after female genital mutilation/cutting (FGM/C) type III

    PubMed Central

    Abdulcadir, Jasmine; Dällenbach, Patrick

    2013-01-01

    A 27-year-old Somali woman with type III a–b female genital mutilation/cutting, consulted because of slow micturition, voiding efforts, urgency and urge incontinence (overactive bladder). She also referred primary dysmenorrhoea and superficial dyspareunia making complete sexual intercourses impossible. We treated her by defibulation and biofeedback re-educative therapy. We also offered a multidisciplinary counselling. At 5 months follow-up, urgency and urge incontinence had resolved and she became pregnant. PMID:24096069

  11. Overactive bladder after female genital mutilation/cutting (FGM/C) type III.

    PubMed

    Abdulcadir, Jasmine; Dällenbach, Patrick

    2013-01-01

    A 27-year-old Somali woman with type III a-b female genital mutilation/cutting, consulted because of slow micturition, voiding efforts, urgency and urge incontinence (overactive bladder). She also referred primary dysmenorrhoea and superficial dyspareunia making complete sexual intercourses impossible. We treated her by defibulation and biofeedback re-educative therapy. We also offered a multidisciplinary counselling. At 5 months follow-up, urgency and urge incontinence had resolved and she became pregnant. PMID:24096069

  12. Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III.

    PubMed

    D'Eufemia, Patrizia; Finocchiaro, Roberto; Celli, Mauro; Raccio, Ivana; Properzi, Enrico; Zicari, Alessandra

    2009-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPD). Few cases have been described with mental retardation or neurological symptoms. Recently it has been demonstrated that 4-HPD participates to nitric oxide (NO) intracellular sequestration in Pseudomonas aeruginosa. 4-HPD is an ubiquitous enzyme with a prominent expression in neutrophils and neurons. In the nervous system NO has been perceived to be a potential neuromodulator although prolonged excessive generation is detrimental. We analyzed NO release by neutrophils of a patient with tyrosinemia type III in order to evaluate a possible influence of 4-HPD deficiency on this process. Our patient, previously described, is a 30-year-old women with persistent tyrosinemia (450-680 micromol/l) and deficient activity of 4-HPD. At 17 months of age she experienced an acute ataxia and drowsiness lasting for 10 days, but further clinical course showed persistent tyrosinemia with normal growth and psychomotor development. Neutrophils isolated from our patient exhibited a NO release greatly higher in respect to the controls (mean+/-SEM 23.2+/-1.8 micromol/10(6) cells vs 3.5+/-0.5 micromol/10(6) cells). Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation but no consistent phenotype has emerged. Therefore the pathogenesis of neurological involvement is yet not well understood. Our results suggest that an excessive neutrophils of NO release could reflect the lack of scavenging action of 4-HPD. Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III. PMID:18657947

  13. Evidence for Type III Restriction and Modification Systems in Mycoplasma pulmonis▿

    PubMed Central

    Dybvig, Kevin; Cao, Z.; French, C. Todd; Yu, Huilan

    2007-01-01

    Mycoplasma pulmonis possesses a cassette of genes that are predicted to code for type III restriction and modification (R-M) enzymes. Transposon disruption of a gene predicted to code for the endonuclease subunit of the enzyme resulted in loss of R-M activity. Genomic data indicate that the cassette was acquired by horizontal gene transfer and possibly located on a mobile element. PMID:17209015

  14. Pyopneumothorax with Stocker type III congenital cystic adenomatoid malformation in a 5-month-old infant

    PubMed Central

    Chilkar, Sujeet M; Leelakumar, Venkat; Ranjani, Chakravarthy P; Musthyala, Bharati; Narayana, Kotte VS

    2016-01-01

    Congenital cystic adenomatoid malformation (CCAM) is a rare, developmental, hamartomatous abnormality of the lung characterized by a cessation of normal bronchiolar maturation, resulting in cystic overgrowth of the terminal bronchioles. We report one such case of CCAM in a 5-month-old female infant who was in perfect health until she suffered from spontaneous pyopneumothorax with type III CCAM of the lung and recovered after lobectomy. PMID:27051113

  15. A comparison of type III solar radio burst theories using satellite radio observations and particle measurements.

    NASA Technical Reports Server (NTRS)

    Evans, L. G.; Fainberg, J.; Stone, R. G.

    1971-01-01

    The required electron density to excite a type III solar burst can be predicted from different theories, using the low frequency radio observations of the RAE-1 satellite. Electron flux measurements by satellite in the vicinity of 1 AU then give an independent means of comparing these predicted exciter electron densities to the measured density. On this basis, one theory predicts the electron density in closest agreement with the measured values.

  16. Anesthetic challenges in managing a case of type III laryngo-tracheo-esophageal cleft

    PubMed Central

    Rajmohan, Nisha; Prakasam, Hassy; Francis, Johny V

    2012-01-01

    Laryngo-tracheo-esophageal cleft (LTEC) is a rare congenital anomaly characterized by failure of fusion of the cricoid cartilage posteriorly and incomplete development of the tracheo-esophageal septum. Securing the airway during anesthesia in patients with LTEC, especially in the severe forms is a challenge. We describe the anesthetic management and the airway challenges in a neonate with type III LTEC who underwent bronchoscopy and repair of LTEC. PMID:23225937

  17. Anesthetic challenges in managing a case of type III laryngo-tracheo-esophageal cleft.

    PubMed

    Rajmohan, Nisha; Prakasam, Hassy; Francis, Johny V

    2012-10-01

    Laryngo-tracheo-esophageal cleft (LTEC) is a rare congenital anomaly characterized by failure of fusion of the cricoid cartilage posteriorly and incomplete development of the tracheo-esophageal septum. Securing the airway during anesthesia in patients with LTEC, especially in the severe forms is a challenge. We describe the anesthetic management and the airway challenges in a neonate with type III LTEC who underwent bronchoscopy and repair of LTEC. PMID:23225937

  18. Estimation of Group B Streptococcus Type III Polysaccharide-Specific Antibody Concentrations in Human Sera Is Antigen Dependent

    PubMed Central

    Bhushan, Reva; Anthony, Bascom F.; Frasch, Carl E.

    1998-01-01

    The presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toxoid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure ≤0.05 μg of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS. PMID:9826364

  19. Evidence for Langmuir Envelope Solitons in Solar Type III Burst Source Regions

    NASA Technical Reports Server (NTRS)

    Thejappa, G.; Goldstein, M. L.; MacDowall, R. J.; Papadopoulos, K.; Stone, R. G.

    1998-01-01

    We present observational evidence for the generation of Langmuir envelope solitons in the source regions of solar type III radio bursts. The solitons appear to be formed by electron beams which excite either the modulational instability or oscillating two-stream instability (OTSI). Millisecond data from the Ulysses Unified Radio and Plasma Wave Experiment (URAP) show that Langmuir waves associated with type III bursts occur as broad intense peaks with time scales ranging from 15 to 90 milliseconds (6 - 27 km). These broad field structures have the properties expected of Langmuir envelope solitons, viz.: the normalized peak energy densities, W(sub L)/n(sub e)T(sub e) approximately 10(exp -5), are well above the modulational instability threshold; the spatial scales, L, which range from 1 - 5 Langmuir wavelengths, show a high degree of inverse correlation with (W(sub L)/n(sub e)T(sub e))(sup 1/2); and the observed widths of these broad peaks agree well with the predicted widths of envelope solitons. We show that the orientation of the Langmuir field structures is random with respect to the ambient magnetic field, indicating that they are probably isotropic structures that have evolved from initially pancake-like solitons. These observations suggest that strong turbulence processes, such as the modulational instability or the OTSI, stabilize the electron beams that produce type III bursts.

  20. Direction-finding measurements of type III radio bursts out of the ecliptic plane

    NASA Technical Reports Server (NTRS)

    Baumback, M. M.; Kurth, W. S.; Gurnett, D. A.

    1976-01-01

    A series of two-dimensional direction-finding measurements for three type III solar radio bursts is presented which is based on spin-modulation measurements from two satellites (IMP 8 and Hawkeye I) whose spin axes were nearly perpendicular to each other. The two-dimensional direction-finding technique is combined with a model of the solar-wind plasma density in order to provide determinations of type III source locations out of the ecliptic plane as well as information on the three-dimensional structure of the solar magnetic field at radial distances of 0.2 to 1.0 AU from the sun. The direction-finding technique is described in detail, characteristics of the bursts observed by the two satellites are summarized, and the solar-wind model is outlined. The results show that the source locations follow an Archimedean spiral when projected onto the ecliptic plane but usually follow a constant heliocentric latitude perpendicular to that plane. It is also found that measured source sizes are a factor of two larger than the angular sizes of previously reported solar-flare electron emissions, that the spin-modulation factor tends to be largest near the beginning of a type III event, and that the arrival direction of the radiation varies systematically during an event.

  1. Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model.

    PubMed

    Martins, Carla; Hůlková, Helena; Dridi, Larbi; Dormoy-Raclet, Virginie; Grigoryeva, Lubov; Choi, Yoo; Langford-Smith, Alexander; Wilkinson, Fiona L; Ohmi, Kazuhiro; DiCristo, Graziella; Hamel, Edith; Ausseil, Jerôme; Cheillan, David; Moreau, Alain; Svobodová, Eva; Hájková, Zuzana; Tesařová, Markéta; Hansíková, Hana; Bigger, Brian W; Hrebícek, Martin; Pshezhetsky, Alexey V

    2015-02-01

    Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety. Cognitive memory decline was detected at 10 months and at 12-13 months mice showed signs of unbalanced hesitant walk and urinary retention. Lysosomal accumulation of heparan sulphate was observed in hepatocytes, splenic sinus endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes. Starting from 5 months, brain neurons showed enlarged, structurally abnormal mitochondria, impaired mitochondrial energy metabolism, and storage of densely packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and amyloid-β. Taken together, our data demonstrate for the first time that deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase causes lysosomal accumulation of heparan sulphate in microglial cells followed by their activation and cytokine release. They also show mitochondrial dysfunction in the neurons and neuronal loss explaining why mucopolysaccharidosis III type C manifests primarily as a neurodegenerative disease. PMID:25567323

  2. Identification, Characterization, and Developmental Expression Pattern of Type III Interferon Receptor Gene in the Chinese Goose

    PubMed Central

    Zhou, Qin; Chen, Shun; Qi, Yulin; Zhou, Hao; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Chen, Xiaoyue; Zhou, Xue; Cheng, Anchun

    2015-01-01

    Interferons, as the first line of defense against the viral infection, play an important role in innate immune responses. Type III interferon (IFN-λ) was a newly identified member of IFN family, which plays IFN-like antiviral activity. Towards a better understanding of the type III interferon system in birds, type III interferon lambda receptor (IFNLR1) was first identified in the Chinese goose. In this paper, we had cloned 1952 bp for goose IFNLR1 (goIFNLR1), including an ORF of 1539 bp, encoding a 512-amino acid protein with a 20 aa predict signal peptide at its N terminal and a 23 aa transmembrane region. The predicted amino acid sequence of goIFNLR1 has 90%, 73%, and 34% identity with duck IFNLR1 (predicted sequence), chicken IFNLR1, and human IFNLR1, respectively. And the age-related tissue distribution of goIFNLR1 was identified by Real Time quantitative PCR (RT-qPCR), we found that the goIFNLR1 has a mainly expression in epithelium-rich tissues similar to other species', such as small intestinal, lung, liver, and stomach. Moreover, a relatively high expression of goIFNLR1 was also observed in the secondary immune tissues (harderian gland and cecal tonsil). The identification and tissue distribution of goIFNLR1 will facilitate further study of the role of IFN-λ in goose antiviral defense. PMID:26064884

  3. Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model

    PubMed Central

    Martins, Carla; Hůlková, Helena; Dridi, Larbi; Dormoy-Raclet, Virginie; Grigoryeva, Lubov; Choi, Yoo; Langford-Smith, Alexander; Wilkinson, Fiona L.; Ohmi, Kazuhiro; DiCristo, Graziella; Hamel, Edith; Ausseil, Jerôme; Cheillan, David; Moreau, Alain; Svobodová, Eva; Hájková, Zuzana; Tesařová, Markéta; Hansíková, Hana; Bigger, Brian W.; Hrebícek, Martin

    2015-01-01

    Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6–8 months mice showed hyperactivity, and reduced anxiety. Cognitive memory decline was detected at 10 months and at 12–13 months mice showed signs of unbalanced hesitant walk and urinary retention. Lysosomal accumulation of heparan sulphate was observed in hepatocytes, splenic sinus endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes. Starting from 5 months, brain neurons showed enlarged, structurally abnormal mitochondria, impaired mitochondrial energy metabolism, and storage of densely packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and amyloid-β. Taken together, our data demonstrate for the first time that deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase causes lysosomal accumulation of heparan sulphate in microglial cells followed by their activation and cytokine release. They also show mitochondrial dysfunction in the neurons and neuronal loss explaining why mucopolysaccharidosis III type C manifests primarily as a neurodegenerative disease. PMID:25567323

  4. Novel Low Fluence Combination Laser Treatment of Solar Lentigines in Type III Asian Skin

    PubMed Central

    Tian, Brian Wei Cheng Anthony

    2015-01-01

    Objective: To demonstrate a novel low fluence combination laser technique [Erbium-doped yttrium aluminum garnet (Erb:YAG) and neodymium-doped yttrium aluminum garnet (Nd:YAG)] to effectively treat solar lentigines in type III Asian skin in a single session. Design: A prospective study. Setting: A Singapore-based clinic. Participants: Five patients (all females) were enrolled into the study. The ages ranged 35-60 years; all patients had Fitzpatrick skin type III. Measurements: Photographs were taken at baseline and at 1-month follow-up. These were reviewed by two independent physicians who were blinded to the study. Changes in pigment severity were assessed by a 5-point scale (1: Aggravation of pigment, 2: No change, 3: 25-50% improvement, 4: 51-75% improvement, and 5: 76-100% improvement). Results: All patients received a single treatment session. At 1-month follow-up, a reduction in pigment was observed in all patients. Both physicians’ reports were independently agreeable. All patients scored 5, having >90% improvement in pigment severity. No hypopigmentation, postinflammatory hyperpigmentation (PIH), or recurrence was seen. Conclusion: Low fluence combination laser is effective and safe for clearance of solar lentigines in type III Asian skin. PMID:26865789

  5. Use of proline mutants to help solve the NMR solution structure of type III antifreeze protein.

    PubMed Central

    Chao, H.; Davies, P. L.; Sykes, B. D.; Sönnichsen, F. D.

    1993-01-01

    To help understand the structure/function relationships in antifreeze proteins (AFP), and to define the motifs required for ice binding, a Type III AFP suitable for two-dimensional (2D) NMR studies was produced in Escherichia coli. A synthetic gene for one of the Type III AFP isoforms was assembled in a T7 polymerase-directed expression vector. The 67-amino acid-long gene product differed from the natural AFP by inclusion of an N-terminal methionine but was indistinguishable in activity. The NMR spectra of this AFP were complicated by cis-trans proline isomerization from the C-terminal sequence YPPA. Substitution of this sequence by YAA eliminated isomer signals without altering the activity or structure of the mutant AFP. This variant (rQAE m1.1) was selected for sequential assignment and the secondary structure determination using 2D 1H NMR spectroscopy. Nine beta-strands are paired to form two triple-stranded antiparallel sheets and one double-stranded antiparallel sheet. Two further proline replacements, P29A and P33A, were made to delineate the role of conserved prolines in Type III AFP. These mutants were valuable in clarifying ambiguous NMR spectral assignments amongst the remaining six prolines of rQAE m1.1. In contrast to the replacement of the C-terminal prolyl residues, the exchange of P29 and P33 caused some structural changes and significantly decreased protein solubility and antifreeze activity. PMID:8401227

  6. Multiple nucleic acid cleavage modes in divergent type III CRISPR systems

    PubMed Central

    Zhang, Jing; Graham, Shirley; Tello, Agnes; Liu, Huanting; White, Malcolm F.

    2016-01-01

    CRISPR-Cas is an RNA-guided adaptive immune system that protects bacteria and archaea from invading nucleic acids. Type III systems (Cmr, Csm) have been shown to cleave RNA targets in vitro and some are capable of transcription-dependent DNA targeting. The crenarchaeon Sulfolobus solfataricus has two divergent subtypes of the type III system (Sso-IIID and a Cmr7-containing variant of Sso-IIIB). Here, we report that both the Sso-IIID and Sso-IIIB complexes cleave cognate RNA targets with a ruler mechanism and 6 or 12 nt spacing that relates to the organization of the Cas7 backbone. This backbone-mediated cleavage activity thus appears universal for the type III systems. The Sso-IIIB complex is also known to possess a distinct ‘UA’ cleavage mode. The predominant activity observed in vitro depends on the relative molar concentration of protein and target RNA. The Sso-IIID complex can cleave plasmid DNA targets in vitro, generating linear DNA products with an activity that is dependent on both the cyclase and HD nuclease domains of the Cas10 subunit, suggesting a role for both nuclease active sites in the degradation of double-stranded DNA targets. PMID:26801642

  7. Multiplex real-time PCR SYBR Green for detection and typing of group III Clostridium botulinum.

    PubMed

    Anniballi, Fabrizio; Auricchio, Bruna; Delibato, Elisabetta; Antonacci, Monia; De Medici, Dario; Fenicia, Lucia

    2012-01-27

    Clostridium botulinum type C and type D belonging to the group III organisms, are mainly responsible for animal botulism outbreaks. Clinical signs alone are often insufficient to make a diagnosis of botulism and a laboratory confirmation is required. Laboratory confirmation can be performed by demonstrating the presence of botulinum neurotoxins in serum, gastrointestinal contents, liver, wound of sick or dead animals, or by demonstrating the presence of C. botulinum in gastrointestinal contents, liver, and wound. Demonstration of spores in gastrointestinal contents or tissue of animals with clinical signs indicative of botulism reinforces the clinical diagnosis. With the aim of detecting and typing C. botulinum group III organisms, a multiplex real-time PCR SYBR Green was developed and in-house validated. Selectivity, limit of detection, relative accuracy, relative specificity, relative sensitivity, and repeatability of the method were investigated. The multiplex real-time PCR SYBR green used showed a 100% selectivity, 100% relative accuracy, 100% relative specificity, 100% relative sensitivity and a limit of detection of 277 and 580 DNA copies for C. botulinum type C and C. botulinum type D, respectively. The method reported here represents a suitable tool for laboratory diagnosis of type C and D botulism and for testing a large number of samples collected during the animal botulism surveillance and prevention activities. PMID:21890285

  8. Comparing comfort and wearability between Type III single-layered and double-layered EVA mouthguards.

    PubMed

    Kenyon, Brian J; Loos, Larry G

    2005-01-01

    This study compared two Type III ethylene vinyl acetate (EVA) mouthguards for wearability, comfort, fit, and patient preference. Twenty-two athletes each received two custom-fabricated athletic mouthguards, a single-layered vacuum-formed EVA mouthguard and a double-layered heat- and pressure-laminated EVA type. Athletes wore each type of mouthguard for a two-week period while playing basketball. At the end of each two-week period, the athletes completed questionnaires that evaluated 17 characteristics of each mouthguard type. Data were analyzed using the binomial test for small numbers. The double-layered heat- and pressure-laminated EVA mouthguard performed as well as or better than the single-layered vacuum-formed type in 14 of the 17 categories. There was a statistically significant patient preference for the double-layered heat- and pressure-laminated mouthguard. PMID:16158793

  9. Dynamical structure of solar radio burst type III as evidence of energy of solar flares

    NASA Astrophysics Data System (ADS)

    Hamidi, Zety Sharizat Binti

    2013-11-01

    Observations of low frequency solar type III radio bursts associated with the ejection of plasma oscillations localized disturbance is due to excitation atoms in the plasma frequency incoherent radiations play a dominant role at the meter and decimeter wavelengths. Here, we report the results of the dynamical structure of solar flare type III that occurred on 9th March 2012 at National Space Centre, Sg Lang, Selangor, Malaysia by using the CALLISTO system. These bursts are associated with solar flare type M6 which suddenly ejected in the active region AR 1429 starting at 03:32 UT and ending at 05:00 UT with the peak at 04:12 UT. The observation showed an initial strong burst occurred due to strong signal at the beginning of the phase. We also found that both solar burst and flares tend to be a numerous on the same day and probability of chance coincidence is high. It is clearly seen that an impulsive lace burst was detected at 4:24 UT and it is more plausible that the energies are confined to the top of the loop when we compared with X-ray results. Associated with this event was type II with velocities 1285 km/s and type IV radio sweeps along with a full halo Coronal Mass Ejections (CMEs) first seen in SOHO/LASCO C2 imagery at 09/0426 Z. We concluded that the significance of study solar burst type III lies in the fact that the emission at decimetric wavelength comes from the role of magnetic field in active region that may provide the key to the energy release mechanism in a flare.

  10. Appurtenance Influence on Type III Hanford Single-Shell Tank Structural Integrity

    SciTech Connect

    Sanborn, Scott E.; Larsen, Brian M.; Julyk, Larry J.; Johnson, Kenneth I.

    2012-02-26

    The interim stabilized Hanford Single Shell Tanks (SSTs) are currently undergoing a state of the art analysis to assess the structural integrity of the waste storage tanks, for cleanup and closure operations, considering their adverse thermal histories and an updated seismic hazard for the Hanford Site near Richland, Washington. The SSTs contain a variety of ancillary pits, piping, piping supports, risers, equipment, and penetrations known as appurtenances. These appurtenances may alter the structural response and ultimately could affect the structural integrity of the SSTs. An important challenge to the structural analysis of the SSTs is determining the impact of these appurtenances on structural integrity. To achieve this, the various appurtenances were reviewed and bounding appurtenance configurations for SST Types II and III tank designs were analyzed using finite element software. The bounding configurations for the Type II tanks considered four heavy offset pits with a central pit with and without a 36-inch diameter central post-construction penetration and four 42-inch diameter offset penetrations. The bounding configuration for the Type III tanks is a tank with two heavy offset pits and one heavy central pit. For each bounding configuration two finite element models are developed: a seismic analysis model and a thermal and operating loads analysis (TOLA) model. The TOLA models include a Type II or III thermal history, concrete cracking and thermal degradation, reinforcement yielding, and soil plasticity. Additionally, operating loads such as internal waste pressure and concentrated and distributed soil surface loads are applied to the TOLA model. The seismic model treats the tank concrete as linear elastic based on the present day degraded concrete properties. Also, in the seismic model the soil is treated as linear elastic while special techniques are used in the soil above the tank dome and along the tank wall to avoid soil arching and achieve the proper