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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. Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis.

    PubMed Central

    Nakatsukasa, H; Nagy, P; Evarts, R P; Hsia, C C; Marsden, E; Thorgeirsson, S S

    1990-01-01

    The cellular distribution and temporal expression of transcripts from transforming growth factor-beta 1 (TGF-beta 1) and procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-beta 1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-beta 1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expression among procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-beta 1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-beta 1 may have an important role in the production of fibrosis. Images PMID:1693377

  3. Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts.

    PubMed Central

    Varga, J; Rosenbloom, J; Jimenez, S A

    1987-01-01

    It has been previously shown that transforming growth factor beta (TGF beta) is capable of stimulating fibroblast collagen and fibronectin biosynthesis. The purpose of this study was to examine the mechanisms involved in TGF beta stimulation of fibroblast biosynthetic activity. Our results indicate that TGF beta causes a marked enhancement of the production of types I and III collagens and fibronectin by cultured normal human dermal fibroblasts. The rate of collagen production by fibroblasts exposed to TGF beta was 2-3-fold greater than that of control cells. These effects were associated with a 2-3-fold increase in the steady-state amounts of types I and III collagen mRNAs and a 5-8-fold increase in the amounts of fibronectin mRNAs as determined by dot-blot hybridization with specific cloned cDNA probes. In addition, the increased production of collagen and fibronectin and the increased amounts of their corresponding mRNAs remained elevated for at least 72 h after removal of TGF beta. These findings suggest that TGF beta may play a major role in the normal regulation of extracellular matrix production in vivo and may contribute to the development of pathological states of fibrosis. Images Fig. 1. Fig. 4. PMID:3501287

  4. Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta.

    PubMed

    Watson, Chris J; Phelan, Dermot; Collier, Patrick; Horgan, Stephen; Glezeva, Nadia; Cooke, Gordon; Xu, Maojia; Ledwidge, Mark; McDonald, Kenneth; Baugh, John A

    2014-06-01

    Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.

  5. 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

  6. Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.

    PubMed

    Connor, T B; Roberts, A B; Sporn, M B; Danielpour, D; Dart, L L; Michels, R G; de Bustros, S; Enger, C; Kato, H; Lansing, M

    1989-05-01

    Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.

  7. The genomic structure of the gene encoding the human transforming growth factor {beta} type II receptor (TGF-{beta} RII)

    SciTech Connect

    Takenoshita, Seiichi; Hagiwara, Koichi; Nagashima, Makoto; Gemma, Akihiko

    1996-09-01

    The genomic structure of the human transforming growth factor-{beta} type II receptor gene (TGF-{beta} RII) was determined by two PCR-based methods, the {open_quotes}long distance sequencer{close_quotes} method and the {open_quotes}promoter finder{close_quotes} method. Genomic fragments containing exons and adjacent introns were amplified by PCR, and the nucleotide sequences were determined by direct sequencing and subcloning sequencing. The TGF-{beta} RII protein is encoded by 567 codons in 7 exons. This is the first report about the genomic structure of a gene that belongs to the serine/threonine kinase type II receptor subfamily. Knowledge of the genomic structure of the TGF-{beta} RII gene will facilitate investigation of the TGF-{beta} RII gene will facilitate investigation of the TGF-{beta} signaling pathway in normal human cells and of the aberrations occurring during carcinogenesis. 18 refs., 2 figs., 1 tab.

  8. 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

  9. Type III burst pair

    NASA Astrophysics Data System (ADS)

    Ning, Zongjun; Fu, Qijun; Lu, Quankang

    2000-05-01

    We present a special solar radio burst detected on 5 January 1994 using the multi-channel (50) spectrometer (1.0-2.0 GHz) of the Beijing Astronomical Observatory (BAO). Sadly, the whole event could not be recorded since it had a broader bandwidth than the limit range of the instrument. The important part was obtained, however. The event is composed of a normal drift type III burst on the lower frequency side and a reverse drift type III burst appearing almost simultaneously on the high side. We call the burst type III a burst pair. It is a typical characteristic of two type III bursts that they are morphologically symmetric about some frequency from 1.64 GHz to 1.78 GHz on the dynamic spectra records, which indicates that there are two different electron beams from the same acceleration region travelling simultaneously in opposite directions (upward and downward). A magnetic reconnection mode is a nice interpretation of type III burst pair since the plasma beta β~=0.01 is much less than 1 and the beams have velocity of about 1.07×10^8 cm s^-1 after leaving the reconnection region if we assume that the ambient magnetic field strength is about 100 G.

  10. Type III burst pair.

    NASA Astrophysics Data System (ADS)

    Zongjun, Ning; Fu, Qijun; Quankang, Lu

    2000-05-01

    Presents a special solar radio burst detected on 5 January 1994 using the multi-channel (50) spectrometer (1.0 - 2.0 GHz) of the Beijing Astronomical Observatory. Sadly, the whole event could not be recorded since it had a broader bandwidth than the limit range of the instrument. The important part was obtained, however. The event is composed of a normal drift type III burst on the lower frequency side and a reverse drift type III burst appearing almost simultaneously on the high side. The authors call the burst type III a burst pair. It is a typical characteristic of two type III bursts that they are morphologically symmetric about some frequency from 1.64 GHz to 1.78 GHz on the dynamic spectra records, which indicates that there are two different electron beams from the same acceleration region travelling simultaneously in opposite directions (upward and downward). A magnetic reconnection mode is an interpretation of type III burst pair.

  11. Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region.

    PubMed Central

    Wieser, R; Attisano, L; Wrana, J L; Massagué, J

    1993-01-01

    The transforming growth factor beta (TGF-beta) type II receptor (T beta R-II) is a transmembrane serine/threonine kinase that contains two inserts in the kinase region and a serine/threonine-rich C-terminal extension. T beta R-II is required for TGF-beta binding to the type I receptor, with which it forms a heteromeric receptor complex, and its kinase activity is required for signaling by this complex. We investigated the role of various cytoplasmic regions in T beta R-II by altering or deleting these regions and determining the signaling activity of the resulting products in cell lines made resistant to TGF-beta by inactivation of the endogenous T beta R-II. TGF-beta binding to receptor I and responsiveness to TGF-beta in these cells can be restored by transfection of wild-type T beta R-II. Using this system, we show that the kinase insert 1 and the C-terminal tail of T beta R-II, in contrast to the corresponding regions in most tyrosine kinase receptors, are not essential to specify ligand-induced responses. Insert 2 is necessary to support the catalytic activity of the receptor kinase, and its deletion yields a receptor that is unable to mediate any of the responses tested. However, substitution of this insert with insert 2 from the activin receptor, ActR-IIB, does not diminish the ability of T beta R-II to elicit these responses. A truncated T beta R-II lacking the cytoplasmic domain still binds TGF-beta, supports ligand binding to receptor I, and forms a complex with this receptor. However, TGF-beta binding to receptor I facilitated by this truncated T beta R-II fails to inhibit cell proliferation, activate extracellular matrix protein production, or activate transcription from a promoter containing TGF-beta-responsive elements. We conclude that the transcriptional and antiproliferative responses to TGF-beta require both components of a heteromeric receptor complex that differs from tyrosine kinase receptors in its mode of signaling. Images PMID:8246946

  12. Type III Hyperlipoproteinaemia

    PubMed Central

    Borrie, Peter

    1969-01-01

    Eighteen patients with type III hyperlipoproteinaemia, diagnosed on the basis of skin lesions, serum lipids, and lipoprotein electrophoresis, have been fully investigated over a period of 15 years. The incidence of coronary artery disease was only slightly increased, and was not increased at all among first-degree relatives. Peripheral occlusive arterial disease was probably more common. An increased incidence of carbohydrate intolerance was found in neither the patients nor their relatives. The effects of treatment on the skin were uniformly good. ImagesFig. 1Fig. 2 PMID:5783124

  13. Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse.

    PubMed

    Charan, S; Palmer, K; Chester, P; Mire-Sluis, A R; Meager, A; Edington, N

    1997-04-01

    Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succumbed to infection while the ones with similar magnitudes of T-cell responses, but no TGF-beta 1 activity, were protected. A definition of this immunosuppressive mechanism and its mode of induction must be central to the design of vaccines and to an understanding of the pathogenesis of EHV-1.

  14. 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

  15. Cranial mononeuropathy III - diabetic type

    MedlinePlus

    ... diabetic type of cranial mononeuropathy III is a complication of diabetes . It causes double vision and eyelid drooping . ... Cooper ME, Vinik AI, Plutzky J, Boulton AJM. Complications of diabetes mellitus. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg ...

  16. Overexpression of transforming growth factor-. beta. in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene

    SciTech Connect

    Kim, Seongjin; Winokur, T.S.; Lee, Hyde; Danielpour, D.; Kim, Kyung Young; Geiser, A.G.; Sporn, M.B.; Roberts, A.B. ); Chen, Liansheng; Jay, G. )

    1991-10-01

    Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-{beta} (TGF-{beta}1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-{beta}1 promoter. To understand further the regulation of TGF-{beta}1 expression by Tax, the authors examined its expression in transgenic mice carrying the HTLV-I tax gene. They show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-{beta}1 mRNA and protein. Moreover, TGF-{beta}1 significantly stimulated the incorporation of tritiated thymidine into one of three cells lines derived from neurofibromas of tax-transgenic mice, which suggest that the excessive production of TGF-{beta}1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-{beta} in vivo.

  17. Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells.

    PubMed Central

    Woodworth, C D; Notario, V; DiPaolo, J A

    1990-01-01

    Human papillomavirus type 16 (HPV16) early proteins E6 and E7 have been implicated in maintenance of the malignant phenotype in cervical cancer. Transforming growth factors beta one and two (TGF betas 1 and 2), polypeptides that regulate cellular growth and differentiation, reversibly inhibited expression of the HPV16 E6 and E7 genes in several immortal genital epithelial cell lines. Loss of E6 and E7 protein expression followed a dramatic time- and dose-dependent decrease in E6 and E7 RNA levels and was accompanied by cessation of cell proliferation. TGF betas 1 and 2 inhibited HPV16 RNA expression at the transcriptional level; inhibition was dependent upon ongoing protein synthesis. TGF betas 1 and 2 also induced a six- to sevenfold increase in TGF beta 1 RNA. Cells became partially resistant to the inhibitory effects of TGF beta 1 on cell growth and HPV early gene expression after prolonged cultivation in vitro or after malignant transformation. Thus, TGF beta 1 may function as an autocrine regulator of HPV gene expression in infected genital epithelial cells. Images PMID:2168964

  18. Transforming growth factor-beta modulates plasminogen activator activity and plasminogen activator inhibitor type-1 expression in human keratinocytes in vitro.

    PubMed

    Wikner, N E; Elder, J T; Persichitte, K A; Mink, P; Clark, R A

    1990-11-01

    Transforming growth factor beta (TGF-beta) is a multifunctional mediator with effects on cellular growth, differentiation, and extracellular matrix (ECM) metabolism. Because TGF-beta stimulates fibronectin expression in cultured human keratinocytes, we wished to determine whether it might also affect ECM degradation through the plasminogen activator (PA)-plasminogen activator inhibitor (PAI) system. Immunofluorescence of human keratinocytes using a monospecific antiserum to type 1 PAI (PAI-1) showed enhanced cellular and ECM staining when they were cultured in the presence of TGF-beta. The antiserum also identified an Mr 50,000 protein in conditioned media that was markedly enhanced by TGF-beta. A corresponding stimulation of PAI-1 mRNA was demonstrated by quantitative RNA blot analysis. Total plasminogen activating activity of conditioned medium was markedly decreased by TGF-beta. Zymography showed this to be at least partially due to decreased secreted urokinase activity. TGF-beta may play an important role in stabilizing the provisional matrix synthesized by keratinocytes in healing wounds.

  19. Gene expression of transforming growth factor-beta 1 and its type II receptor in giant cell tumors of bone. Possible involvement in osteoclast-like cell migration.

    PubMed Central

    Zheng, M. H.; Fan, Y.; Wysocki, S. J.; Lau, A. T.; Robertson, T.; Beilharz, M.; Wood, D. J.; Papadimitriou, J. M.

    1994-01-01

    Giant cell tumor of bone (GCT) is a relatively rare skeletal neoplasm characterized by multinuclear giant cells (osteoclast-like cells) scattered in a mass of mononuclear cells. The currently favored hypothesis for the origin of cells within GCT is that the multinuclear giant cells are reactive osteoclasts, whereas the truly neoplastic cells are the major component of the mononuclear population. However, the pathological significance and the precise relationship of tumor cells and osteoclast-like cells in GCT have not been fully established. In this study, we evaluated two GCTs for the presence of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta type II receptor gene transcripts and attempted to establish a possible role for TGF-beta 1 in the interaction between tumor cells and osteoclast-like cells. By using in situ hybridization and Northern blot analysis, we have demonstrated that TGF-beta 1 mRNA transcript is consistently detected in both tumor mononuclear cells and osteoclast-like cells, whereas TGF-beta type II receptor gene transcript is only present in osteoclast-like cells. Moreover, isolated rat osteoclasts were tested for their ability to migrate in response to GCT-conditioned medium (GCTCM) in an in vitro chemotactic assay. Our results showed that GCTCM stimulates the migration of osteoclasts in a dose-dependent manner. Interestingly, only osteoclasts containing less than three nuclei can migrate through 12-mu pore filters. Addition of monoclonal antibody against TGF-beta significantly reduced but did not abolish the chemotactic activity of GCTCM. Moreover, TGF-beta type II receptor mRNA has been demonstrated in the normal rat osteoclasts and may be involved in the chemotactic action of TGF-beta 1. We concluded that TGF-beta 1, possibly in concert with other cytokines, is involved in the recruitment of osteoclast-like cells in GCT by acting in an autocrine or paracrine fashion. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

  20. Jovian type III radio bursts

    NASA Technical Reports Server (NTRS)

    Kurth, W. S.; Gurnett, D. A.; Scarf, F. L.

    1989-01-01

    Radio bursts have been observed in the Voyager plasma wave data from Jupiter that bear a striking resemblance to solar type III radio bursts. The emissions lie in the frequency range near 10 kHz, have durations of a minute or so, and occur in a set of periodically spaced bursts. The spacing between primary bursts is typically 15 min, but the bursts may have additional components which recur on time scales of about 3 min. The similarity with solar type III radio bursts suggests a source mechanism involving the movement of energetic electrons through a density gradient in the plasma surrounding Jupiter. The periodicity of bursts suggests Io may be involved in the generation of waves, since the timing is similar to the Alfven wave travel time from one hemisphere to the other through the Io torus.

  1. Opposite and independent actions of cyclic AMP and transforming growth factor beta in the regulation of type 1 plasminogen activator inhibitor expression.

    PubMed Central

    Thalacker, F W; Nilsen-Hamilton, M

    1992-01-01

    We have investigated the mechanisms by which type 1 plasminogen activator inhibitor (PAI-1) is regulated by transforming growth factor beta (TGF-beta) and by epidermal growth factor (EGF) in CCL64 mink lung epithelial cells, BSC-1 monkey kidney epithelial cells, mouse embryo fibroblast (AKR-2B 84A) cells and normal rat kidney fibroblasts (NRK). TGF-beta increases PAI-1 expression in all four cell lines, and EGF acts synergistically with TGF-beta to increase PAI-1 expression in CCL64 cells but not in the other three cell lines. Here we show that PAI-1 expression can be regulated independently through two different signal transduction pathways. One pathway involves protein kinase C and is stimulated by the tumour promoter phorbol myristate acetate (PMA). Whereas preincubation with PMA completely eliminated PMA-induced PAI-1 synthesis and secretion in both CCL64 and BSC-1 cells, this treatment had no effect on TGF-beta- and EGF-induced PAI-1 levels. Therefore we conclude that protein kinase C does not mediate the effects of either EGF or TGF-beta on PAI-1 expression. The expression of PAI-1 was decreased by agents increasing intracellular cyclic AMP: (cAMP) cholera toxin, forskolin and dibutyryl cAMP lowered both the basal level and the TGF-beta- and PMA-induced levels of PAI-1 expression. These effects of cAMP-elevating agents and of TGF-beta on PAI-1 protein synthesis were also reflected in changes in TGF-beta-induced PAI-1 gene transcription, as measured by nuclear run-on. These results show that PAI-1 gene expression is sensitive to high levels of intracellular cAMP and that this effect occurs at the transcriptional level. Although increased intracellular cAMP concentrations decrease the absolute level of PAI-1 expression, the ability of TGF-beta and EGF to induce PAI-1 gene expression is unchanged. These results are discussed in relation to the observation that sensitivity to cAMP is a common feature of TGF-beta-regulated genes. Images Fig. 1. Fig. 2. Fig. 3. Fig

  2. 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

  3. Differential in vitro phenotype pattern, transforming growth factor-beta(1) activity and mRNA expression of transforming growth factor-beta(1) in Apert osteoblasts.

    PubMed

    Locci, P; Baroni, T; Pezzetti, F; Lilli, C; Marinucci, L; Martinese, D; Becchetti, E; Calvitti, M; Carinci, F

    1999-09-01

    The phenotype of Apert osteoblasts differs from that of normal osteoblasts in the accumulation of macromolecules in the extracellular matrix. Apert osteoblasts increase type I collagen, fibronectin and glycosaminoglycans secretion compared with normal osteoblasts. Because the extracellular matrix macromolecule accumulation is greatly modulated by transforming growth factor-beta(1), we examined the ability of normal and Apert osteoblasts to secrete transforming growth factor-beta(1) by CCL-64 assay and to produce transforming growth factor-beta(1 )by analysis of the mRNA expression of transforming growth factor-beta(1). Northern blot analysis revealed an increased amount of transforming growth factor-beta(1) mRNA expression in Apert osteoblasts compared with normal ones. Moreover, the level of the active transforming growth factor-beta(1) isoform was higher in Apert than in normal media. In pathologic cells, the increase in transforming growth factor-beta(1) gene expression was associated with a parallel increase in the factor secreted into the medium. The level of transforming growth factor-beta(1) was decreased by the addition of basic fibroblast growth factor. Transforming growth factor-beta(1) is controlled temporally and spatially during skeletal tissue development and produces complex stimulatory and inhibitory changes in osteoblast functions. We hypothesise that in vitro differences between normal and Apert osteoblasts may be correlated to different transforming growth factor-beta(1) cascade patterns, probably due to an altered balance between transforming growth factor-beta(1) and basic fibroblast growth factor.

  4. Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

    PubMed Central

    Rudnicka, L; Varga, J; Christiano, A M; Iozzo, R V; Jimenez, S A; Uitto, J

    1994-01-01

    A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-beta in the skin of patients with SSc. Indirect immunofluorescence showed an abundance of type VII collagen in the patients' skin, including the dermis. Ultrastructural analysis of SSc skin revealed an abundance of fibrillar material, possibly representing type VII collagen. The increased expression of type VII collagen epitopes was accompanied by the elevated expression of immunodetectable TGF-beta 1 and TGF-beta 2. Dermal fibroblasts cultured from the affected individuals showed a statistically significant (P < 0.02) increase in the expression of type VII collagen at the mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an internal standard, and increased deposition of the protein as assessed by indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc patients' dermis, a location not characteristic of its normal distribution, and its aberrant expression may relate to the presence of TGF-beta in the same topographic distribution. The presence of type VII collagen in the dermis may contribute to the tightly bound and indurated appearance of the affected skin in SSc patients. Images PMID:7512991

  5. Decameter Type III-Like Bursts

    NASA Astrophysics Data System (ADS)

    Melnik, V. N.; Konovalenko, A. A.; Rutkevych, B. P.; Rucker, H. O.; Dorovskyy, V. V.; Abranin, E. P.; Lecacheux, A.; Brazhenko, A. I.; Stanislavskyy, A. A.

    2007-12-01

    Starting from 1960s Type III-like bursts (Type III bursts with high drift rates) in a wide frequency range from 300 to 950MHz have been observed. These new bursts observed at certain frequency being compared to the usual Type III bursts at the same frequency show similar behaviour but feature frequency drift 2-6 times higher than the normal bursts. In this paper we report the first observations of Type III-like bursts in decameter range, carried out during summer campaigns 2002 - 2004 at UTR-2 radio telescope. The circular polarization of the bursts was measured by the radio telescope URAN-2 in 2004. The observed bursts are analyzed and compared with usual Type III bursts in the decameter range. From the analysis of over 1100 Type III-like bursts, their main parameters have been found. Characteristic feature of the observed bursts is similar to Type III-like bursts at other frequencies, i.e. measured drift rates (5-10 MHz/s) of this bursts are few times larger than that for usual Type III bursts, and their durations (1-2 s) are few times smaller than that for usual Type III bursts in this frequency band.

  6. Incisional wound healing in transforming growth factor-beta1 null mice.

    PubMed

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B

    2000-01-01

    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  7. Cyanoacrylate glue for type iii lad perforation.

    PubMed

    Trehan, V K; Nigam, Arima

    2008-01-01

    Coronary artery perforation especially type III is a rare and catastrophic complication of percutaneous coronary intervention. It mandates emergency open heart surgery if hemostasis is not achieved promptly. We report a case of type III left anterior descending artery (LAD) perforation which was managed successfully with cyanoacrylate glue.

  8. Time course, distribution and cell types of induction of transforming growth factor betas following middle cerebral artery occlusion in the rat brain.

    PubMed

    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.

  9. Impact analysis of Minuteman III Payload Transporter Type III

    SciTech Connect

    Stirbis, P.P.

    1993-12-01

    An analysis of the impact of the Minuteman III Payload Transporter Type III into a nonyielding target at 46 m.p.h. and 30 m.p.h., and into a yielding target at 46 m.p.h. is presented. The analysis considers the structural response of the tiedown system which secures the Minuteman III re-entry system to the floor of the payload transporter. A finite element model of the re-entry system, its tiedown system, which includes tie-rods and shear pins, and the pallet plate which is attached to the transporter floating plate, was constructed. Because accelerations of the payload transporter are not known, acceleration data from one-quarter scale testing of the Safe Secure Trailer was used to investigate the response of the tiedown system. These accelerations were applied to the pallet plate. The ABAQUS computer code was used to predict the forces in the members of the tiedown system.

  10. Solidity of Type III Bernoulli Crossed Products

    NASA Astrophysics Data System (ADS)

    Marrakchi, Amine

    2017-03-01

    We generalize a theorem of Chifan and Ioana by proving that for any, possibly type III, amenable von Neumann algebra A 0, any faithful normal state φ_0 and any discrete group {Γ}, the associated Bernoulli crossed product von Neumann algebra {M=(A_0,φ_0)^{overline{⊗} Γ} rtimes Γ} is solid relatively to L(Γ). In particular, if L(Γ) is solid then M is solid and if {Γ} is non-amenable and {A_0 ≠ C then M is a full prime factor. This gives many new examples of solid or prime type III factors. Following Chifan and Ioana, we also obtain the first examples of solid non-amenable type III equivalence relations.

  11. Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.

    PubMed

    Qiao, Yong-Chao; Shen, Jian; Hong, Xue-Zhi; Liang, Ling; Bo, Chao-Sheng; Sui, Yi; Zhao, Hai-Lu

    2016-09-01

    Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level of TGF-β (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the changes remained significant when the studies with low NOS scores and publication bias were excluded. In conclusion, peripheral Treg and serum TGF-β are reduced in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant.

  12. Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

    PubMed Central

    Capocasale, R J; Lamb, R J; Vonderheid, E C; Fox, F E; Rook, A H; Nowell, P C; Moore, J S

    1995-01-01

    Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease. Images Fig. 2 PMID:7777538

  13. Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    PubMed Central

    Riccio, A; Pedone, P V; Lund, L R; Olesen, T; Olsen, H S; Andreasen, P A

    1992-01-01

    Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action. Images PMID:1549130

  14. Type III-B rotaxane dendrimers.

    PubMed

    Ho, Watson K-W; Lee, Siu-Fung; Wong, Chi-Hin; Zhu, Xiao-Ming; Kwan, Chak-Shing; Chak, Chun-Pong; Mendes, Paula M; Cheng, Christopher H K; Leung, Ken Cham-Fai

    2013-11-28

    Type III-B first generation [3]rotaxane and second generation [4]rotaxane dendrimers have been synthesized via (1) a modified copper-catalyzed alkyne-azide cycloaddition (CuAAC), (2) Glaser-Hay's acetylenic oxidative homo-coupling, and (3) amide formation. The dendron does not reveal obvious cytotoxicities in L929 fibroblast cells. The rotaxane dendrimers can capture ammonia and are switchable both in solution and on surfaces.

  15. Coronal type III radio bursts and their X-ray flare and interplanetary type III counterparts

    NASA Astrophysics Data System (ADS)

    Reid, Hamish A. S.; Vilmer, Nicole

    2017-01-01

    Context. Type III bursts and hard X-rays are both produced by flare energetic electron beams. The link between both emissions has been investigated in many previous studies, but no statistical studies have compared both coronal and interplanetary type III bursts with X-ray flares. Aims: Using events where the coronal radio emission above 100 MHz is exclusively from type III bursts, we revisited some long-standing questions regarding the relation between type III bursts and X-ray flares: Do all coronal type III bursts have X-ray counterparts? What correlation, if any, occurs between radio and X-ray intensities? What X-ray and radio signatures above 100 MHz occur in connection with interplanetary type III bursts below 14 MHz? Methods: We analysed ten years of data from 2002 to 2011 starting with a selection of coronal type III bursts above 100 MHz. We used X-ray flare information from RHESSI >6 keV to make a list of 321 events that have associated type III bursts and X-ray flares, encompassing at least 28% of the initial sample of type III events. We then examined the timings, intensities, associated GOES class, and whether there was an associated interplanetary radio signature in both radio and X-rays. Results: For our 321 events with radio and X-ray signatures, the X-ray emission at 6 keV usually lasted much longer than the groups of type III bursts at frequencies >100 MHz. The selected events were mostly associated with GOES B and C class flares. A weak correlation was found between the type III radio flux at frequencies below 327 MHz and the X-ray intensity at 25-50 keV, with an absence of events at high X-ray intensity and low type III radio flux. The weakness of the correlation is related to the coherent emission mechanism of radio type IIIs which can produce high radio fluxes by low density electron beams. Interplanetary type III bursts (<4 MHz) were observed for 54% of the events. The percentage of association increased when events were observed with 25-50 ke

  16. The type III effectors of Xanthomonas.

    PubMed

    White, Frank F; Potnis, Neha; Jones, Jeffrey B; Koebnik, Ralf

    2009-11-01

    A review of type III effectors (T3 effectors) from strains of Xanthomonas reveals a growing list of candidate and known effectors based on functional assays and sequence and structural similarity searches of genomic data. We propose that the effectors and suspected effectors should be distributed into 39 so-called Xop groups reflecting sequence similarity. Some groups have structural motifs for putative enzymatic functions, and recent studies have provided considerable insight into the interaction with host factors in their function as mediators of virulence and elicitors of resistance for a few specific T3 effectors. Many groups are related to T3 effectors of plant and animal pathogenic bacteria, and several groups appear to have been exploited primarily by Xanthomonas species based on available data. At the same time, a relatively large number of candidate effectors remain to be examined in more detail with regard to their function within host cells.

  17. 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.

  18. Breast Cancer Research Program (BCRP) - Predoctoral Traineeship - Elucidating the Role of the Type III Transforming Growth Factor-beta Receptor in Bone Morphogenetic Signaling in Breast Cancer

    DTIC Science & Technology

    2008-03-01

    andMiyazono, K. (2002) Genes Cells 7, 1191–1204 9. Kirkbride, K. C ., Ray, B. N., and Blobe, G. C . (2005) Trends Biochem. Sci. 30, 611–621 10. Cheifetz, S...techniques dealing with C . elegans , including vector constructions, PCR, ligation and cloning procedures. My project included the generation of transgenic...b. ABSTRACT U c . THIS PAGE U UU 30 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std

  19. Type III Radio Burst Duration and SEP Events

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Makela, P.; Xie, H.

    2010-01-01

    Long-duration (>15 min), low-frequency (<14 MHz) type III radio bursts have been reported to be indicative of solar energetic particle events. We measured the durations of type III bursts associated with large SEP events of solar cycle 23. The Type III durations are distributed symmetrically at 1 MHz yielding a mean value of approximately 33 min (median = 32 min) for the large SEP events. When the SEP events with ground level enhancement (GLE,) are considered, the distribution is essentially unchanged (mean = 32 min, median = 30 min). To test the importance of type III bursts in indicating SEP events, we considered a set of six type III bursts from the same active region (AR 10588) whose durations fit the "long duration" criterion. We analyzed the coronal mass ejections (CMEs), flares, and type II radio bursts associated with the type III bursts. The CMEs were of similar speeds and the flares are also of similar size and duration. All but one of the type III bursts was not associated with a type II burst in the metric or longer wavelength domains. The burst without type II burst also lacked a solar energetic particle (SEP) event at energies >25 MeV. The 1-MHz duration of the type III burst (28 rein) 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. This study suggests that the type III burst duration may not be a good indicator of an SEP event, consistent with the statistical study of Cliver and Ling (2009, ApJ ).

  20. Genetics Home Reference: mucopolysaccharidosis type III

    MedlinePlus

    ... diagnosis of mucopolysaccharidosis III (Sanfilippo syndrome): A changing landscape. Mol Genet Metab. 2014 Sep-Oct;113(1- ... j.1651-2227.2010.01800.x. Epub 2010 Mar 14. Citation on PubMed Meyer A, Kossow K, ...

  1. Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

    PubMed

    Odendall, Charlotte; Dixit, Evelyn; Stavru, Fabrizia; Bierne, Helene; Franz, Kate M; Durbin, Ann Fiegen; Boulant, Steeve; Gehrke, Lee; Cossart, Pascale; Kagan, Jonathan C

    2014-08-01

    Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.

  2. 46 CFR 171.075 - Subdivision requirements-Type III.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Subdivision requirements-Type III. 171.075 Section 171...—Type III. (a) Each vessel must be shown by design calculations to comply with the requirements of... Organization (IMO). (b) International Maritime Organization Resolution A.265 (VIII) is incorporated...

  3. Structure-function analyses of plant type III polyketide synthases.

    PubMed

    Weng, Jing-Ke; Noel, Joseph P

    2012-01-01

    Plant type III polyketide synthases (PKSs) form a superfamily of biosynthetic enzymes involved in the production of a plethora of polyketide-derived natural products important for ecological adaptations and the fitness of land plants. Moreover, tremendous interest in bioengineering of type III PKSs to produce high-value compounds is increasing. Compared to type I and type II PKSs, which form either large modular protein complexes or dissociable molecular assemblies, type III PKSs exist as smaller homodimeric proteins, technically more amenable for detailed quantitative biochemical and phylogenetic analyses. In this chapter, we summarize a collection of approaches, including bioinformatics, genetics, protein crystallography, in vitro biochemistry, and mutagenesis, together affording a comprehensive interrogation of the structure-function-evolutionary relationships in the plant type III PKS family.

  4. Transforming growth factor beta1 and aldosterone

    PubMed Central

    Matsuki, Kota; Hathaway, Catherine K.; Chang, Albert S.; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    Purpose of review It is well established that blocking renin-angiotensin II-aldosterone system (RAAS) is effective for the treatment of cardiovascular and renal complications in hypertension and diabetes mellitus. Although the induction of transforming growth factor beta1 (TGFbeta1) by components of RAAS mediates the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it is still controversial as to whether TGFbeta1 can be a target to prevent such complications. Here we review recent findings on the role of TGFbeta1 in fluid homeostasis, focusing on the relationship with aldosterone. Recent findings TGFbeta1 suppresses adrenal production of aldosterone and renal tubular sodium reabsorption. We have generated mice with TGFbeta1 mRNA expression graded in five steps from 10% to 300% normal, and found that blood pressure and plasma volume are negatively regulated by TGFbeta1. Notably, the 10 % hypomorph exhibits primary aldosteronism and sodium and water retention due to markedly impaired urinary excretion of water and electrolytes. Summary These results identify TGFbeta signaling as an important counterregulatory system against aldosterone. Understanding the molecular mechanisms for the suppressive effects of TGFbeta1 on adrenocortical and renal function may further our understanding of primary aldosteronism as well as assist in the development of novel therapeutic strategies for hypertension. PMID:25587902

  5. 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…

  6. Numerical Simulation of the Propagation of Type III Radio Emission

    NASA Astrophysics Data System (ADS)

    Rutkevych, B. P.; Melnik, V. N.

    Recently solar Type III bursts with fine time structure have been observed by radio telescope UTR-2 at frequencies 10 - 30 MHz. For the first time Type III-like bursts with high frequency drift rates were observed at these frequencies too. All this became possible due to both high sensitivity and high time resolution of UTR-2. The properties of decameter Type III bursts can be understood if we take into account the spatial dependence of the electromagnetic wave group velocity as well as the fine spatial structure of the cloud of fast electrons responsible for Type III bursts. These effects are considered numerically in this paper. The fine time structure of Type III bursts is shown to be observed in the days when the associated active region is situated near the central meridian. In other days such structures disappeared. The Type III-like bursts with frequency drift rates of 10 - 20 MHz/s should also be observed, when the associated active region is near the central meridian. These peculiarities are confirmed by observations.

  7. 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.

  8. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

    PubMed Central

    Henneman, Peter; van der Sman-de Beer, Femke; Moghaddam, Payman Hanifi; Huijts, Petra; Stalenhoef, Anton FH; Kastelein, John JP; van Duijn, Cornelia M; Havekes, Louis M; Frants, Rune R; van Dijk, Ko Willems; Smelt, Augustinus HM

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. PMID:19034316

  9. 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.

  10. Type III CRISPR complexes from Thermus thermophilus.

    PubMed

    Szychowska, Marta; Siwek, Wojciech; Pawolski, Damian; Kazrani, Asgar Abbas; Pyrc, Krzysztof; Bochtler, Matthias

    2016-01-01

    Pathogen-specific acquired immunity in bacteria is mediated by the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas systems. Thermus thermophilus strain HB8 contains CRISPR systems of several major subtypes (type I, IIIA and IIIB), and has become a widely studied model for CRISPR biology. We have selected two highly expressed CRISPR spacers, crRNA 2.1 and crRNA 2.2, and have enriched endogenous T. thermophilus proteins that co-purify with these crRNAs. Mass spectroscopy indicates that the chromatography protocol enriches predominantly Csm complex subunits, but also Cmr subunits. After several chromatographic steps, size exclusion chromatography indicated a molecular mass of the crRNA associated complex of 265±69 kDa. In agreement with earlier work, crRNAs of different lengths (containing the selected spacers) were observed. Most of these were completely lost when several T. thermophilus csm genes were ablated.

  11. 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.

  12. Transforming growth factor-beta and wound healing.

    PubMed

    Faler, Byron J; Macsata, Robyn A; Plummer, Dahlia; Mishra, Lopa; Sidawy, Anton N

    2006-03-01

    Acute and chronic wounds are a source of significant morbidity for patients, and they demand a growing portion of health-care time and finances to be devoted to their care. Transforming growth factor-beta (TGF-beta) has surfaced from abundant research as a key signal in orchestrating wound repair. In beginning this review, we discuss the inflammatory, proliferative, and maturational phases of wound healing. We then focus on TGF-beta by first discussing the pathway from its production to the target cell where Smad proteins execute an intracellular signaling cascade. To review TGF-beta's role in wound healing, we discuss the actions of it individually on keratinocytes, fibroblasts, endothelial cells, and monocytes, which are the major cell types involved in wound repair. From illustrating these cellular actions of TGF-beta, we summarize its multipotent role in the process of wound repair. As a clinical correlation, we also review research dedicated to the involvement of TGF-beta in venous stasis ulcers.

  13. Transforming Growth Factor Beta, Bioenergetics and Mitochondria in Renal Disease

    PubMed Central

    Gabriella, Casalena; Ilse, Daehn; Erwin, Bottinger

    2012-01-01

    The transforming growth factor beta (TGF-β ) family is comprised of over 30 family members that are structurally related secreted dimeric cytokines, including TGF-β, activins, and bone morphogenetic proteins (BMPs)/growth and differentiation factors (GDFs). TGF-β are pluripotent regulators of cell proliferation, differentiation, apoptosis, migration, and adhesion of many different cell types. TGF-β pathways are highly evolutionarily conserved and control embryogenesis, tissue repair, and tissue homeostasis in invertebrates and vertebrates. Aberrations in TGF-β activity and signaling underlie a broad spectrum of developmental disorders and major pathologies in humans, including cancer, fibrosis and autoimmune diseases. Recent observations indicate an emerging role for TGF-β in regulation of mitochondrial bioenergetics and oxidative stress responses characteristic of chronic degenerative diseases and ageing. Conversely, energy and metabolic sensory pathways cross-regulate mediators of TGF-β signaling. Here we review TGF-β and regulation of bioenergetic and mitochondrial functions, including energy and oxidant metabolism and apoptotic cell death, as well as their emerging relevance in renal biology and disease. PMID:22835461

  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. [Central motor conduction evaluation in glycogenosis type III].

    PubMed

    Alaejos Fuentes, J A; López-Alburquerque, T; De Portugal Alvarez, J

    1997-05-01

    We report a 20-year-old man affected by glycogenosis type III with distal muscle weakness, more severe in distal leg muscles. The electromyogram showed myopathic features. Nerve conduction studies and central motor conduction after magnetic stimulation of the brain were normal. Our results suggest that there is no involvement of central motor pathways in this disease.

  16. Computational prediction shines light on type III secretion origins

    PubMed Central

    Goldberg, Tatyana; Rost, Burkhard; Bromberg, Yana

    2016-01-01

    Type III secretion system is a key bacterial symbiosis and pathogenicity mechanism responsible for a variety of infectious diseases, ranging from food-borne illnesses to the bubonic plague. In many Gram-negative bacteria, the type III secretion system transports effector proteins into host cells, converting resources to bacterial advantage. Here we introduce a computational method that identifies type III effectors by combining homology-based inference with de novo predictions, reaching up to 3-fold higher performance than existing tools. Our work reveals that signals for recognition and transport of effectors are distributed over the entire protein sequence instead of being confined to the N-terminus, as was previously thought. Our scan of hundreds of prokaryotic genomes identified previously unknown effectors, suggesting that type III secretion may have evolved prior to the archaea/bacteria split. Crucially, our method performs well for short sequence fragments, facilitating evaluation of microbial communities and rapid identification of bacterial pathogenicity – no genome assembly required. pEffect and its data sets are available at http://services.bromberglab.org/peffect. PMID:27713481

  17. 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.

  18. Sequence-Based Prediction of Type III Secreted Proteins

    PubMed Central

    Arnold, Roland; Brandmaier, Stefan; Kleine, Frederick; Tischler, Patrick; Heinz, Eva; Behrens, Sebastian; Niinikoski, Antti; Mewes, Hans-Werner; Horn, Matthias; Rattei, Thomas

    2009-01-01

    The type III secretion system (TTSS) is a key mechanism for host cell interaction used by a variety of bacterial pathogens and symbionts of plants and animals including humans. The TTSS represents a molecular syringe with which the bacteria deliver effector proteins directly into the host cell cytosol. Despite the importance of the TTSS for bacterial pathogenesis, recognition and targeting of type III secreted proteins has up until now been poorly understood. Several hypotheses are discussed, including an mRNA-based signal, a chaperon-mediated process, or an N-terminal signal peptide. In this study, we systematically analyzed the amino acid composition and secondary structure of N-termini of 100 experimentally verified effector proteins. Based on this, we developed a machine-learning approach for the prediction of TTSS effector proteins, taking into account N-terminal sequence features such as frequencies of amino acids, short peptides, or residues with certain physico-chemical properties. The resulting computational model revealed a strong type III secretion signal in the N-terminus that can be used to detect effectors with sensitivity of ∼71% and selectivity of ∼85%. This signal seems to be taxonomically universal and conserved among animal pathogens and plant symbionts, since we could successfully detect effector proteins if the respective group was excluded from training. The application of our prediction approach to 739 complete bacterial and archaeal genome sequences resulted in the identification of between 0% and 12% putative TTSS effector proteins. Comparison of effector proteins with orthologs that are not secreted by the TTSS showed no clear pattern of signal acquisition by fusion, suggesting convergent evolutionary processes shaping the type III secretion signal. The newly developed program EffectiveT3 (http://www.chlamydiaedb.org) is the first universal in silico prediction program for the identification of novel TTSS effectors. Our findings will

  19. Transforming growth factor beta 1: an autocrine regulator of adrenocortical steroidogenesis.

    PubMed

    Feige, J J; Cochet, C; Savona, C; Shi, D L; Keramidas, M; Defaye, G; Chambaz, E M

    1991-01-01

    Transforming growth factor beta 1 (TGF beta 1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGF beta 1, TGF beta 2, TGF beta 3, TGF beta 4 and TGF beta 5) and functionally distinct proteins. In the past few years, TGF beta 1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroidogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGF beta 1 on bovine adrenocortical cell (zona fasciculata-reticularis) functions. We identified the steroid 17 alpha-hydroxylase (P-450 17 alpha) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGF beta 1 in these cells. We characterized TGF beta 1 receptors at the surface of adrenocortical cells (mainly type I and type III receptors) and observed that their number is increased under ACTH treatment. Furthermore, we could detect the presence of immunoreactive TGF beta 1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2-macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum. Taken together, these observations led us to a working hypothesis, proposing TGF beta 1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGF beta 1 complex as the important limiting step controlling its action in the adrenal cortex.

  20. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome)

    PubMed Central

    2011-01-01

    Background Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder caused by a deficiency of one of the enzymes involved in the degradation of heparan sulfate. MPS III is characterized by progressive mental deterioration resulting in severe dementia. A number of potentially disease-modifying therapies are studied. As preservation of cognitive function is the ultimate goal of treatment, assessment of cognitive development will be essential in order to evaluate treatment efficacy. However, no large scale studies on cognitive levels in MPS III patients, using formal psychometric tests, have been reported. Methods We aimed to assess cognitive development in all 73 living patients with MPS III in the Netherlands. Results Cognitive development could be assessed in 69 patients. In 39 of them developmental level was estimated > 3 months and formal psychometric testing was attempted. A remarkable variation in the intellectual disability was detected. Conclusions Despite special challenges encountered, testing failed in only three patients. The observed broad variation in intellectual disability, should be taken into account when designing therapeutic trials. PMID:21689409

  1. 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

  2. Onset and progression of pathological lesions in transforming growth factor-beta 1-deficient mice.

    PubMed Central

    Boivin, G. P.; O'Toole, B. A.; Orsmby, I. E.; Diebold, R. J.; Eis, M. J.; Doetschman, T.; Kier, A. B.

    1995-01-01

    Null-mutant (knockout) mice were obtained through disruption of the sixth exon of the endogenous transforming growth factor-beta 1 allele in murine embryonic stem cells via homologous recombination. Mice lacking transforming growth factor-beta 1 (mutants) were born grossly indistinguishable from wild-type littermates. With time, mutant mice exhibited a wasting phenotype that manifested itself in severe weight loss and dishevelled appearance (between 15 and 36 days of age). Examination of these moribund mice histologically revealed that transforming growth factor-beta 1-deficient mice exhibit a moderate to severe, multifocal, organ-dependent, mixed inflammatory cell response adversely affecting the heart, stomach, diaphragm, liver, lung, salivary gland, and pancreas. Because of the known multifunctional nature of transforming growth factor-beta 1 on the control of growth and differentiation of many different cell types, it is important to determine the degree to which the inflammatory response interacts with or masks other deficiencies that are present. To this end, we examined the extent and nature of the inflammatory lesions in different ages of neonatal knockout mice (5, 7, 10, and 14 days of age) and older moribund mice (> 15 days of age) and compared them with the histology seen in wild-type normal animals. Mild inflammatory infiltrates were first observed in 5-day mutant mice in the heart, by day 7 in the lung, salivary gland, and pancreas, and by day 14 inflammatory lesions were found in almost all organs examined. Moderate to severe inflammation was not present until the mice were 10 to 14 days old. In the older animals, there was a slight increase in the severity of the inflammatory lesions as the mice aged. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7856734

  3. TYPE III EXCITABILITY, SLOPE SENSITIVITY AND COINCIDENCE DETECTION

    PubMed Central

    Meng, Xiangying; Huguet, Gemma; Rinzel, John

    2013-01-01

    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

  4. Murine pregnancy-specific glycoprotein 23 induces the proangiogenic factors transforming-growth factor beta 1 and vascular endothelial growth factor a in cell types involved in vascular remodeling in pregnancy.

    PubMed

    Wu, Julie A; Johnson, Briana L; Chen, Yongqing; Ha, Cam T; Dveksler, Gabriela S

    2008-12-01

    Haemochorial placentation is a unique physiological process in which the fetal trophoblast cells remodel the maternal decidual spiral arteries to establish the fetoplacental blood supply. Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen family. PSGs are produced by the placenta of rodents and primates and are secreted into the bloodstream. PSG23 is one of 17 members of the murine PSG family (designated PSG16 to PSG32). Previous studies determined that PSGs have immunoregulatory functions due to their ability to modulate macrophage cytokine secretion. Here we show that recombinant PSG23 induces transforming growth factor (TGF) beta1, TGFB1, and vascular endothelial growth factor A (VEGFA) in primary murine macrophages and the macrophage cell line RAW 264.7 cells. In addition, we identified new cell types that responded to PSG23 treatment. Dendritic cells, endothelial cells, and trophoblasts, which are involved in maternal vasculature remodeling during pregnancy, secreted TGFB1 and VEGFA in response to PSG23. PSG23 showed cross-reactivity with human cells, including human monocytes and the trophoblast cell line, HTR-8/SVneo cells. We analyzed the binding of PSG23 to the tetraspanin CD9, the receptor for PSG17, and found that CD9 is not essential for PSG23 binding and activity in macrophages. Overall these studies show that PSGs can modulate the secretion of important proangiogenic factors, TGFB1 and VEGFA, by different cell types involved in the development of the placenta.

  5. Structural Insights into Fibronectin Type III Domain Mediated Signaling

    PubMed Central

    Bencharit, Sompop; Cui, Cai Bin; Siddiqui, Adnan; Howard-Williams, Escher L.; Sondek, John; Zuobi-Hasona, Kheir; Aukhil, Ikramuddin

    2007-01-01

    The alternatively spliced type-III extradomain B (EIIIB) of Fibronectin (FN) is only expressed during embryogenesis, wound healing and tumorigenesis. The biological function of this domain remains unclear. We describe here the first crystal structure of the interface between alternatively-spliced domain EIIIB and its adjacent FN type-III domain 8 (FN B-8). The opened CC′ loop of EIIIB and the rotation and tilt of EIIIB domain allows good access to the FG loop of FN-8 which is normally hindered by the CC′ loop of FN-7. In addition, the AGEGIP sequence of the CC′ loop of EIIIB replaces the NGQQGN sequence of the CC′ loop of FN-7. Finally, the CC” loop of EIIIB forms an acidic groove with FN-8. These structural findings warrant future studies directed at identifying potential binding partners for FN B-8 interface, linking EIIIB to skeletal and cartilagenous development, wound healing, and tumorigenesis, respectively. PMID:17261313

  6. 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

  7. Type III effector-mediated processes in Salmonella infection.

    PubMed

    van der Heijden, Joris; Finlay, B Brett

    2012-06-01

    Salmonella is one of the most successful bacterial pathogens that infect humans in both developed and developing countries. In order to cause infection, Salmonella uses type III secretion systems to inject bacterial effector proteins into host cells. In the age of antibiotic resistance, researchers have been looking for new strategies to reduce Salmonella infection. To understand infection and to analyze type III secretion as a potential therapeutic target, research has focused on identification of effectors, characterization of effector functions and how they contribute to disease. Many effector-mediated processes have been identified that contribute to infection but thus far no specific treatment has been found. In this perspective we discuss our current understanding of effector-mediated processes and discuss new techniques and approaches that may help us to find a solution to this worldwide problem.

  8. Identification of novel type III effectors using latent Dirichlet allocation.

    PubMed

    Yang, Yang

    2012-01-01

    Among the six secretion systems identified in Gram-negative bacteria, the type III secretion system (T3SS) plays important roles in the disease development of pathogens. T3SS has attracted a great deal of research interests. However, the secretion mechanism has not been fully understood yet. Especially, the identification of effectors (secreted proteins) is an important and challenging task. This paper adopts machine learning methods to identify type III secreted effectors (T3SEs). We extract features from amino acid sequences and conduct feature reduction based on latent semantic information by using latent Dirichlet allocation model. The experimental results on Pseudomonas syringae data set demonstrate the good performance of the new methods.

  9. On the theory of the type III burst exciter

    NASA Technical Reports Server (NTRS)

    Smith, R. A.; Goldstein, M. L.; Papadopoulos, K.

    1976-01-01

    In situ satellite observations of type III burst exciters at 1 AU show that the beam does not evolve into a plateau in velocity space, contrary to the prediction of quasilinear theory. The observations can be explained by a theory that includes mode coupling effects due to excitation of the parametric oscillating two-stream instability and its saturation by anomalous resistivity. The time evolution of the beam velocity distribution is included in the analysis.

  10. 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.

  11. Toremifene decreases type I, type II and increases type III receptors in desmoid and fibroma and inhibits TGFbeta1 binding in desmoid fibroblasts.

    PubMed

    Stabellini, Giordano; Balducci, Chiara; Lilli, Cinzia; Marinucci, Lorella; Becchetti, Ennio; Carinci, Francesco; Calastrini, Carla; Dolci, Claudia; Lumare, Eleonora; Locci, Paola

    2008-09-01

    Tissue infiltration is different in desmoid and fibroma tumours. Both produce high levels of transforming growth factor beta1 (TGFbeta1), which is related to extracellular matrix (ECM) accumulation which in turn regulates cell function and cell migration. Interactions between collagen, proteoglycans and cell surface fibronectin are involved in the assembly and functions of the ECM. As toremifene inhibits collagen and TGFbeta1 synthesis, we tested it in normal, desmoid and fibroma fibroblasts. We will report the changes in glycosaminoglycan (GAG) and collagen synthesis, TGFbeta1 activity, fibronectin mRNA expression and TGFbeta1 receptors after toremifene treatment in normal, fibroma and desmoid fibroblasts. We evaluated GAG and collagen synthesis with 3H-glucosamine and 3H-proline incorporation, TGFbeta1 activity with the ELISA method, TGFbeta1 receptor affinity with 125I-TGFbeta1 binding and total RNA with Northern blot analysis. GAG and collagen synthesis, TGFbeta1 activity and fibronectin levels were higher in fibroma and desmoid than normal fibroblasts. The increase was greater in desmoid than fibroma tumour cells. Toremifene treatment reduced GAG and collagen synthesis, TGFbeta1 activity and fibronectin levels in all cell cultures. The percentage reduction in GAG was similar in all cultures; the reduction in collagen synthesis and TGFbeta1 activity was the highest in desmoid fibroblasts. TGFbeta1 receptors were higher in fibroma and desmoid cells than controls. Toremifene reduced TGFbeta1 receptors only in desmoid fibroblasts, with no effect on the changes in type I, II, and III receptors. Our data show that toremifene modifies the ECM components that regulate cytokine activity and cell migration. The reduction in receptor number only in desmoid cells suggests that toremifene may reduce TGFbeta1's affinity for its receptors. Synthesis of a substance regulating protein kinase activity, which is directly involved in the link between TGFbeta1 and its receptors

  12. 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.

  13. 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

  14. Glycogen storage disease type III in the Irish population.

    PubMed

    Crushell, Ellen; Treacy, Eileen P; Dawe, J; Durkie, M; Beauchamp, Nicholas J

    2010-12-01

    Glycogen storage disease type III (GSD III) results from mutations of the AGL gene encoding the glycogen debrancher enzyme. The disease has clinical and biochemical heterogeneity reflecting the severity of the AGL mutations. We sought to characterise the molecular defects in our cohort of Irish patients with GSD III. Fifteen patients from eight unrelated Irish families were identified: six males and nine females. The age ranged from 2-39 years old, and all presented in the first 3 years of life. Four patients (of three families) had mild disease with hepatomegaly, mild hypoglycaemia and normal creatine kinase (CK) levels. Five families had more severe disease, with liver and skeletal muscle involvement and elevated CK. Eleven different mutations were identified amongst the eight families. Of the 11, six were novel: p.T512fs, p.S736fs, p.A1400fs, p.K1407fs, p.Y519X and p.D627Y. The family homozygous for p.A1400fs had the most severe phenotype (early-onset hypoglycaemia, massive hepatomegaly, myopathy and hypertrophic cardiomyopathy before age 2 years), which was not halted by aggressive carbohydrate and protein supplementation. Conversely, the only missense mutation identified in the cohort, p.D627Y, was associated with a mild phenotype. The phenotypic diversity in our GSD III cohort is mirrored by the allelic heterogeneity. We describe two novel null mutations in exon 32 in two families with severe GSD III resistant to current treatment modalities. Knowledge of the specific mutations segregating in this cohort may allow for the development of new therapeutic interventions.

  15. Transforming growth factor beta1 regulates melanocyte proliferation and differentiation in mouse neural crest cells via stem cell factor/KIT signaling.

    PubMed

    Kawakami, Tamihiro; Soma, Yoshinao; Kawa, Yoko; Ito, Masaru; Yamasaki, Emiko; Watabe, Hidenori; Hosaka, Eri; Yajima, Kenji; Ohsumi, Kayoko; Mizoguchi, Masako

    2002-03-01

    Stem cell factor is essential to the migration and differentiation of melanocytes during embryogenesis based on the observation that mutations in either the stem cell factor gene, or its ligand, KIT, result in defects in coat pigmentation in mice. Stem cell factor is also required for the survival of melanocyte precursors while they are migrating towards the skin. Transforming growth factor beta1 has been implicated in the regulation of both cellular proliferation and differentiation. NCC-melb4, an immortal cloned cell line, was cloned from a mouse neural crest cell. NCC-melb4 cells provide a model to study the specific stage of differentiation and proliferation of melanocytes. They also express KIT as a melanoblast marker. Using the NCC-melb4 cell line, we investigated the effect of transforming growth factor beta1 on the differentiation and proliferation of immature melanocyte precursors. Immunohistochemically, NCC-melb4 cells showed transforming growth factor beta1 expression. The anti-transforming growth factor beta1 antibody inhibited the cell growth, and downregulated the KIT protein and mRNA expression. To investigate further the activation of autocrine transforming growth factor beta1, NCC-melb4 cells were incubated in nonexogenous transforming growth factor beta1 culture medium. KIT protein decreased with anti-transforming growth factor beta1 antibody concentration in a concentration-dependent manner. We concluded that in NCC-melb4 cells, transforming growth factor beta1 promotes melanocyte precursor proliferation in autocrine and/or paracrine regulation. We further investigated the influence of transforming growth factor beta1 in vitro using a neural crest cell primary culture system from wild-type mice. Anti-transforming growth factor beta1 antibody decreased the number of KIT positive neural crest cell. In addition, the anti-transforming growth factor beta1 antibody supplied within the wild-type neural crest explants abolished the growth of the neural

  16. Numerical simulations of type-III solar radio bursts.

    PubMed

    Li, B; Robinson, P A; Cairns, I H

    2006-04-14

    The first numerical simulations are presented for type-III solar radio bursts in the inhomogeneous solar corona and interplanetary space, that include microscale quasilinear and nonlinear processes, intermediate-scale driven ambient density fluctuations, and large scale evolution of electron beams, Langmuir and ion sound waves, and fundamental and harmonic electromagnetic emission. Bidirectional coronal emission is asymmetric between the upward and downward directions, and harmonic emission dominates fundamental emission. In interplanetary space, fundamental and/or harmonic emission can be important. Langmuir and ion sound waves are bursty and the statistics of Langmuir wave energy agree well with the predictions of stochastic growth theory.

  17. Characteristics of type I and type III ELM precursors in ASDEX upgrade

    NASA Astrophysics Data System (ADS)

    Kass, T.; Günter, S.; Maraschek, M.; Suttrop, W.; Zohm, H.; ASDEX Upgrade Team

    1998-01-01

    The temporal evolution of the edge electron pressure gradient during the development of a type I ELM shows that proximity of ∇pedge to the ideal ballooning limit is not sufficient to trigger a type I ELM. Thus, the MHD structure of ELMs is investigated further. The present discussion focuses on the phenomenology of type I and type III ELM precursors. The ELM precursor types are well distinguished by their frequency behaviour and mode structure. The type I ELM precursor oscillation originates from a thin layer close to the plasma edge. For type III ELMs, on the contrary, ∇pedge has a much stronger influence as indicated by their occurrence during L mode.

  18. 77 FR 76426 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

    ... organizations that are not functionally integrated. The withdrawal affects Type III supporting organizations... ``Type III Supporting Organizations''). Those regulations reflect changes to the law made by the Pension... Revenue Service 26 CFR Part 1 [REG 155929-06] RIN 1545-BL44 Payout Requirements for Type III...

  19. Fundamental and harmonic radiation in type III solar radio bursts

    NASA Technical Reports Server (NTRS)

    Robinson, P. A.; Cairns, I. H.

    1994-01-01

    Type III solar radio bursts are investigated by modeling the propagation of the electron beam and the generation and subsequent propagation of waves to the observer. Predictions from this model are compared in detail with particle, Langmuir wave, and radio data from the International Sun Earth Explorer-3 (ISSE-3) spacecraft and with other observations to clarify the roles of fundamental and harmonic emission in type III radio bursts. Langmuir waves are seen only after the arrival of the beam, in accord with the standard theory. These waves persist after a positive beam slope is last resolved, implying that sporadic positive slopes persist for some time, unresolved but in accord with the predictions of stochastic growth theory. Local electromagnetic emission sets in only after Langmuir waves are seen, in accord with the standard theory, which relies on nonlinear processes involving Langmuir waves. In the events investigated here, fundamental radiation appears to dominate early in the event, followed and/or accompanied by harmonic radiation after the peak, with a long-lived tail of multiply scattered fundamental or harmonic emission extending long afterwards. These results are largely independent of, but generally consistent with, the conclusions of earlier works.

  20. 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.

  1. Radio frequency interference affecting type III solar burst observations

    NASA Astrophysics Data System (ADS)

    Anim, N. M.; Hamidi, Z. S.; Abidin, Z. Z.; Monstein, C.; Rohizat, N. S.

    2013-05-01

    The solar burst extinguish from the Sun's corona atmosphere and it dynamical structure of the magnetic field in radio wavelength are studied. Observation of solar radio burst with Compact Astronomical Low cost Low frequency Instrument for Spectroscopy and Transportable Observatory (CALLISTO) from ETH, Zurich in frequency range of 45 until 870 MHz. Observation done at Pusat Angkasa Negara, Banting, Selangor and successfully detected the solar burst type III on 9th March 2012 from 4:22:00 UT until 4:28:00 UT. The solar burst emission is associated with M6.3 solar flare which occurred at sunspot AR1429 at 03:58UT were observed by NOAA. Frequency ranges chosen as the best ranges for solar monitoring in Malaysia is 150 MHz until 400 MHz. The highest signal amplitude within this frequency ranges is 1.7619 dB at 153.188 MHz (Government Use) have potential to influence the detection of solar radio burst type III within 20 until 400 MHz.

  2. 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.

  3. Type III secretion systems: the bacterial flagellum and the injectisome

    PubMed Central

    Diepold, Andreas; Armitage, Judith P.

    2015-01-01

    The flagellum and the injectisome are two of the most complex and fascinating bacterial nanomachines. At their core, they share a type III secretion system (T3SS), a transmembrane export complex that forms the extracellular appendages, the flagellar filament and the injectisome needle. Recent advances, combining structural biology, cryo-electron tomography, molecular genetics, in vivo imaging, bioinformatics and biophysics, have greatly increased our understanding of the T3SS, especially the structure of its transmembrane and cytosolic components, the transcriptional, post-transcriptional and functional regulation and the remarkable adaptivity of the system. This review aims to integrate these new findings into our current knowledge of the evolution, function, regulation and dynamics of the T3SS, and to highlight commonalities and differences between the two systems, as well as their potential applications. PMID:26370933

  4. 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

  5. Symbiotic implications of type III protein secretion machinery in Rhizobium.

    PubMed

    Viprey, V; Del Greco, A; Golinowski, W; Broughton, W J; Perret, X

    1998-06-01

    The symbiotic plasmid of Rhizobium sp. NGR234 carries a cluster of genes that encodes components of a bacterial type III secretion system (TTSS). In both animal and plant pathogens, the TTSS is an essential component of pathogenicity. Here, we show that secretion of at least two proteins (y4xL and NolX) is controlled by the TTSS of NGR234 and occurs after the induction with flavonoids. Polar mutations in two TTSS genes, rhcN and the nod-box controlled regulator of transcription y4xl, block the secretion of both proteins and strongly affect the ability of NGR234 to nodulate a variety of tropical legumes including Pachyrhizus tuberosus and Tephrosia vogelii.

  6. 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.

  7. Type III Secretion: Building and Operating a Remarkable Nanomachine.

    PubMed

    Portaliou, Athina G; Tsolis, Konstantinos C; Loos, Maria S; Zorzini, Valentina; Economou, Anastassios

    2016-02-01

    The Type III secretion system (T3SS) is a protein export pathway that is widespread in Gram-negative bacteria and delivers effector proteins directly into eukaryotic cells. At its core lie the injectisome (a sophisticated transmembrane secretion apparatus) and a complex network of specialized chaperones that target secretory proteins to the antechamber of the injectisome. The assembly of the system, and the subsequent secretion of proteins through it, undergo fine-tuned, hierarchical regulation. Here, we present the current understanding of the injectisome assembly process, secretion hierarchy, and the role of chaperones. We discuss these events in light of available structural and biochemical dissection and propose future directions essential to revealing mechanistic insight into this fascinating nanomachine.

  8. 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.

  9. Radiative type III seesaw model and its collider phenomenology

    NASA Astrophysics Data System (ADS)

    von der Pahlen, Federico; Palacio, Guillermo; Restrepo, Diego; Zapata, Oscar

    2016-08-01

    We analyze the present bounds of a scotogenic model, the radiative type III seesaw, in which an additional scalar doublet and at least two fermion triplets of S U (2 )L are added to the Standard Model. In the radiative type III seesaw, the new physics (NP) sector is odd under an exact global Z2 symmetry. This symmetry guaranties that the lightest NP neutral particle is stable, providing a natural dark matter candidate, and leads to naturally suppressed neutrino masses generated by a one-loop realization of an effective Weinberg operator. We focus on the region with the highest sensitivity in present and future LHC searches, with light scalar dark matter and at least one NP fermion triplet at the sub-TeV scale. This region allows for significant production cross sections of NP fermion pairs at the LHC. We reinterpret a set of searches for supersymmetric particles at the LHC obtained using the package CheckMATE, to set limits on our model as a function of the masses of the NP particles and their Yukawa interactions. The most sensitive search channel is found to be dileptons plus missing transverse energy. In order to target the case of tau enhanced decays and the case of compressed spectra, we reinterpret the recent slepton and chargino search bounds by ATLAS. For a lightest NP fermion triplet with a maximal branching ratio to either electrons or muons, we exclude NP fermion masses of up to 650 GeV, while this bound is reduced to approximately 400 GeV in the tau-philic case. Allowing for a general flavor structure, we set limits on the Yukawa couplings, which are directly related to the neutrino flavor structure.

  10. Type III-L Solar Radio Bursts and Their Associations with Solar Energetic Proton Events

    NASA Astrophysics Data System (ADS)

    Duffin, Robert T.; White, S. M.; Ray, P. S.; Kaiser, M. L.

    2010-05-01

    Type III-L bursts are a sub-class of type III solar radio bursts that tend to occur after the impulsive phase of flares; are longer in duration than individual type IIIs and tend to be low-frequency. There has been a proposal that type III-Ls are connected to solar energetic proton (SEP) events. Most work on this connection has started from samples of SEP events, but if type III-Ls are to be useful for prediction of SEP events, then we need to understand the properties of samples of type III-L bursts. This talk reports preliminary results from such a study. An operating definition based on previous work is used to identify type III-L events amongst M- and X-class flares from 2001; and then associations with other properties of these events are investigated, including association with SEP events. If there is an association with SEP events, one important factor that these bursts allow us to address is the question of whether acceleration takes place at an associated CME, or closer to the flare site well below the CME. Work has been developed on a type III fitting tool. A Template is chosen from a representative individual type III burst and fit to individual type III bursts and components of Complex type III bursts in order to help analyze and distinguish these bursts. This type III fitting tool can also be used to fit and distinguish Impulsive type III and type III-L bursts and help analyze various characteristics of the components of these bursts such as drift-rate and change in the duration of their intensity-time profiles with frequency. Funding for this research came from the Naval Research Laboratory where basic research in radio astronomy is funded by the Office of Naval Research, and from NASA LWS Grant FRS 526249.

  11. [Quantitative polarization microscopy demonstration of collagen type I and type III in histologic paraffin sections].

    PubMed

    Ogbuihi, S; Müller, Z; Zink, P

    1988-01-01

    The industrial dye Solophenyl Red 3 BL (Ciba-Geigy) dissolved in a saturated aquaeous solution of picric acid has proved suitable for differentiating between collagen types I and III in histological sections. When examined under polarization microscopy, type I fibers are radiant orange while type III fibers are green. Using 5 micron paraffin sections, an optimal staining procedure was determined: sections were first stained with Resorcin Fuchsin for elastic fibers and with Celestin Blue/Mayer's Hematoxylin for nuclear structures. The staining was then completed with 0.1 g Solophenyl Red/100 ml saturated aqueous solution of picric acid for 60 min at a pH value of 1.25. It was shown that the dye stained collagen selectively. With the aid of a photomultiplier, the spectral distribution of a series of lung sections adequately stained according to the optimized procedure was carried out using a monochromator and an interference filter, respectively. Both methods yielded identical peaks at 590 nm for the orange colored light of collagen type I and 490 nm for the green light of collagen type III. Application of appropriate filters permitted the intensity of the orange and green light at 590 nm and 490 nm to be measured. Long postmortem intervals did not affect the measured values. Quantitative inferences on the ratio of collagen I to collagen III could then be deduced from the ratio of the intensity of orange to green light. This index I/III is often applied in the diagnosis of discrete fibrotic changes in various organs.

  12. Surface proteome analysis identifies platelet derived growth factor receptor-alpha as a critical mediator of transforming growth factor-beta-induced collagen secretion.

    PubMed

    Heinzelmann, Katharina; Noskovičová, Nina; Merl-Pham, Juliane; Preissler, Gerhard; Winter, Hauke; Lindner, Michael; Hatz, Rudolf; Hauck, Stefanie M; Behr, Jürgen; Eickelberg, Oliver

    2016-05-01

    Fibroblasts are extracellular matrix-producing cells in the lung. Fibroblast activation by transforming growth factor-beta leads to myofibroblast-differentiation and increased extracellular matrix deposition, a hallmark of pulmonary fibrosis. While fibroblast function with respect to migration, invasion, and extracellular matrix deposition has been well-explored, little is known about the surface proteome of lung fibroblasts in general and its specific response to fibrogenic growth factors, in particular transforming growth factor-beta. We thus performed a cell-surface proteome analysis of primary human lung fibroblasts in presence/absence of transforming growth factor-beta, followed by characterization of our findings using FACS analysis, Western blot, and siRNA-mediated knockdown experiments. We identified 213 surface proteins significantly regulated by transforming growth factor-beta, platelet derived growth factor receptor-alpha being one of the top down-regulated proteins. Transforming growth factor beta-induced downregulation of platelet derived growth factor receptor-alpha induced upregulation of platelet derived growth factor receptor-beta expression and phosphorylation of Akt, a downstream target of platelet derived growth factor signaling. Importantly, collagen type V expression and secretion was strongly increased after forced knockdown of platelet derived growth factor receptor-alpha, an effect that was potentiated by transforming growth factor-beta. We therefore show previously underappreciated cross-talk of transforming growth factor-beta and platelet derived growth factor signaling in human lung fibroblasts, resulting in increased extracellular matrix deposition in a platelet derived growth factor receptor-alpha dependent manner. These findings are of particular importance for the treatment of lung fibrosis patients with high pulmonary transforming growth factor-beta activity.

  13. 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

  14. 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.

  15. 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

  16. 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}.

  17. ACTIVE IMMUNIZATION OF MICE WITH THE POLYSACCHARIDES OF PNEUMOCOCCI TYPES I, II AND III

    PubMed Central

    Zozaya, José; Clark, Janet

    1933-01-01

    1. Pneumococcus polysaccharides Types I, II and III adsorbed on collodion particles, and Types I and III adsorbed on carbon (norit) are antigenic in mice. 2. Unadsorbed pneumococcus polysaccharide of Type I is antigenic in mice in proper dilution. One preparation of Type II polysaccharide was not antigenic, while another one immunized against Types I and II. Type III polysaccharide was only slightly antigenic against Type III but immunized against Type I. 3. The antigenicity of pneumococcus polysaccharide in optimal dosage is tentatively explained by an adsorption phenomenon taking place in the body in instances in which the polysaccharides had not been adsorbed before injection. 4. The aggressin-like action of large doses of pneumococcus polysaccharides Types I, II and III is further established. PMID:19870119

  18. Assembly, structure, function and regulation of type III secretion systems.

    PubMed

    Deng, Wanyin; Marshall, Natalie C; Rowland, Jennifer L; McCoy, James M; Worrall, Liam J; Santos, Andrew S; Strynadka, Natalie C J; Finlay, B Brett

    2017-04-10

    Type III secretion systems (T3SSs) are protein transport nanomachines that are found in Gram-negative bacterial pathogens and symbionts. Resembling molecular syringes, T3SSs form channels that cross the bacterial envelope and the host cell membrane, which enable bacteria to inject numerous effector proteins into the host cell cytoplasm and establish trans-kingdom interactions with diverse hosts. Recent advances in cryo-electron microscopy and integrative imaging have provided unprecedented views of the architecture and structure of T3SSs. Furthermore, genetic and molecular analyses have elucidated the functions of many effectors and key regulators of T3SS assembly and secretion hierarchy, which is the sequential order by which the protein substrates are secreted. As essential virulence factors, T3SSs are attractive targets for vaccines and therapeutics. This Review summarizes our current knowledge of the structure and function of this important protein secretion machinery. A greater understanding of T3SSs should aid mechanism-based drug design and facilitate their manipulation for biotechnological applications.

  19. 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.

  20. 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

  1. Identification of type II and III DDR2 inhibitors.

    PubMed

    Richters, André; Nguyen, Hoang D; Phan, Trang; Simard, Jeffrey R; Grütter, Christian; Engel, Julian; Rauh, Daniel

    2014-05-22

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

  2. Type-III secretion filaments as scaffolds for inorganic nanostructures

    PubMed Central

    Azam, Anum; Tullman-Ercek, Danielle

    2016-01-01

    Nanostructured materials exhibit unique magnetic, electrical and catalytic properties. These characteristics are determined by the chemical composition, size and shape of the nanostructured components, which are challenging to modulate on such small size scales and to interface with living cells. To address this problem, we are using a self-assembling filament protein, PrgI, as a scaffold for bottom-up inorganic nanostructure synthesis. PrgI is a small protein (80 amino acids) that oligomerizes to form the type-III secretion system needle of Salmonella enterica. We demonstrate that purified PrgI monomers also spontaneously self-assemble into long filaments and that high-affinity peptide tags specific for attachment to functionalized particles can be integrated into the N-terminal region of PrgI. The resulting filaments selectively bind to gold, whether the filaments are assembled in vitro, sheared from cells or remain attached to live S. enterica cell membranes. Chemical reduction of the gold-modified PrgI variants results in structures that are several micrometres in length and which incorporate a contiguous gold surface. Mutant strains with genomically incorporated metal-binding tags retain the secretion phenotype. We anticipate that self-assembled, cell-tethered protein/metal filamentous structures have applications in sensing and energy transduction in vivo. PMID:26763334

  3. 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

  4. Remote flare brightenings and type III reverse slope bursts

    NASA Technical Reports Server (NTRS)

    Tang, F.; Moore, R. L.

    1982-01-01

    Observations are presented on two large (H-alpha class 2) flares that each produced an extensive chain of discrete H-alpha brightenings spanning 370,000-470,000 km in length in remote quiet regions more than 100,000 km from the main flare site. A large group of Type III RS bursts was also observed accompanying each flare. The onset of about half the remote H-alpha emission patches were nearly simultaneous with the RS bursts. One flare was observed in hard X-rays, and it is noted that the RS bursts occurred during hard X-ray spikes. For the other flare, soft X-ray filtergrams indicate coronal loops connecting from the main flare site to the remote H-alpha brightenings. Observations indicate that the RS burst electrons were generated in the flares, and it is proposed that the remote H-alpha brightenings were initiated by direct heating of the chromosphere by RS burst electrons traveling in closed magnetic loops connecting the flare site to the remote patches. It is also suggested that after onset, the brightenings were heated by thermal conduction by slower thermal electrons.

  5. 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.

  6. Type III Interferons in Hepatitis C Virus Infection

    PubMed Central

    Boisvert, Maude; Shoukry, Naglaa H.

    2016-01-01

    The interferon (IFN)-λ family of type III cytokines includes the closely related interleukin (IL)-28A (IFN-λ2), IL-28B (IFN-λ3), and IL-29 (IFN-λ1). They signal through the Janus kinases (JAK)-signal transducers and activators of transcription pathway and promote an antiviral state by the induction of expression of several interferon-stimulated genes (ISGs). Contrary to type I IFNs, the effect of IFN-λ cytokines is largely limited to epithelial cells due to the restricted pattern of expression of their specific receptor. Several genome-wide association studies have established a strong correlation between polymorphism in the region of IL-28B gene (encoding for IFN-λ3) and both spontaneous and therapeutic IFN-mediated clearance of hepatitis C virus (HCV) infection, but the mechanism(s) underlying this enhanced viral clearance are not fully understood. IFN-λ3 directly inhibits HCV replication, and in vitro studies suggest that polymorphism in the IFN-λ3 and its recently identified overlapping IFN-λ4 govern the pattern of ISGs induced upon HCV infection of hepatocytes. IFN-λ can also be produced by dendritic cells, and apart from its antiviral action on hepatocytes, it can regulate the inflammatory response of monocytes/macrophages, thus acting at the interface between innate and adaptive immunity. Here, we review the current state of knowledge about the role of IFN-λ cytokines in mediating and regulating the immune response during acute and chronic HCV infections. PMID:28066437

  7. Mucopolysaccharidosis type III (Sanfilippo Syndrome): emerging treatment strategies.

    PubMed

    de Ruijter, J; Valstar, M J; Wijburg, F A

    2011-06-01

    Mucopolysaccharosis III (MPS III) is a lysosomal storage disorder and belongs to the group of mucopolysaccharidoses. MPS III is caused by a deficiency of one of the four enzymes catalyzing the degradation of the glycosaminoglycan heparan sulfate. MPS III is clinically characterized by progressive dementia with distinct behavioral disturbances and relatively mild somatic disease. This review will summarize and discuss the available and potential future therapeutic options for patients with MPS III. This includes enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), substrate reduction therapy (SRT), chaperone-mediated therapy, and gene therapy. Although clinical efficacy has not yet been fully demonstrated for any of these therapies, it is likely that future developments will lead to disease-modifying treatment for this devastating disease.

  8. 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.

  9. Disulfide isoforms of recombinant glia maturation factor beta.

    PubMed

    Zaheer, A; Lim, R

    1990-09-14

    Recombinant human glia maturation factor beta (r-hGMF-beta) is a single-chain polypeptide (141 amino acid residues) containing three cysteines, at positions 7, 86 and 95. Nascent r-hGMF-beta exists in the reduced state and has no biological activity. The protein can be activated through oxidative refolding by incubation with a mixture of reduced and oxidized glutathione. Reverse-phase HPLC analysis of the refolded r-hGMF-beta shows the presence of four peaks, corresponding to the reduced form plus three newly generated intrachain disulfide-containing isoforms predicted from the number of cysteine residues. Only one isoform shows biological activity when tested for growth suppression on C6 glioma cells. We infer from the HPLC elution pattern that the active form contains the disulfide bridge Cys86-Cys95.

  10. Cross-link analysis of the C-telopeptide domain from type III collagen.

    PubMed Central

    Henkel, W

    1996-01-01

    Several peptides were isolated from tryptic digests of insoluble calf aorta matrix by chromatography. Reductive pyridylethylation of a tryptic 15 kDa pool released fragments deriving from the C-terminus of type III collagen. A 50-residue peptide Tc(III) was shown by sequence analysis to be the C-terminal peptide from the alpha 1(III)-chain, containing a helical and non-helical region of equal sizes. The peptide was further digested with collagenase to give Colc(III), comprising the complete C-terminal non-helical region of alpha 1(III) including a hydroxylysine in position 16c. The peptide Tc(III) x TN(III) was isolated, demonstrating covalent cross-linking between the C-terminal non-helical region of one type III molecule and the N-terminal helical cross-linking region of another. Its digestion with cyanogen bromide yielded the small fragments alpha 1(III)CB3B* and alpha 1(III)CB3C, confirming TN(III) as an N-terminal helical crosslink site. Sequence analysis of both Tc(III) x TN(III) and its collagenase-derived cross-linked peptide Colc(III) x TN(III) established the 4D-staggered alignment of adjacent collagen III molecules. The cross-link structure of both peptides was mainly dihydroxylysinonorleucine with a small amount of hydroxylysinonorleucine, indicating that the lysine residues involved in formation of the cross-links are both hydroxylated. No pyridinoline or histidinohydroxylysinonorleucine cross-links were found within the non-reduced C-telopeptide region of type III collagen. PMID:8809038

  11. Transforming growth factor-beta induces endothelin-1 expression through activation of the Smad signaling pathway.

    PubMed

    Rodríguez-Pascual, Fernando; Reimunde, Francisco Manuel; Redondo-Horcajo, Mariano; Lamas, Santiago

    2004-11-01

    Expression of the endothelin-1 gene is subject to complex regulation by different factors, among which transforming growth factor-beta is one of the most important. We have analyzed the mechanism by which transforming growth factor-beta increases endothelin-1 expression in vascular endothelial cells. Transcriptional activation of the endothelin-1 promoter accounted for the transforming growth factor-beta-induced increase in endothelin-1 mRNA levels. Two DNA elements within the promoter are responsible for this effect: a Smad binding element and a proximal activator protein-1 site. Mutation of both elements abolished transforming growth factor-beta responsiveness. Overexpression of the Smad3 isoform strongly potentiates transforming growth factor-beta- induced endothelin-1 promoter activity in a phosphorylation-dependent manner. These results demonstrate that transforming growth factor-beta induces endothelin-1 expression by a functional cooperation between Smads and activator protein-1 through activation of the Smad signaling pathway.

  12. 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.

  13. 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

  14. Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

    PubMed Central

    Grubeck-Loebenstein, B; Buchan, G; Sadeghi, R; Kissonerghis, M; Londei, M; Turner, M; Pirich, K; Roka, R; Niederle, B; Kassal, H

    1989-01-01

    The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter. Images PMID:2921318

  15. The Effects of Non-Normality on Type III Error for Comparing Independent Means

    ERIC Educational Resources Information Center

    Mendes, Mehmet

    2007-01-01

    The major objective of this study was to investigate the effects of non-normality on Type III error rates for ANOVA F its three commonly recommended parametric counterparts namely Welch, Brown-Forsythe, and Alexander-Govern test. Therefore these tests were compared in terms of Type III error rates across the variety of population distributions,…

  16. 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...

  17. 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......

  18. 46 CFR 170.135 - Operating information for a vessel with Type III subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Operating information for a vessel with Type III... Operating Personnel § 170.135 Operating information for a vessel with Type III subdivision. (a) In addition to the information required in 46 CFR 170.110, the stability booklet of a passenger vessel with...

  19. 78 FR 9802 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... requirements to qualify as a Type III supporting organization that is operated in connection with one or more... Internal Revenue Service 26 CFR Part 1 RIN 1545-BG31; 1545-BL38 Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated; Correction AGENCY: Internal Revenue Service (IRS),...

  20. 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... Damage stability standards for vessels with Type III subdivision. (a) Each vessel must be shown by design... the International Maritime Organization (IMO). (b) International Maritime Organization Resolution...

  1. 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.

  2. Behind the lines–actions of bacterial type III effector proteins in plant cells

    PubMed Central

    Büttner, Daniela

    2016-01-01

    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Type III effectors also interfere with additional plant cellular processes including proteasome-dependent protein degradation, phytohormone signaling, the formation of the cytoskeleton, vesicle transport and gene expression. This review summarizes our current knowledge on the molecular functions of type III effector proteins with known plant target molecules. Furthermore, plant defense strategies for the detection of effector protein activities or effector-triggered alterations in plant targets are discussed. PMID:28201715

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

    PubMed

    Lin, Jian-Da; Feng, Ningguo; Sen, Adrish; 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

    2016-04-01

    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

  4. Transforming growth factor Beta-releasing scaffolds for cartilage tissue engineering.

    PubMed

    Madry, Henning; Rey-Rico, Ana; Venkatesan, Jagadeesh K; Johnstone, Brian; Cucchiarini, Magali

    2014-04-01

    The maintenance of a critical threshold concentration of transforming growth factor beta (TGF-β) for a given period of time is crucial for the onset and maintenance of chondrogenesis. Thus, the development of scaffolds that provide temporal and/or spatial control of TGF-β bioavailability has appeal as a mechanism to induce the chondrogenesis of stem cells in vitro and in vivo for articular cartilage repair. In the past decade, many types of scaffolds have been designed to advance this goal: hydrogels based on polysaccharides, hyaluronic acid, and alginate; protein-based hydrogels such as fibrin, gelatin, and collagens; biopolymeric gels and synthetic polymers; and solid and hybrid composite (hydrogel/solid) scaffolds. In this study, we review the progress in developing strategies to deliver TGF-β from scaffolds with the aim of enhancing chondrogenesis. In the future, such scaffolds could prove critical for tissue engineering cartilage, both in vitro and in vivo.

  5. Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.

    PubMed Central

    Picarella, D E; Kratz, A; Li, C B; Ruddle, N H; Flavell, R A

    1992-01-01

    Tumor necrosis factor beta (TNF-beta) (lymphotoxin) may play an important role in the immune response and pathologic inflammatory diseases. Insulitis is an important early step in the development of insulin-dependent diabetes mellitus. To understand better the role of TNF-beta in the regulation of inflammation and type 1 diabetes, we produced transgenic mice in which the murine TNF-beta gene was regulated by the rat insulin II promoter. The transgene was expressed in the pancreas, kidney, and skin of transgenic mice. The expression of TNF-beta in the pancreas of transgenic mice resulted in a leukocytic inflammatory infiltrate consisting primarily of B220+ IgM+ B cells and CD4+ and CD8+ T cells. The insulitis is reminiscent of the early stages of diabetes, though the mice did not progress to diabetes. Images PMID:1279667

  6. 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

  7. Type III protein secretion systems in bacterial pathogens of animals and plants.

    PubMed

    Hueck, C J

    1998-06-01

    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

  8. 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

  9. 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.

  10. Type III intermediate filament peripherin inhibits neuritogenesis in type II spiral ganglion neurons in vitro

    PubMed Central

    Barclay, Meagan; Julien, Jean-Pierre; Ryan, Allen F.; Housley, Gary D.

    2010-01-01

    Peripherin, a type III intermediate filament protein, forms part of the cytoskeleton in a subset of neurons, most of which have peripheral fibre projections. Studies suggest a role for peripherin in axon outgrowth and regeneration, but evidence for this in sensory and brain tissues is limited. The exclusive expression of peripherin in a sub-population of primary auditory neurons, the type II spiral ganglion neurons (SGN) prompted our investigation of the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal immunofluorescence to examine the establishment of the innervation of the cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1 spiral ganglion explants under culture conditions where the majority of neurites were derived from type II SGN, pphKO resulted in increased numbers of neurites/explant compared WT controls. Type II SGN neurites from pphKO explants extended ~ double the distance of WT neurites, and had reduced complexity based on greater distance between turning points. Addition of brain-derived neurotrophic factor (BDNF) to the culture media increased neurite number in WT and KO explants ~30-fold, but did not affect neurite length or distance between turning. These results indicate that peripherin may interact with other cytoskeletal elements to regulate outgrowth of the peripheral neurites of type II SGN, distinguishing these neurons from the type I SGN innervating the inner hair cells. PMID:20132868

  11. Do Type III-associated Escaping Electron Beams Cool The Corona?

    NASA Astrophysics Data System (ADS)

    Saint-Hilaire, Pascal; Wang, L.; Christe, S. D.; Vilmer, N.; Kerdraon, A.; Lin, R. P.

    2012-05-01

    A recent study of decimetric Type III radio burst emission from data from the Nancay Radio Heliograph (NRH) will be presented. It examined sizes, locations, and fluxes of close to 10'000 decimetric Type III bursts. The flux study suggests that electron beams related to Type III emission could be responsible for carrying energy away from the corona in a proportion similar to that of EUV nanoflare heating. This tentative conclusion was reached from comparing Type III dN/dS distributions to the dN/dS of EUV/SXR nano-/micro-flares. The biggest uncertainty is the radiative efficiency, i.e. the ratio of radiated energy in decimetric Type III bursts and the energy of the electrons in the beams associated with them. We will constrain this value through other, new observations: we have already computed the amount of Type III radiated energy from NRH observations, and we will now compare them with the amount of energy in the corresponding beam electron detected in-situ by the Wind spacecraft. Given our sample of close to 10'000 decimetric Type IIIs, we expect a decent amount of in-situ beam energy estimates from magnetically connected events. Moreover, we will compare with X-ray-derived energies from corresponding RHESSI (micro)flares, when such an association exists.

  12. Type III-L Solar Radio Bursts and their Associations with Solar Energetic Proton Events

    NASA Astrophysics Data System (ADS)

    Duffin, R. T.; White, S. M.; Ray, P. S.; Kaiser, M. L.

    2009-12-01

    Type III-L bursts are a sub-class of type III solar radio bursts that tend to occur after the impulsive phase of flares; are longer in duration than individual type IIIs and tend to be low-frequency. There has been a proposal that type III-Ls are connected to solar energetic proton (SEP) events. Most work on this connection has started from samples of SEP events, but if type III-Ls are to be useful for prediction of SEP events, then we need to understand the properties of samples of type III-L bursts. This talk reports preliminary results from such a study. An operating definition based on previous work is used to identify type III-L events amongst M- and X-class flares from 2001; and then associations with other properties of these events are investigated, including association with SEP events. If there is an association with SEP events, one important factor that these bursts allow us to address is the question of whether acceleration takes place at an associated CME, or closer to the flare site well below the CME.

  13. "Do Type III-associated escaping electron beams cool the corona?"

    NASA Astrophysics Data System (ADS)

    Saint-Hilaire, P.; Wang, L.; Vilmer, N.; Kerdraon, A.

    2012-12-01

    A recent study of decimetric Type III radio burst emission from data from the Nancay Radio Heliograph will be presented. It examined sizes, locations, and fluxes of close to 10'000 decimetric Type III bursts. The flux study suggests that electron beams related to Type III emission could be responsible for carrying energy away from the corona in a proportion similar to EUV nanoflares. This tentative conclusion was reached from comparing Type III dN/dS distributions to the dN/dS of EUV/SXR nano-/micro-flares. The biggest uncertainty is the radiative efficiency, i.e. the ratio of radiated energy in decimetric Type III bursts and the energy of the electrons in the beams associated with them. We will constrain this value through other, new observations: we have already computed the amount of Type III radiated energy from NRH observations, and we will now compare them with the amount of energy in the corresponding beam electron detected in-situ by the Wind spacecraft. Given our sample of close to 10'000 decimetric Type IIIs, we expect a decent amount of in-situ beam energy estimates from magnetically connected events. Moreover, we will compare with X-ray-derived energies from corresponding RHESSI (micro)flares, when such an association exists.

  14. [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.

  15. Human transforming growth factor. beta. -. cap alpha. /sub 2/-macroglobulin complex is a latent form of transforming growth factor. beta

    SciTech Connect

    Huang, S.S.; O'Grady, P.; Huang, J.S.

    1987-05-01

    Human platelet-derived transforming growth factor ..beta.. (TGF..beta..) has been shown to be present as a high molecular weight latent form in human serum. Appearance of transforming growth factor activity, along with the change from high molecular weight form to low molecular weight form, was observed following treatment of the latent form of TGF..beta.. with acid or urea, suggesting that the latent form of TGF..beta.. is a complex of TGF..beta.. and a high molecular weight binding protein. Human ..cap alpha../sub 2/-M has been found to be a plasma binding protein for platelet-derived growth factor (PDGF) in serum or plasma. TGF..beta.. and PDGF share similar properties. They, therefore, investigated the interaction between /sup 125/I-TGF..beta.. and ..cap alpha../sub 2/M. /sup 125/I-TGF..beta.. and purified human ..cap alpha../sub 2/M formed a complex as demonstrated by polyacrylamide gel electrophoresis. Most of the /sup 125/I-TGF..beta..-..cap alpha../sub 2/M complex could be dissociated by acid or urea treatment. These results suggest that ..cap alpha../sub 2/M is a binding protein for TGF..beta.. and that TGF..beta..-..cap alpha../sub 2/M complex may be the latent form of TGF..beta.. in serum.

  16. Transforming growth factor beta 1, a cytokine with regenerative functions

    PubMed Central

    Sulaiman, Wale; Nguyen, Doan H.

    2016-01-01

    We review the biology and role of transforming growth factor beta 1 (TGF-β1) in peripheral nerve injury and regeneration, as it relates to injuries to large nerve trunks (i.e., sciatic nerve, brachial plexus), which often leads to suboptimal functional recovery. Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets, which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves. Using an established chronic nerve injury and delayed repair animal model that accurately mimics chronic nerve injuries in humans, we summarize our key findings as well as others to better understand the pathophysiology of poor functional recovery. We demonstrated that 6 month TGF-β1 treatment for chronic nerve injury significantly improved Schwann cell capacity to support axonal regeneration. When combined with forskolin, the effect was additive, as evidenced by a near doubling of regenerated axons proximal to the repair site. We showed that in vivo application of TGF-β1 and forskolin directly onto chronically injured nerves reactivated chronically denervated Schwann cells, induced their proliferation, and upregulated the expression of regeneration-associated proteins. The effect of TGF-β1 and forskolin on old nerve injuries is quite impressive and the treatment regiment appears to mediate a growth-supportive milieu in the injured peripheral nerves. In summary, TGF-β1 and forskolin treatment reactivates chronically denervated Schwann cells and could potentially be used to extend and prolong the regenerative responses to promote axonal regeneration. PMID:27904475

  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.

  18. Spectroscopic identification of type 2 quasars at z < 1 in SDSS-III/BOSS

    NASA Astrophysics Data System (ADS)

    Yuan, Sihan; Strauss, Michael A.; Zakamska, Nadia L.

    2016-10-01

    The physics and demographics of type 2 quasars remain poorly understood, and new samples of such objects selected in a variety of ways can give insight into their physical properties, evolution, and relationship to their host galaxies. We present a sample of 2758 type 2 quasars at z ≲ 1 from the Sloan Digital Sky Survey-III (SDSS-III)/Baryon Oscillation Spectroscopic Survey (BOSS) spectroscopic data base, selected on the basis of their emission-line properties. We probe the luminous end of the population by requiring the rest-frame equivalent width of [O III] to be >100 Å. We distinguish our objects from star-forming galaxies and type 1 quasars using line widths, standard emission line ratio diagnostic diagrams at z < 0.52 and detection of [Ne V]λ3426 Å at z > 0.52. The majority of our objects have [O III] luminosities in the range 1.2 × 1042-3.8 × 1043 erg s-1 and redshifts between 0.4 and 0.65. Our sample includes over 400 type 2 quasars with incorrectly measured redshifts in the BOSS data base; such objects often show kinematic substructure or outflows in the [O III] line. The majority of the sample has counterparts in the Wide-field Infrared Survey Explorer survey, with median infrared luminosity νLν[12 μm] = 4.2 × 1044 erg s- 1. Only 34 per cent of the newly identified type 2 quasars would be selected by infrared colour cuts designed to identify obscured active nuclei, highlighting the difficulty of identifying complete samples of type 2 quasars. We make public the multi-Gaussian decompositions of all [O III] profiles for the new sample and for 568 type 2 quasars from SDSS I/II, together with non-parametric measures of the [O III] line profile shapes. We also identify over 600 candidate double-peaked [O III] profiles.

  19. 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.

  20. 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.

  1. Decameter type III bursts with positive and negative frequency drift rates

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

    We report about observations of decameter type III bursts whose frequency drift rates vary their signs from negative to positive. Moreover drift rates of some bursts vary the sign some times. Positive drift rates for some bursts are changed from 0.44 MHz/s to 12 MHz/s. At the same time the negative drift rates of these bursts are standard values for decameter type III bursts. A possible interpretation of such phenomenon on the base of plasma mechanism of type III burst generation is discussed. The sense of this interpretation is that group velocity of type III electromagnetic waves generated by fast electrons at some conditions can be smaller than velocity of these electrons.

  2. 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.

  3. 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.

  4. SOLAR MICRO-TYPE III BURST STORMS AND LONG DIPOLAR MAGNETIC FIELD IN THE OUTER CORONA

    SciTech Connect

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

    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 R{sub S}. The distribution of the apex altitude has a sharp upper limit around 50 R{sub S} suggesting that an unknown but universal condition regulates the upper boundary of the streamer dipolar field.

  5. 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

  6. Mutant p53 can induce tumorigenic conversion of human bronchial epithelial cells and reduce their responsiveness to a negative growth factor, transforming growth factor beta 1.

    PubMed Central

    Gerwin, B I; Spillare, E; Forrester, K; Lehman, T A; Kispert, J; Welsh, J A; Pfeifer, A M; Lechner, J F; Baker, S J; Vogelstein, B

    1992-01-01

    Loss of normal functions and gain of oncogenic functions when the p53 tumor suppressor gene is mutated are considered critical events in the development of the majority of human cancers. Human bronchial epithelial cells (BEAS-2B) provide an in vitro model system to study growth, differentiation, and neoplastic transformation of progenitor cells of lung carcinoma. When wild-type (WT) or mutant (MT; codon 143Val-Ala) human p53 cDNA was transfected into nontumorigenic BEAS-2B cells, we observed that (i) transfected WT p53 suppresses and MT p53 enhances the colony-forming efficiency of these cells, (ii) MT p53 increases resistance to transforming growth factor beta 1, and (iii) clones of MT p53 transfected BEAS-2B cells are tumorigenic when inoculated into athymic nude mice. These results are consistent with the hypothesis that certain mutations in p53 may function in multistage lung carcinogenesis by reducing the responsiveness of bronchial epithelial cells to negative growth factors. Images PMID:1557382

  7. Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase.

    PubMed Central

    Heck, L W; Morihara, K; McRae, W B; Miller, E J

    1986-01-01

    Purified Pseudomonas aeruginosa elastase cleaved human type III and IV collagens with the formation of specific cleavage products. Furthermore, type I collagen appeared to be slowly cleaved by both P. aeruginosa elastase and alkaline protease. These cleavage fragments from type III and IV collagens were separated from the intact collagen chains by SDS polyacrylamide gradient gel electrophoresis run under reducing conditions, and they were detected by their characteristic Coomassie blue staining pattern. The results of these studies suggest that the pathogenesis of tissue invasion and hemorrhagic tissue necrosis observed in P. aeruginosa infections may be related to the degradation of these collagen types by bacterial extracellular proteases. Images PMID:3079727

  8. Contribution of Type III Interferons to Antiviral Immunity; Location, Location, Location.

    PubMed

    Kotenko, Sergei V; Durbin, Joan E

    2017-03-13

    Type I interferons (IFN-α/β) and the more recently identified type III IFNs (IFN-λ) function as the first line of defense against virus infection, and regulate the development of both innate and adaptive immune responses. Type III IFNs were originally identified as a novel ligand-receptor system acting in parallel with type I IFNs, but subsequent studies have provided increasing evidence for distinct roles for each IFN family. In addition to their compartmentalized antiviral actions, these two systems appear to have multiple levels of cross-regulation, and act coordinately to achieve effective anti-microbial protection with minimal collateral damage to the host.

  9. 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

  10. TYPE III RADIO BURSTS IN CORONAL PLASMAS WITH KAPPA PARTICLE DISTRIBUTIONS

    SciTech Connect

    Li, B.; Cairns, Iver H.

    2013-02-01

    We present the first simulations of type III bursts produced in the corona with suprathermal non-Maxwellian background particles, as inferred from solar wind data and proposed by theories for the corona and solar wind. The coronal background particles are assumed to follow kappa ({kappa}) distributions. The predicted f{sub p} emission of type III bursts is sensitive via the {kappa} index to the presence of suprathermal background particles, where f{sub p} is the local plasma frequency. The simulations show that (1) the speeds v{sub b} of type III beams are much larger (e.g., v{sub b} Almost-Equal-To 0.58c for {kappa} = 5) and so type III bursts drift much faster for low {kappa} ({<=}5) background plasmas than for Maxwellian backgrounds (producing v{sub b} < 0.3c), and (2) f{sub p} emission generated in a {kappa}-distributed background corona has a larger total bandwidth than in a Maxwellian background, for similar onset frequencies. Type III beams are thus more persistent, i.e., extending over larger distances, in {kappa}-distributed corona. Consequently, observations of fast-drifting coronal type III bursts and associated fast electron beams suggest that the ambient electrons in the corona are {kappa}-distributed, at least when such bursts are observed. These results support, from the new viewpoint of nonthermal radio emission, the occasional presence of suprathermal background electrons in the corona and the associated mechanisms (e.g., 'velocity filtration') for coronal heating and solar wind acceleration. The new results also help resolve longstanding issues regarding the speeds and persistence of type III beams, and the production of remotely observable levels of f{sub p} emission despite severe losses during propagation.

  11. 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

  12. Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III.

    PubMed

    Sun, Baodong; Fredrickson, Keri; Austin, Stephanie; Tolun, Adviye A; Thurberg, Beth L; Kraus, William E; Bali, Deeksha; Chen, Yuan-Tsong; Kishnani, Priya S

    2013-02-01

    We investigated the feasibility of using recombinant human acid-α glucosidase (rhGAA, Alglucosidase alfa), an FDA approved therapy for Pompe disease, as a treatment approach for glycogen storage disease type III (GSD III). An in vitro disease model was established by isolating primary myoblasts from skeletal muscle biopsies of patients with GSD IIIa. We demonstrated that rhGAA significantly reduced glycogen levels in the two GSD IIIa patients' muscle cells (by 17% and 48%, respectively) suggesting that rhGAA could be a novel therapy for GSD III. This conclusion needs to be confirmed in other in vivo models.

  13. 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.

  14. On the three harmonics of solar type III bursts at the decameter wavelengths

    NASA Astrophysics Data System (ADS)

    Brazhenko, Anatolii; Pylaev, Oleg; Melnik, Valentin; Konovalenko, Alexandr; Zaqarashvili, Teimuraz; Rucker, Helmut; Frantsuzenko, Anatolii; Dorovskyy, Vladimir

    2014-05-01

    Harmonic structure of type III bursts are explained in terms of plasma emission mechanism. The second harmonic emission is well known. But there are theoretical papers about the third harmonic of type III bursts. And there were observations of the third harmonic of such types of bursts as U, J, V, II. We observed triple type III bursts where frequency ratio is close to 1:2:3. They are structures where type III emission is repeated at the double and triple frequencies. Incidentally, components of triple type III bursts are not only standard type III but also type IIIb bursts. We registered 30 triple bursts during 2011 and 2012 years. Observations were made by radio telescope URAN-2, Poltava, Ukraine. It enables polarization measurements at the frequencies 8 - 32 MHz. URAN-2 allows registration of radio emission with time and frequency resolution 10 ms and 4 kHz correspondingly. We analyze properties of the components of triple bursts and their dependencies on frequency, type of burst and on the position of the component within the triplet. The main properties of the components of triple bursts such as duration and drift rate are similar to those of standard type III and IIIb bursts. We find usual for type III bursts dependencies such as follow: duration decreases with frequency, the type IIIb bursts have always smaller duration at the same frequencies, all bursts drift from high to low frequencies. But we also find the linear dependence of drift rate on frequency. All components of a trio have the same sign of polarization. Polarization of the first component is always the highest in triple bursts. It corresponds to the generally accepted viewpoint about the first harmonic emission. The second and the third components of trio have low polarization. It is typical for the second and the third harmonics according to the plasma radiation mechanism. We discuss possible emission mechanisms and theoretical aspects of observed dependencies. The most of detected regularities

  15. Type III-L Solar Radio Bursts and Solar Energetic Particle Events

    NASA Astrophysics Data System (ADS)

    Duffin, R. T.; White, S. M.; Ray, P. S.; Kaiser, M. L.

    2015-09-01

    A radio-selected sample of fast drift radio bursts with complex structure occurring after the impulsive phase of the associated flare (“Type III-L bursts”) is identified by inspection of radio dynamic spectra from 1 to 180 MHz for over 300 large flares in 2001. An operational definition that takes into account previous work on these radio bursts starting from samples of solar energetic particle (SEP) events is applied to the data, and 66 Type III-L bursts are found in the sample. In order to determine whether the presence of these radio bursts can be used to predict the occurrence of SEP events, we also develop a catalog of all SEP proton events in 2001 using data from the ERNE detector on the SOHO satellite. 68 SEP events are found, for 48 of which we can identify a solar source and hence look for associated Type III-L emission. We confirm previous work that found that most (76% in our sample) of the solar sources of SEP events exhibit radio emission of this type. However, the correlation in the opposite direction is not as strong: starting from a radio-selected sample of Type III-L events, around 64% of the bursts that occur at longitudes magnetically well-connected to the Earth, and hence favorable for detection of SEPs, are associated with SEP events. The degree of association increases when the events have durations over 10 minutes at 1 MHz, but in general Type III-L bursts do not perform any better than Type II bursts in our sample as predictors of SEP events. A comparison of Type III-L timing with the arrival of near-relativistic electrons at the ACE spacecraft is not inconsistent with a common source for the accelerated electrons in both phenomena.

  16. 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.

  17. Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.

    PubMed Central

    Sankar, S; Mahooti-Brooks, N; Bensen, L; McCarthy, T L; Centrella, M; Madri, J A

    1996-01-01

    Microvascular endothelial cells (RFCs) cultured in two-dimensional (2D) cultures proliferate rapidly and exhibit an undifferentiated phenotype. Addition of transforming growth factor beta1 (TGFbeta1) increases fibronectin expression and inhibits proliferation. RFCs cultured in three-dimensional (3D) type I collagen gels proliferate slowly and are refractory to the anti-proliferative effects of TGF beta1. TGF beta1 promotes tube formation in 3D cultures. TGF beta1 increases fibronectin expression and urokinase plasminogen activator (uPA) activity and plasminogen activator inhibitor-1 (PAI-1) levels in 3D cultures. Since the TGF beta type I and II receptors have been reported to regulate different activities induced by TGF beta1, we compared the TGF beta receptor profiles on cells in 2D and 3D cultures. RFCs in 3D cultures exhibited a significant loss of cell surface type II receptor compared with cells in 2D cultures. The inhibitory effect of TGF beta1 on proliferation is suppressed in transfected 2D cultures expressing a truncated form of the type II receptor, while its stimulatory effect on fibronectin production is reduced in both 2D and 3D transfected cultures expressing a truncated form of the type I receptor. These data suggest that the type II receptor mediates the antiproliferative effect of TGF beta1 while the type I receptor mediates the matrix response of RFCs to TGF beta1 and demonstrate that changes in the matrix environment can modulate the surface expression of TGF beta receptors, altering the responsiveness of RFCs to TGF beta1. PMID:8617876

  18. Characterization of the Type III restriction endonuclease PstII from Providencia stuartii.

    PubMed

    Sears, Alice; Peakman, Luke J; Wilson, Geoffrey G; Szczelkun, Mark D

    2005-01-01

    A new Type III restriction endonuclease designated PstII has been purified from Providencia stuartii. PstII recognizes the hexanucleotide sequence 5'-CTGATG(N)(25-26/27-28)-3'. Endonuclease activity requires a substrate with two copies of the recognition site in head-to-head repeat and is dependent on a low level of ATP hydrolysis ( approximately 40 ATP/site/min). Cleavage occurs at just one of the two sites and results in a staggered cut 25-26 nt downstream of the top strand sequence to generate a two base 5'-protruding end. Methylation of the site occurs on one strand only at the first adenine of 5'-CATCAG-3'. Therefore, PstII has characteristic Type III restriction enzyme activity as exemplified by EcoPI or EcoP15I. Moreover, sequence asymmetry of the PstII recognition site in the T7 genome acts as an historical imprint of Type III restriction activity in vivo. In contrast to other Type I and III enzymes, PstII has a more relaxed nucleotide specificity and can cut DNA with GTP and CTP (but not UTP). We also demonstrate that PstII and EcoP15I cannot interact and cleave a DNA substrate suggesting that Type III enzymes must make specific protein-protein contacts to activate endonuclease activity.

  19. Type III chaperones & Co in bacterial plant pathogens: a set of specialized bodyguards mediating effector delivery.

    PubMed

    Lohou, David; Lonjon, Fabien; Genin, Stéphane; Vailleau, Fabienne

    2013-11-22

    Gram-negative plant pathogenic bacteria possess a type III secretion system (T3SS) to inject bacterial proteins, called type III effectors (T3Es), into host cells through a specialized syringe structure. T3Es are virulence factors that can suppress plant immunity but they can also conversely be recognized by the plant and trigger specific resistance mechanisms. The T3SS and injected T3Es play a central role in determining the outcome of a host-pathogen interaction. Still little is known in plant pathogens on the assembly of the T3SS and the regulatory mechanisms involved in the temporal control of its biosynthesis and T3E translocation. However, recent insights point out the role of several proteins as prime candidates in the role of regulators of the type III secretion (T3S) process. In this review we report on the most recent advances on the regulation of the T3S by focusing on protein players involved in secretion/translocation regulations, including type III chaperones (T3Cs), type III secretion substrate specificity switch (T3S4) proteins and other T3S orchestrators.

  20. 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.

  1. Electron plasma oscillations associated with type III radio emissions and solar electrons

    NASA Technical Reports Server (NTRS)

    Gurnett, D. A.; Frank, L. A.

    1975-01-01

    Results of an extensive search for electron plasma oscillations associated with type III radio noise bursts are presented which were obtained by analyzing 87 type III bursts detected in plasma-wave and charged-particle measurements carried out by IMP 6, 7, and 8. Only one case is found for which plasma oscillations were associated with electrons of solar origin; at least eight events are identified in which no plasma oscillations were detected even though electrons from solar flares were clearly evident. The type III emissions are compared with similar radiation coming from upstream of earth's bow shock at the harmonic of the local electron plasma frequency, and quantitative calculations of the rate of conversion from plasma oscillatory energy to electromagnetic radiation are performed. The results show that electron plasma oscillations are seldom observed in association with solar electron events and type III radio bursts at 1.0 AU and that neither the type III emissions nor the radiation from upstream of the bow shock can be adequately explained by a current model for the coupling of electron plasma oscillations to electromagnetic radiation. Several possible explanations are considered for this discrepancy between theory and observations.

  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.

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

    PubMed Central

    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

  4. Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology

    PubMed Central

    Pott, Johanna; Stockinger, Silvia

    2017-01-01

    The intestinal mucosa forms an active interface to the outside word, facilitating nutrient and water uptake and at the same time acts as a barrier toward the highly colonized intestinal lumen. A tight balance of the mucosal immune system is essential to tolerate harmless antigens derived from food or commensals and to effectively defend against potentially dangerous pathogens. Interferons (IFN) provide a first line of host defense when cells detect an invading organism. Whereas type I IFN were discovered almost 60 years ago, type III IFN were only identified in the early 2000s. It was initially thought that type I IFN and type III IFN performed largely redundant functions. However, it is becoming increasingly clear that type III IFN exert distinct and non-redundant functions compared to type I IFN, especially in mucosal tissues. Here, we review recent progress made in unraveling the role of type I/III IFN in intestinal mucosal tissue in the steady state, in response to mucosal pathogens and during inflammation. PMID:28352268

  5. Linking insulin with Alzheimer's disease: emergence as type III diabetes.

    PubMed

    Ahmed, Sara; Mahmood, Zahra; Zahid, Saadia

    2015-10-01

    Alzheimer's disease (AD) has characteristic neuropathological abnormalities including regionalized neurodegeneration, neurofibrillary tangles, amyloid beta (Aβ) deposition, activation of pro-apoptotic genes, and oxidative stress. As the brain functions continue to disintegrate, there is a decline in person's cognitive abilities, memory, mood, spontaneity, and socializing behavior. A framework that sequentially interlinks all these phenomenons under one event is lacking. Accumulating evidence has indicated the role of insulin deficiency and insulin resistance as mediators of AD neurodegeneration. Herein, we reviewed the evidence stemming from the development of diabetes agent-induced AD animal model. Striking evidence has attributed loss of insulin receptor-bearing neurons to precede or accompany initial stage of AD. This state seems to progress with AD such that, in the terminal stages, it worsens and becomes global. Oxidative stress, tau hyperphosphorylation, APP-Aβ deposition, and impaired glucose and energy metabolism have all been linked to perturbation in insulin/IGF signaling. We conclude that AD could be referred to as "type 3 diabetes". Moreover, owing to common pathophysiology with diabetes common therapeutic regime could be effective for AD patients.

  6. Transforming growth factor-beta receptor requirements for the induction of the endothelin-1 gene.

    PubMed

    Castañares, Cristina; Redondo-Horcajo, Mariano; Magan-Marchal, Noemi; Lamas, Santiago; Rodriguez-Pascual, Fernando

    2006-06-01

    Expression of the endothelin (ET)-1 gene is subject to complex regulation by numerous factors, among which the cytokine transforming growth factor-beta (TGF-beta) is one of the most important. TGF-beta action is based on the activation of the Smad signaling pathway. Smad proteins activate transcription of the gene by cooperation with activator protein-1 (AP-1) at specific sites on the ET-1 promoter. Smad signaling pathway is initiated by binding of the cytokine to a heteromeric complex of type I and type II receptors. Signal is then propagated to the nucleus by specific members of the Smad family. Most cell types contain a type I receptor known as ALK5. However, endothelial cells are unique because they coexpress an additional type I receptor named ALK1. These forms do not constitute redundant receptors with the same function, but they actually activate different Smad-mediated expression programs that lead to specific endothelial phenotypes. TGF-beta/ALK5/Smad3 pathway is associated to a mature endothelium because it leads to inhibition of cell migration/proliferation. Conversely, TGF-beta/ALK1/Smad5 activates both processes and is more related to the angiogenic state. We have analyzed the TGF-beta receptor subtype requirements for the activation of the ET-1 gene. For that purpose, we have overexpressed type I receptor and Smad isoforms in endothelial cells and analyzed the effect on ET-1 expression. Our experiments indicate that TGF-beta induces ET-1 expression preferentially through the activation of the ALK5/Smad3 pathway and, therefore, the expression of the vaso-constrictor may be associated to a quiescent and mature endothelial phenotype.

  7. An immunohistochemical and serum ELISA study of type I and III procollagen aminopropeptides in primary biliary cirrhosis.

    PubMed Central

    Davis, B. H.; Madri, J. A.

    1987-01-01

    By means of ELISA methodology, the aminopropeptides of Type I and Type III procollagen were measured in the serum of a group of patients with primary biliary cirrhosis. The corresponding liver biopsies were graded blindly for degrees of fibrosis and inflammation. When available, paraffin-embedded liver specimens underwent immunoperoxidase staining for mature Type I and III collagen as well as the aminopropeptides of Type I and III procollagen. Regardless of the degree of fibrosis or inflammation, serum levels of the aminopropeptide of Type I remained within normal limits. In contrast, serum levels of the aminopropeptide of Type III procollagen were elevated uniformly. Immunohistochemistry demonstrated that the aminopropeptide of Type III procollagen persists extracellularly. This finding may explain the previously reported relationship between levels of inflammation and serum levels of the Type III aminopropeptide. Images Figure 7 Figure 8 PMID:3303951

  8. Isolation and characterization of type III group B streptococcal mutants defective in biosynthesis of the type-specific antigen.

    PubMed Central

    Yeung, M K; Mattingly, S J

    1983-01-01

    Four classes of mutants of type III group B streptococcus were isolated by serial subculture of the wild-type strain in the presence of type III-specific rabbit antiserum. Class I mutants no longer synthesized sialic acid but still elaborated the core antigen. Class II mutants maintained the ability to synthesize sialic acid but could not attach it to the core antigen. Class III mutants did not produce the core antigen but still synthesized intracellular sialic acid. Class IV mutants synthesized the complete antigen; however, only approximately 4% of the antigen synthesized was found associated with the cell wall peptidoglycan (in the wild-type strain greater than 85% of the antigen synthesized is covalently attached to the cell wall peptidoglycan), whereas greater than 90% of the antigen was secreted into the growth medium. Production of other components (CAMP factor, group B antigen, beta-hemolysin, neuraminidase) by these mutants appeared similar to those of the wild-type strain. Mouse lethality studies of these strains indicated that all four classes have greater than 3 log10-higher 50% lethal dose values than that of the wild-type strain. To understand the basis for this variation, the invasive ability of the wild-type strain and the sialic acid-deficient mutant strain M-10 (class I) was examined. Mice received 10(5) CFU of each organism; they were then sacrificed at various times postinoculation, and viable group B streptococci from different organs were enumerated. Mice were able to clear M-10 more efficiently, with greater than 80% of M-10 cells being phagocytized by macrophages within 1 h, whereas the wild-type strain was able to evade phagocytic killing and disseminate to other tissues. These data, therefore, strongly indicate that the sialic acid moiety greatly enhances the virulence of the type III antigen. In addition, the level of cell-associated type-specific antigen appears to contribute significantly to the pathogenicity of the organism. PMID

  9. Translational regulation of Yersinia enterocolitica mRNA encoding a type III secretion substrate.

    PubMed

    Kopaskie, Karyl S; Ligtenberg, Katherine Given; Schneewind, Olaf

    2013-12-06

    Yersinia enterocolitica type III secretion machines transport YopQ and other Yop effectors into host immune cells. YopD and its chaperone LcrH are essential components of the Yersinia type III pathway, enabling effector translocation into host cells. YopD, LcrH, and YscM1 also regulate yop expression post-transcriptionally in response to environmental signals; however, the molecular mechanisms for this regulation and Yop secretion are unknown. We show here that YopD associates with 30 S ribosomal particles in a manner requiring LcrH. When added to ribosomes, YopD, LcrH, and YscM1 block the translation of yopQ mRNA. We propose a model whereby LcrH-dependent association of YopD with 30 S ribosomal particles enables YscM1 to block yopQ translation unless type III machines are induced to secrete the effector.

  10. 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

  11. 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.

  12. Structure and interactions of fish type III antifreeze protein in solution.

    PubMed

    Salvay, Andrés G; Gabel, Frank; Pucci, Bernard; Santos, Javier; Howard, Eduardo I; Ebel, Christine

    2010-07-21

    It has been suggested that above a critical protein concentration, fish Type III antifreeze protein (AFP III) self-assembles to form micelle-like structures that may play a key role in antifreeze activity. To understand the complex activity of AFP III, a comprehensive description of its association state and structural organization in solution is necessary. We used analytical ultracentrifugation, analytical size-exclusion chromatography, and dynamic light scattering to characterize the interactions and homogeneity of AFP III in solution. Small-angle neutron scattering was used to determine the low-resolution structure in solution. Our results clearly show that at concentrations up to 20 mg mL(-1) and at temperatures of 20 degrees C, 6 degrees C, and 4 degrees C, AFP III is monomeric in solution and adopts a structure compatible with that determined by crystallography. Surface tension measurements show a propensity of AFP III to localize at the air/water interface, but this surface activity is not correlated with any aggregation in the bulk. These results support the hypothesis that each AFP III molecule acts independently of the others, and that specific intermolecular interactions between monomers are not required for binding to ice. The lack of attractive interactions between monomers may be functionally important, allowing for more efficient binding and covering of the ice surface.

  13. Structure and Interactions of Fish Type III Antifreeze Protein in Solution

    PubMed Central

    Salvay, Andrés G.; Gabel, Frank; Pucci, Bernard; Santos, Javier; Howard, Eduardo I.; Ebel, Christine

    2010-01-01

    Abstract It has been suggested that above a critical protein concentration, fish Type III antifreeze protein (AFP III) self-assembles to form micelle-like structures that may play a key role in antifreeze activity. To understand the complex activity of AFP III, a comprehensive description of its association state and structural organization in solution is necessary. We used analytical ultracentrifugation, analytical size-exclusion chromatography, and dynamic light scattering to characterize the interactions and homogeneity of AFP III in solution. Small-angle neutron scattering was used to determine the low-resolution structure in solution. Our results clearly show that at concentrations up to 20 mg mL−1 and at temperatures of 20°C, 6°C, and 4°C, AFP III is monomeric in solution and adopts a structure compatible with that determined by crystallography. Surface tension measurements show a propensity of AFP III to localize at the air/water interface, but this surface activity is not correlated with any aggregation in the bulk. These results support the hypothesis that each AFP III molecule acts independently of the others, and that specific intermolecular interactions between monomers are not required for binding to ice. The lack of attractive interactions between monomers may be functionally important, allowing for more efficient binding and covering of the ice surface. PMID:20643081

  14. Intron-containing type I and type III IFN coexist in amphibians: refuting the concept that a retroposition event gave rise to type I IFNs.

    PubMed

    Qi, Zhitao; Nie, Pin; Secombes, Chris J; Zou, Jun

    2010-05-01

    Type I and III IFNs are structurally related cytokines with similar antiviral functions. They have different genomic organizations and bind to distinct receptor complexes. It has been vigorously debated whether the recently identified intron containing IFN genes in fish and amphibians belong to the type I or III IFN family or diverged from a common ancestral gene, that subsequently gave rise to both types. In this report, we have identified intron containing type III IFN genes that are tandemly linked in the Xenopus tropicalis genome and hence demonstrate for the first time that intron containing type I and III genes diverged relatively early in vertebrate evolution, and at least by the appearance of early tetrapods, a transition period when vertebrates migrated from an aquatic environment to land. Our data also suggest that the intronless type I IFN genes seen in reptiles, birds, and mammals have originated from a type I IFN transcript via a retroposition event that led to the disappearance of intron-containing type I IFN genes in modern vertebrates. In vivo and in vitro studies in this paper show that the Xenopus type III IFNs and their cognate receptor are ubiquitously expressed in tissues and primary splenocytes and can be upregulated by stimulation with synthetic double-stranded RNA, suggesting they are involved in antiviral defense in amphibians.

  15. Hepatocellular Adenomas and Carcinoma in Asymptomatic, Non-Cirrhotic Type III Glycogen Storage Disease.

    PubMed

    Oterdoom, Leendert H; Verweij, K Evelyne; Biermann, Katharina; Langeveld, Mirjam; van Buuren, Henk R

    2015-12-01

    Glycogen storage diseases (GSDs) are a group of inherited metabolic disorders characterized by accumulation of abnormal glycogen in muscle or liver or both. Specific hepatic complications include liver adenomas and hepatocellular carcinoma (HCC). Hepatocellular carcinomas described in GSD type I are often due to the degeneration of liver adenomas. Hepatocellular carcinoma in GSD type III, however, is rare and is thought to be associated with underlying cirrhosis.We present the case of a 63-year old male who was admitted for assessment of suitability for liver transplantation because of development of recurrent HCC in the presence of multiple liver adenomas. A diagnosis of GSD type III was made in this patient without underlying cirrhosis or metabolic disturbances resembling GSD. This case report is the first documentation of HCC development in an asymptomatic, non-cirrhotic patient with GSD type III. This raises the possibility that in GSD type III, the adenoma - carcinoma sequence can occur as it is also seen in GSD type I. Physicians taking care of GSD patients should be aware of this and some form of surveillance for cirrhosis and HCC should be considered. Also male patients with adenomas should have a thorough workup to reveal any underlying disease such as GSD.

  16. Sphincter of Oddi dysfunction Type III: New studies suggest new approaches are needed.

    PubMed

    Wilcox, C Mel

    2015-05-21

    Sphincter of Oddi dysfunction (SOD) has been classified into three types based upon the presence or absence of objective findings including liver test abnormalities and bile duct dilatation. Type III is the most controversial and is classified as biliary type pain in the absence of any these objective findings. Many prior studies have shown that the clinical response to endoscopic therapy is higher based upon the presence of these objective criteria. However, there has been variable correlation of the manometry findings to outcome after endoscopic therapy. Nevertheless, manometry and sphincterotomy has been recommended for Type III patients given the overall response rate of 33%, although the reported response rates are highly variable. However, all of the prior data was non-blinded and non-randomized with variable follow-up. The evaluating predictors in SOD study - a prospective randomized blinded sham controlled one year outcome study showed no correlation between manometric findings and outcome after sphincterotomy. Furthermore, patients receiving sham therapy had a statistically significantly better outcome than those undergoing biliary or dual sphincterotomy. This study calls into question the whole concept of SOD Type III and, based upon prior physiologic studies, one can suggest that SOD Type III likely represents a right upper quadrant functional abdominal pain syndrome and should be treated as such.

  17. The fibril core of transforming growth factor beta-induced protein (TGFBIp) facilitates aggregation of corneal TGFBIp

    PubMed Central

    Sørensen, Charlotte S.; Runager, Kasper; Scavenius, Carsten; Jensen, Morten M.; Nielsen, Nadia S.; Christiansen, Gunna; Petersen, Steen V.; Karring, Henrik; Sanggaard, Kristian W.; Enghild, Jan J.

    2016-01-01

    Mutations in the transforming growth factor beta-induced (TGFBI) gene result in a group of hereditary diseases of the cornea that are collectively known as TGFBI corneal dystrophies. These mutations translate into amino acid substitutions mainly within the fourth fasciclin 1 domain (FAS1-4) of the transforming growth factor beta-induced protein (TGFBIp) and cause either amyloid or non-amyloid protein aggregates in the anterior and central parts of the cornea, depending on the mutation. The A546T substitution in TGFBIp causes lattice corneal dystrophy (LCD), which manifests as amyloid-type aggregates in the corneal stroma. We previously showed that the A546T substitution renders TGFBIp and the FAS1-4 domain thermodynamically less stable compared with the wild-type (WT) protein, and the mutant FAS1-4 is prone to amyloid formation in vitro. In the present study, we identified the core of A546T FAS1-4 amyloid fibrils. Significantly, we identified the Y571-R588 region of TGFBIp, which we previously found to be enriched in amyloid deposits in LCD patients. We further found that the Y571-R588 peptide seeded fibrillation of A546T FAS1-4 and, more importantly, we demonstrated that native TGFBIp aggregates in the presence of fibrils formed by the core peptide. Collectively, these data suggest an involvement of the Y571-R588 peptide in LCD pathophysiology. PMID:25910219

  18. 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.

  19. Vlasov simulations of Langmuir Electrostatic Decay and consequences for Type III observations

    SciTech Connect

    Henri, P.; Califano, F.; Briand, C.; Mangeney, A.

    2010-03-25

    The electrostatic decay enables energy transfer from a finite amplitude Langmuir to a backscattered daughter Langmuir wave and ion acoustic density fluctuations. This mechanism is thought to be a first step for the generation of type III solar radio emissions at twice the plasma frequency. The electrostatic decay is here investigated through Vlasov-Poisson simulations by considering Langmuir localized wave packets in the case T{sub e} = T{sub p}. Simulation results are found to be in good agreement with recently reported observations from the STEREO mission of the electrostatic decay of beam-driven Langmuir waves during a type III burst.

  20. 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.

  1. Type III Radio Bursts and the Structure of the Inner Heliosphere

    NASA Astrophysics Data System (ADS)

    Reiner, M. J.

    2003-12-01

    Type III solar radio bursts provide important information on the origin, acceleration, and propagation of particles associated with solar flares and coronal shocks. Since these radio emissions are generated by the plasma emission mechanism, observations of these solar radio transients also provide remote sensing of the plasma conditions in the corona and of the magnetic and plasma structure of the inner heliosphere. In this talk I will review the progress of type III research from their discovery in the late 40s to the most recent advances from low-frequency spacecraft observations, primarily from ISEE-3, Wind and Ulysses.

  2. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    PubMed

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively.

  3. [Advances in studies of the type III secretion system in Ralstonia solanacearum--A review].

    PubMed

    Zhang, Yong; Li, Muyuan; Luo, Feng

    2015-06-04

    Bacterial wilt caused by Ralstonia solanacearum is one of the most devastating plant diseases worldwide. The syringe-like type III secretion system (T3SS) plays a crucial role in its pathogenicity. R. solanacearum uses the T3SS to inject effector proteins (Type III effectors) into the cytoplasm of host cells, causing diseases in susceptible plants or triggering the hypersensitive response in resistant plants. In this article we review recent advances in studies of R. solanacearum T3SS and highlight their unique features.

  4. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey

    PubMed Central

    Zanichelli, A.; Caballero, T.; Bouillet, L.; Aberer, W.; Maurer, M.; Fain, O.; Fabien, V.; Andresen, I.

    2017-01-01

    Summary Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1‐INH‐HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1‐INH‐AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1‐INH‐AAE and compare disease characteristics with those with C1‐INH‐HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6‐month intervals during patient follow‐up visits. In the icatibant‐treated population, 16 patients with C1‐INH‐AAE had 287 attacks and 415 patients with C1‐INH‐HAE types I/II had 2245 attacks. Patients with C1‐INH‐AAE versus C1‐INH‐HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33–64·53) versus 14·0 (12·70–15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1‐INH‐AAE versus C1‐INH‐HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1‐INH‐AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1‐INH‐HAE types I/II versus C1‐INH‐AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1‐INH‐AAE versus C1‐INH‐HAE types I/II, respectively. PMID:27936514

  5. The visibility of type III radio bursts originating behind the sun

    NASA Technical Reports Server (NTRS)

    Dulk, G. A.; Steinberg, J. L.; Lecacheux, A.; Hoang, S.; Macdowall, R. J.

    1985-01-01

    More than 95 percent of the solar type III bursts observed by the two Voyager spacecraft when they were in the solar hemisphere opposite the earth were also recorded by ISEE-3, and 10 of 21 type III bursts whose electron streams were directed toward the earth were recorded on the far side of the sun by Voyager. It is presently suggested that the reason for this widespread visibility is a high degree of radio wave scattering that originates at or near the local plasma frequency. Such other observed features of solar bursts as large apparent source heights may be explained by the strong scattering.

  6. Scaling up the predator functional response in heterogeneous environment: when Holling type III can emerge?

    PubMed

    Cordoleani, Flora; Nerini, David; Morozov, Andrey; Gauduchon, Mathias; Poggiale, Jean-Christophe

    2013-11-07

    Accurate parametrization of functional terms in model equations is of great importance for reproducing the dynamics of real food webs. Constructing models over large spatial and temporal scales using mathematical expressions obtained based on microcosm experiments can be erroneous. Here, using a generic spatial predator-prey model, we show that scaling up the microscale functional response of a predator can result in qualitative alterations of functional response on macroscales. In particular, a global functional response of sigmoid type (Holling type III) can emerge as a result of non-linear averaging of non-sigmoid local responses (Holling type I or II). We demonstrate that alteration between the local and the global response in the model is a result of the interplay between density-dependent dispersal of the predator across the habitat and heterogeneity of the environment. Using the method of aggregation of variables, we analytically derive the mathematical formulation of the global functional response as a function of the total amount of prey in the system, and reveal the key parameters which control the emergence of a Holling type III global response. We argue that this mechanism by which a global Holling type III emerges from a local Holling type II response has not been reported in the literature yet: in particular, Holling type III can emerge in the case of a fixed gradient of resource distribution across the habitat, which would be impossible in priorly suggested mechanisms. As a case study, we consider the interaction between phytoplankton and zooplankton grazers in the water column; and we show that the emergence of a Holling type III global response can allow for the efficient top-down regulation of primary producers and stabilization of planktonic ecosystems under eutrophic conditions.

  7. Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-beta.

    PubMed

    Kulyk, W M; Rodgers, B J; Greer, K; Kosher, R A

    1989-10-01

    This study represents a first step in investigating the possible involvement of transforming growth factor-beta (TGF-beta) in the regulation of embryonic chick limb cartilage differentiation. TGF-beta 1 and 2 (1-10 ng/ml) elicit a striking increase in the accumulation of Alcian blue, pH 1-positive cartilage matrix, and a corresponding twofold to threefold increase in the accumulation of 35S-sulfate- or 3H-glucosamine-labeled sulfated glycosaminoglycans (GAG) by high density micromass cultures prepared from the cells of whole stage 23/24 limb buds or the homogeneous population of chondrogenic precursor cells comprising the distal subridge mesenchyme of stage 25 wing buds. Moreover, TGF-beta causes a striking (threefold to sixfold) increase in the steady-state cytoplasmic levels of mRNAs for cartilage-characteristic type II collagen and the core protein of cartilage-specific proteoglycan. Only a brief (2 hr) exposure to TGF-beta at the initiation of culture is sufficient to stimulate chondrogenesis, indicating that the growth factor is acting at an early step in the process. Furthermore, TGF-beta promotes the formation of cartilage matrix and cartilage-specific gene expression in low density subconfluent spot cultures of limb mesenchymal cells, which are situations in which little, or no chondrogenic differentiation normally occurs. These results provide strong incentive for considering and further investigating the role of TGF-beta in the control of limb cartilage differentiation.

  8. Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

    PubMed

    Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

    2011-04-01

    Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

  9. Group B Streptococcal Type II and III Conjugate Vaccines: Physicochemical Properties That Influence Immunogenicity

    PubMed Central

    Michon, Francis; Uitz, Catherine; Sarkar, Arun; D'Ambra, Anello J.; Laude-Sharp, Maryline; Moore, Samuel; Fusco, Peter C.

    2006-01-01

    Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity. PMID:16893995

  10. Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems

    PubMed Central

    Goeders, Nathalie; Chai, Ray; Chen, Bihe; Day, Andrew; Salmond, George P. C.

    2016-01-01

    Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed. PMID:27690100

  11. Type-specific capsular antigen is associated with virulence in late-onset group B Streptococcal type III disease.

    PubMed Central

    Klegerman, M E; Boyer, K M; Papierniak, C K; Levine, L; Gotoff, S P

    1984-01-01

    Strain differences have been postulated to explain the observation that group B Streptococcus type III (GBS III) late-onset disease occurs in only a fraction of colonized infants. To determine the distribution of type-specific polysaccharide antigen (Ag) in GBS III, Ag was measured by rocket immunoelectrophoresis in both supernatant fluids and EDTA extracts and by radial immunodiffusion in multiple HCl extracts of the pellet from cultures of 10 strains of GBS III. Capsular Ag was defined as the sum of Ag in EDTA extracts + Ag in multiple HCl extracts. Both Ag in EDTA extracts and Ag in supernatant fluids correlated with capsular Ag (r = 0.94). GBS III strains were obtained from the blood of 19 infants with late-onset sepsis, from the cerebrospinal fluid or blood of 22 infants with late-onset meningitis, and from mucosal surfaces of both 18 infants and 12 mothers of infants with low levels of type-specific antibody and asymptomatic colonization. Mean values of Ag in supernatant fluids in strains from infants with late-onset sepsis (1.50 +/- 0.08 micrograms/ml) and late-onset meningitis (1.67 +/- 0.09 micrograms/ml) were significantly greater than those in asymptomatic colonization strains (1.14 +/- 0.05 micrograms/ml; P less than 0.001). The number of organisms required for a 50% lethal dose in the chick embryo, determined in 29 strains, was inversely related to Ag in supernatant fluids (r = -0.60). The demonstration that the quantity of capsular Ag produced by GBS III strains is related to their virulence in chick embryos and to their invasiveness in susceptible infants supports the hypothesis that Ag is a virulence factor in humans. Images PMID:6423540

  12. Tracking Type III Radio Burst Sources in the Solar Corona by Heliographic Means

    NASA Astrophysics Data System (ADS)

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

    We present the preliminary results of heliographic measurements of solar type III radio bursts in the low-frequency range (16.5-33 MHz) using the UTR-2 radio heliograph. The radio astronomy tools permit us to obtain two-dimensional spatial structures of burst sources in dependence of frequency and time. Each heliogram consists of 40 pixels (beams) as a result of the serial sweep in UV-plane wherein signals of each beam are recorded in a dynamic spectrum with both high temporal (˜ 2.482 ms) and top spectral (˜ 4 kHz) resolutions. The rate of output heliograph is one image per 3 seconds. Over a session in April, 2013 many type III radio and IIIb-III bursts were observed. On the heliograms the source motion direction in the upper corona is clearly detectable. The heliogram features are discussed.

  13. Angular Study of the III Type Solar Bursts by Ukrainian Decameter Heliograph of UTR-2

    NASA Astrophysics Data System (ADS)

    Koval, Artem; Stanislavsky, Aleksander; Konovalenko, Aleksander

    2014-05-01

    Solar radio bursts are attractive manifestations of solar activity. They contain useful information about physical processes in solar corona. The type III radio bursts are the most frequent events among many different types of solar bursts studied since middle of the last century. The type III bursts are generated by beams of fast electrons (beams velocity ~ 0.3c) ejected into the corona and propagated through coronal plasma to interplanetary medium. It is assumed that such an electron beam passing coronal plasma generates plasma waves that converse to electromagnetic waves registered as type III radio bursts. They are observed in a wide frequency range from 1 GHz to tens kHz. In particular, the decameter emission (10-30 MHz) of III type bursts arises at heights about 2-3 solar radii from the center of the Sun. In the last decades the various ground-based, satellite and spacecraft observations have provided detailed information about features of the bursts. Due to non-thermal emission mechanism their intensity can be very high that allows ones to record the bursts even by amateur radio astronomers with help of elementary antennas (for example, half-wave dipole) and simple radio equipment. At dynamic spectra the type III radio bursts are characterized by very fast frequency drifts. Usually, the analysis of such two-dimensional spectrograms reveals also duration and intensity of the events in time and frequency; if the antenna facilities permit, as well as degree of polarization. It should be noticed that the observations of angular three-dimensional structure of the burst source are also of great interest. Our knowledge about angular structure of type III radio bursts in decameter wavelengths was very restricted because of the absence of appropriate radio astronomy instruments. Recently, the difficulty has been overcome by means of the UTR-2 radio telescope (Kharkiv, Ukraine) in heliographic modes. It was successfully used for heliographic observations of solar

  14. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

    PubMed Central

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G.; Muñiz, Jesus; Ramirez-Archila, Mario V.; Sanchez-Pastor, Enrique A.; Andrade, Felipa; Soñanez-Organis, Jose G.; Moran-Palacio, Edgar F.; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. PMID:25147829

  15. Pregnancy differentially regulates the collagens types I and III in left ventricle from rat heart.

    PubMed

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G; Muñiz, Jesus; Ramirez-Archila, Mario V; Sanchez-Pastor, Enrique A; Andrade, Felipa; Soñanez-Organis, Jose G; Moran-Palacio, Edgar F; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum.

  16. 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...

  17. Group B Streptococcus Serotype III Sequence Type 283 Bacteremia Associated with Consumption of Raw Fish, Singapore

    PubMed Central

    Lin, Yijun; Foo, Kelly; Koh, Han Fang; Tow, Charlene; Zhang, Yiwen; Ang, Li Wei; Cui, Lin; Badaruddin, Hishamuddin; Ooi, Peng Lim; Lin, Raymond Tzer Pin; Cutter, Jeffery

    2016-01-01

    We conducted a retrospective study of 40 case-patients and 58 controls as part of a nationwide investigation of a group B Streptococcus outbreak in Singapore in 2015. Eating a Chinese-style raw fish dish (yusheng) was a major risk factor for bacteremia, particularly caused by serotype III sequence type 283. PMID:27767904

  18. Hypervirulent Clone of Group B Streptococcus Serotype III Sequence Type 283, Hong Kong, 1993–2012

    PubMed Central

    Ang, Irene; Fung, Kitty; Liyanapathirana, Veranja; Luo, Ming Jing; Lai, Raymond

    2016-01-01

    We describe a hypervirulent clone of group B Streptococcus serotype III, subtype 4, sequence type 283, that caused invasive disease with a predilection for meningitis in Hong Kong during 1993–2012. The organism is associated with high mortality and increased summer prevalence and is linked to diseased fish from freshwater fish farms. PMID:27648702

  19. The role of the magnetic field intensity and geometry in the type III burst generation

    NASA Astrophysics Data System (ADS)

    Zlobec, P.; Messerotti, M.; Ruzdjak, V.; Vrsnak, B.; Karlicky, M.

    1990-12-01

    The association of type III bursts related to H-alpha flares in different magnetic environments were studied in the period 1970-1981. Special attention is paid to flares which partly cover a major spot umbra (Z-flares). In particular, the location of the spots in the active regions and the magnetic field intensities of spots covered by a ribbon are considered. The association rate with type III bursts decreases to 17 percent when the flare is located inside the bipolar pattern of a large active region, compared with an association rate of 54 percent when the flare is situated outside it. The association rate increases with the magnetic field intensity of the spot covered by H-alpha emission; this is most clearly revealed for the flares occurring outside the bipolar pattern of active regions. Ninety-three percent of the flare-associated type III burst were accompanied by 10 cm radio bursts. For the most general case, in which a flare is developing anywhere in an active region, the association with type III bursts generation increases with the increasing magnetic field intensity of the main spot of the group.

  20. On the speed and acceleration of electron beams triggering interplanetary type III radio bursts

    NASA Astrophysics Data System (ADS)

    Krupar, V.; Kontar, E. P.; Soucek, J.; Santolik, O.; Maksimovic, M.; Kruparova, O.

    2015-08-01

    Aims: Type III radio bursts are intense radio emissions triggered by beams of energetic electrons often associated with solar flares. These exciter beams propagate outwards from the Sun along an open magnetic field line in the corona and in the interplanetary (IP) medium. Methods: We performed a statistical survey of 29 simple and isolated IP type III bursts observed by STEREO/Waves instruments between January 2013 and September 2014. We investigated their time-frequency profiles in order to derive the speed and acceleration of exciter electron beams. Results: We show these beams noticeably decelerate in the IP medium. Obtained speeds range from ~0.02c up to ~0.35c depending on initial assumptions. It corresponds to electron energies between tens of eV and hundreds of keV, and in order to explain the characteristic energies or speeds of type III electrons (~0.1c) observed simultaneously with Langmuir waves at 1 au, the emission of type III bursts near the peak should be predominately at double plasma frequency. Derived properties of electron beams can be used as input parameters for computer simulations of interactions between the beam and the plasma in the IP medium. Appendix A is available in electronic form at http://www.aanda.org

  1. Diagnosis of type III endoleak and endovascular treatment with aortouniiliac stent-graft.

    PubMed

    Juszkat, Robert; Staniszewski, Ryszard; Zarzecka, Anna; Majewski, Wacław

    2009-01-01

    The present report describes a case of type III endoleak from a tear in the fabric of a Zenith bifurcated stent-graft approximately 6 months after implantation. The reason of the fabric tear was unknown. The complication was successfully treated by aortouniiliac stent-graft implantation followed by creation of a femorofemoral bypass.

  2. 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…

  3. 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...

  4. 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, ...

  5. Search for the Third Harmonic of Type III Bursts Radio Emission at Decameter Wavelengths

    NASA Astrophysics Data System (ADS)

    Brazhenko, A. I.; Melnik, V. N.; Konovalenko, A. A.; Pylaev, O. S.; Frantsuzenko, A. V.; Dorovskyy, V. V.; Vashchishin, R. V.; Rucker, H. O.

    The results of observations of trio bursts consisting of type III bursts are presented in this paper. The instantaneous frequency ratio of trio components is near 1:2:3. We analyze flow, duration, frequency drift rate and polarization of trio components as well as dependencies of these characteristics on frequency.

  6. Programmable RNA shredding by the type III-A CRISPR-Cas system of Streptococcus thermophilus.

    PubMed

    Tamulaitis, Gintautas; Kazlauskiene, Migle; Manakova, Elena; Venclovas, Česlovas; Nwokeoji, Alison O; Dickman, Mark J; Horvath, Philippe; Siksnys, Virginijus

    2014-11-20

    Immunity against viruses and plasmids provided by CRISPR-Cas systems relies on a ribonucleoprotein effector complex that triggers the degradation of invasive nucleic acids (NA). Effector complexes of type I (Cascade) and II (Cas9-dual RNA) target foreign DNA. Intriguingly, the genetic evidence suggests that the type III-A Csm complex targets DNA, whereas biochemical data show that the type III-B Cmr complex cleaves RNA. Here we aimed to investigate NA specificity and mechanism of CRISPR interference for the Streptococcus thermophilus Csm (III-A) complex (StCsm). When expressed in Escherichia coli, two complexes of different stoichiometry copurified with 40 and 72 nt crRNA species, respectively. Both complexes targeted RNA and generated multiple cuts at 6 nt intervals. The Csm3 protein, present in multiple copies in both Csm complexes, acts as endoribonuclease. In the heterologous E. coli host, StCsm restricts MS2 RNA phage in a Csm3 nuclease-dependent manner. Thus, our results demonstrate that the type III-A StCsm complex guided by crRNA targets RNA and not DNA.

  7. 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.

  8. 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...

  9. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 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...

  10. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 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...

  11. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 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...

  12. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 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...

  13. 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.

  14. 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.

  15. 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.

  16. Transforming growth factor-beta stimulates the expression of fibronectin by human keratinocytes.

    PubMed

    Wikner, N E; Persichitte, K A; Baskin, J B; Nielsen, L D; Clark, R A

    1988-09-01

    Transforming growth factor beta (TGF-beta) is a 25-kD protein which has regulatory activity over a variety of cell types. It is distinct from epidermal growth factor (EGF) and EGF analogs, and exerts its action via a distinct receptor. Its effect on proliferation or differentiation can be positive or negative depending on the cell type and the presence of other growth factors. It also modulates the expression of cellular products. TGF-beta causes fibroblasts to increase their production of the extracellular matrix components, fibronectin and collagen. Human keratinocytes (HK) are known to have TGF-beta receptors. We wished to study the effect of TGF-beta on the production of extracellular matrix proteins by human keratinocytes in culture. Human keratinocytes were grown in serum-free defined medium (MCDB-153) to about 70% confluence. Following a 16-h incubation in medium lacking EGF and TGF-beta, cells were incubated for 12 h in medium containing varying concentrations of EGF and TGF-beta. Cells were then labeled with 35S-methionine for 10 h in the same conditions. Labeled proteins from the medium were analyzed by SDS-PAGE and autoradiography. TGF-beta at 10 ng/ml induced a sixfold increase in the secretion of fibronectin, as well as an unidentified 50-kD protein. Thrombospondin production was also increased, but not over a generalized twofold increase in the production of all other proteins. EGF, at 10 ng/ml, caused a smaller additive effect. TGF-beta may be an important stimulator of extracellular matrix production by human keratinocytes.

  17. Resistance of human squamous carcinoma cells to transforming growth factor beta 1 is a recessive trait.

    PubMed Central

    Reiss, M; Muñoz-Antonia, T; Cowan, J M; Wilkins, P C; Zhou, Z L; Vellucci, V F

    1993-01-01

    Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell genetics. Two stable hybrid cell lines (FaDu-HKc.1 and FaDu-HKc.2) were obtained by fusing a TGF beta 1-resistant human squamous carcinoma cell line, FaDu-HygR, with a human papilloma virus 16-immortalized, TGF beta 1-sensitive, human foreskin keratinocyte cell line, HKc-neoR. Whereas TGF beta 1 did not inhibit DNA synthesis in parental FaDu-HygR cells, it reduced DNA synthetic activity of HKc-neoR, FaDu-HKc.1, and FaDu-HKc.2 cells by 75-85% (IC50, 2-5 pM). Although squamous carcinoma cells express lower than normal levels of TGF beta 1 type II receptors on their cell surface, TGF beta 1 type II receptor mRNA was detected in all four cell lines. Recessive genes involved in TGF beta 1 signaling may be localized to the distal portion of chromosome 18q, as this was the sole chromosomal region of homozygous deletion in parental FaDu-HygR cells. Furthermore, our previous observation that mutant p53 decreases sensitivity of keratinocytes to TGF beta 1 was supported by the finding that the level of the mutant p53 protein expressed by the hybrid cell lines was greatly reduced. In summary, TGF beta 1 resistance of FaDu cells appears to be recessive and is presumably due to the loss of one or more post-receptor elements of the signaling pathway. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8327510

  18. Folding of beta-sandwich proteins: three-state transition of a fibronectin type III module.

    PubMed Central

    Cota, E.; Clarke, J.

    2000-01-01

    An analysis of the folding of the 94 residue tenth fibronectin type III (fnIII) domain of human fibronectin (FNfn10) is presented. Use of guanidine isothiocyanate as a denaturant allows us to obtain equilibrium and kinetic data across a broad range of denaturant concentrations that are unavailable in guanidine hydrochloride. Equilibrium unfolding experiments show that FNfn10 is significantly more stable than has been reported previously. Comparison of equilibrium and kinetic parameters reveals the presence of an intermediate that accumulates at low denaturant concentrations. This is the first demonstration of three-state folding kinetics for a fnIII domain. We have previously shown that a homologous domain from human tenascin (TNfn3) folds by a two-state mechanism, but this does not necessarily indicate that the two proteins fold by different folding pathways. PMID:10739253

  19. 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.

  20. Complete amino acid sequence of the N-terminal extension of calf skin type III procollagen.

    PubMed Central

    Brandt, A; Glanville, R W; Hörlein, D; Bruckner, P; Timpl, R; Fietzek, P P; Kühn, K

    1984-01-01

    The N-terminal extension peptide of type III procollagen, isolated from foetal-calf skin, contains 130 amino acid residues. To determine its amino acid sequence, the peptide was reduced and carboxymethylated or aminoethylated and fragmented with trypsin, Staphylococcus aureus V8 proteinase and bacterial collagenase. Pyroglutamate aminopeptidase was used to deblock the N-terminal collagenase fragment to enable amino acid sequencing. The type III collagen extension peptide is homologous to that of the alpha 1 chain of type I procollagen with respect to a three-domain structure. The N-terminal 79 amino acids, which contain ten of the 12 cysteine residues, form a compact globular domain. The next 39 amino acids are in a collagenase triplet sequence (Gly- Xaa - Yaa )n with a high hydroxyproline content. Finally, another short non-collagenous domain of 12 amino acids ends at the cleavage site for procollagen aminopeptidase, which cleaves a proline-glutamine bond. In contrast with type I procollagen, the type III procollagen extension peptides contain interchain disulphide bridges located at the C-terminus of the triple-helical domain. PMID:6331392

  1. Arnold-Chiari Malformation Type III With Meningoencephalocele: A Case Report.

    PubMed

    Jeong, Dae Ho; Kim, Chang Hwan; Kim, Myeong Ok; Chung, Hyung; Kim, Tae Hyun; Jung, Han Young

    2014-06-01

    Arnold-Chiari malformation type III (CM III) is an extremely rare anomaly with poor prognosis. An encephalocele with brain anomalies as seen in CM II, and herniation of posterior fossa contents like the cerebellum are found in CM III. The female infant was a twin, born at 33 weeks, weighing 1.7 kg with a huge hydrocele on the craniocervical junction. After operations were performed, she was referred to the department of rehabilitation medicine for poor motor development, swallowing dysfunction, and poor eye fixation at 22 months. The child was managed with neurodevelopmental treatment, oromotor facilitation, and light perception training. After 14 months, improvement of gross motor function was observed, including more stable head control, rolling, and improvement of visual perception. CM III has been known as a condition with poor prognosis. However, with the improvement in operative techniques and intensive rehabilitations, the prognosis is more promising than ever before. Therefore, more attention must be paid to the rehabilitation issues concerning patients with CM III.

  2. Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III.

    PubMed

    Mili, Amira; Ben Charfeddine, Ilhem; Mamaï, Ons; Abdelhak, Sonia; Adala, Labiba; Amara, Abdelbasset; Pagliarani, Serena; Lucchiarri, Sabrina; Lucchiari, Sabrina; Ayadi, Abdelkarim; Tebib, Neji; Harbi, Abdelaziz; Bouguila, Jihene; H'Mida, Dorra; Saad, Ali; Limem, Khalifa; Comi, G P; Gribaa, Moez

    2012-03-01

    Glycogen storage disease type III (GSD III) is an autosomal recessive inborn error of metabolism caused by mutations in the glycogen debranching enzyme amylo-1,6-glucosidase gene, which is located on chromosome 1p21.2. GSD III is characterized by the storage of structurally abnormal glycogen, termed limit dextrin, in both skeletal and cardiac muscle and/or liver, with great variability in resultant organ dysfunction. The spectrum of AGL gene mutations in GSD III patients depends on ethnic group. The most prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe Islands. Here, we present the molecular and biochemical analyses of 22 Tunisian GSD III patients. Molecular analysis revealed three novel mutations: nonsense (Tyr1148X) and two deletions (3033_3036del AATT and 3216_3217del GA) and five known mutations: three nonsense (R864X, W1327X and W255X), a missense (R524H) and an acceptor splice-site mutation (IVS32-12A>G). Each mutation is associated to a specific haplotype. This is the first report of screening for mutations of AGL gene in the Tunisian population.

  3. Transforming growth factor-beta1 to the bone.

    PubMed

    Janssens, Katrien; ten Dijke, Peter; Janssens, Sophie; Van Hul, Wim

    2005-10-01

    TGF-beta1 is a ubiquitous growth factor that is implicated in the control of proliferation, migration, differentiation, and survival of many different cell types. It influences such diverse processes as embryogenesis, angiogenesis, inflammation, and wound healing. In skeletal tissue, TGF-beta1 plays a major role in development and maintenance, affecting both cartilage and bone metabolism, the latter being the subject of this review. Because it affects both cells of the osteoblast and osteoclast lineage, TGF-beta1 is one of the most important factors in the bone environment, helping to retain the balance between the dynamic processes of bone resorption and bone formation. Many seemingly contradictory reports have been published on the exact functioning of TGF-beta1 in the bone milieu. This review provides an overall picture of the bone-specific actions of TGF-beta1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine.

  4. The Class of Type III-L Solar Radio Bursts and Their Associations with Solar Energetic Proton Events

    NASA Astrophysics Data System (ADS)

    Duffin, Robert Thomas

    2011-05-01

    The source protons of Solar Energetic particle Proton events (defined as "SEP" events for this research) not associated with the Coronal Mass Ejection (CME) shock front are thought to come from either the flare site or the reconnection region beneath the CME. The Type III-L, a new class of solar radio burst has been defined by Cane et al. (2002) and MacDowall et al. (2003) as a sub-set of the Type III burst, beginning after the onset of the soft X-ray (SXR) flare, is long lasting and extends down to at least 1 MHz. The emission source region of Type III-Ls is believed to be at the reconnection region beneath the CME or on the flanks of the CME. Past association studies between SEP events and Type III-Ls began with a biased SEP-selected sample set to see if there can be found support for the emission source region of Type III-Ls and SEPs to come from the same accelerator site at the reconnection region beneath the CME. Unlike previous studies using an SEP-selected sample, I find that when using a radio-selected sample for well-connected SEP events with a solar source in the western hemisphere, the majority of the Type III-L events are associated with SEP events, but not all, and that Type III-L events associated with M- and X- class SXR flares, do not appear to be better predictors of SEP events than do Type II bursts which are associated with the CME shock. Also, I find that the occurrence of Type II events in the radio spectra of SEPs is just as common as the occurrence of Type III-Ls. This indicates that Type III-Ls should not be used as a predictor for SEP events, that the emission source region of Type III-Ls might not be at the reconnection region beneath the CME and reduces the strength of the support found by previous SEP-Type III-L association studies, that the source protons for SEP events necessarily come from the reconnection region beneath the CME. I found that Type III-L events have no strong longitude preference, but SEP events do have a 60

  5. 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.

  6. 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.

  7. Propionibacterium Acnes Phylogenetic Type III is Associated with Progressive Macular Hypomelanosis

    PubMed Central

    Petersen, Rolf L. W.; Scholz, Christian F. P.; Jensen, Anders; Brüggemann, Holger; Lomholt, Hans B.

    2017-01-01

    Progressive macular hypomelanosis (PMH) is a skin disorder that is characterized by hypopigmented macules and usually seen in young adults. The skin microbiota, in particular the bacterium Propionibacterium acnes, is suggested to play a role. Here, we compared the P. acnes population of 24 PMH lesions from eight patients with corresponding nonlesional skin of the patients and matching control samples from eight healthy individuals using an unbiased, culture-independent next-generation sequencing approach. We also compared the P. acnes population before and after treatment with a combination of lymecycline and benzoylperoxide. We found an association of one subtype of P. acnes, type III, with PMH. This type was predominant in all PMH lesions (73.9% of reads in average) but only detected as a minor proportion in matching control samples of healthy individuals (14.2% of reads in average). Strikingly, successful PMH treatment is able to alter the composition of the P. acnes population by substantially diminishing the proportion of P. acnes type III. Our study suggests that P. acnes type III may play a role in the formation of PMH. Furthermore, it sheds light on substantial differences in the P. acnes phylotype distribution between the upper and lower back and abdomen in healthy individuals. PMID:28386469

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Design and synthesis of type-III mimetics of ShK toxin

    NASA Astrophysics Data System (ADS)

    Baell, Jonathan B.; Harvey, Andrew J.; Norton, Raymond S.

    2002-04-01

    ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.

  14. Subversion of plant cellular functions by bacterial type-III effectors: beyond suppression of immunity.

    PubMed

    Macho, Alberto P

    2016-04-01

    Most bacterial plant pathogens employ a type-III secretion system to inject type-III effector (T3E) proteins directly inside plant cells. These T3Es manipulate host cellular processes in order to create a permissive niche for bacterial proliferation, allowing development of the disease. An important role of T3Es in plant pathogenic bacteria is the suppression of plant immune responses. However, in recent years, research has uncovered T3E functions different from direct immune suppression, including the modulation of plant hormone signaling, metabolism or organelle function. This insight article discusses T3E functions other than suppression of immunity, which may contribute to the modulation of plant cells in order to promote bacterial survival, nutrient release, and bacterial replication and dissemination.

  15. Evidence for halo-like radio sources from kilometric type III burst observations

    NASA Technical Reports Server (NTRS)

    Reiner, M. J.; Stone, R. G.

    1990-01-01

    The radio azimuths for many kilometric type III bursts that originate near or behind the limb of the sun are observed to drift far to the east or far to the west of the spacecraft-sun line. It is shown that the behavior of the observed burst parameters for these events corresponds to the response of a spinning dipole antenna to halolike sources of radiation around the sun. These results provide evidence for a previous suggestion that behind-the-limb type III events should appear as halolike sources of radiation to an observer on the opposite side of the sun, due to scattering of the radiation from the primary source back around the sun.

  16. Discovery of a novel superfamily of type III polyketide synthases in Aspergillus oryzae.

    PubMed

    Seshime, Yasuyo; Juvvadi, Praveen Rao; Fujii, Isao; Kitamoto, Katsuhiko

    2005-05-27

    Identification of genes encoding type III polyketide synthase (PKS) superfamily members in the industrially useful filamentous fungus, Aspergillus oryzae, revealed that their distribution is not specific to plants or bacteria. Among other Aspergilli (Aspergillus nidulans and Aspergillus fumigatus), A. oryzae was unique in possessing four chalcone synthase (CHS)-like genes (csyA, csyB, csyC, and csyD). Expression of csyA, csyB, and csyD genes was confirmed by RT-PCR. Comparative genome analyses revealed single putative type III PKS in Neurospora crassa and Fusarium graminearum, two each in Magnaporthe grisea and Podospora anserina, and three in Phenarocheate chrysosporium, with a phylogenic distinction from bacteria and plants. Conservation of catalytic residues in the CHSs across species implicated enzymatically active nature of these newly discovered homologs.

  17. The first plant type III polyketide synthase that catalyzes formation of aromatic heptaketide.

    PubMed

    Abe, Ikuro; Utsumi, Yoriko; Oguro, Satoshi; Noguchi, Hiroshi

    2004-03-26

    A cDNA encoding a novel plant type III polyketide synthase (PKS) was cloned from rhubarb (Rheum palmatum). A recombinant enzyme expressed in Escherichia coli accepted acetyl-CoA as a starter, carried out six successive condensations with malonyl-CoA and subsequent cyclization to yield an aromatic heptaketide, aloesone. The enzyme shares 60% amino acid sequence identity with chalcone synthases (CHSs), and maintains almost identical CoA binding site and catalytic residues conserved in the CHS superfamily enzymes. Further, homology modeling predicted that the 43-kDa protein has the same overall fold as CHS. This provides new insights into the catalytic functions of type III PKSs, and suggests further involvement in the biosynthesis of plant polyketides.

  18. Efficient n-type doping of zinc-blende III-V semiconductor nanowires

    NASA Astrophysics Data System (ADS)

    Besteiro, Lucas V.; Tortajada, Luis; Souto, J.; Gallego, L. J.; Chelikowsky, James R.; Alemany, M. M. G.

    2014-03-01

    We demonstrate that it is preferable to dope III-V semiconductor nanowires by n-type anion substitution as opposed to cation substitution. Specifically, we show the dopability of zinc-blende nanowires is more efficient when the dopants are placed at the anion site as quantified by formation energies and the stabilization of DX-like defect centers. The comparison with previous work on n - type III-V semiconductor nanocrystals also allows to determine the role of dimensionality and quantum confinement on doping characteristics of materials. Our results are based on first-principles calculations of InP nanowires by using the PARSEC code. Work supported by the Spanish MICINN (FIS2012-33126) and Xunta de Galicia (GPC2013-043) in conjunction with FEDER. JRC acknowledges support from DoE (DE-FG02-06ER46286 and DESC0008877). Computational support was provided in part by CESGA.

  19. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report.

    PubMed

    Hu, Soo-Young; Choi, Jin-Gyu; Son, Byung-Chul

    2015-10-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia.

  20. Type III radio bursts in the interplanetary medium - The role of propagation

    NASA Technical Reports Server (NTRS)

    Steinberg, J. L.; Hoang, S.; Lecacheux, A.; Aubier, M. G.; Dulk, G. A.

    1984-01-01

    Interplanetary type III radio burst observations are analyzed in order to ascertain the role played by propagation effects between the true source and the observer. Large source altitudes are noted, together with an increasing angular size of sources with increasing angular distance from the sun's center. These and other observations furnish strong evidence for the theory that propagation effects, group delays, ducting and/or scattering significantly affect the observed heights, sizes, and brightness temperatures of interplanetary type III bursts. This would be true irrespective of whether the bursts are due to plasma radiation at the fundamental or at the harmonic, and the effects would extend to the arrival times of the radiation to a greater or lesser extent, depending on the path from the source to the observer.

  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.

  2. Observation of local radio emission associated with type III radio bursts and Langmuir waves

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    The first clear detection of fundamental and harmonic radiation from the type III radio source region is presented. This radiation is characterized by its lack of frequency drift, its short rise and decay times, its relative weakness compared to the remotely observed radiation and its temporal coincidence with observed Langmuir waves. The observations were made with the radio and plasma frequency (URAP) receivers on the Ulysses spacecraft between about 1 and 2 AU from the Sun.

  3. Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome.

    PubMed

    Encha Razavi, F; Larroche, J C; Roume, J; Gonzales, M; Kondo, H C; Mulliez, N

    1996-03-01

    We report on a distinct pattern of primary central nervous system (CNS) degeneration affecting neuronal survival in the brain and spinal cord in 5 fetuses with fetal akinesia sequence (FAS). This neuropathological pattern is characteristic of a lethal entity that we propose calling type III lissencephaly syndrome. Parental consanguinity and the recurrence in sibs support a genetic cause. The mechanism of neuronal death is not yet understood; abnormal apoptosis and/or deficiency in neurotropic factors may be considered possible causes.

  4. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia

    PubMed Central

    Carlson, Dustin A.; Kahrilas, Peter J.; Pandolfino, John E.

    2016-01-01

    The clinical significance of minor esophageal motility disorders is unclear, though they typically carry a benign course. Distal esophageal spasm progressing to achalasia has been reported, although it appears to be rare. We report a case of a patient with dysphagia and chest pain who was found to have ineffective esophageal motility on high-resolution manometry, which developed into distal esophageal spasm and then progressed to type III achalasia. PMID:28119934

  5. The Xanthomonas Hrp type III system secretes proteins from plant and mammalian bacterial pathogens

    PubMed Central

    Rossier, Ombeline; Wengelnik, Kai; Hahn, Karoline; Bonas, Ulla

    1999-01-01

    Studies of essential pathogenicity determinants in Gram-negative bacteria have revealed the conservation of type III protein secretion systems that allow delivery of virulence factors into host cells from plant and animal pathogens. Ten of 21 Hrp proteins of the plant pathogen Xanthomonas campestris pv. vesicatoria have been suggested to be part of a type III machinery. Here, we report the hrp-dependent secretion of two avirulence proteins, AvrBs3 and AvrRxv, by X. campestris pv. vesicatoria strains that constitutively express hrp genes. Secretion occurred without leakage of a cytoplasmic marker in minimal medium containing BSA, at pH 5.4. Secretion was strictly hrp-dependent because a mutant carrying a deletion in hrcV, a conserved hrp gene, did not secrete AvrBs3 and AvrRxv. Moreover, the Hrp system of X. campestris pv. vesicatoria was able to secrete proteins from two other plant pathogens: PopA, a protein secreted via the Hrp system in Ralstonia solanacearum, and AvrB, an avirulence protein from Pseudomonas syringae pv. glycinea. Interestingly, X. campestris pv. vesicatoria also secreted YopE, a type III-secreted cytotoxin of the mammalian pathogen Yersinia pseudotuberculosis in a hrp-dependent manner. YerA, a YopE-specific chaperone, was required for YopE stability but not for secretion in X. campestris pv. vesicatoria. Our results demonstrate the functional conservation of the type III system of X. campestris for secretion of proteins from both plant and mammalian pathogens and imply recognition of their respective secretion signals. PMID:10430949

  6. Evaluation of the Mangled Extremity Severity Score in Combat-Related Type III Tibia Fracture

    DTIC Science & Technology

    2014-09-01

    Krueger, MD,* Matthew A. Napierala, MD,* Daniel J. Stinner, MD,* and Joseph R. Hsu, MD,† on behalf of the Skeletal Trauma and Research Consortium (STReC...center. Intervention: Amputation or limb salvage. Main Outcome Measurements: MESS, amputation or limb salvage. Results: Complete data were available...for 155 patients treated for type III open tibia fractures. One hundred ten patients had salvaged limbs , and 45 patients had lower extremity amputations

  7. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia.

    PubMed

    Samo, Salih; Carlson, Dustin A; Kahrilas, Peter J; Pandolfino, John E

    2016-08-01

    The clinical significance of minor esophageal motility disorders is unclear, though they typically carry a benign course. Distal esophageal spasm progressing to achalasia has been reported, although it appears to be rare. We report a case of a patient with dysphagia and chest pain who was found to have ineffective esophageal motility on high-resolution manometry, which developed into distal esophageal spasm and then progressed to type III achalasia.

  8. The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

    PubMed Central

    2009-01-01

    Background This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects. Methods The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ). One-hundred healthy volunteers were recruited as a control group. Results The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result) and 2.2% in the control group (p < 0.05). An inverse significant nonparametric correlation was found between the NPQ value and the lordosis degree in the AC dislocation group (p = 0.001) wheras results were not correlated (p = 0.27) in the control group. Conclusions Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis. PMID:20015356

  9. 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

  10. Bacterial type III secretion systems are ancient and evolved by multiple horizontal-transfer events.

    PubMed

    Gophna, Uri; Ron, Eliora Z; Graur, Dan

    2003-07-17

    Type III secretion systems (TTSS) are unique bacterial mechanisms that mediate elaborate interactions with their hosts. The fact that several of the TTSS proteins are closely related to flagellar export proteins has led to the suggestion that TTSS had evolved from flagella. Here we reconstruct the evolutionary history of four conserved type III secretion proteins and their phylogenetic relationships with flagellar paralogs. Our analysis indicates that the TTSS and the flagellar export mechanism share a common ancestor, but have evolved independently from one another. The suggestion that TTSS genes have evolved from genes encoding flagellar proteins is effectively refuted. A comparison of the species tree, as deduced from 16S rDNA sequences, to the protein phylogenetic trees has led to the identification of several major lateral transfer events involving clusters of TTSS genes. It is hypothesized that horizontal gene transfer has occurred much earlier and more frequently than previously inferred for TTSS genes and is, consequently, a major force shaping the evolution of species that harbor type III secretion systems.

  11. 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

  12. Diversifying selection drives the evolution of the type III secretion system pilus of Pseudomonas syringae.

    PubMed

    Guttman, David S; Gropp, Susan J; Morgan, Robyn L; Wang, Pauline W

    2006-12-01

    The plant pathogenic bacterium Pseudomonas syringae uses a type III secretion system to inject virulence proteins directly into the cytoplasm of its hosts. The P. syringae type III secretion apparatus is encoded, in part, by the HrpZ operon, which carries the hrpA gene encoding the pilin subunit of the pilus, various components of the structural apparatus, and the HrpZ harpin protein that is believed to produce pores in the host cell membrane. The pilus of the type III system comes into direct contact with the host cell and is, therefore, a likely target of the host's pathogen surveillance systems. We sequenced and analyzed 22 HrpZ operons from P. syringae strains spanning the diversity of the species. Selection analyses, including K(a)/K(s) tests and Tajima's D, revealed strong diversifying selection acting on the hrpA gene. This form of selection enables pathogens to maintain genetic diversity within their populations and is often driven by selection imposed by host defense systems. The HrpZ operon also revealed a single significant recombination event that dramatically changed the evolutionary relationships among P. syringae strains from 2 quite distinct phylogroups. This recombination event appears to have introduced genetic diversity into a clade of strains that may now be undergoing positive selection. The identification of diversifying selection acting on the Hrp pilus across the whole population sample and positive selection within one P. syringae lineage supports a trench warfare coevolutionary model between P. syringae and its plant hosts.

  13. 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.

  14. 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

  15. Functional relatedness in the Inv/Mxi-Spa type III secretion system family.

    PubMed

    Klein, Jessica A; Dave, Biren M; Raphenya, Amogelang R; McArthur, Andrew G; Knodler, Leigh A

    2017-03-01

    Type III Secretion Systems (T3SSs) are structurally conserved nanomachines that span the inner and outer bacterial membranes, and via a protruding needle complex contact host cell membranes and deliver type III effector proteins. T3SS are phylogenetically divided into several families based on structural basal body components. Here we have studied the evolutionary and functional conservation of four T3SS proteins from the Inv/Mxi-Spa family: a cytosolic chaperone, two hydrophobic translocators that form a plasma membrane-integral pore, and the hydrophilic 'tip complex' translocator that connects the T3SS needle to the translocon pore. Salmonella enterica serovar Typhimurium (S. Typhimurium), a common cause of food-borne gastroenteritis, possesses two T3SSs, one belonging to the Inv/Mxi-Spa family. We used invasion-deficient S. Typhimurium mutants as surrogates for expression of translocator orthologs identified from an extensive phylogenetic analysis, and type III effector translocation and host cell invasion as a readout for complementation efficiency, and identified several Inv/Mxi-Spa orthologs that can functionally substitute for the S. Typhimurium chaperone and translocator proteins. Functional complementation correlates with amino acid sequence identity between orthologs, but varies considerably between the four proteins. This is the first in-depth survey of the functional interchangeability of Inv/Mxi-Spa T3SS proteins acting directly at the host-pathogen interface.

  16. 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.

  17. 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.

  18. 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.

  19. Highly strained Esaki tunnel diodes on InP substrate with type-III band alignment

    NASA Astrophysics Data System (ADS)

    Karl, S.; Sprengel, S.; Amann, M.-C.

    2016-12-01

    The first of a kind InP-based Esaki tunnel diodes with type-III (broken gap) band alignment are presented. This type is expected to have the highest tunneling current densities at equal doping concentration and structure geometry, compared to homo-, type-I or type-II junctions. The broken gap alignment is achieved by highly strained n-Ga0.2In0.8As/p-GaAs0.2Sb0.8 junction layers. Samples were fabricated by molecular beam epitaxy, the junction doping was varied between 2 × 1018 cm-3 and 2 × 1019 cm-3. Peak current densities up to 34.0 kA cm-2, for a doping of 2 × 1019 cm-3, are reached. The peak tunneling current shows a low dependence on the doping level for the type-III aligned junction layers. For example, highly strained diodes with a doping concentration of 2 × 1018 cm-3 can reach peak tunnel current densities of 3.6 A cm-2, whereas, with the lattice-matched junction, one order of magnitude higher doping is required.

  20. Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling

    PubMed Central

    Schulz, Alexander; Kyselyova, Anna; Baader, Stephan L.; Jung, Marie Juliane; Zoch, Ansgar; Mautner, Victor-Felix

    2014-01-01

    Axonal surface proteins encompass a group of heterogeneous molecules, which exert a variety of different functions in the highly interdependent relationship between axons and Schwann cells. We recently revealed that the tumour suppressor protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type 2, impacts significantly on axon structure maintenance in the peripheral nervous system. We now report on a role of neuronal merlin in the regulation of the axonal surface protein neuregulin 1 important for modulating Schwann cell differentiation and myelination. Specifically, neuregulin 1 type III expression is reduced in sciatic nerve tissue of neuron-specific knockout animals as well as in biopsies from seven patients with neurofibromatosis type 2. In vitro experiments performed on both the P19 neuronal cell line and primary dorsal root ganglion cells demonstrate the influence of merlin on neuregulin 1 type III expression. Moreover, expression of ERBB2, a Schwann cell receptor for neuregulin 1 ligands is increased in nerve tissue of both neuron-specific merlin knockout animals and patients with neurofibromatosis type 2, demonstrating for the first time that axonal merlin indirectly regulates Schwann cell behaviour. Collectively, we have identified that neuronally expressed merlin can influence Schwann cell activity in a cell-extrinsic manner. PMID:24309211

  1. Expression and Quorum Sensing Regulation of Type III Secretion System Genes of Vibrio harveyi during Infection of Gnotobiotic Brine Shrimp.

    PubMed

    Ruwandeepika, H A Darshanee; Karunasagar, Indrani; Bossier, Peter; Defoirdt, Tom

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells.

  2. NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives.

    PubMed

    Brisson, J R; Uhrinova, S; Woods, R J; van der Zwan, M; Jarrell, H C; Paoletti, L C; Kasper, D L; Jennings, H J

    1997-03-18

    The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

  3. 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.

  4. G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein

    SciTech Connect

    Chen, Chang Lan; Shim, Myoung Sup; Chung, Jiyeol; Yoo, Hyun-Seung; Ha, Ji Min; Kim, Jin Young; Choi, Jinmi; Zang, Shu Liang; Hou, Xiao; Carlson, Bradley A.; Hatfield, Dolph L.; Lee, Byeong Jae . E-mail: imbglmg@plaza.snu.ac.kr

    2006-10-06

    G-rich is a Drosophila melanogaster selenoprotein, which is a homologue of human and mouse SelK. Subcellular localization analysis using GFP-tagged G-rich showed that G-rich was localized in the Golgi apparatus. The fusion protein was co-localized with the Golgi marker proteins but not with an endoplasmic reticulum (ER) marker protein in Drosophila SL2 cells. Bioinformatic analysis of G-rich suggests that this protein is either type II or type III transmembrane protein. To determine the type of transmembrane protein experimentally, GFP-G-rich in which GFP was tagged at the N-terminus of G-rich, or G-rich-GFP in which GFP was tagged at the C-terminus of G-rich, were expressed in SL2 cells. The tagged proteins were then digested with trypsin, and analyzed by Western blot analysis. The results showed that the C-terminus of the G-rich protein was exposed to the cytoplasm indicating it is a type III microsomal membrane protein. G-rich is First selenoprotein identified in the Golgi apparatus.

  5. Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste.

    PubMed

    Huang, Yijen A; Maruyama, Yutaka; Stimac, Robert; Roper, Stephen D

    2008-06-15

    Taste buds contain two types of cells that directly participate in taste transduction - receptor (Type II) cells and presynaptic (Type III) cells. Receptor cells respond to sweet, bitter and umami taste stimulation but until recently the identity of cells that respond directly to sour (acid) tastants has only been inferred from recordings in situ, from behavioural studies, and from immunostaining for putative sour transduction molecules. Using calcium imaging on single isolated taste cells and with biosensor cells to identify neurotransmitter release, we show that presynaptic (Type III) cells specifically respond to acid taste stimulation and release serotonin. By recording responses in cells isolated from taste buds and in taste cells in lingual slices to acetic acid titrated to different acid levels (pH), we also show that the active stimulus for acid taste is the membrane-permeant, uncharged acetic acid moiety (CH(3)COOH), not free protons (H(+)). That observation is consistent with the proximate stimulus for acid taste being intracellular acidification, not extracellular protons per se. These findings may also have implications for other sensory receptors that respond to acids, such as nociceptors.

  6. Management of Oehler's Type III Dens Invaginatus Using Cone Beam Computed Tomography

    PubMed Central

    Ranganathan, Jaya; Rangarajan Sundaresan, Mohan Kumar; Ramasamy, Srinivasan

    2016-01-01

    Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT) are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler's classification (1957) for Dens Invaginatus (DI) into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler's Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation. PMID:27069697

  7. Identification and functional characterization of three type III polyketide synthases from Aquilaria sinensis calli.

    PubMed

    Wang, Xiaohui; Zhang, Zhongxiu; Dong, Xianjuan; Feng, Yingying; Liu, Xiao; Gao, Bowen; Wang, Jinling; Zhang, Le; Wang, Juan; Shi, Shepo; Tu, Pengfei

    2017-03-30

    Type III polyketide synthases (PKSs) play an important role in biosynthesis of various plant secondary metabolites and plant adaptation to environmental stresses. Aquilaria sinensis is the main plant species for production of agarwood, little is known about the PKS family. In this study, AsCHS1 and two new type III PKSs, AsPKS1 and AsPKS2, were isolated and characterized in Aquilaria sinensis calli. The comparative sequence and phylogenetic analysis indicated that AsPKS1 and AsPKS2 belong to non-CHS group different from AsCHS1. The recombinant AsPKS1 and AsPKS2 produced the lactone-type products, suggesting different enzyme activities with AsCHS1. Three PKS genes had a tissues-specific pattern in A. sinensis. Moreover, we examined the expression profiles of three PKS genes in calli under different abiotic stresses and hormone treatments. AsCHS1 transcript was significantly induced by salt stress, AsPKS1 abundance was most remarkably enhanced by CdCl2 treatment, while AsPKS2 expression was most significantly induced by mannitol treatment. Furthermore, AsCHS1, AsPKS1 and AsPKS2 transcript were enhanced upon gibberellins (GA3), methyl jasmonate (MeJA), salicylic acid (SA) treatments, while three PKS genes displayed low transcript levels at the early stage under abscisic acid (ABA) treatment. In addition, three GFP:PKSs fusion proteins were localized in the cytoplasm and cell wall in Nicotiana benthamiana cells. These results indicated the multifunctional role of three type III PKSs in polyketide biosynthesis, plant resistance in abiotic stresses and signal transduction.

  8. Directivity Patterns of Complex Solar Type III Radio Bursts: Stereoscopic Observations

    NASA Astrophysics Data System (ADS)

    Golla, T.; MacDowall, R. J.

    2014-12-01

    Complex solar type III-like radio bursts are a group of type III bursts that occur in association with slowly drifting type II radio bursts excited by coronal mass ejection (CME) driven shock waves. We presentsimultaneous observations of these radio bursts from the STEREO A, B and WIND spacecraft at low frequencies, located at different vantage points in the ecliptic plane. Using these stereoscopic observations, wedetermine the directivity of these complex radio bursts. We estimate the angles between the directions of the magnetic field at the sources and the lines connecting the source to the spacecraft (viewing angles) by assuming that the sources are located on the Parker spiral magnetic field lines emerging from the associated active regions into the spherically symmetric solar atmosphere. We estimate the normalized peak intensities of these bursts (directivity factors) at each spacecraft using their time profiles at each spacecraft. These observations indicate that the complex type III bursts can be divided into two groups: (1) bursts emitting into a very narrow cone centered around the tangent to the magnetic field, and (2) bursts emitting into a wider cone. We show that the bursts , which are emitted along the tangent to the spiral magnetic field lines at the source are very intense, and their intensities steadily fall as the viewing angles increase to higher values. We have developed a ray tracing code and computed the distributions of the trajectories of rays emitted at the fundamental and second harmonic of the electron plasma frequency. The comparison of the observed 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 relativelyweaker bursts visible to a wide range of angles are probably emitted in the harmonic mode.

  9. Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome

    PubMed Central

    Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema

    2017-01-01

    Introduction Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Methods Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Results Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. Conclusion A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort. PMID:28288174

  10. Alterations in biosynthetic accumulation of collagen types I and III during growth and morphogenesis of embryonic mouse salivary glands

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1992-01-01

    We examined the biosynthetic patterns of interstitial collagens in mouse embryonic submandibular and sublingual glands cultured in vitro. Rudiments explanted on day 13 of gestation and cultured for 24, 48, and 72 h all synthesized collagen types I, III, and V. However, while the total incorporation of label into collagenous proteins did not change over the three-day culture period, the rate of accumulation of newly synthesized types I and III did change. At 24 h, the ratio of newly synthesized collagen types I:III was approximately 2, whereas at 72 h, the ratio was approximately 5. These data suggest that collagen types I and III may be important in initiation of branching in this organ, but that type I may become dominant in the later stages of development and in maintenance of the adult organ.

  11. Control of transforming growth factor-beta activity: latency vs. activation.

    PubMed

    Harpel, J G; Metz, C N; Kojima, S; Rifkin, D B

    1992-01-01

    Transforming growth factor-beta is a pluripotent regulator of cell growth and differentiation. The growth factor is expressed as a latent complex that must be converted to an active form before interacting with its ubiquitous high affinity receptors. This conversion involves the release of the mature growth factor through disruption of the non-covalent interactions with its pro-peptide or latency associated peptide. The mechanisms for this release in vivo have not been fully characterized but appear to be cell specific and might involve processes such as acidification or proteolysis. Although several factors including transcriptional regulation, receptor modulation and scavenging of the active growth factor have been implicated, the critical step controlling the biological effects of transforming growth factor-beta may be the activation of the latent molecule.

  12. Effect of sulodexide on plasma transforming growth factor-beta1 in healthy volunteers.

    PubMed

    Borawski, Jacek; Dubowski, Miroslaw; Pawlak, Krystyna; Mysliwiec, Michal

    2010-02-01

    It is unknown whether the glycosaminoglycan drug sulodexide interferes with transforming growth factor-beta1--a member of heparin-binding family and a potent regulator of human biology and diseases. Hence, a 2-week pilot study was performed in 11 healthy men. Sulodexide was initially administered intravenously in a single dose, then--orally for 12 days and--again intravenously on study completion. Initial injection had no effect on activated form of the growth factor measured in plasma after 10 and 120 min; no change was also observed after 120 min from drug ingestion on day 7. On final intravenous administration, the growth factor levels increased by almost 60% after 10 min and remained elevated; the 120-min levels directly correlated with sulodexide dosage. Baseline cytokine levels decreased during the 2-week trial by more than 50%. In conclusion, transforming growth factor-beta1 release and likely downregulation of its expression may constitute novel pharmacological effects of sulodexide.

  13. Attenuated Transforming Growth Factor Beta Signaling as a Therapeutic for Prostate Cancer Progression

    DTIC Science & Technology

    2008-04-01

    upregulates VEGF expression only. Circulation 1994;90:649-52. 4. Igarashi A, Okochi H , Bradham DM, Grotendorst GR. Regulation of connective tissue growth...2005;65:8887-95. 10. Uhl M, Aulwurm S, Wischhusen J, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth...cancer. Endocr Relat Cancer 2005;12:805-22. 18. Kawada M, Inoue H , Masuda T, Ikeda D. Insulin-like growth factor I secreted from prostate stromal

  14. Inhibition of Nb2 T-lymphoma cell growth by transforming growth factor-beta.

    PubMed Central

    Rayhel, E J; Prentice, D A; Tabor, P S; Flurkey, W H; Geib, R W; Laherty, R F; Schnitzer, S B; Chen, R; Hughes, J P

    1988-01-01

    Transforming growth factor-beta (TGF-beta) inhibits proliferation of Nb2 cells, a rat T lymphoma, in response to lactogens and interleukin-2. Prostaglandins may play an important role in the pathway through which TGF-beta exerts its inhibitory actions, because prostaglandin E2 also inhibits proliferation of Nb2 cells, and indomethacin, an inhibitor of prostaglandin synthesis, reverses the inhibitory effects of TGF-beta on Nb2 cell proliferation. PMID:3262338

  15. Type III photosensitization: attempt for quantification and a way toward new sensitizers

    NASA Astrophysics Data System (ADS)

    Kriska, Tamas; Jakus, Judit; Keszler, Agnes; Vanyur, Rozalia; Nemeth, Andras; Gal, Dezso

    1999-02-01

    Earlier results studying the effect of excited triplet photosensitizer on the zymosan-stimulated and luminol- dependent chemiluminescence of macrophages have been quantitatively re-evaluated and rate constant data indicate that the effect is due to triplet-doublet interactions between sensitizer and free radicals generated. Such interactions, named Type III mechanism, compete with Type I and Type II mechanisms depending on the experimental environment. This suggestion resulted in the synthesis of new sensitizers being the first members of the Antioxidant Carrier Sensitizer (ACS) group of molecules. According to preliminary experiments the PDT treatment of tumor bearing mice seems promising with two of such compounds which demonstrate an inhibitory effect in chemical systems already in their ground state.

  16. Beat-type Langmuir wave emissions associated with a type III solar radio burst: Evidence of parametric decay

    NASA Technical Reports Server (NTRS)

    Hospodarsky, G. B.; Gurnett, D. A.

    1995-01-01

    Recent measurements from the plasma wave instrument on the Galileo spacecraft have shown that Langmuir waves observed in conjunction with a type III solar radio burst contain many beat-type waveforms, with beat frequencies ranging from about 150 to 650 Hz. Strong evidence exists that the beat pattern is produced by two closely spaced narrowband components. The most likely candidates for these two waves are a beam-generated Langmuir wave and an oppositely propagating Langmuir wave produced by parametric decay. In the parametric decay process, nonlinear interactions cause the beam-driven Langmuir wave to decay into a Langmuir wave and a low-frequency ion sound wave. Comparisons of the observed beat frequency are in good agreement with theoretical predictions for a three-wave parametric decay process. Weak low-frequency emissions are also sometimes observed at the predicted frequency of the ion sound wave.

  17. LOFAR tied-array imaging of Type III solar radio bursts

    NASA Astrophysics Data System (ADS)

    Morosan, D. E.; Gallagher, P. T.; Zucca, P.; Fallows, R.; Carley, E. P.; Mann, G.; Bisi, M. M.; Kerdraon, A.; Konovalenko, A. A.; MacKinnon, A. L.; Rucker, H. O.; Thidé, B.; Magdalenić, J.; Vocks, C.; Reid, H.; Anderson, J.; Asgekar, A.; Avruch, I. M.; Bentum, M. J.; Bernardi, G.; Best, P.; Bonafede, A.; Bregman, J.; Breitling, F.; Broderick, J.; Brüggen, M.; Butcher, H. R.; Ciardi, B.; Conway, J. E.; de Gasperin, F.; de Geus, E.; Deller, A.; Duscha, S.; Eislöffel, J.; Engels, D.; Falcke, H.; Ferrari, C.; Frieswijk, W.; Garrett, M. A.; Grießmeier, J.; Gunst, A. W.; Hassall, T. E.; Hessels, J. W. T.; Hoeft, M.; Hörandel, J.; Horneffer, A.; Iacobelli, M.; Juette, E.; Karastergiou, A.; Kondratiev, V. I.; Kramer, M.; Kuniyoshi, M.; Kuper, G.; Maat, P.; Markoff, S.; McKean, J. P.; Mulcahy, D. D.; Munk, H.; Nelles, A.; Norden, M. J.; Orru, E.; Paas, H.; Pandey-Pommier, M.; Pandey, V. N.; Pietka, G.; Pizzo, R.; Polatidis, A. G.; Reich, W.; Röttgering, H.; Scaife, A. M. M.; Schwarz, D.; Serylak, M.; Smirnov, O.; Stappers, B. W.; Stewart, A.; Tagger, M.; Tang, Y.; Tasse, C.; Thoudam, S.; Toribio, C.; Vermeulen, R.; van Weeren, R. J.; Wucknitz, O.; Yatawatta, S.; Zarka, P.

    2014-08-01

    Context. The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), the Sun has not been imaged extensively because of the instrumental limitations of previous radio telescopes. Aims: Here, the combined high spatial, spectral, and temporal resolution of the LOw Frequency ARray (LOFAR) was used to study solar Type III radio bursts at 30-90 MHz and their association with CMEs. Methods: The Sun was imaged with 126 simultaneous tied-array beams within ≤5 R⊙ of the solar centre. This method offers benefits over standard interferometric imaging since each beam produces high temporal (~83 ms) and spectral resolution (12.5 kHz) dynamic spectra at an array of spatial locations centred on the Sun. LOFAR's standard interferometric output is currently limited to one image per second. Results: Over a period of 30 min, multiple Type III radio bursts were observed, a number of which were found to be located at high altitudes (~4 R⊙ from the solar center at 30 MHz) and to have non-radial trajectories. These bursts occurred at altitudes in excess of values predicted by 1D radial electron density models. The non-radial high altitude Type III bursts were found to be associated with the expanding flank of a CME. Conclusions: The CME may have compressed neighbouring streamer plasma producing larger electron densities at high altitudes, while the non-radial burst trajectories can be explained by the deflection of radial magnetic fields as the CME expanded in the low corona. Movie associated to Fig. 2 is available in electronic form at http://www.aanda.org

  18. Cell growth rate regulates expression of group B Streptococcus type III capsular polysaccharide.

    PubMed Central

    Paoletti, L C; Ross, R A; Johnson, K D

    1996-01-01

    The capsular polysaccharide (CPS) of group B streptococci (GBS) is an important virulence factor that also serves to protect cells from nonspecific host defense mechanisms. Expression of CPS by GBS, as with other encapsulated bacterial pathogens, is not constitutive but varies during growth in vitro and in primary cultures isolated from different sites of infection. Despite this understanding, little is known about regulation of this surface-expressed carbohydrate antigen in GBS. Here we report that expression of type III CPS by GBS strain M781 grown in continuous culture with a modified chemically defined medium is regulated by growth rate. Cells in steady state at mass doubling times (tds) of 0.8, 1.4, and 1.6 h expressed an average of sixfold more cell-associated CPS than did cells held at tds of 2.3 and 11 h. Strain M781 grown at a td of 1.4 h repeatedly produced more type III CPS than those held at a td of 11.0 h, even when limited for glucose, pyridoxamine, or thiamine. In our studies, > or = 93% of the total CPS expressed by strain M781 was cell associated. Strain M781 grown at a td of 11.0 h (i.e., lowered CPS expression) was susceptible to in vitro complement-mediated opsonophagocytosis and killing by human peripheral blood leukocytes, whereas cells grown at a td of 1.4 h (i.e., higher CPS expression) were not killed unless type III CPS-specific antibody was present. Factors that allow GBS to asymptomatically colonize women yet cause invasive infection to both mother and infant are poorly understood. Our results shed new light on parameters that regulate the pathogenic potential of GBS and may also serve as a way to discern more fully the genetics and biochemistry of GBS capsule synthesis. PMID:8606082

  19. Secretion of Pseudomonas aeruginosa Type III Cytotoxins is Dependent on Pseudomonas Quinolone Signal Concentration

    PubMed Central

    Singh, G.; Wu, B.; Baek, M.S.; Camargo, A.; Nguyen, A.; Slusher, N.A.; Srinivasan, R.; Wiener-Kronish, J.P.; Lynch, S.V.

    2010-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two-component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent posttranslational control, specifically governing type III cytotoxin secretion, exists in this species. PMID:20570614

  20. Epithelial-mesenchymal interactions and lung branching morphogenesis. Role of polyamines and transforming growth factor beta1.

    PubMed

    Stabellini, G; Locci, P; Calvitti, M; Evangelisti, R; Marinucci, L; Bodo, M; Caruso, A; Canaider, S; Carinci, P

    2001-01-01

    Lung branching morphogenesis is a result of epithelial-mesenchymal interactions, which are in turn dependent on extracellular matrix composition and cytokine regulation. Polyamines have recently been demonstrated as able to modify chick embryo skin differentiation. In this work we have examined the effects of putrescine and spermidine during chick embryo lung morphogenesis in organotypic cultures by morphological, histochemical and biochemical examination. To verify the role of polyamines, we used specific inhibitors, such as bis-cyclohexylammonium sulphate and alfa-difluoromethylornithine, and transforming growth factor beta1, an ornithine decarboxylase and polyamine stimulator. Our data show that lung morphogenesis is significantly altered following the induced mesenchymal glycosaminoglycan changes. The increase of mesenchymal glycosaminoglycans is correlated with a stimulation of lung development in the presence of polyamines, and with its inhibition when transforming growth factor beta1 is added to the culture medium. The morphometric data show a uniform increase of both the mesenchyme and epithelial branching with spermidine and putrescine stimulus, whereas the mesenchymal substance alone is significantly increased in apical-median lung sections with transforming growth factor beta1 and transforming growth factor beta1 + spermidine lung cultures. Transforming growth factor beta1 and transforming growth factor beta1 + spermidine confirm the blocking of epithelial branching formations and fibroblast activation, and show that polyamines are unable to prevent the blocking of epithelial cells due to the inhibitory effect of transforming growth factor beta1.

  1. A new type of stereoisomer in Cobalt (III) dioxines with Thiocarbamid.

    NASA Astrophysics Data System (ADS)

    Rusanovskij, M. E.; Samus', I. D.; Proskina, N.; Zavodnik, V.; Khalak, M.

    1992-12-01

    The crystal structure of the cobalt (III) dioxine water modification with thioseicarbazide ligands,[Co(DH)_2(Thio]NO_3H_2O was determined by the anisotropic method of least squares. The Co(III) atom coordination has the form a slightly distorted octahedron formed by the four nitrogen atoms of dioximinesmolcules with non symmetric chemical bounds of O-H-O type (2.52...2.49)A. The Co(III) atom coordination is completed by two sulphur atoms of the thiosemicarbazide ligand,(Co-S)_av=2.279 and 2.309A. the structure of this modification is different fromthat of the prismatic modification, [Co(DH)^2(Thio)_2]NO_3.Both contain polyhedra in which that of the prismatic modification,[Co(DH)_2(Thio)_2]NO_3. Both contain polyhedra in which the ligand molecules are in trans-position,but in the case of I the molecule planes are oriented practically perpendicular (81.7^)to each other,while in the case of II they are antiparallel forming stereoisomers.

  2. Electro-optical properties characterization of fish type III antifreeze protein.

    PubMed

    Salvay, Andrés G; Santos, Javier; Howard, Eduardo I

    2007-12-01

    Antifreeze proteins (AFPs) are ice-binding proteins that depress the freezing point of water in a non-colligative manner without a significant modification of the melting point. Found in the blood and tissues of some organisms (such as fish, insects, plants, and soil bacteria), AFPs play an important role in subzero temperature survival. Fish Type III AFP is present in members of the subclass Zoarcoidei. AFPIII are small 7-kDa-or 14-kDa tandem-globular proteins. In the present work, we study the behavior of several physical properties, such as the low-frequency dielectric permittivity spectrum, circular dichroism, and electrical conductivity of Fish Type III AFP solutions measured at different concentrations. The combination of the information obtained from these measurements could be explained through the formation of AFP molecular aggregates or, alternatively, by the existence of some other type of interparticle interactions. Thermal stability and electro-optical behavior, when proteins are dissolved in deuterated water, were also investigated.

  3. Identification and functional analysis of type III effector proteins in Mesorhizobium loti.

    PubMed

    Okazaki, Shin; Okabe, Saori; Higashi, Miku; Shimoda, Yoshikazu; Sato, Shusei; Tabata, Satoshi; Hashiguchi, Masatsugu; Akashi, Ryo; Göttfert, Michael; Saeki, Kazuhiko

    2010-02-01

    Mesorhizobium loti MAFF303099, a microsymbiont of the model legume Lotus japonicus, possesses a cluster of genes (tts) that encode a type III secretion system (T3SS). In the presence of heterologous nodD from Rhizobium leguminosarum and a flavonoid naringenin, we observed elevated expression of the tts genes and secretion of several proteins into the culture medium. Inoculation experiments with wild-type and T3SS mutant strains revealed that the presence of the T3SS affected nodulation at a species level within the Lotus genus either positively (L. corniculatus subsp. frondosus and L. filicaulis) or negatively (L. halophilus and two other species). By inoculating L. halophilus with mutants of various type III effector candidate genes, we identified open reading frame mlr6361 as a major determinant of the nodulation restriction observed for L. halophilus. The predicted gene product of mlr6361 is a protein of 3,056 amino acids containing 15 repetitions of a sequence motif of 40 to 45 residues and a shikimate kinase-like domain at its carboxyl terminus. Homologues with similar repeat sequences are present in the hypersensitive-response and pathogenicity regions of several plant pathogens, including strains of Pseudomonas syringae, Ralstonia solanacearum, and Xanthomonas species. These results suggest that L. halophilus recognizes Mlr6361 as potentially pathogen derived and subsequently halts the infection process.

  4. Type III polyketide synthase is involved in the biosynthesis of protocatechuic acid in Aspergillus niger.

    PubMed

    Lv, Yangyong; Xiao, Jing; Pan, Li

    2014-11-01

    Genomic studies have shown that not only plants but also filamentous fungi contain type III polyketide synthases. To study the function of type III polyketide synthase (AnPKSIII) in Aspergillus niger, a deletion strain (delAnPKSIII) and an overexpression strain (oeAnPKSIII) were constructed in A. niger MA169.4, a derivative of the wild-type (WT) A. niger ATCC 9029 that produces large quantities of gluconic acid. Alterations in the metabolites were analyzed by HPLC when the extract of the overexpression strain was compared with extracts of the WT and deletion strains. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid, 3.2 mg/l) was isolated and identified as the main product of AnPKSIII when inductively expressed in A. niger MA169.4. The molecular weight of PCA was 154.1 (m/z 153.1 [M-H](-)), was detected by ESI-MS in the negative ionization mode, and (1)H and (13)C NMR data confirmed its structure.

  5. Electro-Optical Properties Characterization of Fish Type III Antifreeze Protein

    PubMed Central

    Salvay, Andrés G.; Santos, Javier

    2008-01-01

    Antifreeze proteins (AFPs) are ice-binding proteins that depress the freezing point of water in a non-colligative manner without a significant modification of the melting point. Found in the blood and tissues of some organisms (such as fish, insects, plants, and soil bacteria), AFPs play an important role in subzero temperature survival. Fish Type III AFP is present in members of the subclass Zoarcoidei. AFPIII are small 7-kDa—or 14-kDa tandem—globular proteins. In the present work, we study the behavior of several physical properties, such as the low-frequency dielectric permittivity spectrum, circular dichroism, and electrical conductivity of Fish Type III AFP solutions measured at different concentrations. The combination of the information obtained from these measurements could be explained through the formation of AFP molecular aggregates or, alternatively, by the existence of some other type of interparticle interactions. Thermal stability and electro-optical behavior, when proteins are dissolved in deuterated water, were also investigated. PMID:19669526

  6. Effects of transforming growth factor-beta on long-term human cord blood monocyte cultures

    SciTech Connect

    Orcel, P.; Bielakoff, J.; De Vernejoul, M.C. )

    1990-02-01

    Transforming growth factor-beta (TGF-beta) modulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH)2D3 acquire some features of osteoclast precursors. Since TGF-beta has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-beta (1-1,000 pg/ml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10(-9) M 1,25(OH)2D3. TGF-beta, from a concentration of 10 pg/ml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-beta of 1 ng/ml, the multinucleated cells were reduced to 2.1% +/- 0.3%, compared to 19.3% +/- 1.5% in control cultures. TGF-beta inhibited in a dose-dependent manner the proliferation of cord blood monocytes as assessed by 3H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by 3 weeks of treatment with TGF-beta. Indomethacin did not reverse the inhibitory effects of TGF-beta. The expression of the osteoclastic phenotype was assessed using two different antibodies: 23C6, a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DR, which is not present on osteoclast. TGF-beta decreased the expression of HLA-DR and increased in a dose-dependent manner the proportion of 23C6-labeled cells; these results suggest that TGF-beta could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with 45Ca, TGF-beta did not induce any 45Ca release from bone cultured with monocytes.

  7. [Prevalence of type III secretion system genes in cholera vibrios from different serogroups].

    PubMed

    Eroshenko, G A; Kutyrev, V V; Fadeeva, A V; Shavina, N Iu; Stepanov, A V

    2008-01-01

    Prevalence of vcs genes coding the type III secretion system (T3SS) in cholera vibrios of different serogroups isolated in Russia and neighboring countries was studied for the first time. Virulent strains of O1 and O139 serogroups as well as toxigenic Vibrio cholerae strains of other serogroups contained no T3SS genes. Unlike mentioned strains, 29.2% of atoxigenic non O1/non O139 cholera vibrios isolated from patients in Russia and neighboring countries contained the T3SS genes cluster, which might contribute to the pathogenic properties of these strains.

  8. Immunosuppression in murine malaria. I. Response to type III pneumococcal polysaccharide.

    PubMed Central

    McBride, J S; Micklem, H S; Ure, J M

    1977-01-01

    Acute Plasmodium yoelii yoelii and chronic Plasmodium berghei malaria infections of CBA mice were accompanied by a reduced capacity to give an antibody response to type III pneumococcal polysaccharide (SIII). The depression of response initiated by acute malaria persisted for several weeks after recovery from clinical infection. During chronic infection, and at the peak of acute parasitaemia, virtually no response to SIII was detected. A substance which crossreacted serologically with SIII was found in blood cells of infected mice. The results suggest that antigen-specific, as well as non-specific, factors may contribute to the depression of the response to this antigen. PMID:67996

  9. Unitarity constraints for Yukawa couplings in the two-Higgs-doublet model type III

    NASA Astrophysics Data System (ADS)

    Castillo, Andrés; Diaz, Rodolfo A.; Morales, Jhon

    2014-06-01

    Unitarity constraints for Yukawa couplings are considered in the Two-Higgs-Doublet Model type III, by using a general expansion in partial waves for fermionic scattering processes. Constraints over general Flavor Changing Neutral Currents are found from that systematic, wherein such bounds compete with those coming from Lagrangian perturbativity requirement but are weaker than those imposed from phenomenological processes and precision tests. Nevertheless, for bounds based on unitarity, the number of assumptions is the lowest among phenomenological and theoretical limits. Indeed, these new theoretical constraints are independent of scalar masses or mixing angles for this extended Higgs sector, making them less model dependent.

  10. Anisotropic Bianchi type-III model in Palatini f (R) gravity

    NASA Astrophysics Data System (ADS)

    Banik, Debika Kangsha; Banik, Sebika Kangsha; Bhuyan, Kalyan

    2017-03-01

    We derive exact solutions for anisotropic Bianchi type-III cosmological model in the Palatini formalism of f (R) gravity using Dynamical System Approach. For the f (R) of the form f(R) =R-β /Rn and f(R) =R+α Rm , we have found the fixed points describing the radiation-dominated, matter dominated and de Sitter evolution periods. Fixed points have also been found which have non-vanishing shear playing a very significant role in describing the anisotropy present in the early universe. In addition, we have also found that the spatial curvature affect isotropisation of this cosmological model.

  11. Type III Klippel-Feil syndrome: case report and review of associated craniofacial anomalies.

    PubMed

    Naikmasur, Venkatesh G; Sattur, Atul P; Kirty, R N; Thakur, Arpita Rai

    2011-07-01

    Klippel-Feil syndrome (KFS) is a complex syndrome of osseous and visceral anomalies that include the classical clinical triad of short neck, limitation of head and neck movements and low posterior hairline. It may also be associated with anomalies of the genitourinary, musculoskeletal, neurologic and cardiac systems. We report a case of type III KFS with associated rib anomalies such as cervical rib, fusion and bifid ribs, scoliosis and fused crossed renal ectopia. The aim of this paper was to summarize all craniofacial anomalies that occur in association with KFS, so that clinicians would be aware of them during diagnosis and treatment planning.

  12. Developmental defects in a Caenorhabditis elegans model for type III galactosemia.

    PubMed

    Brokate-Llanos, Ana M; Monje, José M; Murdoch, Piedad Del Socorro; Muñoz, Manuel J

    2014-12-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosylation process. We also observed that gale-1 mutants are hypersensitive to galactose as well as to infections. Interestingly, we found interactions between gale-1 and the unfolded protein response.

  13. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    SciTech Connect

    Bisceglia, L.; Totaro, A.; Melchionda, S.

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  14. Molecular tectonics: heterometallic (Ir,Cu) grid-type coordination networks based on cyclometallated Ir(III) chiral metallatectons.

    PubMed

    Xu, Chaojie; Guenet, Aurélie; Kyritsakas, Nathalie; Planeix, Jean-Marc; Hosseini, Mir Wais

    2015-10-11

    A chiral-at-metal Ir(III) organometallic metallatecton was synthesised as a racemic mixture and as enantiopure complexes and combined with Cu(II) to afford a heterobimetallic (Ir,Cu) grid-type 2D coordination network.

  15. Hyperleptinemia in children with autosomal recessive spinal muscular atrophy type I-III

    PubMed Central

    Kölbel, Heike; Hauffa, Berthold P.; Wudy, Stefan A.; Bouikidis, Anastasios; Della Marina, Adela; Schara, Ulrike

    2017-01-01

    Background Autosomal-recessive proximal spinal muscular atrophies (SMA) are disorders characterized by a ubiquitous deficiency of the survival of motor neuron protein that leads to a multisystemic disorder, which mostly affects alpha motor neurons. Disease progression is clinically associated with failure to thrive or weight loss, mainly caused by chewing and swallowing difficulties. Although pancreatic involvement has been described in animal models, systematic endocrinological evaluation of the energy metabolism in humans is lacking. Methods In 43 patients with SMA type I-III (8 type I; 22 type II; 13 type III), aged 0.6–21.8 years, auxological parameters, pubertal stage, motor function (Motor Function Measurement 32 –MFM32) as well as levels of leptin, insulin glucose, hemoglobin A1c, Homeostasis Model Assessment index and an urinary steroid profile were determined. Results Hyperleptinemia was found in 15/35 (43%) of our patients; 9/15 (60%) of the hyperleptinemic patients were underweight, whereas 1/15 (7%) was obese. Hyperleptinemia was associated with SMA type (p = 0.018). There was a significant association with decreased motor function (MFM32 total score in hyperleptinemia 28.5%, in normoleptinemia 54.7% p = 0.008, OR 0.969; 95%-CI: 0.946–0.992). In addition, a higher occurrence of hirsutism, premature pubarche and a higher variability of the urinary steroid pattern were found. Conclusion Hyperleptinemia is highly prevalent in underweight children with SMA and is associated with disease severity and decreased motor function. Neuronal degradation of hypothalamic cells or an increase in fat content by muscle remodeling could be the cause of hyperleptinemia. PMID:28278160

  16. Type III and type IV hypersensitivity reactions due to mitomycin C.

    PubMed

    Kunkeler, L; Nieboer, C; Bruynzeel, D P

    2000-02-01

    A 71-year-old man developed an exfoliative dermatitis of the palms of the hands and soles of the feet, and a generalized itch, during treatment with intravesical instillations of mitomycin C for an undifferentiated carcinoma of the bladder. Patch tests with mitomycin C 0.03%, 0.1% and 0.3% aq. were positive. Because of the serious consequences of this finding, the patient was retested with mitomycin C in pet. (same concentrations), a more stable preparation. This showed clear positive reactions. During this last series of patch tests, he developed palpable purpura on the legs. We postulated that this reaction was an immune-complex-mediated reaction, caused by the 2nd series of patch tests with mitomycin C. To prove this, we performed histopathological and immunofluorescence investigations, and these showed the reaction to be consistent with Henoch-Schonlein-type purpura. We therefore conclude that this patient developed systemic reactions to mitomycin C, characterized by an eczematous dermatitis as well as purpuric reactions. The intravesical installations with mitomycin C have been stopped. The patient's skin problems (the purpura as well as the eczema) have completely resolved and have not recurred.

  17. Diverse evolutionary mechanisms shape the type III effector virulence factor repertoire in the plant pathogen Pseudomonas syringae.

    PubMed Central

    Rohmer, Laurence; Guttman, David S; Dangl, Jeffery L

    2004-01-01

    Many gram-negative pathogenic bacteria directly translocate effector proteins into eukaryotic host cells via type III delivery systems. Type III effector proteins are determinants of virulence on susceptible plant hosts; they are also the proteins that trigger specific disease resistance in resistant plant hosts. Evolution of type III effectors is dominated by competing forces: the likely requirement for conservation of virulence function, the avoidance of host defenses, and possible adaptation to new hosts. To understand the evolutionary history of type III effectors in Pseudomonas syringae, we searched for homologs to 44 known or candidate P. syringae type III effectors and two effector chaperones. We examined 24 gene families for distribution among bacterial species, amino acid sequence diversity, and features indicative of horizontal transfer. We assessed the role of diversifying and purifying selection in the evolution of these gene families. While some P. syringae type III effectors were acquired recently, others have evolved predominantly by descent. The majority of codons in most of these genes were subjected to purifying selection, suggesting selective pressure to maintain presumed virulence function. However, members of 7 families had domains subject to diversifying selection. PMID:15280247

  18. Plant flavonoids target Pseudomonas syringae pv. tomato DC3000 flagella and type III secretion system.

    PubMed

    Vargas, Paola; Farias, Gabriela A; Nogales, Joaquina; Prada, Harold; Carvajal, Vivian; Barón, Matilde; Rivilla, Rafael; Martín, Marta; Olmedilla, Adela; Gallegos, María-Trinidad

    2013-12-01

    Flavonoids are among the most abundant plant secondary metabolites involved in plant protection against pathogens, but micro-organisms have developed resistance mechanisms to those compounds. We previously demonstrated that the MexAB-OprM efflux pump mediates resistance of Pseudomonas syringae pv. tomato (Pto) DC3000 to flavonoids, facilitating its survival and the colonization of the host. Here, we have shown that tomato plants respond to Pto infection producing flavonoids and other phenolic compounds. The effects of flavonoids on key traits of this model plant-pathogen bacterium have also been investigated observing that they reduce Pto swimming and swarming because of the loss of flagella, and also inhibited the expression and assembly of a functional type III secretion system. Those effects were more severe in a mutant lacking the MexAB-OprM pump. Our results suggest that flavonoids inhibit the function of the GacS/GacA two-component system, causing a depletion of rsmY RNA, therefore affecting the synthesis of two important virulence factors in Pto DC3000, flagella and the type III secretion system. These data provide new insights into the flavonoid role in the molecular dialog between host and pathogen.

  19. Oleanolic Acid Induces the Type III Secretion System of Ralstonia solanacearum

    PubMed Central

    Wu, Dousheng; Ding, Wei; Zhang, Yong; Liu, Xuejiao; Yang, Liang

    2015-01-01

    Ralstonia solanacearum, the causal agent of bacterial wilt, can naturally infect a wide range of host plants. The type III secretion system (T3SS) is a major virulence determinant in this bacterium. Studies have shown that plant-derived compounds are able to inhibit or induce the T3SS in some plant pathogenic bacteria, though no specific T3SS inhibitor or inducer has yet been identified in R. solanacearum. In this study, a total of 50 different compounds were screened and almost half of them (22 of 50) significantly inhibited or induced the T3SS expression of R. solanacearum. Based on the strong induction activity on T3SS, the T3SS inducer oleanolic acid (OA) was chosen for further study. We found that OA induced the expression of T3SS through the HrpG-HrpB pathway. Some type III effector genes were induced in T3SS inducing medium supplemented with OA. In addition, OA targeted only the T3SS and did not affect other virulence determinants. Finally, we observed that induction of T3SS by OA accelerated disease progress on tobacco. Overall our results suggest that plant-derived compounds are an abundant source of R. solanacearum T3SS regulators, which could prove useful as tools to interrogate the regulation of this key virulence pathway. PMID:26732647

  20. Surgical treatment of intraarticular calcaneous fractures of sanders' types II and III. Systematic review

    PubMed Central

    Pelliccioni, Adriano Augusto Antoniazzi; Bittar, Cíntia Kelly; Zabeu, José Luis Amim

    2012-01-01

    Objective This paper aims to identify the most effective surgical technique for intraarticular calcaneal fractures of Sanders' types II and III. Methods Systematic review of comparative randomized clinical trials on surgical treatment of the intraarticular fractures of the calcaneus (Sanders types II and III) that used the questionnaire of the American Orthopaedic Foot and Ankle Society. The studies were identified and retrieved in the following databases - LILACS, MEDLINE/PubMed, Cochrane Library, SciELO, EMBASE, Science Direct, Scopus, Journals@Ovid, ISI Web of Knowledge, Evidence Based Medicine, besides consulting the references of studies accessed. The keywords used Boolean logic (AND and OR): "calcaneus fracture, calcaneous, calcaneal; surgical treatment, management; open reduction, minimally invasive, percutaneous reduction; internal fixation, external fixation. Results We identified only three randomized comparative trials. Each study compared a different technique (external fixation, percutaneous fixation with Kirchner wires and cannulated screws fixation) to the open reduction with internal fixation using plate and screws (considered the standard technique). Conclusion Comparing the series, percutaneous fixation using Kirschner wires presented the best results, however, evidence is insufficient to assert superiority of this treatment in comparison with other surgical techniques. PMID:24453579

  1. Degradation of phage transcripts by CRISPR-associated RNases enables type III CRISPR-Cas immunity

    PubMed Central

    Jiang, Wenyan; Samai, Poulami; Marraffini, Luciano A.

    2016-01-01

    SUMMARY Type III-A CRISPR-Cas systems defend prokaryotes against viral infection using CRISPR RNA (crRNA)-guided nucleases that perform co-transcriptional cleavage of the viral target DNA and its transcripts. Whereas DNA cleavage is essential for immunity, the function of RNA targeting is unknown. Here we show that transcription-dependent targeting results in a sharp increase of viral genomes in the host cell when the target is located in a late-expressed phage gene. In this targeting condition, mutations in the active sites of the type III-A RNases Csm3 and Csm6 lead to the accumulation of the target phage mRNA and abrogate immunity. Csm6 is also required to provide defense in the presence of mutated phage targets, when DNA cleavage efficiency is reduced. Our results show that the degradation of phage transcripts by CRISPR-associated RNases ensures robust immunity in situations that lead to a slow clearance of the target DNA. PMID:26853474

  2. The insect endosymbiont Sodalis glossinidius utilizes a type III secretion system for cell invasion

    PubMed Central

    Dale, Colin; Young, Simon A.; Haydon, Daniel T.; Welburn, Susan C.

    2001-01-01

    Sodalis glossinidius is a maternally transmitted secondary endosymbiont residing intracellularly in tissues of the tsetse flies, Glossina spp. In this study, we have used Tn5 mutagenesis and a negative selection procedure to derive a S. glossinidius mutant that is incapable of invading insect cells in vitro and is aposymbiotic when microinjected into tsetse. This mutant strain harbors Tn5 integrated into a chromosomal gene sharing high sequence identity with a type III secretion system invasion gene (invC) previously identified in Salmonella enterica. With the use of degenerate PCR, we have amplified a further six Sodalis inv/spa genes sharing high sequence identity with type III secretion system genes encoded by Salmonella pathogenicity island 1. Phylogenetic reconstructions based on the inv/spa genes of Sodalis and other members of the family Enterobacteriaceae have consistently identified a well-supported clade containing Sodalis and the enteric pathogens Shigella and Salmonella. These results suggest that Sodalis may have evolved from an ancestor with a parasitic intracellular lifestyle, possibly a latter-day entomopathogen. These observations lend credence to a hypothesis suggesting that vertically transmitted mutualistic endosymbionts evolve from horizontally transmitted parasites through a parasitism–mutualism continuum. PMID:11172045

  3. Immunoglobulin G and M composition of naturally occurring antibody to type III group B streptococci.

    PubMed Central

    Anthony, B F; Concepcion, N F; Wass, C A; Heiner, D C

    1984-01-01

    Human sera were examined by an enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgM antibodies to purified type III polysaccharide of group B streptococci. The antigen-binding capacity of a reference human serum was determined by a radioimmunoassay, and the total antibody content was determined by quantitative precipitation. The serum was then depleted of IgM and IgA to determine the effect on the antigen-binding capacity. Duplicate samples of 81 sera were tested by the enzyme-linked assay in comparison with reference standard serum. Although levels of IgG antibody were greater in subjects who had carried type III streptococci during pregnancy, concentrations of this antibody were generally low. Only 2 of 28 sera (7%) from parturient subjects and 7 of 25 sera (28%) from adult volunteers contained greater than or equal to 1 microgram of IgG antibody per ml; the mean levels were 0.13 and 0.53 micrograms/ml, respectively. In contrast, 19 of 28 maternal sera (68%) and 22 of 25 (88%) volunteer adult sera contained greater than or equal to 1 microgram/ml of IgM antibody; mean levels were 1.33 and 1.54 micrograms/ml, respectively. The cord serum levels of IgG antibody were almost identical to maternal serum concentrations, whereas IgM antibody was essentially undetected. Images PMID:6384050

  4. Pore-forming Activity of the Escherichia coli Type III Secretion System Protein EspD*

    PubMed Central

    Chatterjee, Abhishek; Caballero-Franco, Celia; Bakker, Dannika; Totten, Stephanie; Jardim, Armando

    2015-01-01

    Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280–320-kDa oligomeric structure consisting of ∼6–7 subunits. PMID:26324713

  5. Study of Flare Energy Release Using Events with Numerous Type III-like Bursts in Microwaves

    NASA Astrophysics Data System (ADS)

    Meshalkina, N. S.; Altyntsev, A. T.; Zhdanov, D. A.; Lesovoi, S. V.; Kochanov, A. A.; Yan, Y. H.; Tan, C. M.

    2012-10-01

    The analysis of narrowband drifting of type III-like structures in radio bursts dynamic spectra allows one to obtain unique information about the primary energy release mechanisms in solar flares. The SSRT (Siberian Solar Radio Telescope) spatially resolved images and its high spectral and temporal resolution allow for direct determination not only of the source positions but also of the exciter velocities along the flare loop. Practically, such measurements are possible during some special time intervals when SSRT is observing the flare region in two high-order fringes near 5.7 GHz; thus, two 1D brightness distributions are recorded simultaneously at two frequency bands. The analysis of type III-like bursts recorded during the flare 14 April 2002 is presented. Using multiwavelength radio observations recorded by the SSRT, the Huairou Solar Broadband Radio Spectrometer (SBRS), the Nobeyama Radio Polarimeters (NoRP), and the Radio Solar Telescope Network (RSTN), we study an event with series of several tens of drifting microwave pulses with drift rates in the range from -7 to 13 GHz s-1. The sources of the fast-drifting bursts were located near the top of a flare loop in a volume of a few Mm in size. The slow drift of the exciters along the flare loop suggests a high pitch anisotropy of the emitting electrons.

  6. Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production

    PubMed Central

    Hashimoto, Shin; Yamamoto, Soh; Ogasawara, Noriko; Sato, Toyotaka; Yamamoto, Keisuke; Katoh, Hiroshi; Kubota, Toru; Shiraishi, Tsukasa; Kojima, Takashi; Himi, Tetsuo; Tsutsumi, Hiroyuki; Yokota, Shin-ichi

    2016-01-01

    Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection. PMID:27560627

  7. Nonsurgical management of a dilacerated maxillary lateral incisor with type III dens invaginatus: a case report.

    PubMed

    Gound, Tom G; Maixner, David

    2004-06-01

    Type III dens invaginatus is a developmental anomaly characterized by an enamel-lined channel that originates on the coronal surface and passes apically through part or all of the root and exits into the periodontal ligament. In this case report, a 13-yr-old male had a Type III dens that exited at the midroot level of tooth #7. At that same level, the root dilacerated severely to the mesial, and a periradicular radiolucency was present on the distal. A 12-mm periodontal defect was present on tooth #6 and a sinus tract was present. All maxillary anterior teeth responded normally to pulp vitality testing, and no other abnormal probing depths were present. The channel opening in the crown was located, and the channel was negotiated, enlarged, and filled with calcium hydroxide. Thirteen weeks later, the probing was normal and the canal was obturated with gutta-percha and restored. Two- and 6-yr recalls showed complete healing of the bony defects and continued normal responses to vitality testing.

  8. A type III polyketide synthase from Wachendorfia thyrsiflora and its role in diarylheptanoid and phenylphenalenone biosynthesis.

    PubMed

    Brand, S; Hölscher, D; Schierhorn, A; Svatos, A; Schröder, J; Schneider, B

    2006-07-01

    Chalcone synthase (CHS) related type III plant polyketide synthases (PKSs) are likely to be involved in the biosynthesis of diarylheptanoids (e.g. curcumin and polycyclic phenylphenalenones), but no such activity has been reported. Root cultures from Wachendorfia thyrsiflora (Haemodoraceae) are a suitable source to search for such enzymes because they synthesize large amounts of phenylphenalenones, but no other products that are known to require CHSs or related enzymes (e.g. flavonoids or stilbenes). A homology-based RT-PCR strategy led to the identification of cDNAs for a type III PKS sharing only approximately 60% identity with typical CHSs. It was named WtPKS1 (W. thyrsiflora polyketide synthase 1). The purified recombinant protein accepted a large variety of aromatic and aliphatic starter CoA esters, including phenylpropionyl- and side-chain unsaturated phenylpropanoid-CoAs. The simplest model for the initial reaction in diarylheptanoid biosynthesis predicts a phenylpropanoid-CoA as starter and a single condensation reaction to a diketide. Benzalacetones, the expected release products, were observed only with unsaturated phenylpropanoid-CoAs, and the best results were obtained with 4-coumaroyl-CoA (80% of the products). With all other substrates, WtPKS1 performed two condensation reactions and released pyrones. We propose that WtPKS1 catalyses the first step in diarylheptanoid biosynthesis and that the observed pyrones are derailment products in the absence of downstream processing proteins.

  9. Structure of Salmonella FlhE, conserved member of a flagellar Type III secretion operon

    DOE PAGES

    Lee, Jaemin; Monzingo, Arthur F.; Keatinge-Clay, Adrian T.; ...

    2014-12-26

    In this paper, the bacterial flagellum is assembled by a multicomponent transport apparatus categorized as a type III secretion system. The secretion of proteins that assemble into the flagellum is driven by the proton motive force. The periplasmic protein FlhE is a member of the flhBAE operon in the majority of bacteria where FlhE is found. FlhA and FlhB are established components of the flagellar type III secretion system. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death, indicating that FlhE regulates an important aspect of proper flagellar biosynthesis. Wemore » isolated FlhE from the periplasm of Salmonella and solved its structure to 1.5 Å resolution. The structure reveals a β-sandwich fold, with no close structural homologs. Finally, possible roles of FlhE, including that of a chaperone, are discussed.« less

  10. Type III Guyon Syndrome in 'B Boy' Break-Dancer: A Case Report

    PubMed Central

    Hu, Soo-young; Choi, Jin-gyu

    2015-01-01

    Although the musculoskeletal injuries associated with break-dancing which is gaining more popularity among adolescent and young people has been reported, the report regarding a peripheral nerve injury associated with breakdance is scarce. We report a rare case of a young amateur break-dancer, 'b-boy' who suffered from a painful paresthesia in his left hand, later diagnosed as type III Guyon's canal syndrome. A 23-year-old, right handed college man presented with a tenderness over the left hypothenar eminence and painful paresthesia over the ring and little fingers of 3 months duration. He trained himself as an amateur 'b boy' break-dancer for the last 10 months. Conservative management under the diagnosis of wrist sprain before presentation did not improve his hand pain. An magnetic resonance imaging and electrodiagnostic study revealed that painful paresthesia was caused by type III Guyon's canal syndrome, and 4 weeks of corticosteroid treatment was given with resolution of pain and paresthesia. PMID:27169091

  11. In Situ Molecular Architecture of the Salmonella Type III Secretion Machine.

    PubMed

    Hu, Bo; Lara-Tejero, Maria; Kong, Qingke; Galán, Jorge E; Liu, Jun

    2017-03-09

    Type III protein secretion systems have specifically evolved to deliver bacterially encoded proteins into target eukaryotic cells. The core elements of this multi-protein machine are the envelope-associated needle complex, the inner membrane export apparatus, and a large cytoplasmic sorting platform. Here, we report a high-resolution in situ structure of the Salmonella Typhimurium type III secretion machine obtained by high-throughput cryo-electron tomography and sub-tomogram averaging. Through molecular modeling and comparative analysis of machines assembled with protein-tagged components or from different deletion mutants, we determined the molecular architecture of the secretion machine in situ and localized its structural components. We also show that docking of the sorting platform results in significant conformational changes in the needle complex to provide the symmetry adaptation required for the assembly of the entire secretion machine. These studies provide major insight into the structure and assembly of a broadly distributed protein secretion machine.

  12. Computational prediction of type III and IV secreted effectors in Gram-negative bacteria

    SciTech Connect

    McDermott, Jason E.; Corrigan, Abigail L.; Peterson, Elena S.; Oehmen, Christopher S.; Niemann, George; Cambronne, Eric; Sharp, Danna; Adkins, Joshua N.; Samudrala, Ram; Heffron, Fred

    2011-01-01

    In this review, we provide an overview of the methods employed by four recent papers that described novel methods for computational prediction of secreted effectors from type III and IV secretion systems in Gram-negative bacteria. The results of the studies in terms of performance at accurately predicting secreted effectors and similarities found between secretion signals that may reflect biologically relevant features for recognition. We discuss the web-based tools for secreted effector prediction described in these studies and announce the availability of our tool, the SIEVEserver (http://www.biopilot.org). Finally, we assess the accuracy of the three type III effector prediction methods on a small set of proteins not known prior to the development of these tools that we have recently discovered and validated using both experimental and computational approaches. Our comparison shows that all methods use similar approaches and, in general arrive at similar conclusions. We discuss the possibility of an order-dependent motif in the secretion signal, which was a point of disagreement in the studies. Our results show that there may be classes of effectors in which the signal has a loosely defined motif, and others in which secretion is dependent only on compositional biases. Computational prediction of secreted effectors from protein sequences represents an important step toward better understanding the interaction between pathogens and hosts.

  13. Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris.

    PubMed

    Jiang, Guo-Feng; Jiang, Bo-Le; Yang, Mei; Liu, San; Liu, Jiao; Liang, Xiao-Xia; Bai, Xian-Fang; Tang, Dong-Jie; Lu, Guang-Tao; He, Yong-Qiang; Yu, Di-Qiu; Tang, Ji-Liang

    2013-01-01

    It is well known that the type III secretion system (T3SS) and type III (T3) effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc) is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2) which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2) is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME). Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.

  14. Role of NSO compounds during primary cracking of a Type II kerogen and a Type III lignite

    USGS Publications Warehouse

    Behar, F.; Lorant, F.; Lewan, M.

    2008-01-01

    The aim of this work is to follow the generation of NSO compounds during the artificial maturation of an immature Type II kerogen and a Type III lignite in order to determine the different sources of the petroleum potential during primary cracking. Experiments were carried out in closed system pyrolysis in the temperature range from 225 to 350 ??C. Two types of NSOs were recovered: one is soluble in n-pentane and the second in dichloromethane. A kinetic scheme was optimised including both kerogen and NSO cracking. It was validated by complementary experiments carried out on isolated asphaltenes generated from the Type II kerogen and on the total n-pentane and DCM extracts generated from the Type III lignite. Results show that kerogen and lignite first decompose into DCM NSOs with minor generation of hydrocarbons. Then, the main source of petroleum potential originates from secondary cracking of both DCM and n-pentane NSOs through successive decomposition reactions. These results confirm the model proposed by Tissot [Tissot, B., 1969. Premie??res donne??es sur les me??canismes et la cine??tique de la formation du pe??trole dans les bassins se??dimentaires. Simulation d'un sche??ma re??actionnel sur ordinateur. Oil and Gas Science and Technology 24, 470-501] in which the main source of hydrocarbons is not the insoluble organic matter, but the NSO fraction. As secondary cracking of the NSOs largely overlaps that of the kerogen, it was demonstrated that bulk kinetics in open system is a result of both kerogen and NSO cracking. Thus, another kinetic scheme for primary cracking in open system was built as a combination of kerogen and NSO cracking. This new kinetic scheme accounts for both the rate and amounts of hydrocarbons generated in a closed pyrolysis system. Thus, the concept of successive steps for hydrocarbon generation is valid for the two types of pyrolysis system and, for the first time, a common kinetic scheme is available for extrapolating results to natural

  15. Design and synthesis of type-III mimetics of ω-conotoxin GVIA

    NASA Astrophysics Data System (ADS)

    Baell, Jonathan B.; Forsyth, Stewart A.; Gable, Robert W.; Norton, Raymond S.; Mulder, Roger J.

    2001-12-01

    Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. Our approach involves interactive design of conformationally defined molecular scaffolds that project certain functional groups in a way that mimics the projection of important binding residues as determined in the parent structure. These design principles are discussed and applied to the structurally defined polypeptide, ω-conotoxin GVIA, which blocks voltage-gated, neuronal N-type calcium channels. These ion channels represent therapeutic targets for the development of new analgesics that can treat chronic pain. It is shown how a discontinuous, 3-residue pharmacophore of GVIA can be mimicked by different molecular scaffolds. It is illustrated how such 1st generation leads must necessarily be weak and that optimisability must therefore be built-in during the design process.

  16. SYNTHESIS OF TYPE III PNEUMOCOCCAL POLYSACCHARIDE BY SUSPENSIONS OF RESTING CELLS

    PubMed Central

    Bernheimer, Alan W.

    1953-01-01

    The capsular polysaccharide (SIII) of type III pneumococci was removed enzymatically, and the cells thus deprived of preformed SIII were washed and examined for capacity to synthesize SIII anew. The washed, decapsulated cocci lost their capacity to be agglutinated in type-specific antiserum but again became agglutinable and formed readily measurable amounts of SIII, after suspension in a solution containing only glucose and salts. Maximal SIII synthesis required the presence of glucose, magnesium, potassium and phosphate ions, and oxygen. Other fermentable sugars could be substituted for glucose but then the yield of SIII was reduced. Synthesis of SIII occurred anaerobically but was increased four- to fivefold by oxygenation of the suspension. The effects of pH and of enzyme poisons on the capacity of the cocci to form SIII are described. PMID:13052821

  17. Synthesis and structures of a pincer-type rhodium(iii) complex: reactivity toward biomolecules.

    PubMed

    Milutinović, Milan M; Bogojeski, Jovana V; Klisurić, Olivera; Scheurer, Andreas; Elmroth, Sofi K C; Bugarčić, Živadin D

    2016-10-04

    A novel rhodium(iii) complex [Rh(III)(H2L(tBu))Cl3] (1) (H2L(tBu) = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine) containing a pincer type, tridentate nitrogen-donor chelate system was synthesized. Single crystal X-ray structure analysis revealed that 1 crystallizes in the orthorhombic space group Pbcn with a = 20.7982(6), b = 10.8952(4), c = 10.9832(4) Å, V = 2488.80(15) Å(3), and eight molecules in the unit cell. The rhodium center in the complex [Rh(III)(H2L(tBu))Cl3] (1) is coordinated in a slightly distorted octahedral geometry by the tridentate N,N,N-donor and three chloro ligands, adopting a mer arrangement with an essentially planar ligand skeleton. Due to the tridentate coordination of the N,N,N-donor, the central nitrogen atom N1 is located closer to the Rh(III) center. The reactivity of the synthesized complex toward small biomolecules (l-methionine (l-Met), guanosine-5'-monophosphate (5'-GMP), l-histidine (l-His) and glutathione (GSH)) and to a series of duplex DNAs and RNA was investigated. The order of reactivity of the studied small biomolecules is: 5'-GMP > GSH > l-Met > l-His. Duplex RNA reacts faster with the [Rh(III)(H2L(tBu))Cl3] complex than duplex DNA, while shorter duplex DNA (15mer GG) reacts faster compared with 22mer GG duplex DNA. In addition, a higher reactivity is achieved with a DNA duplex with a centrally located GG-sequence than with a 22GTG duplex DNA, in which the GG-sequence is separated by a T base. Furthermore, the interaction of this metal complex 1 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was examined by absorption (UV-Vis) and emission spectral studies (EthBr displacement studies). Overall, the studied complex exhibited good DNA and BSA interaction ability.

  18. Piericidin A1 Blocks Yersinia Ysc Type III Secretion System Needle Assembly

    PubMed Central

    Morgan, Jessica M.; Duncan, Miles C.; Johnson, Kevin S.; Diepold, Andreas; Lam, Hanh; Dupzyk, Allison J.; Martin, Lexi R.; Wong, Weng Ruh; Linington, Roger G.

    2017-01-01

    ABSTRACT The type III secretion system (T3SS) is a bacterial virulence factor expressed by dozens of Gram-negative pathogens but largely absent from commensals. The T3SS is an attractive target for antimicrobial agents that may disarm pathogenic bacteria while leaving commensal populations intact. We previously identified piericidin A1 as an inhibitor of the Ysc T3SS in Yersinia pseudotuberculosis. Piericidins were first discovered as inhibitors of complex I of the electron transport chain in mitochondria and some bacteria. However, we found that piericidin A1 did not alter Yersinia membrane potential or inhibit flagellar motility powered by the proton motive force, indicating that the piericidin mode of action against Yersinia type III secretion is independent of complex I. Instead, piericidin A1 reduced the number of T3SS needle complexes visible by fluorescence microscopy at the bacterial surface, preventing T3SS translocator and effector protein secretion. Furthermore, piericidin A1 decreased the abundance of higher-order YscF needle subunit complexes, suggesting that piericidin A1 blocks YscF needle assembly. While expression of T3SS components in Yersinia are positively regulated by active type III secretion, the block in secretion by piericidin A1 was not accompanied by a decrease in T3SS gene expression, indicating that piericidin A1 may target a T3SS regulatory circuit. However, piericidin A1 still inhibited effector protein secretion in the absence of the T3SS regulator YopK, YopD, or YopN. Surprisingly, while piericidin A1 also inhibited the Y. enterocolitica Ysc T3SS, it did not inhibit the SPI-1 family Ysa T3SS in Y. enterocolitica or the Ysc family T3SS in Pseudomonas aeruginosa. Together, these data indicate that piericidin A1 specifically inhibits Yersinia Ysc T3SS needle assembly. IMPORTANCE The bacterial type III secretion system (T3SS) is widely used by both human and animal pathogens to cause disease yet remains incompletely understood

  19. Genetic heterogeneity in cystinuria: the SLC3A1 gene is linked to type I but not to type III cystinuria.

    PubMed Central

    Calonge, M J; Volpini, V; Bisceglia, L; Rousaud, F; de Sanctis, L; Beccia, E; Zelante, L; Testar, X; Zorzano, A; Estivill, X

    1995-01-01

    Cystinuria is an autosomal recessive amino-aciduria where three urinary phenotypes have been described (I, II, and III). An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. To assess whether mutations in SLC3A1 are involved in different cystinuria phenotypes, linkage with this gene and its nearest marker (D2S119) was analyzed in 22 families with type I and/or type III cystinuria. Linkage with heterogeneity was proved (alpha = 0.45; P < 0.008). Type I/I families showed homogeneous linkage to SLC3A1 (Zmax > 3.0 at theta = 0.00; alpha = 1), whereas types I/III and III/III were not linked. Our data suggest that type I cystinuria is due to mutations in the SLC3A1 gene, whereas another locus is responsible for type III. This result establishes genetic heterogeneity for cystinuria, classically considered as a multiallelic monogenic disease. Images Fig. 2 Fig. 3 PMID:7568194

  20. The evidence for the role of transforming growth factor-beta in the formation of abnormal scarring.

    PubMed

    Chalmers, Richard L

    2011-06-01

    The complex biological and physiological mechanisms that result in poor quality scarring are still not fully understood. This review looks at current evidence of the role of transforming growth factor-beta (TGFβ) in this pathological process.

  1. Role of CD14 and TLR4 in type I, type III collagen expression, synthesis and secretion in LPS-induced normal human skin fibroblasts

    PubMed Central

    Yang, Hongming; Li, Juncong; Wang, Yihe; Hu, Quan

    2015-01-01

    Objectives: The primary aim of this study was to investigate the role of CD14 and TLR4 in type I, type III collagen expression, synthesis and secretion in LPS-induced normal human skin fibroblasts. The secondary aim was to provide theoretical basis for the molecular mechanisms of scar formation induced by LPS. Methods: The normal skin fibroblasts cultured in vitro were randomly divided into four groups: 0.1 μg/mL LPS reference group, CD14 pretreatment + LPS, TLR4 pretreatment + LPS, CD14 and TLR4 pretreatment + LPS. The collagen DNA synthesis was assessed by 3H-proline incorporation method. Real-time Quantitative PCR was used to detect type I, type III collagen mRNA expression. Results: Similar results were revealed for mRNA expression levels. The immunofluorescence staining suggested that type I and type III collagen were expressed in all investigated groups and that the expression was differentially downregulated in groups B, C, D. ELISA demonstrated markedly decreased levels in secreting type I, type III collagens and hydroxyproline in groups B, C, D (P<0.05), and the lowest level was detected in group D (P<0.01). Conclusion: Pretreatment with CD14 or TLR4 alone or their combination can significantly reduce the levels of type I and type III collagen expression, synthesis and secretion, with the most notable reduction detected in case of CD14 and TLR4 combined. We could thus conclude that both CD14 and TLR4 are involved in type I and type III collagen expression, synthesis and secretion in LPS-induced skin fibroblasts. PMID:25932184

  2. A case of autoimmune urticaria accompanying autoimmune polyglandular syndrome type III associated with Hashimoto's disease, type 1 diabetes mellitus, and vitiligo.

    PubMed

    Kasznicki, Jacek; Drzewoski, Józef

    2014-01-01

    We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.

  3. STRUCTURE OF THE TYPE III PANTOTHENATE KINASE FROM Bacillus anthracis AT 2.0 Å RESOLUTION

    PubMed Central

    Nicely, Nathan I.; Parsonage, Derek; Paige, Carleitta; Newton, Gerald L.; Fahey, Robert C.; Leonardi, Roberta; Jackowski, Suzanne; Mallett, T. Conn; Claiborne, Al

    2008-01-01

    Coenzyme A (CoASH) is the major low-molecular weight thiol in Staphylococcus aureus and a number of other bacteria; the crystal structure of the S. aureus coenzyme A-disulfide reductase (CoADR), which maintains the reduced intracellular state of CoASH, has recently been reported [Mallett, T.C., Wallen, J.R., Karplus, P.A., Sakai, H., Tsukihara, T., and Claiborne, A. (2006) Biochemistry 45, 11278-11289]. In this report we demonstrate that CoASH is the major thiol in Bacillus anthracis; a bioinformatics analysis indicates that three of the four proteins responsible for the conversion of pantothenate (Pan) to CoASH in Escherichia coli are conserved in B. anthracis. In contrast, a novel type III pantothenate kinase (PanK) catalyzes the first committed step in the biosynthetic pathway in B. anthracis; unlike the E. coli type I PanK, this enzyme is not subject to feedback inhibition by CoASH. The crystal structure of B. anthracis PanK (BaPanK), solved using multiwavelength anomalous dispersion data and refined at a resolution of 2.0 Å, demonstrates that BaPanK is a new member of the Acetate and Sugar Kinase/Hsc70/Actin (ASKHA) superfamily. The Pan and ATP substrates have been modeled into the active-site cleft; in addition to providing a clear rationale for the absence of CoASH inhibition, analysis of the Pan-binding pocket has led to the development of two new structure-based motifs (the PAN and INTERFACE motifs). Our analyses also suggest that the type III PanK in the spore-forming B. anthracis plays an essential role in the novel thiol/disulfide redox biology of this category A biodefense pathogen. PMID:17323930

  4. Human T-cell lymphotropic virus type III infection of the central nervous system: a preliminary in situ analysis

    SciTech Connect

    Stoler, M.H.; Eskin, T.A.; Benn, S.; Angerer, R.C.; Angerer, L.M.

    1986-11-07

    Patients with acquired immunodeficiency syndrome (AIDS) are subject to a spectrum of central nervous system (CNS) disorders. Recent evidence implicates the human T-cell lymphotropic virus type III (HTLV-III) in the pathogenesis of some of these illnesses, although the cells infected by the virus have yet to be identified. Using in situ hybridization, the authors examined brain tissue from two patients with AIDS encephalopathy for the presence of HTLV-III RNA. In both cases, viral RNA was detected and concentrated in, though not limited to, the white matter. The CNS cells most frequently infected included macrophages, pleomorphic microglia, and multinucleated giant cells. Less frequently, cells morphologically consistent with astrocytes, oligodendroglia, and rarely neurons were also infected. The findings strengthen the association of HTLV-III with the pathogenesis of AIDS encephalopathy. In situ hybridization can be applied to routinely prepared biopsy tissue in the diagnosis of HTLV-III infection of the CNS.

  5. Asymptotic variance of flood quantile in log Pearson Type III distribution with historical information

    NASA Astrophysics Data System (ADS)

    Pilon, Paul J.; Adamowski, Kaz

    1993-03-01

    Maximum likelihood and censored sample theory are applied for flood frequency analysis purposes to the log Pearson Type III (LP3) distribution. The logarithmic likelihood functions are developed and solved in terms of fully specified floods, historical information, and parameters to be estimated. The asymptotic standard error of estimate of the T-year flood is obtained using the general equation for the variance of estimate of a function. The variances and covariances of the parameters are obtained through inversion of Fisher's information matrix. Monte Carlo studies to verify the accuracy of the derived asymptotic expression for the standard errors of the 10, 50, 100, and 500 year floods, indicate that these are accurate for both Type I and Type II censored samples, while the bias is less than 2.5%. Subsequently, the Type II censored data were subjected to a random, multiplicative error. Results indicate that historical information contributes greatly to the accuracy of estimation of the quantiles even when the error of its measurement becomes excessive.

  6. Evidence for Gently Sloping Plasma Density Profiles in the Deep Corona: Type III Observations

    NASA Astrophysics Data System (ADS)

    Lobzin, V. V.; Cairns, I. H.; Robinson, P. A.; Warmuth, A.; Mann, G.; Gorgutsa, R. V.; Fomichev, V. V.

    2010-12-01

    Type III radio bursts are produced near the local electron plasma frequency fp and near its harmonic 2fp by fast electrons ejected from the solar active regions and moving through the corona and solar wind. The coronal bursts have dynamic spectra with frequency rapidly falling with time, the typical duration being about 1-3 s. In the present paper, 37 well-defined coronal type III radio bursts (25-450 MHz) are analyzed. The results obtained substantiate an earlier statement that the dependence of the central frequency of the emission on time can be fitted to a power-law model, f(t) vprop (t - t 0)-α, where α can be as low as 1. In the case of negligible plasma acceleration and conical flow, it means that the electron number density within about 1 solar radius above the photosphere will decrease as r -2, like in the solar wind. For the data set chosen, the index α varies in the range from 0.2 to 7 or bigger, with mean and median values of 1.2 and 0.5, respectively. A surprisingly large fraction of events, 84%, have α <= 1.2. These results provide strong evidence that in the type III source regions the electron number density scales as n(r) vprop (r - r 0)-β, with minimum, mean, and median β = 2α of 0.4, 2.4, and 1.0, respectively. Hence, the typical density profiles are more gently sloping than those given by existing empirical coronal models. Several events are found with a wind-like dependence of burst frequency on time. Smaller power-law indices could result from the effects of non-conical geometry of the plasma flow tubes, deceleration of coronal plasma, and/or the curvature of the magnetic field lines. The last effect is shown to be too weak to explain such low power-law indices. A strong tendency is found for bursts from the same group to have similar power-law indices, thereby favoring the hypothesis that they are usually produced by the same source region.

  7. Evidence for Gently Sloping Plasma Density Profiles in the Deep Corona: Type III Observations

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Lobzin, V.; Robinson, P. A.; Warmuth, A.; Mann, G. J.; Gorgutsa, R.; Fomichev, V.

    2010-12-01

    Type III radio bursts are produced near the local electron plasma frequency fp and near its harmonic 2fp by fast electrons ejected from the solar active regions and moving through the corona and solar wind. These bursts have dynamic spectra with frequency rapidly falling with time, the typical duration of the coronal burst being about 1--3 seconds. In the present paper, 37 well-defined coronal type III radio bursts (25--450 MHz) are analyzed. It is found that the dependence of the central frequency of the emission on time can be fitted to a power-law model, f(t) ∝ (t-t0)-α . The index α varies in the range 0.2 to ∞ , with mean and median values of 1.2 and 0.5, respectively. A surprisingly large fraction of events, 84%, has α ≤1.2. Assuming a constant speed of the electron beam, these results provide strong evidence that in the type III source regions within about 1 solar radius above the photosphere the electron number density scales as n(r) ∝ (r-r0)-β , with minimum, mean, and median β =2α of 0.4, 2.4, and 1.0, respectively. Hence, the typical density profiles are more gently sloping than could be expected from the existing empirical coronal models. In the case of negligible plasma acceleration and conical flow, from conservation of the number of electrons it follows that the electron number density will decrease as r-2 with α =1, like in the solar wind. Several events are found with such a wind-like dependence of burst frequency on time. Smaller power-law indices could result from the effects of non-conical geometry of the plasma flow tubes, deceleration of coronal plasma, and/or the curvature of the magnetic field lines. The effects of curvature of the magnetic field lines are shown to be too weak to explain such low power-law indices. A strong tendency is found for bursts from the same group to have similar power-law indices, thereby favoring the hypothesis that they are usually produced by the same source region.

  8. Identification of novel type III secretion effectors in Xanthomonas oryzae pv. oryzae.

    PubMed

    Furutani, Ayako; Takaoka, Minako; Sanada, Harumi; Noguchi, Yukari; Oku, Takashi; Tsuno, Kazunori; Ochiai, Hirokazu; Tsuge, Seiji

    2009-01-01

    Many gram-negative bacteria secrete so-called effector proteins via a type III secretion (T3S) system. Through genome screening for genes encoding potential T3S effectors, 60 candidates were selected from rice pathogen Xanthomonas oryzae pv. oryzae MAFF311018 using these criteria: i) homologs of known T3S effectors in plant-pathogenic bacteria, ii) genes with expression regulated by hrp regulatory protein HrpX, or iii) proteins with N-terminal amino acid patterns associated with T3S substrates of Pseudomonas syringae. Of effector candidates tested with the Bordetella pertussis calmodulin-dependent adenylate cyclase reporter for translocation into plant cells, 16 proteins were translocated in a T3S system-dependent manner. Of these 16 proteins, nine were homologs of known effectors in other plant-pathogenic bacteria and seven were not. Most of the effectors were widely conserved in Xanthomonas spp.; however, some were specific to X. oryzae. Interestingly, all these effectors were expressed in an HrpX-dependent manner, suggesting coregulation of effectors and the T3S system. In X. campestris pv. vesicatoria, HpaB and HpaC (HpaP in X. oryzae pv. oryzae) have a central role in recruiting T3S substrates to the secretion apparatus. Secretion of all but one effector was reduced in both HpaB() and HpaP() mutant strains, indicating that HpaB and HpaP are widely involved in efficient secretion of the effectors.

  9. Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection.

    PubMed

    Travar, Maja; Petkovic, Miroslav; Verhaz, Antonija

    2016-02-01

    Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-α and IFN-β synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-γ has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, γδ T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-γ in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-γ. The balance between IFN-γ and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-γ responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up-regulation of IFN-λ genes in vitro. IFN-λs also have a role in modulation of Th1/Th2 response. IFN-λs are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen.

  10. Identification of a mutation in the human raloxifene response element of the transforming growth factor-beta 3 gene.

    PubMed Central

    Han, K. O.; Kang, Y. S.; Hwang, C. S.; Moon, I. G.; Yim, C. H.; Chung, H. Y.; Jang, H. C.; Yoon, H. K.; Han, I. K.; Choi, Y. K.

    2001-01-01

    The human transforming growth factor-beta 3 (TGF-beta 3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-beta 3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass. PMID:11641521

  11. Diagnosis and Treatment of a Type III Dens Invagination Using Cone-Beam Computed Tomography

    PubMed Central

    Bahmani, Mohsen; Adl, Alireza; Javanmardi, Samane; Naghizadeh, Sina

    2016-01-01

    A 20-year-old man presented with the history of pain and swelling in the anterior maxillary segment. The periapical radiography was indicative of a dental anomaly in right maxillary lateral incisor. Due to the insufficient information from conventional radiography, cone-beam computed tomography (CBCT) was ordered. CBCT showed apical root resorption, large apical lucency and two separate canals with distinct apical foramen (Oehlers type III dens invagination). The CBCT image was used as a guide for dentine removal with an ultrasonic tip. Conventional root canal therapy was done using lateral compaction technique. One-and two-year follow-up radiographies revealed periapical repair and absence of symptoms. PMID:27790268

  12. Successful stabilisation of a type III paediatric tibial eminence fracture using a tensioned wire technique.

    PubMed

    Archer, Matthew; Parkin, Tom; Latimer, Mark David

    2016-09-19

    We report the case of an 11-year-old boy presenting with a type III tibial eminence fracture. The fracture fragment was reduced arthroscopically. Two 1.6 mm retrograde K-wires were inserted from the tibial metaphysis across the physis and into the fracture fragment using a standard anterior cruciate ligament tibial tunnel guide. Once the wires were clearly visible within the joint the tips were bent over by ∼120°. The wires were then tensioned around a single small fragment screw inserted into the tibial metaphysis. An exceptionally strong fixation was achieved. The boy was mobilised without a brace. The wires were removed at 12 weeks and he returned to full activity at 14 weeks.

  13. Non-linear Effects Associated with Solar Type III Radio Bursts

    NASA Astrophysics Data System (ADS)

    Thejappa, G.; MacDowall, R. J.

    2014-05-01

    Some of the Langmuir wave packets and associated density cavities observed by the STEREO spacecraft in the source regions of solar type III radio bursts indicate that they probably correspond to collapsing envelope soliton-caviton pairs. We present the observations of one of such wave packets, whose spectrum contains harmonic peaks at fpe, 2fpe and 3fpe (fpe is the electron plasma frequency). We show that frequencies, wave numbers and phases of the waves corresponding to these spectral peaks satisfy the resonance conditions of three wave interactions: L1+L2→T2fpe and L+T2fpe→T3fpe, where L1, L2 and L correspond to Langmuir waves, and T2fpe and T3fpe correspond to second and third harmonic electromagnetic waves, respectively.

  14. Bacterial flagella and Type III secretion: case studies in the evolution of complexity.

    PubMed

    Pallen, M J; Gophna, U

    2007-01-01

    Bacterial flagella at first sight appear uniquely sophisticated in structure, so much so that they have even been considered 'irreducibly complex' by the intelligent design movement. However, a more detailed analysis reveals that these remarkable pieces of molecular machinery are the product of processes that are fully compatible with Darwinian evolution. In this chapter we present evidence for such processes, based on a review of experimental studies, molecular phylogeny and microbial genomics. Several processes have played important roles in flagellar evolution: self-assembly of simple repeating subunits, gene duplication with subsequent divergence, recruitment of elements from other systems ('molecular bricolage'), and recombination. We also discuss additional tentative new assignments of homology (FliG with MgtE, FliO with YscJ). In conclusion, rather than providing evidence of intelligent design, flagellar and non-flagellar Type III secretion systems instead provide excellent case studies in the evolution of complex systems from simpler components.

  15. Type III Monteggia fracture with posterior interosseous nerve injury in a child

    PubMed Central

    Wang, Jing; Chen, Min; Du, Jiang

    2017-01-01

    Abstract Rationale: Elbow injury in children by improper treatment or a delay of more than 3 weeks could lead to old unreduced Monteggia fracture, which are difficult to manage. Conservative or normal surgical methods usually fail. Patient concerns: Herein, we present a 6-year-old boy with sustaining injury approximately 1 month to his left elbow. Activity in his elbow was restricted, and his ability to extend his wrist and fingers was impaired. Diagnoses: Type III Monteggia elbow fracture-dislocation consisting of radial head dislocation and malunion of the ulna associated with posterior interosseous nerve palsy were confirmed, which requiring surgical treatment. Interventions: A closed reduction was performed with hyperplastic scar tissues erased and the radial head relocated. Outcomes: Follow-up 4 months later showed satisfactory recovery of function. Lessons: Forearm fractures in children may be misjudged, and that early anatomical reduction rather than conservative treatment may be required. PMID:28296780

  16. A common assembly module in injectisome and flagellar type III secretion sorting platforms

    NASA Astrophysics Data System (ADS)

    Notti, Ryan Q.; Bhattacharya, Shibani; Lilic, Mirjana; Stebbins, C. Erec

    2015-05-01

    Translocating proteins across the double membrane of Gram-negative bacteria, type III secretion systems (T3SS) occur in two evolutionarily related forms: injectisomes, delivering virulence factors into host cells, and the flagellar system, secreting the polymeric filament used for motility. While both systems share related elements of a cytoplasmic sorting platform that facilitates the hierarchical secretion of protein substrates, its assembly and regulation remain unclear. Here we describe a module mediating the assembly of the sorting platform in both secretion systems, and elucidate the structural basis for segregation of homologous components among these divergent T3SS subtypes sharing a common cytoplasmic milieu. These results provide a foundation for the subtype-specific assembly of T3SS sorting platforms and will support further mechanistic analysis and anti-virulence drug design.

  17. Production and physicochemical characterization of resistant starch type III derived from pea starch.

    PubMed

    Lehmann, Undine; Rössler, Christine; Schmiedl, Detlef; Jacobasch, Gisela

    2003-02-01

    Smooth pea starch was used for the production of physiological important resistant starch type III. For reduction of the molecular weight of the starch, different strategies including enzymatic debranching and acid hydrolysis (lintnerization), were tested to obtain an optimal starting material for retrogradation. The resulting polymer chain lengths were analyzed by high-performance anion-exchange chromatography. Temperature regimes and starch concentrations in gel were optimized during the retrogradation with the aim to obtain a high yield of resistant starch. Optimal conditions led to resistant starch contents up to 74%. The products were thermostable and showed no loss of resistant structures after autoclaving. The peak temperatures of the thermal transition were at approximately 147 degrees C. The resulting resistant starch products are suitable for the generation of functional foods.

  18. Lepton flavor violating {tau} decays in the type-III seesaw mechanism

    SciTech Connect

    Arhrib, Abdesslam; Benbrik, Rachid; Chen, C.-H.

    2010-06-01

    In this paper, the lepton flavor violating {tau}{yields}lP(V) (P, V={pi}{sup 0}, {eta}, {eta}{sup '}, {rho}{sup 0}, {omega}, {phi}) and {tau}{yields}3l (l=e, {mu}) decays are studied in the framework of the type-III seesaw model, in which new triplet fermions with a zero hypercharge (Y=0) interact with ordinary lepton doublets via Yukawa couplings, and affect tree-level leptonic Z-boson couplings. We investigate the experimental bound from the leptonic Z decay to get constraints on the existing parameters space. We predict that the upper limits on the branching ratios of {tau}{yields}lP(V) and {tau}{yields}3l can reach the experimental current limits.

  19. Dynamics of Langmuir and ion-sound waves in type III solar radio sources

    NASA Technical Reports Server (NTRS)

    Robinson, P. A.; Willes, A. J.; Cairns, I. H.

    1993-01-01

    The study traces the evolution of Langmuir and ion-sound waves in type III sources, incorporating linear growth, linear damping, and nonlinear electrostatic decay. Improved estimates are obtained for the wavenumber range of growing waves and the nonlinear coupling coefficient for the decay process. It is shown that the conditions in the solar wind do not allow a steady state to be attained; instead, bursty linear and nonlinear interactions take place, consistent with the highly inhomogeneous and impulsive waves actually observed. Nonlinear growth is found to be rapid enough to saturate the growth of the parent Langmuir waves in the available interaction time. The competing processes of nonlinear wave collapse and quasi-linear relaxation are discussed, and it is concluded that neither is responsible for the saturation of Langmuir growth.

  20. Model interpretation of type III radio burst characteristics. I - Spatial aspects

    NASA Technical Reports Server (NTRS)

    Reiner, M. J.; Stone, R. G.

    1988-01-01

    The ways that the finite size of the source region and directivity of the emitted radiation modify the observed characteristics of type III radio bursts as they propagate through the interplanetary medium are investigated. A simple model that simulates the radio source region is developed to provide insight into the spatial behavior of the parameters that characterize radio bursts. The model is used to demonstrate that observed radio azimuths are systematically displaced from the geometric centroid of the exciter electron beam in such a way as to cause trajectories of the radio bursts to track back to the observer at low frequencies, rather than to follow expected Archimedean spiral-like paths. The source region model is used to investigate the spatial behavior of the peak intensities of radio bursts, and it is found that the model can qualitatively account for both the frequency dependence and the east-west asymmetry of the observed peak flux densities.

  1. Relationship of Type III Radio Bursts with Quasi-periodic Pulsations in a Solar Flare

    NASA Astrophysics Data System (ADS)

    Kupriyanova, E. G.; Kashapova, L. K.; Reid, H. A. S.; Myagkova, I. N.

    2016-11-01

    We studied a solar flare with pronounced quasi-periodic pulsations detected in the microwave, X-ray, and radio bands. We used correlation, Fourier, and wavelet analyses methods to examine the temporal fine structures and relationships between the time profiles in each wave band. We found that the time profiles of the microwaves, hard X-rays, and type III radio bursts vary quasi-periodically with a common period of 40 - 50 s. The average amplitude of the variations is high, above 30 % of the background flux level, and reaches 80 % after the flare maximum. We did not find this periodicity in either the thermal X-ray flux component or in the source size dynamics. Our findings indicate that the detected periodicity is probably associated with periodic dynamics in the injection of non-thermal electrons, which can be produced by periodic modulation of magnetic reconnection.

  2. Anesthetic management of a parturient with type III Klippel-Feil syndrome.

    PubMed

    Hsu, G; Manabat, E; Huffnagle, S; Huffnagle, H J

    2011-01-01

    Klippel-Feil syndrome is believed to occur from failure of normal segmentation of cervical somites during gestation. We present the case of a 38-year-old primiparous woman with type III Klippel-Feil syndrome for elective cesarean delivery. Our patient had a short webbed neck, short stature, limited neck flexion and extension, and thoraco-lumbar abnormalities. A multidisciplinary approach, involving obstetrics, medical subspecialties, anesthesiology, otolaryngology, and radiology, were utilized to evaluate and manage this patient. Pulmonary function testing revealed a restrictive defect, but transthoracic echocardiography was normal without pulmonary hypertension. We planned a combined spinal-epidural technique; however, only the epidural technique was obtained. Cesarean delivery was commenced with favorable maternal and fetal outcomes. Post-operative pain management was provided with intravenous morphine patient-controlled analgesia.

  3. Opening the Ralstonia solanacearum type III effector tool box: insights into host cell subversion mechanisms.

    PubMed

    Deslandes, Laurent; Genin, Stephane

    2014-08-01

    Effectors delivered to host cells by the Type III secretion system are essential to Ralstonia solanacearum pathogenicity, as in several other plant pathogenic bacteria. The establishment of exhaustive effector repertoires in multiple R. solanacearum strains drew a first picture of the evolutionary dynamics of the pathogen effector suites. Effector repertoires are diversified, with a core of 20-30 effectors present in most of the strains and the obtention of mutants lacking one or more effector genes revealed the functional overlap among this effector network. Recent functional studies have provided insights into the ability of single effectors to manipulate the host proteasome, elicit cell death, trigger the expression of plant genes, and/or display biochemical activities on plant protein targets.

  4. Crystallization and preliminary crystallographic analysis of an octaketide-producing plant type III polyketide synthase

    SciTech Connect

    Morita, Hiroyuki; Kondo, Shin; Kato, Ryohei; Wanibuchi, Kiyofumi; Noguchi, Hiroshi; Sugio, Shigetoshi; Abe, Ikuro; Kohno, Toshiyuki

    2007-11-01

    Octaketide synthase from A. arborescens has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.6 Å. Octaketide synthase (OKS) from Aloe arborescens is a plant-specific type III polyketide synthase that produces SEK4 and SEK4b from eight molecules of malonyl-CoA. Recombinant OKS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group I422, with unit-cell parameters a = b = 110.2, c = 281.4 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.6 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  5. Control of type III secretion activity and substrate specificity by the cytoplasmic regulator PcrG

    PubMed Central

    Lee, Pei-Chung; Zmina, Stephanie Elizabeth; Stopford, Charles Morgan; Toska, Jonida; Rietsch, Arne

    2014-01-01

    Pathogenic Gram-negative bacteria use syringe-like type III secretion systems (T3SS) to inject effector proteins directly into targeted host cells. Effector secretion is triggered by host cell contact, and before contact is prevented by a set of conserved regulators. How these regulators interface with the T3SS apparatus to control secretion is unclear. We present evidence that the proton motive force (pmf) drives T3SS secretion in Pseudomonas aeruginosa, and that the cytoplasmic regulator PcrG interacts with distinct components of the T3SS apparatus to control two important aspects of effector secretion: (i) It coassembles with a second regulator (Pcr1) on the inner membrane T3SS component PcrD to prevent effectors from accessing the T3SS, and (ii) In conjunction with PscO, it controls protein secretion activity by modulating the ability of T3SS to convert pmf. PMID:24778208

  6. The type III secretion system as a source of novel antibacterial drug targets.

    PubMed

    Kline, Toni; Felise, Heather B; Sanowar, Sarah; Miller, Samuel I

    2012-03-01

    Type III Secretion Systems (T3SSs) are highly organized multi-protein nanomachines which translocate effector proteins from the bacterial cytosol directly into host cells. These systems are required for the pathogenesis of a wide array of Gram-negative bacterial pathogens, and thus have attracted attention as potential antibacterial drug targets. A decade of research has enabled the identification of natural products, conventional small molecule drug-like structures, and proteins that inhibit T3SSs. The mechanism(s) of action and molecular target(s) of the majority of these inhibitors remain to be determined. At the same time, structural biology methods are providing an increasingly detailed picture of the functional arrangement of the T3SS component proteins. The confluence of these two research areas may ultimately identify non-classical drug targets and facilitate the development of novel therapeutics.

  7. Diversity and Evolutionary Analysis of Iron-Containing (Type-III) Alcohol Dehydrogenases in Eukaryotes

    PubMed Central

    Gaona-López, Carlos; Julián-Sánchez, Adriana

    2016-01-01

    Background Alcohol dehydrogenase (ADH) activity is widely distributed in the three domains of life. Currently, there are three non-homologous NAD(P)+-dependent ADH families reported: Type I ADH comprises Zn-dependent ADHs; type II ADH comprises short-chain ADHs described first in Drosophila; and, type III ADH comprises iron-containing ADHs (FeADHs). These three families arose independently throughout evolution and possess different structures and mechanisms of reaction. While types I and II ADHs have been extensively studied, analyses about the evolution and diversity of (type III) FeADHs have not been published yet. Therefore in this work, a phylogenetic analysis of FeADHs was performed to get insights into the evolution of this protein family, as well as explore the diversity of FeADHs in eukaryotes. Principal Findings Results showed that FeADHs from eukaryotes are distributed in thirteen protein subfamilies, eight of them possessing protein sequences distributed in the three domains of life. Interestingly, none of these protein subfamilies possess protein sequences found simultaneously in animals, plants and fungi. Many FeADHs are activated by or contain Fe2+, but many others bind to a variety of metals, or even lack of metal cofactor. Animal FeADHs are found in just one protein subfamily, the hydroxyacid-oxoacid transhydrogenase (HOT) subfamily, which includes protein sequences widely distributed in fungi, but not in plants), and in several taxa from lower eukaryotes, bacteria and archaea. Fungi FeADHs are found mainly in two subfamilies: HOT and maleylacetate reductase (MAR), but some can be found also in other three different protein subfamilies. Plant FeADHs are found only in chlorophyta but not in higher plants, and are distributed in three different protein subfamilies. Conclusions/Significance FeADHs are a diverse and ancient protein family that shares a common 3D scaffold with a patchy distribution in eukaryotes. The majority of sequenced FeADHs from

  8. Observational evidence for the collapsing Langmuir wave packet in a solar type III radio burst

    NASA Astrophysics Data System (ADS)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2013-07-01

    High time resolution observations from the STEREO spacecraft show that in solar type III radio bursts, Langmuir waves often occur as very intense one-dimensional magnetic field aligned field structures. One of these events represents the most intense Langmuir wave packet with WLneTe~7.2×10-3 ever detected in a type III radio burst until now (WL is the peak energy density, and ne and Te are the electron density and temperature, respectively). The detailed analysis of this wave packet indicates that (1) its peak intensity is well above the threshold for the oscillating two-stream instability (OTSI) and supersonic collapse; (2) its peak intensity and spatial scale satisfy the criterion for it to be a collapsing envelope soliton; (3) its low-frequency components provide evidence for a density cavity, whose depth, width, and temporal coincidence indicate that probably it is the ponderomotive force generated density cavity; and (4) its spectrum contains harmonic peaks at 2fpe and 3fpe (in addition to the main Langmuir wave peak at the electron plasma frequency, fpe), which, as indicated by the bispectral analysis, probably are of the electromagnetic waves generated as a result of coalescence of two oppositely propagating Langmuir waves, and a Langmuir wave and a second harmonic electromagnetic wave, respectively. These characteristics strongly suggest that this wave packet and its associated density cavity represent the collapsing envelope soliton-caviton pair formed as a result of OTSI, and in the present case, the strong turbulence processes probably play key roles in the beam stabilization as well as conversion of Langmuir waves into escaping radiation at 2fpe and 3fpe.

  9. Neutron structure of type-III antifreeze protein allows the reconstruction of AFP-ice interface.

    PubMed

    Howard, Eduardo I; Blakeley, Matthew P; Haertlein, Michael; Petit-Haertlein, Isabelle; Mitschler, Andre; Fisher, Stuart J; Cousido-Siah, Alexandra; Salvay, Andrés G; Popov, Alexandre; Muller-Dieckmann, Christoph; Petrova, Tatiana; Podjarny, Alberto

    2011-01-01

    Antifreeze proteins (AFPs) inhibit ice growth at sub-zero temperatures. The prototypical type-III AFPs have been extensively studied, notably by X-ray crystallography, solid-state and solution NMR, and mutagenesis, leading to the identification of a compound ice-binding surface (IBS) composed of two adjacent ice-binding sections, each which binds to particular lattice planes of ice crystals, poisoning their growth. This surface, including many hydrophobic and some hydrophilic residues, has been extensively used to model the interaction of AFP with ice. Experimentally observed water molecules facing the IBS have been used in an attempt to validate these models. However, these trials have been hindered by the limited capability of X-ray crystallography to reliably identify all water molecules of the hydration layer. Due to the strong diffraction signal from both the oxygen and deuterium atoms, neutron diffraction provides a more effective way to determine the water molecule positions (as D(2) O). Here we report the successful structure determination at 293 K of fully perdeuterated type-III AFP by joint X-ray and neutron diffraction providing a very detailed description of the protein and its solvent structure. X-ray data were collected to a resolution of 1.05 Å, and neutron Laue data to a resolution of 1.85 Å with a "radically small" crystal volume of 0.13 mm(3). The identification of a tetrahedral water cluster in nuclear scattering density maps has allowed the reconstruction of the IBS-bound ice crystal primary prismatic face. Analysis of the interactions between the IBS and the bound ice crystal primary prismatic face indicates the role of the hydrophobic residues, which are found to bind inside the holes of the ice surface, thus explaining the specificity of AFPs for ice versus water.

  10. Computational Analysis and Binding Site Identification of Type III Secretion System ATPase from Pseudomonas aeruginosa.

    PubMed

    Dash, Raju; Hosen, S M Zahid; Sultana, Tasniha; Junaid, Md; Majumder, Mohuya; Ishat, Ismat Ara; Uddin, Mir Muhammad Nasir

    2016-12-01

    In many gram-negative bacteria, the type III secretion system (T3SS), as a virulence factor, is an attractive target for developing novel antibacterial. Regarding this, in our study, we aimed to identify the putative drug target for Pseudomonas aeruginosa, considering ATPase enzyme involved in the type III secretion system. Selective protein sequence of P. aeruginosa involved in the T3SS was retrieved from NCBI databases, and its homologues were subjected to phylogenetic analysis. Its association in T3SS was analyzed via STRING, and the 3D structure was determined by means of homology modeling followed by intensive optimization and validation. The binding site was predicted by 3DLigandSite and examined through molecular docking simulation by Autodock Vina with salicylidene acylhydrazide class of virulence-blocking compounds. PROCHECK analysis showed that 96.7 % of the residues were in the most favored regions, 1.9 % were in the additional allowed region, and 1.4 % were in the generously allowed region of the Ramachandran plot. The refined model yielded ERRAT scores of 88.124 and Verify3D value of 0.2, which indicates that the environmental profile of the model is good. The best binding affinity was observed by ME0055 compound, and ALA160, ALA161, GlY162, GLY163, GLY164, GLY165, SER166, THR167, TYR338, and PRO339 residues were found to be having complementary in the ligand-binding site. However, these findings should be further confirmed by wet lab studies for design a targeted therapeutic agent.

  11. Global impact of Salmonella type III secretion effector SteA on host cells

    SciTech Connect

    Cardenal-Muñoz, Elena Gutiérrez, Gabriel Ramos-Morales, Francisco

    2014-07-11

    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration.

  12. A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain.

    PubMed

    Rodríguez-Soriano, Juan; Vallo, Alfredo; Pérez de Nanclares, Gustavo; Bilbao, José Ramón; Castaño, Luis

    2005-07-01

    The term "Bartter syndrome" encompasses a group of closely related inherited tubulopathies characterized by markedly reduced NaCl transport by the distal nephron. At present, five different genetic variants have been demonstrated. The majority of patients with so-called classic Bartter syndrome carry inactivating mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel (Bartter syndrome type III). The purpose of this study was to investigate the underlying mutation in cases of classic Bartter syndrome followed at our center. Ten patients, including two sisters, with clinical and biochemical features of classic Bartter syndrome were included in the mutational analysis. They originated from different regions of Spain with either Basque or Spanish ancestry. There was no history of consanguineous marriage in any of the kindreds. The parents and siblings of each patient, as well as a population of 300 healthy control adult subjects, were also analyzed. All ten patients were found to be homozygous for an identical missense mutation in the CLCNKB gene, substituting a threonine for an alanine at codon 204 (A204T) in the putative fifth transmembrane domain of the protein. None of the 300 control subjects were homozygous for the A204T allele. Overall, the A204T mutation was detected on 2/600 control chromosomes. Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms to severe growth retardation. Demonstration of a point mutation within the CLCNKB gene as the apparently unique cause of Bartter syndrome type III in Spain is highly suggestive of a founder effect. Our results also support the lack of correlation between genotype and phenotype in this disease.

  13. A DECADE OF SOLAR TYPE III RADIO BURSTS OBSERVED BY THE NANCAY RADIOHELIOGRAPH 1998-2008

    SciTech Connect

    Saint-Hilaire, P.; Vilmer, N.; Kerdraon, A.

    2013-01-01

    We present a statistical survey of almost 10,000 radio type III bursts observed by the Nancay Radioheliograph from 1998 to 2008, covering nearly a full solar cycle. In particular, sources sizes, positions, and fluxes were examined. We find an east-west asymmetry in source positions that could be attributed to a 6 Degree-Sign {+-} 1 Degree-Sign eastward tilt of the magnetic field, that source FWHM sizes s roughly follow a solar-cycle-averaged distribution (dN/ds) Almost-Equal-To 14 {nu}{sup -3.3} s {sup -4} arcmin{sup -1} day{sup -1}, and that source fluxes closely follow a solar-cycle-averaged (dN/ds {sub {nu}}) Almost-Equal-To 0.34 {nu}{sup -2.9} S {sup -1.7} {sub {nu}} sfu{sup -1} day{sup -1} distribution (when {nu} is in GHz, s in arcminutes, and S {sub {nu}} in sfu). Fitting a barometric density profile yields a temperature of 0.6 MK, while a solar wind-like ({proportional_to}h {sup -2}) density profile yields a density of 1.2 Multiplication-Sign 10{sup 6} cm{sup -3} at an altitude of 1 R{sub S} , assuming harmonic emission. Finally, we found that the solar-cycle-averaged radiated type III energy could be similar in magnitude to that radiated by nanoflares via non-thermal bremsstrahlung processes, and we hint at the possibility that escaping electron beams might carry as much energy away from the corona as is introduced into it by accelerated nanoflare electrons.

  14. Structural Analysis of a Specialized Type III Secretion System Peptidoglycan-cleaving Enzyme*

    PubMed Central

    Burkinshaw, Brianne J.; Deng, Wanyin; Lameignère, Emilie; Wasney, Gregory A.; Zhu, Haizhong; Worrall, Liam J.; Finlay, B. Brett; Strynadka, Natalie C.J.

    2015-01-01

    The Gram-negative bacterium enteropathogenic Escherichia coli uses a syringe-like type III secretion system (T3SS) to inject virulence or “effector” proteins into the cytoplasm of host intestinal epithelial cells. To assemble, the T3SS must traverse both bacterial membranes, as well as the peptidoglycan layer. Peptidoglycan is made of repeating N-acetylmuramic acid and N-acetylglucosamine disaccharides cross-linked by pentapeptides to form a tight mesh barrier. Assembly of many macromolecular machines requires a dedicated peptidoglycan lytic enzyme (PG-lytic enzyme) to locally clear peptidoglycan. Here we have solved the first structure of a T3SS-associated PG-lytic enzyme, EtgA from enteropathogenic E. coli. Unexpectedly, the active site of EtgA has features in common with both lytic transglycosylases and hen egg white lysozyme. Most notably, the β-hairpin region resembles that of lysozyme and contains an aspartate that aligns with lysozyme Asp-52 (a residue critical for catalysis), a conservation not observed in other previously characterized lytic transglycosylase families to which the conserved T3SS enzymes had been presumed to belong. Mutation of the EtgA catalytic glutamate, Glu-42, conserved across lytic transglycosylases and hen egg white lysozyme, and this differentiating aspartate diminishes type III secretion in vivo, supporting its essential role in clearing the peptidoglycan for T3SS assembly. Finally, we show that EtgA forms a 1:1 complex with the building block of the polymerized T3SS inner rod component, EscI, and that this interaction enhances PG-lytic activity of EtgA in vitro, collectively providing the necessary strict localization and regulation of the lytic activity to prevent overall cell lysis. PMID:25678709

  15. Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms

    PubMed Central

    Sukumaran, Sunil K.; Margolskee, Robert F.; Bachmanov, Alexander A.

    2016-01-01

    Responses in the amiloride-insensitive (AI) pathway, one of the two pathways mediating salty taste in mammals, are modulated by the size of the anion of a salt. This “anion effect” has been hypothesized to result from inhibitory transepithelial potentials (TPs) generated across the lingual epithelium as cations permeate through tight junctions and leave their larger and less permeable anions behind (Ye et al., 1991). We tested directly the necessity of TPs for the anion effect by measuring responses to NaCl and Na-gluconate (small and large anion sodium salts, respectively) in isolated taste cells from mouse circumvallate papillae. Using calcium imaging, we identified AI salt-responsive type III taste cells and demonstrated that they compose a subpopulation of acid-responsive taste cells. Even in the absence of TPs, many (66%) AI salt-responsive type III taste cells still exhibited the anion effect, demonstrating that some component of the transduction machinery for salty taste in type III cells is sensitive to anion size. We hypothesized that osmotic responses could explain why a minority of type III cells (34%) had AI salt responses but lacked anion sensitivity. All AI type III cells had osmotic responses to cellobiose, which were significantly modulated by extracellular sodium concentration, suggesting the presence of a sodium-conducting osmotically sensitive ion channel. However, these responses were significantly larger in AI type III cells that did not exhibit the anion effect. These findings indicate that multiple mechanisms could underlie AI salt responses in type III taste cells, one of which may contribute to the anion effect. SIGNIFICANCE STATEMENT Understanding the mechanisms underlying salty taste will help inform strategies to combat the health problems associated with NaCl overconsumption by humans. Of the two pathways underlying salty taste in mammals, the amiloride-insensitive (AI) pathway is the least understood. Using calcium imaging of

  16. Genetic heterogeneity in type III familial cutaneous syndactyly and linkage to chromosome 7q36.

    PubMed

    Al-Qattan, Mohammad M; Shamseldin, Hanan E; Al Mazyad, Mohammed; Al Deghaither, Saud; Alkuraya, Fowzan S

    2013-07-01

    The ZRS (zone of polarizing activity regulatory sequence) is a long-range limb-specific Sonic Hedgehog (SHH) enhancer. In humans, the ZRS is located in chromosome 7q36 within intron 5 of LMBR1; approximately 1 Mb telomeric of SHH. Point mutations and duplications of the ZRS lead to a variable phenotype of preaxial polydactyly/triphalangeal thumb, tibial hypoplasia, radial ray deficiency, and type IV familial syndactyly (syndactyly of all digits with polydactyly). The ZRS is conserved among mammals and fish and regulates the expression of SHH. In mice, the conserved ZRS within the Lmbr1 gene is found in chromosome 5. The Hammertoe (Hm) mouse mutants have a mutation in the Lmbr1 locus and show syndactyly of digits 2-5 without polydactyly. No previous reports have described isolated syndactyly without polydactyly to be related to the LMBR1 locus in humans. In this report, we describe a family with simple cutaneous syndactyly involving digits 2-5, without polydactyly which is consistent with the phenotype of type III syndactyly. The locus we identified on ch7q36.3 is syntenic to the Hm locus; and affected members of the family had a phenotype analogous to Hm. Hence, the type of syndactyly described in the current report may be equivalent to Hm mice.

  17. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.

    PubMed

    Schwartz, Daniella M; Bonelli, Michael; Gadina, Massimo; O'Shea, John J

    2016-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.

  18. Focal adhesion kinase is involved in type III group B streptococcal invasion of human brain microvascular endothelial cells.

    PubMed

    Shin, Sooan; Paul-Satyaseela, Maneesh; Maneesh, Paul-Satyaseela; Lee, Jong-Seok; Romer, Lewis H; Kim, Kwang Sik

    2006-01-01

    Group B streptococcus (GBS), the leading cause of neonatal meningitis, has been shown to invade human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. GBS invasion of HBMEC has been shown to require the host cell actin cytoskeleton rearrangements. The present study examined the mechanisms underlying actin cytoskeleton rearrangements that are involved in type III GBS invasion of HBMEC. We showed that type III GBS invasion was inhibited by genistein, a general tyrosine kinase inhibitor (mean 54% invasion decrease at 100 microM), and LY294002, a phosphatidylinositol 3 (PI3) kinase inhibitor (mean 70% invasion decrease at 50 microM), but not by PP2, an inhibitor of the Src family tyrosine kinases. We subsequently showed that the focal adhesion kinase (FAK) was the one of the host proteins tyrosine phosphorylated by type III GBS. Over-expression of a dominant negative form of the FAK C-terminal domain significantly decreased type III GBS invasion of HBMEC (mean 51% invasion decrease). In addition, we showed that FAK phosphorylation correlated with its association of paxillin, an adapter protein of actin filament, and PI3-kinase subunit p85. This is the first demonstration that FAK phosphorylation and its association with paxillin and PI3 kinase play a key role in type III GBS invasion of HBMEC.

  19. Why so narrow: Distribution of anti-sense regulated, type I toxin-antitoxin systems compared with type II and type III systems

    PubMed Central

    Coray, Dorien S.; Heinemann, Jack A.; Gardner, Paul P.

    2017-01-01

    ABSTRACT Toxin-antitoxin (TA) systems are gene modules that appear to be horizontally mobile across a wide range of prokaryotes. It has been proposed that type I TA systems, with an antisense RNA-antitoxin, are less mobile than other TAs that rely on direct toxin-antitoxin binding but no direct comparisons have been made. We searched for type I, II and III toxin families using iterative searches with profile hidden Markov models across phyla and replicons. The distribution of type I toxin families were comparatively narrow, but these patterns weakened with recently discovered families. We discuss how the function and phenotypes of TA systems as well as biases in our search methods may account for differences in their distribution. PMID:28067598

  20. Identification and classification of bacterial Type III toxin–antitoxin systems encoded in chromosomal and plasmid genomes

    PubMed Central

    Blower, Tim R.; Short, Francesca L.; Rao, Feng; Mizuguchi, Kenji; Pei, Xue Y.; Fineran, Peter C.; Luisi, Ben F.; Salmond, George P. C.

    2012-01-01

    Toxin–antitoxin systems are widespread in bacteria and archaea. They perform diverse functional roles, including the generation of persistence, maintenance of genetic loci and resistance to bacteriophages through abortive infection. Toxin–antitoxin systems have been divided into three types, depending on the nature of the interacting macromolecules. The recently discovered Type III toxin–antitoxin systems encode protein toxins that are inhibited by pseudoknots of antitoxic RNA, encoded by short tandem repeats upstream of the toxin gene. Recent studies have identified the range of Type I and Type II systems within current sequence databases. Here, structure-based homology searches were combined with iterative protein sequence comparisons to obtain a current picture of the prevalence of Type III systems. Three independent Type III families were identified, according to toxin sequence similarity. The three families were found to be far more abundant and widespread than previously known, with examples throughout the Firmicutes, Fusobacteria and Proteobacteria. Functional assays confirmed that representatives from all three families act as toxin–antitoxin loci within Escherichia coli and at least two of the families confer resistance to bacteriophages. This study shows that active Type III toxin–antitoxin systems are far more diverse than previously known, and suggests that more remain to be identified. PMID:22434880

  1. [In vitro effect of total flavones of Fructus Chorspondiatis on expression of collagen type I and type III mRNA and protein of cultured rat cardiac fibroblasts].

    PubMed

    Bao, Jun-Ping; Jin, Ming; Yang, Yu-Min; Gao, Xiao-Hui; Shu, Liang; Xing, Hui-Hui; Jia, Lei

    2014-01-01

    This study aims to investigate the effect of total flavones of Fructus Chorspondiatis (TFFC) on the mRNA and protein expression of collagen type I and III of rat cardiac fibroblasts (CFs) induced by angiotensin II (Ang II), and explore its anti-myocardial fibrosis molecular mechanism. Neonatal rat CFs were prepared from Sprague-Dawley rats (1-3 d after birth). The expression of collagen type I and III mRNA and protein were measured by RT-PCR and Western blotting, respectively. The study showed that stimulation of neonatal rat CFs with 100 nmol.L-1 of Ang II for 72 h resulted in a significant increase of the expression of collagen type I and III mRNA and protein. The changes on the expression level were blocked by TFFC. The results demonstrated that TFFC can inhibit myocardial fibrosis induced by Ang II in rats, which is probably associated with the collagen type I and III mRNA and protein levels up-regulated by Ang II, and TFFC was shown to decrease the expression levels of collagen type I and III mRNA and protein.

  2. Detection of fundamental and harmonic type III radio emission and the associated Langmuir waves at the source region

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    Type III radio emission generated in the vicinity of the Ulysses spacecraft has been detected at both the fundamental and harmonic of the local plasma frequency. The observations represent the first clear evidence of locally generated type III radio emission. This local emission shows no evidence of frequency drift, exhibits a relatively short rise time, is less intense than the observed remotely generated radio emission, and is temporally correlated with observed in situ Langmuir waves. The observations were made with the unified radio astronomy and wave (URAP) experiment on the Ulysses spacecraft between 1990 November 4 and 1991 April 30, as it traveled from 1 to 3 AU from the sun. During this time period many thousands of bursts were observed. However, only three examples of local emission and associated Langmuir waves were identified. This supports previous suggestions that type III radio emission is generated in localized regions of the interplanetary medium, rather than uniformly along the extent of the electron exciter beam.

  3. The association of Chiari type III malformation and Klippel-Feil syndrome with mirror movement: a case report.

    PubMed

    Erol, Fatih Serhat; Ucler, Necati; Yakar, Huseyin

    2011-01-01

    Basically Chiari type III malformation is a combination of encephalocele with of brain stem and cerebellar abnormality. Although Klippel-Feil syndrome may be associated with other congenital anomalies, this syndrome is mainly associated with varying degrees of cervical vertebral fusion anomalies. In this study, we reported the association of Chiari type III malformation and Klippel-Feil syndrome with the mirror movement by imaging studies. The main involvement in Chiari type III malformation and Klippel-Feil syndrome is in the craniocervical junction. In such a small area, the emergence of these complex pathologies in our case was remarkable. Our patient had reconstruction surgery of the posterior fossa and his encephalocele was excised successfully. Hydrocephaly and/or deterioration in the functions of other posterior fossa structures have not been seen in the patient's follow-up.

  4. Immunohistochemical expression of types I and III collagen antibodies in the temporomandibular joint disc of human foetuses

    PubMed Central

    de Moraes, L.O.C.; Lodi, F.R.; Gomes, T.S.; Marques, S.R.; Oshima, C.T.F.; Lancellotti, C.L.P.; Rodríguez-Vázquez, J.F.; Mérida-Velasco, J.R.; Alonso, L.G.

    2011-01-01

    The objective was to study the morphology of the articular disc and analyse the immunohistochemical expression of types I and III collagen markers in the temporomandibular joint (TMJ) disc of human foetuses of different gestational ages. Twenty TMJ from human foetuses supplied by Universidade Federal de Uberaba with gestational ages from 17 to 24 weeks were studied. The gestational age of the foetuses was determined by measuring the crown-rump (CR) length. Macroscopically, the foetuses were fixed in 10% formalin solution and dissected by removing the skin and subcutaneous tissue and exposing the deep structures. Immunohistochemical markers of type I and III were used to characterize the existence of collagen fibres. Analysis of the immunohistochemical markers of types I and III collagen revealed the presence of heterotypical fibril networks. PMID:22073371

  5. Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures

    SciTech Connect

    Morales, T.I. )

    1991-04-01

    Previous work showed that transforming growth factor-beta 1 (TGF-beta 1), added alone to bovine cartilage organ cultures, stimulated (35S)sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-beta 1 stimulation: (1) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (2) link-stable proteoglycan aggregates are assembled, (3) the hybrid chondroitin sulfate/keratan sulfate monomeric species is synthesized, and (4) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-beta 1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-beta 1 to basal samples respectively, the monomers were larger (Kav on Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by approximately 3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from approximately 4% (basal) to approximately 6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function.

  6. Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland.

    PubMed

    Silberstein, G B; Strickland, P; Coleman, S; Daniel, C W

    1990-06-01

    Exogenous transforming growth factor beta (TGF-beta 1) was shown in earlier studies to reversibly inhibit mouse mammary ductal growth. Using small plastic implants to treat regions of developing mammary glands in situ, we now report that TGF-beta 1 growth inhibition is associated with an ectopic accumulation of type I collagen messenger RNA and protein, as well as the glycosaminoglycan, chondroitin sulfate. Both macromolecules are normal components of the ductal extracellular matrix, which, under the influence of exogenous TGF-beta 1, became unusually concentrated immediately adjacent to the epithelial cells at the tip of the ductal growth points, the end buds. Stimulation of extracellular matrix was confined to aggregations of connective tissue cells around affected end buds and was not present around the TGF-beta 1 implants themselves, indicating that the matrix effect was epithelium dependent. Ectopic matrix synthesis was specific for TGF-beta 1 insofar as it was absent at ducts treated with other growth inhibitors, or at ducts undergoing normal involution in response to endogenous regulatory processes. These findings are consistent with the matrix-stimulating properties of TGF-beta 1 reported for other systems, but differ in their strict dependence upon epithelium. A possible role for endogenous TGF-beta 1 in modulating a mammary epithelium-stroma interaction is suggested.

  7. Prostaglandin F(2alpha) receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-beta.

    PubMed

    Oga, Toru; Matsuoka, Toshiyuki; Yao, Chengcan; Nonomura, Kimiko; Kitaoka, Shiho; Sakata, Daiji; Kita, Yoshihiro; Tanizawa, Kiminobu; Taguchi, Yoshio; Chin, Kazuo; Mishima, Michiaki; Shimizu, Takao; Narumiya, Shuh

    2009-12-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix (ECM) proteins, which lead to distorted lung architecture and function. Given that anti-inflammatory or immunosuppressive therapy currently used for IPF does not improve disease progression therapies targeted to blocking the mechanisms of fibrogenesis are needed. Although transforming growth factor-beta (TGF-beta) functions are crucial in fibrosis, antagonizing this pathway in bleomycin-induced pulmonary fibrosis, an animal model of IPF, does not prevent fibrosis completely, indicating an additional pathway also has a key role in fibrogenesis. Given that the loss of cytosolic phospholipase A(2) (cPLA(2)) suppresses bleomycin-induced pulmonary fibrosis, we examined the roles of prostaglandins using mice lacking each prostoaglandin receptor. Here we show that loss of prostaglandin F (PGF) receptor (FP) selectively attenuates pulmonary fibrosis while maintaining similar levels of alveolar inflammation and TGF-beta stimulation as compared to wild-type (WT) mice, and that FP deficiency and inhibition of TGF-beta signaling additively decrease fibrosis. Furthermore, PGF(2alpha) is abundant in bronchoalveolar lavage fluid (BALF) of subjects with IPF and stimulates proliferation and collagen production of lung fibroblasts via FP, independently of TGF-beta. These findings show that PGF(2alpha)-FP signaling facilitates pulmonary fibrosis independently of TGF-beta and suggests this signaling pathway as a therapeutic target for IPF.

  8. Vascular smooth muscle cells from injured rat aortas display elevated matrix production associated with transforming growth factor-beta activity.

    PubMed Central

    Rasmussen, L. M.; Wolf, Y. G.; Ruoslahti, E.

    1995-01-01

    The arterial response to injury is characterized by a short period of increased proliferation and migration of vascular smooth muscle cells, followed by an extended period of extracellular matrix accumulation in the intima. Transforming growth factor-beta (TGF-beta) has been implicated as a causative factor in the formation of extracellular matrix in this process, which leads to progressive thickening of the intima, known as intimal hyperplasia. In vitro analysis of vascular smooth muscle cells harvested from normal rat aortas and from aortas injured 14 days earlier showed that both types of cells attached equally well to culture dishes but that the initial spreading of the cells was increased in cells derived from injured vessels. Cells from the injured arteries produced more fibronectin and proteoglycans into the culture medium than the cells from normal arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan synthesis by normal smooth muscle cells, and the presence of a neutralizing anti-TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured arteries in culture. Fibronectin synthesis was not altered by these treatments. These results indicate that the accumulation of extracellular matrix components in neointimal lesions is at least partially caused by autocrine TGF-beta activity in vascular smooth muscle cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7573349

  9. Characterization of a novel transcriptionally active domain in the transforming growth factor beta-regulated Smad3 protein.

    PubMed

    Prokova, Vassiliki; Mavridou, Sofia; Papakosta, Paraskevi; Kardassis, Dimitris

    2005-01-01

    Transforming growth factor beta (TGFbeta) regulates transcriptional responses via activation of cytoplasmic effector proteins termed Smads. Following their phosphorylation by the type I TGFbeta receptor, Smads form oligomers and translocate to the nucleus where they activate the transcription of TGFbeta target genes in cooperation with nuclear cofactors and coactivators. In the present study, we have undertaken a deletion analysis of human Smad3 protein in order to characterize domains that are essential for transcriptional activation in mammalian cells. With this analysis, we showed that Smad3 contains two domains with transcriptional activation function: the MH2 domain and a second middle domain that includes the linker region and the first two beta strands of the MH2 domain. Using a protein-protein interaction assay based on biotinylation in vivo, we were able to show that a Smad3 protein bearing an internal deletion in the middle transactivation domain is characterized by normal oligomerization and receptor activation properties. However, this mutant has reduced transactivation capacity on synthetic or natural promoters and is unable to interact physically and functionally with the histone acetyltransferase p/CAF. The loss of interaction with p/CAF or other coactivators could account, at least in part, for the reduced transactivation capacity of this Smad3 mutant. Our data support an essential role of the previously uncharacterized middle region of Smad3 for nuclear functions, such as transcriptional activation and interaction with coactivators.

  10. Growth Hormone Induces Transforming Growth Factor-Beta-Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria.

    PubMed

    Chitra, P Swathi; Swathi, T; Sahay, Rakesh; Reddy, G Bhanuprakash; Menon, Ram K; Kumar, P Anil

    2015-09-01

    The glomerular podocytes form a major size selective barrier for the filtration of serum proteins and reduced podocyte number is a critical event in the pathogenesis of proteinuria during diabetic nephropathy (DN). An elevated level of growth hormone (GH) is implicated as a causative factor in the development of nephropathy in patients with type 1 diabetes mellitus. We have previously shown that podocytes express GH receptor and are a target for GH action. To elucidate the molecular basis for the effects of GH on podocyte depletion, we conducted PCR-array analyses for extracellular matrix and adhesion molecules in podocytes. Our studies reveal that GH increases expression of a gene that encodes transforming growth factor-beta-induced protein (TGFBIp) expression. Similarly, microarray data retrieved from the Nephromine database revealed elevation of TGFBIp in patients with DN. Treatment with GH results in increased secretion of extracellular TGFBIp by podocytes. Both GH and TGFBIp induced apoptosis and epithelial mesenchymal transition (EMT) of podocytes. Exposure of podocytes to GH and TGFBIp resulted in increased migration of cells and altered podocyte permeability to albumin across podocyte monolayer. Administration of GH to rats induced EMT and apoptosis in the glomerular fraction of the kidney. Therefore, we conclude that the GH-dependent increase in TGFBIp in the podocyte is one of the mechanisms responsible for podocyte depletion in DN.

  11. Modulation of Type III Secretion System in Pseudomonas aeruginosa: Involvement of the PA4857 Gene Product

    PubMed Central

    Zhu, Miao; Zhao, Jingru; Kang, Huaping; Kong, Weina; Zhao, Yuanyu; Wu, Min; Liang, Haihua

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that causes serious acute or chronic infections in humans. Acute infections typically involve the type III secretion systems (T3SSs) and bacterial motility, whereas chronic infections are often associated with biofilm formation and the type VI secretion system. To identify new genes required for pathogenesis, a transposon mutagenesis library was constructed and the gene PA4857, named tspR, was found to modulate T3SS gene expression. Deletion of P. aeruginosa tspR reduced the virulence in a mouse acute lung infection model and diminished cytotoxicity. Suppression of T3SS gene expression in the tspR mutant resulted from compromised translation of the T3SS master regulator ExsA. TspR negatively regulated two small RNAs, RsmY and RsmZ, which control RsmA. Our data demonstrated that defects in T3SS expression and biofilm formation in retS mutant could be partially restored by overexpression of tspR. Taken together, our results demonstrated that the newly identified retS-tspR pathway is coordinated with the retS-gacS system, which regulates the genes associated with acute and chronic infections and controls the lifestyle choice of P. aeruginosa. PMID:26858696

  12. Erwinia amylovora modifies phenolic profiles of susceptible and resistant apple through its type III secretion system.

    PubMed

    Pontais, Isabelle; Treutter, Dieter; Paulin, Jean-Pierre; Brisset, Marie-Noëlle

    2008-03-01

    Fire blight is a disease affecting Maloideae caused by the necrogenic bacterium Erwinia amylovora, which requires the type III protein secretion system (TTSS) for pathogenicity. Profiles of methanol-extractable leaf phenolics of two apple (Malus x domestica) genotypes with contrasting susceptibility to this disease were analyzed by HPLC after infection. Some qualitative differences were recorded between the constitutive compositions of the two genotypes but in both of them dihydrochalcones accounted for more than 90% of total phenolics. Principal component analysis separated leaves inoculated with a virulent wild-type strain from those inoculated with a non-pathogenic TTSS-defective mutant or with water. The changes in levels of the various groups of phenolics in response to the virulent bacterium were similar between the two genotypes, with a significant decrease of dihydrochalcones and a significant increase of hydroxycinnamate derivatives. Differences between genotypes were, however, recorded in amplitude and kinetic of variation in these groups. Occurrence of oxidation and polymerization reactions is proposed, based on the browning process of infected tissues, but whether some by-products act in defense as toxic compounds remain to be tested. Among direct antibacterial constitutive compounds present in apple leaves, the dihydrochalcone phloretin only was found at levels close to lethal concentrations in both genotypes. However, E. amylovora exhibited the ability to stabilize this compound at sublethal levels even in the resistant apple, rejecting the hypothesis of its involvement in the resistance of this genotype.

  13. The type III protein secretion system contributes to Xanthomonas citri subsp. citri biofilm formation

    PubMed Central

    2014-01-01

    Background Several bacterial plant pathogens colonize their hosts through the secretion of effector proteins by a Type III protein secretion system (T3SS). The role of T3SS in bacterial pathogenesis is well established but whether this system is involved in multicellular processes, such as bacterial biofilm formation has not been elucidated. Here, the phytopathogen Xanthomonas citri subsp. citri (X. citri) was used as a model to gain further insights about the role of the T3SS in biofilm formation. Results The capacity of biofilm formation of different X. citri T3SS mutants was compared to the wild type strain and it was observed that this secretion system was necessary for this process. Moreover, the T3SS mutants adhered proficiently to leaf surfaces but were impaired in leaf-associated growth. A proteomic study of biofilm cells showed that the lack of the T3SS causes changes in the expression of proteins involved in metabolic processes, energy generation, exopolysaccharide (EPS) production and bacterial motility as well as outer membrane proteins. Furthermore, EPS production and bacterial motility were also altered in the T3SS mutants. Conclusions Our results indicate a novel role for T3SS in X. citri in the modulation of biofilm formation. Since this process increases X. citri virulence, this study reveals new functions of T3SS in pathogenesis. PMID:24742141

  14. Adenylate Cyclase Type III Is Not a Ubiquitous Marker for All Primary Cilia during Development

    PubMed Central

    Antal, Maria Cristina; Bénardais, Karelle; Samama, Brigitte; Auger, Cyril; Schini-Kerth, Valérie; Ghandour, Said; Boehm, Nelly

    2017-01-01

    Adenylate cyclase type III (AC3) is localized in plasma membrane of neuronal primary cilium and can be used as a marker of this cilium. AC3 has also been detected in some other primary cilia such as those of fibroblasts, synoviocytes or astrocytes. Despite the presence of a cilium in almost all cell types, we show that AC3 is not a common marker of all primary cilia of different human and mouse tissues during development. In peripheral organs, AC3 is present mainly in primary cilia in cells of the mesenchymal lineage (fibroblasts, chondroblasts, osteoblasts-osteocytes, odontoblasts, muscle cells and endothelial cells). In epithelia, the apical cilium of renal and pancreatic tubules and of ductal plate in liver is AC3-negative whereas the cilium of basal cells of stratified epithelia is AC3-positive. Using fibroblasts cell culture, we show that AC3 appears at the plasma membrane of the primary cilium as soon as this organelle develops. The functional significance of AC3 localization at the cilium membrane in some cells but not others has to be investigated in relationship with cell physiology and expression at the cilium plasma membrane of specific upstream receptors. PMID:28122017

  15. Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer.

    PubMed

    Brisson, Becky K; Mauldin, Elizabeth A; Lei, Weiwei; Vogel, Laurie K; Power, Ashley M; Lo, Albert; Dopkin, Derek; Khanna, Chand; Wells, Rebecca G; Puré, Ellen; Volk, Susan W

    2015-05-01

    Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3(+/-) mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3(+/-) mice compared to Col3(+/+) littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma.

  16. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    PubMed Central

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  17. RfaL Is Required for Yersinia pestis Type III Secretion and Virulence

    PubMed Central

    Houppert, Andrew S.; Bohman, Lesley; Merritt, Peter M.; Cole, Christopher B.; Caulfield, Adam J.; Lathem, Wyndham W.

    2013-01-01

    Yersinia pestis, the causative agent of plague, uses a type III secretion system (T3SS) to inject cytotoxic Yop proteins directly into the cytosol of mammalian host cells. The T3SS can also be activated in vitro at 37°C in the absence of calcium. The chromosomal gene rfaL (waaL) was recently identified as a virulence factor required for proper function of the T3SS. RfaL functions as a ligase that adds the terminal N-acetylglucosamine to the lipooligosaccharide core of Y. pestis. We previously showed that deletion of rfaL prevents secretion of Yops in vitro. Here we show that the divalent cations calcium, strontium, and magnesium can partially or fully rescue Yop secretion in vitro, indicating that the secretion phenotype of the rfaL mutant may be due to structural changes in the outer membrane and the corresponding feedback inhibition on the T3SS. In support of this, we found that the defect can be overcome by deleting the regulatory gene lcrQ. Consistent with a defective T3SS, the rfaL mutant is less virulent than the wild type. We show here that the virulence defect of the mutant correlates with a decrease in both T3SS gene expression and ability to inject innate immune cells, combined with an increased sensitivity to cationic antimicrobial peptides. PMID:23357388

  18. Collider signatures for the heavy lepton triplet in the type I+III seesaw mechanism

    SciTech Connect

    Arhrib, Abdesslam; Bajc, Borut; Ghosh, Dilip Kumar; Han, Tao; Huang, Gui-Yu; Puljak, Ivica; Senjanovic, Goran

    2010-09-01

    The minimal SU(5) theory augmented by the fermionic adjoint representation restores the coupling constant unification and gives realistic neutrino masses and mixing through the hybrid Type I and Type III seesaw. The crucial prediction of the theory is an SU(2) lepton triplet with the mass below TeV. We study the signature of these heavy leptons at the hadron and lepton colliders. The smoking gun evidence of the theory, as in general seesaw mechanisms, is {Delta}L=2 lepton-number violation through events of a pair of like-sign leptons plus four jets without significant missing energy at hadron colliders. We find that via this unique channel the heavy lepton can be searched for up to a mass of 200 GeV at the Tevatron with 8 fb{sup -1}, and up to 450 (700) GeV at the LHC of 14 TeV C.M. energy with 10(100) fb{sup -1}. The 7 TeV LHC run of 1 fb{sup -1} is expected to probe a mass window of 110-200 GeV. We also comment on how to distinguish this theory from other models with similar heavy leptons. Finally, we compare the production rates and angular distributions of heavy leptons in e{sup +}e{sup -} collisions for various models.

  19. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.

    PubMed

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M; Drouet, Christian; Braley, Hal; Nolte, Marc W; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-08-03

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.

  20. Evidence for an evolutionary antagonism between Mrr and Type III modification systems

    PubMed Central

    Tesfazgi Mebrhatu, Mehari; Wywial, Ewa; Ghosh, Anirban; Michiels, Chris W.; Lindner, Ariel B.; Taddei, François; Bujnicki, Janusz M.; Van Melderen, Laurence; Aertsen, Abram

    2011-01-01

    The Mrr protein of Escherichia coli is a laterally acquired Type IV restriction endonuclease with specificity for methylated DNA. While Mrr nuclease activity can be elicited by high-pressure stress in E. coli MG1655, its (over)expression per se does not confer any obvious toxicity. In this study, however, we discovered that Mrr of E. coli MG1655 causes distinct genotoxicity when expressed in Salmonella typhimurium LT2. Genetic screening enabled us to contribute this toxicity entirely to the presence of the endogenous Type III restriction modification system (StyLTI) of S. typhimurium LT2. The StyLTI system consists of the Mod DNA methyltransferase and the Res restriction endonuclease, and we revealed that expression of the LT2 mod gene was sufficient to trigger Mrr activity in E. coli MG1655. Moreover, we could demonstrate that horizontal acquisition of the MG1655 mrr locus can drive the loss of endogenous Mod functionality present in S. typhimurium LT2 and E. coli ED1a, and observed a strong anti-correlation between close homologues of MG1655 mrr and LT2 mod in the genome database. This apparent evolutionary antagonism is further discussed in the light of a possible role for Mrr as defense mechanism against the establishment of epigenetic regulation by foreign DNA methyltransferases. PMID:21504983

  1. Common pathways regulate Type III TGFβ receptor-dependent cell invasion in epicardial and endocardial cells.

    PubMed

    Clark, Cynthia R; Robinson, Jamille Y; Sanchez, Nora S; Townsend, Todd A; Arrieta, Julian A; Merryman, W David; Trykall, David Z; Olivey, Harold E; Hong, Charles C; Barnett, Joey V

    2016-06-01

    Epithelial-Mesenchymal Transformation (EMT) and the subsequent invasion of epicardial and endocardial cells during cardiac development is critical to the development of the coronary vessels and heart valves. The transformed cells give rise to cardiac fibroblasts and vascular smooth muscle cells or valvular interstitial cells, respectively. The Type III Transforming Growth Factor β (TGFβR3) receptor regulates EMT and cell invasion in both cell types, but the signaling mechanisms downstream of TGFβR3 are not well understood. Here we use epicardial and endocardial cells in in vitro cell invasion assays to identify common mechanisms downstream of TGFβR3 that regulate cell invasion. Inhibition of NF-κB activity blocked cell invasion in epicardial and endocardial cells. NF-κB signaling was found to be dysregulated in Tgfbr3(-/-) epicardial cells which also show impaired cell invasion in response to ligand. TGFβR3-dependent cell invasion is also dependent upon Activin Receptor-Like Kinase (ALK) 2, ALK3, and ALK5 activity. A TGFβR3 mutant that contains a threonine to alanine substitution at residue 841 (TGFβR3-T841A) induces ligand-independent cell invasion in both epicardial and endocardial cells in vitro. These findings reveal a role for NF-κB signaling in the regulation of epicardial and endocardial cell invasion and identify a mutation in TGFβR3 which stimulates ligand-independent signaling.

  2. The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy

    PubMed Central

    Bruening, Janina

    2017-01-01

    The human interferon (IFN) response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs) with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses. As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment. In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA) exist. Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C. PMID:28255563

  3. Immunohistochemical analysis of type III collagen expression in the lingual mucosa of rats during organogenesis of the tongue.

    PubMed

    Iwasaki, Shin-Ichi; Asami, Tomoichiro; Wanichanon, Chaitip; Yoshizawa, Hideki; Aoyagi, Hidekazu

    2008-07-01

    We examined the distribution of immunofluorescence due to immunostaining of type III collagen, differential interference contrast (DIC) images and images obtained in the transmission mode after toluidine blue staining by laser-scanning microscopy of semi-ultrathin sections of epoxy resin-embedded samples, during morphogenesis of the filiform papillae, keratinization of the lingual epithelium, and myogenesis of the rat tongue. Immunoreactivity specific for type III collagen was distributed widely in the mesenchymal connective tissue in fetuses on day 15 after conception (E15), at which time the lingual epithelium was composed of one or two layers of cuboidal cells and the lingual muscle was barely recognizable. Immunoreactivity specific for type III collagen was clearly detected on the lamina propria in fetuses on E17 and E19, and it was relatively distinct just beneath the lingual epithelium. Immunoreactivity specific for type III collagen was sparsely distributed on the connective tissue around the developing lingual muscle. In fetuses on E19, the epithelium became clearly stratified and squamous. At postnatal stages from newborn (P0) to postnatal day 14 (P14), keratinization of the lingual epithelium advanced gradually with the development of filiform papillae. On P0, myogenesis of the tongue was almost completed. The intensity of the fluorescence immunoreactivity specific for type III collagen at postnatal stages was almost same as that on E19. The immunoreactivity around the fully mature muscle was relatively distinct between P0 and P14. Thus, type III collagen appeared in conjunction with the morphogenesis of filiform papillae and the keratinization of the lingual epithelium as well as in the connective tissue that surrounded the lingual muscle during myogenesis of the rat tongue.

  4. Biochemical analysis of callus tissue in osteogenesis imperfecta type IV. Evidence for transient overmodification in collagen types I and III.

    PubMed Central

    Brenner, R E; Vetter, U; Nerlich, A; Wörsdorfer, O; Teller, W M; Müller, P K

    1989-01-01

    We analyzed tissue and cells from a stationary and a rapidly growing hyperplastic callus from a patient with osteogenesis imperfecta (OI) type IV and compared the results with those of compact bone and skin fibroblasts of an age-matched control. Collagen and protein contents per cell were low in the callus tissues and collagen I and III were overmodified as evidenced by an elevated level of hydroxylysine. The degree of lysyl hydroxylation was highest in those regions that appeared most immature by histological examination. Lysyl hydroxylation approached normal levels in collagen from the stationary callus and from the center of the growing callus. Overmodification of collagen was not seen in compact bone or cell cultures (neither skin fibroblasts nor callus cells) from the patient. Elevation of hydroxylysine in collagen from OI patients is generally attributed to mutations that delay triple helix formation. Our observations suggest that the varying degree of collagen modifications may occur in consequence of regulatory mechanisms during bone development and tissue repair. These mechanisms may be defective in some patients with OI as seen in this case with hyperplastic callus formation. Images PMID:2760218

  5. Strains of the Propionibacterium acnes type III lineage are associated with the skin condition progressive macular hypomelanosis

    PubMed Central

    Barnard, Emma; Liu, Jared; Yankova, Eliza; Cavalcanti, Silvana M.; Magalhães, Marcelo; Li, Huiying; Patrick, Sheila; McDowell, Andrew

    2016-01-01

    Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P. acnes isolates recovered from paired lesional and non-lesional skin of PMH patients. Our results demonstrate a strong statistical association between strains from the type III phylogenetic lineage and PMH lesions (P = 0.0019), but not those representing other phylogroups, including those associated with acne (type IA1). We also demonstrate, based on in silico 16S rDNA analysis, that PMH isolates previously recovered from patients in Europe are also consistent with the type III lineage. Using comparative genome analysis, we identified multiple genomic regions that are specific for, or absent from, type III strains compared to other phylogroups. In the former case, these include open reading frames with putative functions in metabolism, transport and transcriptional regulation, as well as predicted proteins of unknown function. Further study of these genomic elements, along with transcriptional and functional analyses, may help to explain why type III strains are associated with PMH. PMID:27555369

  6. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    SciTech Connect

    Stevens, C.E.; Taylor, P.E.; Zang, E.A.; Morrison, J.M.; Harley, E.J.; de Cordoba, S.R.; Bacino, C.; Ting, R.C.; Bodner, A.J.; Sarngadharan, M.G.; Gallo, R.C.

    1986-04-25

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men.

  7. Qualitative study of Bianchi type-I, III and Kantowski-Sachs cosmological models with scalar field

    NASA Astrophysics Data System (ADS)

    Chaubey, Raghavendra; Raushan, Rakesh

    2016-08-01

    A qualitative analysis of Bianchi type-I, III and Kantowski-Sachs (KS) cosmological models with a scalar field and matter fluid is performed. The analysis of the resulting equations is made by the dynamical system method. To analyze the evolution equations, we have introduced suitable transformation of variables. The evolution of the corresponding solutions is represented by curves in the phase-plane diagram. We analyze the evolution of the effective equation of state parameter for Bianchi type-I, III and KS cosmological models. The nature of critical points are analyzed and stable attractors are examined for each cosmological model.

  8. Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling

    PubMed Central

    2013-01-01

    Background Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion System), present in the genome of Salmonella typhimurium have been implicated in the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both encoding components of the Type III Secretion System - T3SS) are well understood, T6SS regulation is comparatively less studied. Interestingly, inter-connections among the regulatory elements of these three virulence determinants have also been suggested to be essential for successful infection. However, till date, an integrated view of gene regulation involving the regulators of these three secretion systems and their cross-talk is not available. Results In the current study, relevant regulatory information available from literature have been integrated into a single Boolean network, which portrays the dynamics of T3SS (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory interactions involving a two-component system response regulator YfhA have also been predicted and included in the Boolean network. These predictions are aimed at deciphering the effects of osmolarity on T6SS regulation, an aspect that has been suggested in earlier studies, but the mechanism of which was hitherto unknown. Simulation of the regulatory network was able to recreate in silico the experimentally observed sequential activation of SPI-1, SPI-2 and T6SS. Conclusions The present study integrates relevant gene regulatory data (from literature and our prediction) into a single network, representing the cross-communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of regulatory interactions is expected to improve the current understanding of pathogenesis of S. typhimurium. PMID:24079299

  9. Calcium and Iron Regulate Swarming and Type III Secretion in Vibrio parahaemolyticus▿ †

    PubMed Central

    Gode-Potratz, Cindy J.; Chodur, Daniel M.; McCarter, Linda L.

    2010-01-01

    Here, we probe the response to calcium during growth on a surface and show that calcium influences the transcriptome and stimulates motility and virulence of Vibrio parahaemolyticus. Swarming (but not swimming) gene expression and motility were enhanced by calcium. Calcium also elevated transcription of one of the organism's two type III secretion systems (T3SS1 but not T3SS2) and heightened cytotoxicity toward host cells in coculture. Calcium stimulation of T3SS gene expression has not been reported before, although low calcium is an inducing signal for the T3SS of many organisms. EGTA was also found to increase T3SS1 gene expression and virulence; however, this was demonstrated to be the consequence of iron rather than calcium chelation. Ectopic expression of exsA, encoding the T3SS1 AraC-type regulator, was used to define the extent of the T3SS1 regulon and verify its coincident induction by calcium and EGTA. To begin to understand the regulatory mechanisms modulating the calcium response, a calcium-repressed, LysR-type transcription factor named CalR was identified and shown to repress swarming and T3SS1 gene expression. Swarming and T3SS1 gene expression were also demonstrated to be linked by LafK, a σ54-dependent regulator of swarming, and additionally connected by a negative-feedback loop on the swarming regulon propagated by ExsA. Thus, calcium and iron, two ions pertinent for a marine organism and pathogen, play a signaling role with global consequences on the regulation of gene sets that are relevant for surface colonization and infection. PMID:20851895

  10. Identification of novel Xanthomonas euvesicatoria type III effector proteins by a machine-learning approach.

    PubMed

    Teper, Doron; Burstein, David; Salomon, Dor; Gershovitz, Michael; Pupko, Tal; Sessa, Guido

    2016-04-01

    The Gram-negative bacterium Xanthomonas euvesicatoria (Xcv) is the causal agent of bacterial spot disease in pepper and tomato. Xcv pathogenicity depends on a type III secretion (T3S) system that delivers effector proteins into host cells to suppress plant immunity and promote disease. The pool of known Xcv effectors includes approximately 30 proteins, most identified in the 85-10 strain by various experimental and computational techniques. To identify additional Xcv 85-10 effectors, we applied a genome-wide machine-learning approach, in which all open reading frames (ORFs) were scored according to their propensity to encode effectors. Scoring was based on a large set of features, including genomic organization, taxonomic dispersion, hypersensitive response and pathogenicity (hrp)-dependent expression, 5' regulatory sequences, amino acid composition bias and GC content. Thirty-six predicted effectors were tested for translocation into plant cells using the hypersensitive response (HR)-inducing domain of AvrBs2 as a reporter. Seven proteins (XopAU, XopAV, XopAW, XopAP, XopAX, XopAK and XopAD) harboured a functional translocation signal and their translocation relied on the HrpF translocon, indicating that they are bona fide T3S effectors. Remarkably, four belong to novel effector families. Inactivation of the xopAP gene reduced the severity of disease symptoms in infected plants. A decrease in cell death and chlorophyll content was observed in pepper leaves inoculated with the xopAP mutant when compared with the wild-type strain. However, populations of the xopAP mutant in infected leaves were similar in size to those of wild-type bacteria, suggesting that the reduction in virulence was not caused by impaired bacterial growth.

  11. Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm.

    PubMed

    García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

    2013-01-01

    The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.

  12. The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi

    PubMed Central

    Johnson, Rebecca; Byrne, Alexander; Berger, Cedric N.; Klemm, Elizabeth; Crepin, Valerie F.; Dougan, Gordon

    2016-01-01

    ABSTRACT Strains of the various Salmonella enterica serovars cause gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (Salmonella pathogenicity island 1 [SPI-1] and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton postinfection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S. enterica serovar Typhimurium and S. Typhi; direct comparison of the protein sequences revealed that S. Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S. Typhi and S. Typhimurium strains demonstrated that, unlike SptP in S. Typhimurium, SptP in S. Typhi was not involved in invasion or cytoskeletal recovery postinfection. Investigation of whether the observed amino acid changes within SptP of S. Typhi affected its function revealed that S. Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that while S. Typhimurium SptP is stable intracellularly within S. Typhi, S. Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S. Typhimurium. Direct assessment of the strength of the interaction between SptP and SicP of both serovars via bacterial two-hybrid analysis demonstrated that S. Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S. Typhimurium. Taken together, our results suggest that changes within the chaperone-binding domain of SptP in S. Typhi hinder binding to its chaperone, resulting in instability, preventing translocation, and therefore restricting the intracellular activity of this effector. IMPORTANCE Studies investigating Salmonella pathogenesis typically rely on Salmonella Typhimurium, even though Salmonella Typhi causes the more severe disease in humans. As such, an understanding of

  13. Identification of type III secretion substrates of Chlamydia trachomatis using Yersinia enterocolitica as a heterologous system

    PubMed Central

    2014-01-01

    Background Chlamydia trachomatis is an obligate intracellular human pathogen causing ocular and urogenital infections that are a significant clinical and public health concern. This bacterium uses a type III secretion (T3S) system to manipulate host cells, through the delivery of effector proteins into their cytosol, membranes, and nucleus. In this work, we aimed to find previously unidentified C. trachomatis T3S substrates. Results We first analyzed the genome of C. trachomatis L2/434 strain for genes encoding mostly uncharacterized proteins that did not appear to possess a signal of the general secretory pathway and which had not been previously experimentally shown to be T3S substrates. We selected several genes with these characteristics and analyzed T3S of the encoding proteins using Yersinia enterocolitica as a heterologous system. We identified 23 C. trachomatis proteins whose first 20 amino acids were sufficient to drive T3S of the mature form of β-lactamase TEM-1 by Y. enterocolitica. We found that 10 of these 23 proteins were also type III secreted in their full-length versions by Y. enterocolitica, providing additional support that they are T3S substrates. Seven of these 10 likely T3S substrates of C. trachomatis were delivered by Y. enterocolitica into host cells, further suggesting that they could be effectors. Finally, real-time quantitative PCR analysis of expression of genes encoding the 10 likely T3S substrates of C. trachomatis showed that 9 of them were clearly expressed during infection of host cells. Conclusions Using Y. enterocolitica as a heterologous system, we identified 10 likely T3S substrates of C. trachomatis (CT053, CT105, CT142, CT143, CT144, CT161, CT338, CT429, CT656, and CT849) and could detect translocation into host cells of CT053, CT105, CT142, CT143, CT161, CT338, and CT429. Therefore, we revealed several C. trachomatis proteins that could be effectors subverting host cell processes. PMID:24533538

  14. IscR Is Essential for Yersinia pseudotuberculosis Type III Secretion and Virulence

    PubMed Central

    Miller, Halie K.; Kwuan, Laura; Schwiesow, Leah; Bernick, David L.; Mettert, Erin; Ramirez, Hector A.; Ragle, James M.; Chan, Patricia P.; Kiley, Patricia J.; Lowe, Todd M.; Auerbuch, Victoria

    2014-01-01

    Type III secretion systems (T3SS) are essential for virulence in dozens of pathogens, but are not required for growth outside the host. Therefore, the T3SS of many bacterial species are under tight regulatory control. To increase our understanding of the molecular mechanisms behind T3SS regulation, we performed a transposon screen to identify genes important for T3SS function in the food-borne pathogen Yersinia pseudotuberculosis. We identified two unique transposon insertions in YPTB2860, a gene that displays 79% identity with the E. coli iron-sulfur cluster regulator, IscR. A Y. pseudotuberculosis iscR in-frame deletion mutant (ΔiscR) was deficient in secretion of Ysc T3SS effector proteins and in targeting macrophages through the T3SS. To determine the mechanism behind IscR control of the Ysc T3SS, we carried out transcriptome and bioinformatic analysis to identify Y. pseudotuberculosis genes regulated by IscR. We discovered a putative IscR binding motif upstream of the Y. pseudotuberculosis yscW-lcrF operon. As LcrF controls transcription of a number of critical T3SS genes in Yersinia, we hypothesized that Yersinia IscR may control the Ysc T3SS through LcrF. Indeed, purified IscR bound to the identified yscW-lcrF promoter motif and mRNA levels of lcrF and 24 other T3SS genes were reduced in Y. pseudotuberculosis in the absence of IscR. Importantly, mice orally infected with the Y. pseudotuberculosis ΔiscR mutant displayed decreased bacterial burden in Peyer's patches, mesenteric lymph nodes, spleens, and livers, indicating an essential role for IscR in Y. pseudotuberculosis virulence. This study presents the first characterization of Yersinia IscR and provides evidence that IscR is critical for virulence and type III secretion through direct regulation of the T3SS master regulator, LcrF. PMID:24945271

  15. Investigations into the synthesis and fluorescence properties of Eu(III), Tb(III), Sm(III) and Gd(III) complexes of a novel bis-beta-diketone-type ligand.

    PubMed

    Luo, Yi-Ming; Chen, Zhe; Tang, Rui-Ren; Xiao, Lin-Xiang; Peng, Hong-Jian

    2008-02-01

    A novel bis-beta-diketon ligand, 1,1'-(2,6-bispyridyl)bis-3-phenyl-1,3-propane-dione (L), was designed and synthesized and its complexes with Eu(III), Tb(III), Sm(III) and Gd(III) ions were successfully prepared. The ligand and the corresponding metal complexes were characterized by elemental analysis, and infrared, mass and proton nuclear magnetic resonance spectroscopy. Analysis of the IR spectra suggested that each of the lanthanide metal ions coordinated to the ligand via the carbonyl oxygen atoms and the nitrogen atom of the pyridine ring. The fluorescence properties of these complexes in solid state were investigated and it was discovered that all of the lanthanide ions could be sensitized by the ligand (L) to some extent. In particular, the Tb(III) complex was an excellent green-emitter and would be a potential candidate material for applications in organic light-emitting devices (OLEDs) and medical diagnosis.

  16. Investigations into the synthesis and fluorescence properties of Eu(III), Tb(III), Sm(III) and Gd(III) complexes of a novel bis- β-diketone-type ligand

    NASA Astrophysics Data System (ADS)

    Luo, Yi-Ming; Chen, Zhe; Tang, Rui-Ren; Xiao, Lin-Xiang; Peng, Hong-Jian

    2008-02-01

    A novel bis- β-diketon ligand, 1,1'-(2,6-bispyridyl)bis-3-phenyl-1,3-propane-dione (L), was designed and synthesized and its complexes with Eu(III), Tb(III), Sm(III) and Gd(III) ions were successfully prepared. The ligand and the corresponding metal complexes were characterized by elemental analysis, and infrared, mass and proton nuclear magnetic resonance spectroscopy. Analysis of the IR spectra suggested that each of the lanthanide metal ions coordinated to the ligand via the carbonyl oxygen atoms and the nitrogen atom of the pyridine ring. The fluorescence properties of these complexes in solid state were investigated and it was discovered that all of the lanthanide ions could be sensitized by the ligand (L) to some extent. In particular, the Tb(III) complex was an excellent green-emitter and would be a potential candidate material for applications in organic light-emitting devices (OLEDs) and medical diagnosis.

  17. Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil.

    PubMed Central

    Weintraub, M S; Eisenberg, S; Breslow, J L

    1987-01-01

    To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial lipoproteins were present for more than 14 h, and chylomicron levels correlated inversely with lipoprotein lipase activity and fasting high density lipoprotein (HDL) cholesterol levels and nonchylomicron levels correlated inversely with hepatic triglyceride lipase activity. The main abnormality in type IV patients was a 5.6-fold increase in the chylomicron fraction, whereas in type III patients it was a 6.4-fold increase in nonchylomicrons. Type IIa patients had abnormally low chylomicron fractions. In type IV patients gemfibrozil decreased, whereas in type IIa patients cholestyramine increased the chylomicron fraction 66 and 88%, respectively. This study demonstrates an unexpectedly large magnitude and long duration of postprandial lipemia in normal subjects and patients. These particles are potentially atherogenic, and their role in human atherosclerosis warrants further study. PMID:3470306

  18. Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium

    PubMed Central

    Platt, James L.; Kent, Nicholas A.; Kimmel, Alan R.

    2017-01-01

    Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states. PMID:28330902

  19. Effect of Wubeizi ointment aqueous solution on the expression of type I and III procollagen genes in keloid fibroblasts

    PubMed Central

    Zhai, Xiao-Xiang; Ding, Ji-Cun; Tang, Zhi-Ming; Li, Jing-Guo; Chen, Xiang-Hui; Zhang, Cui-Xia

    2017-01-01

    We evaluated the effect of Wubeizi (WBZ) ointment on keloids. Keloid-derived fibroblast primary cultures were used to evaluate the effect of the different concentration of WBZ ointment on the expression of type I and III procollagen in keloid fibroblast primary cultures using dot blot assay. Type I and II precollagen cDNA probes labeled with non-radioactive digoxin were used for dot blot. Cell cultures were divided into 4 groups: The large dose group received 1 g/ml of WBZ, middle dose, and small dose groups received 0.5 and 0.25 g/ml of WBZ, respectively. The control group received serum-free medium without WBZ. Our results showed that type I and III procollagen mRNA expression was reduced significantly in the large dose and middle dose groups compared to the control group. Type I and III procollagen mRNA expression level in the small dose group had no statistically significant difference with the control group. However, the difference between the large dose group and the small dose group was statistically significant. We concluded that WBZ ointment aqueous solution restricted keloid fibroblast proliferation by downregulating the expression of type I and III procollagen and therefore reducing collagen deposition in keloid tissue.

  20. Arabidopsis CYP86A2 represses Pseudomonas syringae type III genes and is required for cuticle development

    PubMed Central

    Xiao, Fangming; Mark Goodwin, S; Xiao, Yanmei; Sun, Zhaoyu; Baker, Douglas; Tang, Xiaoyan; Jenks, Matthew A; Zhou, Jian-Min

    2004-01-01

    Pseudomonas syringae relies on type III secretion system to deliver effector proteins into the host cell for parasitism. Type III genes are induced in planta, but host factors affecting the induction are poorly understood. Here we report on the identification of an Arabidopsis mutant, att1 (for aberrant induction of type three genes), that greatly enhances the expression of bacterial type III genes avrPto and hrpL. att1 plants display enhanced disease severity to a virulent strain of P. syringae, suggesting a role of ATT1 in disease resistance. ATT1 encodes CYP86A2, a cytochrome P450 monooxygenase catalyzing fatty acid oxidation. The cutin content is reduced to 30% in att1, indicating that CYP86A2 plays a major role in the biosynthesis of extracellular lipids. att1 has a loose cuticle membrane ultrastructure and shows increased permeability to water vapor, demonstrating the importance of the cuticle membrane in controlling water loss. The enhanced avrPto-luc expression is specific to att1, but not another cuticle mutant, wax2. The results suggest that certain cutin-related fatty acids synthesized by CYP86A2 may repress bacterial type III gene expression in the intercellular spaces. PMID:15241470

  1. Correlating Type II and III Radio Bursts with Solar Energetic Particle Events

    NASA Astrophysics Data System (ADS)

    Ledbetter, K.; Winter, L. M.; Quinn, R. A.

    2013-12-01

    Solar energetic particles (SEPs) are high-energy particles, such as protons, which are accelerated at the Sun and speed outward into the solar system. If they reach Earth, they can be harmful to satellites, ionospheric communications, and humans in space or on polar airline routes. NOAA defines an SEP event as an occasion when the flux of protons with energies higher than 10 MeV exceeds 10 pfu (particle flux units) as measured by the GOES satellites in geosynchronous orbit. The most intense SEP events are associated with shocks, driven by coronal mass ejections (CMEs), which accelerate particles as they move through the corona. However, very few CMEs result in SEP events. To determine what factors are most important in distinguishing the shock waves that will result in SEP acceleration toward Earth, we take into account several variables and perform a principal component analysis (PCA) to examine their correlations. First, we examine Type II radio bursts, which are caused by electrons accelerating in the same CME-driven shocks that can accelerate SEPs. Using data from the WAVES instrument on the WIND satellite, these Type II radio bursts, as well as the Type III bursts that often accompany them, can be characterized by slope in 1/f space and by intensity. In addition, local Langmuir waves detected by WIND, which are caused by electrons speeding through the plasma surrounding the satellite, can be an indicator of the magnetic connectivity between the active region and Earth. Finally, X-ray flares directly preceding the Type II burst are also taken into consideration in the PCA analysis. The accompanying figure illustrates an example of the WAVES solar radio bursts along with the GOES solar proton flux >= 10 MeV during the SEP event on April 11, 2013. Using PCA to determine which of these factors are most relevant to the onset, intensity, and duration of SEP events will be valuable in future work to predict such events. In total, we present the analysis of all type

  2. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses.

    PubMed

    Volpe, Elisabetta; Servant, Nicolas; Zollinger, Raphaël; Bogiatzi, Sofia I; Hupé, Philippe; Barillot, Emmanuel; Soumelis, Vassili

    2008-06-01

    Interleukin 17 (IL-17)-producing T helper 17 cells (T(H)-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T(H)-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-beta, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1beta and IL-6) were all essential for human T(H)-17 differentiation. However, individual T(H)-17 cell-derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global T(H)-17 cytokine profile, were differentially modulated by T(H)-17-promoting cytokines. Transforming growth factor-beta was critical, and its absence induced a shift from a T(H)-17 profile to a T(H)1-like profile. Our results shed new light on the regulation of human T(H)-17 differentiation and provide a framework for the global analysis of T helper responses.

  3. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

    PubMed

    Gonzalo-Gil, Elena; Galindo-Izquierdo, María

    2014-01-01

    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis.

  4. Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

    PubMed Central

    Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

    2015-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  5. Polyclonal antibody localizes glia maturation factor beta-like immunoreactivity in neurons and glia.

    PubMed

    Wang, B R; Zaheer, A; Lim, R

    1992-09-18

    A rabbit polyclonal antibody (91-01) was raised against recombinant human glia maturation factor beta (r-hGMF-beta). The antibody did not cross-react with a number of other growth factors on ELISA test. When compared with the monoclonal antibody G2-09 previously obtained, 91-01 immunoblotted the same protein band in rat brain extract. However, unlike G2-09 which immunostained only astrocytes and Bergmann glia, 91-01 stained neurons as well. Many but not all neurons in the central and peripheral nervous system were positive for GMF-beta. The larger cell population stained by the polyclonal antibody was most likely due to its increased sensitivity, although other explanations are possible. The presence of GMF-beta-like immunoreactivity in both neurons and glia raises the possibility of a wider range of cell-cell interaction than was previously considered.

  6. MicroRNAs, transforming growth factor beta-1, and tissue fibrosis.

    PubMed

    Bowen, Timothy; Jenkins, Robert H; Fraser, Donald J

    2013-01-01

    MicroRNAs are short noncoding RNA regulators that repress synthesis of their targets post-transcriptionally. On average, each microRNA is estimated to regulate several hundred protein-coding genes, and about 60% of proteins are thought to be regulated by microRNAs in total. A subset of these genes, including the key profibrotic cytokine transforming growth factor beta-1 (TGF-β1), exhibits particularly strong levels of post-transcriptional control of protein synthesis, involving microRNAs and other mechanisms. Changes in microRNA expression pattern are linked to profound effects on cell phenotype, and microRNAs have an emerging role in diverse physiological and pathological processes. In this review, we provide an overview of microRNA biology with a focus on their emerging role in diseases typified by organ fibrosis.

  7. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    SciTech Connect

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

    2006-01-13

    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  8. Phosphorylation of the human-transforming-growth-factor-beta-binding protein endoglin.

    PubMed Central

    Lastres, P; Martín-Perez, J; Langa, C; Bernabéu, C

    1994-01-01

    Endoglin is an homodimeric membrane antigen with capacity to bind transforming growth factor-beta (TGF-beta). Phosphorylation of human endoglin was demonstrated in endothelial cells as well as in mouse fibroblast transfectants expressing two isoforms, L-endoglin or S-endoglin, with distinct cytoplasmic domains. The extent of L-endoglin phosphorylation was found to be 8-fold higher than that of S-endoglin, and phosphopeptide analyses revealed at least three different phosphorylation sites for L-endoglin, whereas S-endoglin produces only one phosphopeptide. The immunoprecipitated L-endoglin was found to be phosphorylated mainly on serine, and, to a minor extent, on threonine, residues. Treatment of the cells with TGF-beta 1 or the protein kinase C inhibitor H-7 resulted in a reduction of the levels of endoglin phosphorylation. Images Figure 1 Figure 2 PMID:8053900

  9. Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

    SciTech Connect

    Choy, M.; Armstrong, M.T.; Armstrong, P.B. )

    1990-10-01

    Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage.

  10. Nitric oxide synthase inhibitors attenuate transforming-growth-factor-beta 1-stimulated capillary organization in vitro.

    PubMed Central

    Papapetropoulos, A.; Desai, K. M.; Rudic, R. D.; Mayer, B.; Zhang, R.; Ruiz-Torres, M. P.; García-Cardeña, G.; Madri, J. A.; Sessa, W. C.

    1997-01-01

    Angiogenesis is a complex process involving endothelial cell (EC) proliferation, migration, differentiation, and organization into patent capillary networks. Nitric oxide (NO), an EC mediator, has been reported to be antigenic as well as proangiogenic in different models of in vivo angiogenesis. Our aim was to investigate the role of NO in capillary organization using rat microvascular ECs (RFCs) grown in three-dimensional (3D) collagen gels. RFCs placed in 3D cultures exhibited extensive tube formation in the presence of transforming growth factor-beta 1. Addition of the NO synthase (NOS) inhibitors L-nitro-arginine methylester (L-NAME, 1 mmol/L) or L-monomethyl-nitro-l-arginine (1 mmol/L) inhibited tube formation and the accumulation of nitrite in the media by approximately 50%. Incubation of the 3D cultures with excess L-arginine reversed the inhibitory effect of L-NAME on tube formation. In contrast to the results obtained in 3D cultures, inhibition of NO synthesis by L-NAME did not influence RFC proliferation in two-dimensional (2D) cultures or antagonize the ability of transforming growth factor-beta 1 to suppress EC proliferation in 2D cultures. Reverse transcriptase-polymerase chain reaction revealed the constitutive expression of all three NOS isoforms, neuronal, inducible, and endothelial NOSs, in 2D and 3D cultures. Moreover, Western blot analysis demonstrated the presence of immunoreactive protein for all NOS isoforms in 3D cultures of RFCs. In addition, in the face of NOS blockade, co-treatment with the NO donor sodium nitroprusside or the stable analog of cGMP, 8-bromo-cGMP, restored capillary tube formation. Thus, the autocrine production of NO and the activation of soluble guanylate cyclase are necessary events in the process of differentiation and in vitro capillary tube organization of RFCs. Images Figure 2 Figure 4 Figure 5 PMID:9137106

  11. Type III secretion chaperones of Pseudomonas syringae protect effectors from Lon-associated degradation.

    PubMed

    Losada, Liliana C; Hutcheson, Steven W

    2005-02-01

    The hrp type III secretion system (TTSS) of Pseudomonas syringae translocates effector proteins into the cytoplasm of host cells. Proteolysis of HrpR by Lon has been shown to negatively regulate the hrp TTSS. The inability to bypass Lon-associated effects on the regulatory system by ectopic expression of the known regulators suggested a second site of action for Lon in TTSS-dependent effector secretion. In this study we report that TTSS-dependent effectors are subject to the proteolytic degradation that appears to be rate-limiting to secretion. The half-lives of the effectors AvrPto, AvrRpt2, HopPsyA, HopPsyB1, HopPtoB2, HopPsyV1, HopPtoG and HopPtoM were substantially higher in bacteria lacking Lon. TTSS-dependent secretion of several effectors was enhanced from Lon mutants. A primary role for chaperones appears to be protection of effectors from Lon-associated degradation prior to secretion. When coexpressed with their cognate chaperone, HopPsyB1, HopPsyV1 and HopPtoM were at least 10 times more stable in strains expressing Lon. Distinct Lon-targeting and chaperone-binding domains were identified in HopPtoM. The results imply that Lon is involved at two distinct levels in the regulation of the P. syringae TTSS: regulation of assembly of the secreton and modulation of effector secretion.

  12. Aquatic therapy for a child with type III spinal muscular atrophy: a case report.

    PubMed

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-11-01

    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 (PDMS-2), and the GAITRite system. The child received aquatic therapy twice per week for 45-min sessions, for 14 weeks. The intervention included aquatic activities designed to improve gross motor skills and age-appropriate functional mobility. The GMFM total score improved by 11% following the intervention. The Standing Dimension score improved by 28% and the Walking, Running, and Jumping Dimension score improved by 18%. The gross motor quotient for the PDMS-2 improved from 66 to 74. The child's gait showed improvement in walking velocity, stride length, and single-limb support time as a percentage of the gait cycle. The outcomes of this case report demonstrate the successful improvement of gross motor function and gait in a 3-year-old child with SMA. This study provides clinical information for therapists utilizing aquatic therapy as a modality for children with neuromuscular disorders.

  13. Distinct Structural Elements Dictate the Specificity of the Type III Pentaketide Synthase from Neurospora crassa

    SciTech Connect

    Rubin-Pitel, Sheryl B.; Zhang, Houjin; Vu, Trang; Brunzelle, Joseph S.; Zhao, Huimin; Nair, Satish K.

    2009-01-15

    The fungal type III polyketide synthase 2'-oxoalkylresorcyclic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C{sub 4}--C{sub 20}) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 {angstrom} resolution, the Phe-252{yields}Gly site-directed mutant to 2.1 {angstrom} resolution, and a binary conplex of ORAS with eicosanoic acid to 2.0 {angstrom} resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accomodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.

  14. Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma.

    PubMed

    González, Raúl; De la Rosa, Ángel J; Romero-Brufau, Santiago; Barrera-Pulido, Lydia; Gallardo-Chamizo, Francisco; Pereira, Sheila; Marín, Luís M; Álamo, José M; Rodríguez-Hernández, Ángeles; Padillo, Francisco J; Muntané, Jordi

    2015-08-01

    Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP) and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

  15. Bispectral Analysis of a Langmuir Wave Packet Associated with a Solar Type III Radio Burst

    NASA Astrophysics Data System (ADS)

    Golla, T.; MacDowall, R. J.; Bergamo, M.

    2012-12-01

    We present the observations of an intense localized wave packet, obtained by the STEREO spacecraft in the source region of a solar type III radio burst. The FFT spectrum of this wave packet contains a primary peak at the local electron plasma frequency, fpe (Langmuir waves), and two secondary peaks, one at 2fpe (second harmonic) and a second one at 3fpe (third harmonic). The wavelet based time-frequency spectrogram indicates that these spectral peaks are coincident in time. It is found that the bicoherence spectrum, computed using the wavelet based bispectral analysis technique contains two peaks, one at (fpe, fpe) and a second one at (2fpe, fpe). The high values of the bicoherences of these spectral peaks, which quantify the phase coherences amongst the harmonic components provide unambiguous evidence for the three wave interactions L + L' -> T2f{pe}, and L + T2f{pe} -> T3f{pe} in the waveform data, where L and L' are the oppositely propagating Langmuir waves, and T2f{pe} and T3f{pe} are the second and third harmonic electromagnetic waves, respectively. The peak intensity and short duration of this wave packet, which indicate that it is probably a collapsing soliton formed as a result of oscillating two stream instability (OTSI), strongly suggest that the L and L' probably correspond to the OTSI excited oppositely propagating Langmuir waves.

  16. Combined tarsal and carpal tunnel syndrome in mucolipidosis type III. A case study and review.

    PubMed

    Smuts, Izelle; Potgieter, Denise; van der Westhuizen, Francois Hendrikus

    2009-01-01

    Mucolipidosis type III (MLIII) (MIM# 252600) is an uncommon autosomal recessive disorder that results from uridine 5'-diphosphate-N-acetylglucosamine: lysosomal hydrolase N-acetyl-1-phosphotransferase or UDP-GlcNAc 1-phosphotransferase deficiency. Clinical manifestations include developmental delay, short stature and other structural abnormalities. Less common clinical features, such as carpal tunnel syndrome, claw hand deformities, trigger fingers, and claw toes have previously been reported, but no specific association with tarsal tunnel syndrome has been reported in the literature. Tarsal tunnel syndrome is caused by entrapment of the posterior tibialis nerve in the tunnel formed by the medial malleolus of the ankle and the flexor retinaculum. It causes pain in the heel and sole of the foot as well as abnormal sensation in the distribution area of nervus tibialis posterior. In adults, the most common cause described is a ganglion. The phenomenon is rare in children and the published series are small. This case report portrays the presentation of a young girl with breath-holding spells secondary to painful bilateral tarsal tunnel syndrome and trigger fingers subsequently diagnosed with MLIII.

  17. Bile salt receptor complex activates a pathogenic type III secretion system

    PubMed Central

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N; Salomon, Dor; Tomchick, Diana R; Grishin, Nick V; Orth, Kim

    2016-01-01

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment. DOI: http://dx.doi.org/10.7554/eLife.15718.001 PMID:27377244

  18. Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

    PubMed Central

    Xie, Hai-Xia; Lu, Jin-Fang; Rolhion, Nathalie; Holden, David W.; Zhou, Ying

    2014-01-01

    Many Gram-negative bacteria utilize a type III secretion system (T3SS) to translocate virulence proteins into host cells to cause diseases. In responding to infection, macrophages detect some of the translocated proteins to activate caspase-1-mediated cell death, called pyroptosis, and secretion of proinflammatory cytokines to control the infection. Edwardsiella tarda is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. In this study, we report that the T3SS of E. tarda facilitates its survival and replication in murine bone marrow-derived macrophages, and E. tarda infection triggers pyroptosis of infected macrophages from mice and fish and increased secretion of the cytokine interleukin 1β in a T3SS-dependent manner. Deletion of the flagellin gene fliC of E. tarda results in decreased cytotoxicity for infected macrophages and does not attenuate its virulence in a fish model of infection, whereas upregulated expression of FliC in the fliC mutant strain reduces its virulence. We propose that the host controls E. tarda infection partially by detecting FliC translocated by the T3SS, whereas the bacteria downregulate the expression of FliC to evade innate immunity. PMID:24891103

  19. Phylogeny and Virulence of Naturally Occurring Type III Secretion System-Deficient Pectobacterium Strains▿

    PubMed Central

    Kim, Hye-Sook; Ma, Bing; Perna, Nicole T.; Charkowski, Amy O.

    2009-01-01

    Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers. PMID:19411432

  20. Phylogeny and virulence of naturally occurring type III secretion system-deficient Pectobacterium strains.

    PubMed

    Kim, Hye-Sook; Ma, Bing; Perna, Nicole T; Charkowski, Amy O

    2009-07-01

    Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers.

  1. Phase Coupling Between Spectral Components of Collapsing Langmuir Solitons in Solar Type III Radio Bursts

    NASA Technical Reports Server (NTRS)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    We present the high time resolution observations of one of the Langmuir wave packets obtained in the source region of a solar type III radio burst. This wave packet satisfies the threshold condition of the supersonic modulational instability, as well as the criterion of a collapsing Langmuir soliton, i.e., the spatial scale derived from its peak intensity is less than that derived from its short time scale. The spectrum of t his wave packet contains an intense spectral peak at local electron plasma frequency, f(sub pe) and relatively weaker peaks at 2f(sub pe) and 3f(sub pe). We apply the wavelet based bispectral analysis technique on this wave packet and compute the bicoherence between its spectral components. It is found that the bicoherence exhibits two peaks at (approximately f(sub pe), approximately f(sub pe)) and (approximately f(sub pe) approximately 2f(sub pe)), which strongly suggest that the spectral peak at 2f(sub pe) probably corresponds to the second harmonic radio emission, generated as a result of the merging of antiparallel propagating Langmuir waves trapped in the collapsing Langmuir soliton, and, the spectral peak at 3f(sub pe) probably corresponds to the third harmonic radio emission, generated as a result of merging of a trapped Langmuir wave and a second harmonic electromagnetic wave.

  2. Pseudomonas aeruginosa uses type III secretion system to kill biofilm-associated amoebae.

    PubMed

    Matz, Carsten; Moreno, Ana Maria; Alhede, Morten; Manefield, Mike; Hauser, Alan R; Givskov, Michael; Kjelleberg, Staffan

    2008-08-01

    Bacteria and protozoa coexist in a wide range of biofilm communities of natural, technical and medical importance. Generally, this interaction is characterized by the extensive grazing activity of protozoa on bacterial prey populations. We hypothesized that the close spatial coexistence in biofilms should allow opportunistic pathogenic bacteria to utilize their eukaryote-targeting arsenal to attack and exploit protozoan host cells. Studying cocultures of the environmental pathogen Pseudomonas aeruginosa and the amoeba Acanthamoeba castellanii, we found that P. aeruginosa rapidly colonized and killed biofilm-associated amoebae by a quorum-sensing independent mechanism. Analysis of the amoeba-induced transcriptome indicated the involvement of the P. aeruginosa type III secretion system (T3SS) in this interaction. A comparison of mutants with specific defects in the T3SS demonstrated the use of the secretion apparatus and the effectors ExoU, ExoS and ExoT in the killing process, of which ExoU had the greatest impact. T3SS-mediated virulence towards A. castellanii was found to be controlled by the global regulators RpoN and RpoS and through modulation of cAMP and alginate biosynthesis. Our findings suggest that conserved virulence pathways and specifically the T3SS play a central role in bacteria-protozoa interactions in biofilms and may be instrumental for the environmental persistence and evolution of opportunistic bacterial pathogens.

  3. Characterization of Nops, nodulation outer proteins, secreted via the type III secretion system of NGR234.

    PubMed

    Marie, Corinne; Deakin, William J; Viprey, Virginie; Kopciñska, Joanna; Golinowski, Wladyslaw; Krishnan, Hari B; Perret, Xavier; Broughton, William J

    2003-09-01

    The nitrogen-fixing symbiotic bacterium Rhizobium species NGR234 secretes, via a type III secretion system (TTSS), proteins called Nops (nodulation outer proteins). Abolition of TTSS-dependent protein secretion has either no effect or leads to a change in the number of nodules on selected plants. More dramatically, Nops impair nodule development on Crotalaria juncea roots, resulting in the formation of nonfixing pseudonodules. A double mutation of nopX and nopL, which code for two previously identified secreted proteins, leads to a phenotype on Pachyrhizus tuberosus differing from that of a mutant in which the TTSS is not functional. Use of antibodies and a modification of the purification protocol revealed that NGR234 secretes additional proteins in a TTSS-dependent manner. One of them was identified as NopA, a small 7-kDa protein. Single mutations in nopX and nopL were also generated to assess the involvement of each Nop in protein secretion and nodule formation. Mutation of nopX had little effect on NopL and NopA secretion but greatly affected the interaction of NGR234 with many plant hosts tested. NopL was not necessary for the secretion of any Nops but was required for efficient nodulation of some plant species. NopL may thus act as an effector protein whose recognition is dependent upon the hosts' genetic background.

  4. Serum type III procollagen peptide in asbestos workers: an early indicator of pulmonary fibrosis.

    PubMed Central

    Cavalleri, A; Gobba, F; Bacchella, L; Luberto, F; Ziccardi, A

    1988-01-01

    Serum type III procollagen peptide (PIIIP) concentrations were determined in 36 male workers exposed to asbestos fibres in the production of asbestos cement items and in 13 healthy male controls. Mean (SD) PIIIP serum concentrations were 9.3 (1.5) ng/ml (range 7-12) in the controls and 13.7 (3.5)ng/ml (range 7.5-20) in the asbestos workers; the difference was statistically significant (p less than 0.01). The exposed workers were subdivided according to presence or absence of radiological signs of asbestosis and intensity and duration of exposure. PIIIP serum values of workers with asbestos related interstitial fibrosis were the highest of the groups at 14.6 (2.3) ng/ml. In workers with heavy exposure the PIIIP values were significantly related to duration of exposure (r = 0.95; p less than 0.01). PIIIP serum values may be a useful index for the early diagnosis of asbestos induced pulmonary fibrosis and its use should be considered as part of the biological monitoring of exposed workers. PMID:3219307

  5. Observations concerning the generation and propagation of Type III solar bursts

    NASA Technical Reports Server (NTRS)

    Kellogg, P. J.

    1986-01-01

    A number of Type III bursts were observed during the Helios missions in which the burst exciter passed over the spacecraft, as evidenced by strong electric field fluctuations near the plasma frequency. Six of these were suitable for detailed study. Of the six events, one was ambiguous, one showed what is interpreted as a switchover from harmonic to fundamental, and the rest all generated fundamental at onset. This would be expected if both fundamental and harmonic are generated, as, at a fixed frequency, the fundamental will be generated earlier. For the event which seems to show both fundamental and harmonic emission, the frequency ratio is not exactly 2. This is explained in terms of a time delay of the fundamental, due to scattering and diffusion in the source region. A time delay of the order of 600 seconds at 1 AU and 20 kHz, and inversely proportional to frequency, is required to explain the observations. Crude estimates show that delay times at least this long may be attributed to trapping and scattering.

  6. Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs

    PubMed Central

    Sawa, Teiji; Hamaoka, Saeko; Kinoshita, Mao; Kainuma, Atsushi; Naito, Yoshifumi; Akiyama, Koichi; Kato, Hideya

    2016-01-01

    Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina) and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium). In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin. PMID:27792159

  7. Steps for Shigella Gatekeeper Protein MxiC Function in Hierarchical Type III Secretion Regulation*

    PubMed Central

    Roehrich, A. Dorothea; Bordignon, Enrica; Mode, Selma; Shen, Da-Kang; Liu, Xia; Pain, Maria; Murillo, Isabel; Martinez-Argudo, Isabel; Sessions, Richard B.

    2017-01-01

    Type III secretion systems are complex nanomachines used for injection of proteins from Gram-negative bacteria into eukaryotic cells. Although they are assembled when the environmental conditions are appropriate, they only start secreting upon contact with a host cell. Secretion is hierarchical. First, the pore-forming translocators are released. Second, effector proteins are injected. Hierarchy between these protein classes is mediated by a conserved gatekeeper protein, MxiC, in Shigella. As its molecular mechanism of action is still poorly understood, we used its structure to guide site-directed mutagenesis and to dissect its function. We identified mutants predominantly affecting all known features of MxiC regulation as follows: secretion of translocators, MxiC and/or effectors. Using molecular genetics, we then mapped at which point in the regulatory cascade the mutants were affected. Analysis of some of these mutants led us to a set of electron paramagnetic resonance experiments that provide evidence that MxiC interacts directly with IpaD. We suggest how this interaction regulates a switch in its conformation that is key to its functions. PMID:27974466

  8. [Cloning, expression and functional identification of a type III polyketide synthase gene from Huperzia serrata].

    PubMed

    Ye, Jin-cui; Zhang, Ping; Sun, Jie-yin; Guo, Chao-tan; Chen, Guo-shen; Abe, Ikuro; Noguchi, Hiroshi

    2011-10-01

    A cDNA encoding novel type III polyketide synthase (PKS) was cloned and sequenced from young leaves of Chinese club moss Huperzia serrata (Thunb.) Trev. by RT-PCR using degenerated primers based on the conserved sequences of known CHSs, and named as H. serrata PKS2. The terminal sequences of cDNA were obtained by the 3'- and 5'-RACE method. The full-length cDNA of H. serrata PKS2 contained a 1212 bp open reading frame encoding a 46.4 kDa protein with 404 amino acids. The deduced amino acid sequence of H. serrata PKS2 showed 50%-66% identities to those of other chalcone synthase super family enzymes of plant origin. The recombinant H. serrata PKS2 was functionally expressed in Escherichia coli with an additional hexahistidine tag at the N-terminus and showed unusually versatile catalytic potency to produce various aromatic tetraketides, including chalcones, benzophenones, phloroglucinols, and acridones. In particular, the enzyme accepted bulky starter substrates N-methylanthraniloyl-CoA, and carried out three condensations with malonyl-CoA to produce 1, 3-dihydroxy-N-methylacridone. Interestingly, H. serrata PKS2 lacks most of the consensus active site sequences with acridone synthase from Ruta graveolens (Rutaceae).

  9. a Computational Approach to Explore Protein Translocation Through Type III Secretion Apparatus

    NASA Astrophysics Data System (ADS)

    Rathinavelan, Thenmalarchelvi; Im, Wonpil

    2010-01-01

    Many Gram-negative bacteria initiate infections by injecting effector proteins into host cells through the type III secretion apparatus (TTSA) that is comprised of a basal body, a needle, and a tip. The needle channel is formed by the assembly of a single needle protein. To explore the export mechanisms of MxiH needle protein through the needle of Shigella flexneri, an essential step during needle assembly, we have performed steered molecular dynamics simulations in implicit solvent. Interestingly, the electronegative channel interior creates an energy barrier for MxiH to enter the channel, while the same may facilitate the ejection of the effectors into host cells. Structurally-known basal regions and ATPase underneath the basal region have also such electronegative interior, while effector proteins have considerable electronegative patches on their surfaces. Based on these observations, we propose a repulsive electrostatic mechanism for protein translocation through the TTSA. This mechanism is supported by the suggestion that an ATPase is required for protein translocation through these nanomachines, which may provide the energy to overcome the initial electrostatic energy barrier. A similar mechanism may be applicable to macromolecular channels in other secretion systems or viruses through which proteins or nucleic acids are transported.

  10. Structure of a bacterial type III secretion system in contact with a host membrane in situ

    NASA Astrophysics Data System (ADS)

    Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R.; Hayward, Richard D.

    2015-12-01

    Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking `pump-action' conformational changes that underpin effector injection.

  11. Type III Secretion-Dependent Sensitivity of Escherichia coli O157 to Specific Ketolides

    PubMed Central

    Fernandez-Brando, Romina J.; Yamaguchi, Nao; Tahoun, Amin; McAteer, Sean P.; Gillespie, Trudi; Wang, Dai; Argyle, Sally A.; Palermo, Marina S.

    2015-01-01

    A subset of Gram-negative bacterial pathogens uses a type III secretion system (T3SS) to open up a conduit into eukaryotic cells in order to inject effector proteins. These modulate pathways to enhance bacterial colonization. In this study, we screened established bioactive compounds for any that could repress T3SS expression in enterohemorrhagic Escherichia coli (EHEC) O157. The ketolides telithromycin and, subsequently, solithromycin both demonstrated repressive effects on expression of the bacterial T3SS at sub-MICs, leading to significant reductions in bacterial binding and actin-rich pedestal formation on epithelial cells. Preincubation of epithelial cells with solithromycin resulted in significantly less attachment of E. coli O157. Moreover, bacteria expressing the T3SS were more susceptible to solithromycin, and there was significant preferential killing of E. coli O157 bacteria when they were added to epithelial cells that had been preexposed to the ketolide. This killing was dependent on expression of the T3SS. Taken together, this research indicates that the ketolide that has accumulated in epithelial cells may traffic back into the bacteria via the T3SS. Considering that neither ketolide induces the SOS response, nontoxic members of this class of antibiotics, such as solithromycin, should be considered for future testing and trials evaluating their use for treatment of EHEC infections. These antibiotics may also have broader significance for treating infections caused by other pathogenic bacteria, including intracellular bacteria, that express a T3SS. PMID:26525795

  12. Structural and Functional Characterization of the Bacterial Type III Secretion Export Apparatus

    PubMed Central

    Brunner, Matthias J.; Yan, Jun; Franz-Wachtel, Mirita; Schärfe, Charlotta; Grin, Iwan; Galán, Jorge E.; Macek, Boris; Marlovits, Thomas C.; Robinson, Carol V.

    2016-01-01

    Bacterial type III protein secretion systems inject effector proteins into eukaryotic host cells in order to promote survival and colonization of Gram-negative pathogens and symbionts. Secretion across the bacterial cell envelope and injection into host cells is facilitated by a so-called injectisome. Its small hydrophobic export apparatus components SpaP and SpaR were shown to nucleate assembly of the needle complex and to form the central “cup” substructure of a Salmonella Typhimurium secretion system. However, the in vivo placement of these components in the needle complex and their function during the secretion process remained poorly defined. Here we present evidence that a SpaP pentamer forms a 15 Å wide pore and provide a detailed map of SpaP interactions with the export apparatus components SpaQ, SpaR, and SpaS. We further refine the current view of export apparatus assembly, consolidate transmembrane topology models for SpaP and SpaR, and present intimate interactions of the periplasmic domains of SpaP and SpaR with the inner rod protein PrgJ, indicating how export apparatus and needle filament are connected to create a continuous conduit for substrate translocation. PMID:27977800

  13. Bile salt receptor complex activates a pathogenic type III secretion system

    SciTech Connect

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

    2016-07-05

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered thatVibrio parahaemolyticusVtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

  14. A bacterial type III secretion-based protein delivery tool for broad applications in cell biology

    PubMed Central

    Ittig, Simon J.; Schmutz, Christoph; Kasper, Christoph A.; Amstutz, Marlise; Schmidt, Alexander; Sauteur, Loïc; Vigano, M. Alessandra; Low, Shyan Huey; Affolter, Markus; Cornelis, Guy R.; Nigg, Erich A.

    2015-01-01

    Methods enabling the delivery of proteins into eukaryotic cells are essential to address protein functions. Here we propose broad applications to cell biology for a protein delivery tool based on bacterial type III secretion (T3S). We show that bacterial, viral, and human proteins, fused to the N-terminal fragment of the Yersinia enterocolitica T3S substrate YopE, are effectively delivered into target cells in a fast and controllable manner via the injectisome of extracellular bacteria. This method enables functional interaction studies by the simultaneous injection of multiple proteins and allows the targeting of proteins to different subcellular locations by use of nanobody-fusion proteins. After delivery, proteins can be freed from the YopE fragment by a T3S-translocated viral protease or fusion to ubiquitin and cleavage by endogenous ubiquitin proteases. Finally, we show that this delivery tool is suitable to inject proteins in living animals and combine it with phosphoproteomics to characterize the systems-level impact of proapoptotic human truncated BID on the cellular network. PMID:26598622

  15. Using Transcriptional Control To Increase Titers of Secreted Heterologous Proteins by the Type III Secretion System

    PubMed Central

    Metcalf, Kevin J.; Finnerty, Casey; Azam, Anum; Valdivia, Elias

    2014-01-01

    The type III secretion system (T3SS) encoded at the Salmonella pathogenicity island 1 (SPI-1) locus secretes protein directly from the cytosol to the culture media in a concerted, one-step process, bypassing the periplasm. While this approach is attractive for heterologous protein production, product titers are too low for many applications. In addition, the expression of the SPI-1 gene cluster is subject to native regulation, which requires culturing conditions that are not ideal for high-density growth. We used transcriptional control to increase the amount of protein that is secreted into the extracellular space by the T3SS of Salmonella enterica. The controlled expression of the gene encoding SPI-1 transcription factor HilA circumvents the requirement of endogenous induction conditions and allows for synthetic induction of the secretion system. This strategy increases the number of cells that express SPI-1 genes, as measured by promoter activity. In addition, protein secretion titer is sensitive to the time of addition and the concentration of inducer for the protein to be secreted and SPI-1 gene cluster. Overexpression of hilA increases secreted protein titer by >10-fold and enables recovery of up to 28 ± 9 mg/liter of secreted protein from an 8-h culture. We also demonstrate that the protein beta-lactamase is able to adopt an active conformation after secretion, and the increase in secreted titer from hilA overexpression also correlates to increased enzyme activity in the culture supernatant. PMID:25038096

  16. The Salmonella Type III Secretion System Inner Rod Protein PrgJ Is Partially Folded*

    PubMed Central

    Zhong, Dalian; Lefebre, Matthew; Kaur, Kawaljit; McDowell, Melanie A.; Gdowski, Courtney; Jo, Sunhwan; Wang, Yu; Benedict, Stephen H.; Lea, Susan M.; Galan, Jorge E.; De Guzman, Roberto N.

    2012-01-01

    The type III secretion system (T3SS) is essential in the pathogenesis of many bacteria. The inner rod is important in the assembly of the T3SS needle complex. However, the atomic structure of the inner rod protein is currently unknown. Based on computational methods, others have suggested that the Salmonella inner rod protein PrgJ is highly helical, forming a folded 3 helix structure. Here we show by CD and NMR spectroscopy that the monomeric form of PrgJ lacks a tertiary structure, and the only well-structured part of PrgJ is a short α-helix at the C-terminal region from residues 65–82. Disruption of this helix by glycine or proline mutation resulted in defective assembly of the needle complex, rendering bacteria incapable of secreting effector proteins. Likewise, CD and NMR data for the Shigella inner rod protein MxiI indicate this protein lacks a tertiary structure as well. Our results reveal that the monomeric forms of the T3SS inner rod proteins are partially folded. PMID:22654099

  17. Towards the Identification of Type III Effectors Associated with Ralstonia solanacearum Virulence on Tomato and Eggplant.

    PubMed

    Pensec, Flora; Lebeau, Aurore; Daunay, M C; Chiroleu, Frédéric; Guidot, Alice; Wicker, Emmanuel

    2015-12-01

    For the development of pathogen-informed breeding strategies, identifying the microbial genes involved in interactions with the plant is a critical step. To identify type III effector (T3E) repertoires associated with virulence of the bacterial wilt pathogen Ralstonia solanacearum on Solanaceous crops, we used an original association genetics approach combining DNA microarray data and pathogenicity data on resistant eggplant, pepper, and tomato accessions. From this first screen, 25 T3Es were further full-length polymerase chain reaction-amplified within a 35-strain field collection, to assess their distribution and allelic diversity. Six T3E repertoire groups were identified, within which 11 representative strains were chosen to challenge the bacterial wilt-resistant egg plants 'Dingras multiple Purple' and 'AG91-25', and tomato Hawaii 7996. The virulence or avirulence phenotypes could not be explained by specific T3E repertoires, but rather by individual T3E genes. We identified seven highly avirulence-associated genes, among which ripP2, primarily referenced as conferring avirulence to Arabidopsis thaliana. Interestingly, no T3E was associated with avirulence to both egg-plants. Highly virulence-associated genes were also identified: ripA5_2, ripU, and ripV2. This study should be regarded as a first step toward investigating both avirulence and virulence function of the highlighted genes, but also their evolutionary dynamics in natural R. solanacearum populations.

  18. Substrate-Activated Conformational Switch on Chaperones Encodes aTargeting Signal in Type III Secretion

    PubMed Central

    Chen, Li; Ai, Xuanjun; Portaliou, Athina G.; Minetti, Conceicao A.S.A.; Remeta, David P.; Economou, Anastassios; Kalodimos, Charalampos G.

    2013-01-01

    SUMMARY Targeting of type III secretion proteins at the injectisome is an important process in bacterial virulence. Nevertheless, how the injectisome specifically recognizes TTS substrates among all bacterial proteins is unknown. A TTS peripheral membrane ATPase protein located at the base of the injectisome has been implicated in the targeting process. We have investigated the targeting of the EspA filament protein and its cognate chaperone CesAB to the EscN ATPase of the enteropathogenic E. coli (EPEC). We show that EscN selectively engages the EspA-loaded CesAB, but not the unliganded CesAB. Structure analysis revealed that the targeting signal is encoded in a disorder-order structural transition in CesAB that is elicited only upon binding of its physiological substrate, EspA. Abrogation of the interaction between the CesAB–EspA complex and EscN resulted in severe secretion and infection defects. We further show that the targeting and secretion signals are distinct and the two processes are likely regulated by different mechanisms. PMID:23523349

  19. A type III ACC synthase, ACS7, is involved in root gravitropism in Arabidopsis thaliana.

    PubMed

    Huang, Shih-Jhe; Chang, Chia-Lun; Wang, Po-Hsun; Tsai, Min-Chieh; Hsu, Pang-Hung; Chang, Ing-Feng

    2013-11-01

    Ethylene is an important plant hormone that regulates developmental processes in plants. The ethylene biosynthesis pathway is a highly regulated process at both the transcriptional and post-translational level. The transcriptional regulation of these ethylene biosynthesis genes is well known. However, post-translational modifications of the key ethylene biosynthesis enzyme 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS) are little understood. In vitro kinase assays were conducted on the type III ACS, AtACS7, fusion protein and peptides to determine whether the AtACS7 protein can be phosphorylated by calcium-dependent protein kinase (CDPK). AtACS7 was phosphorylated at Ser216, Thr296, and Ser299 by AtCDPK16 in vitro. To investigate further the function of the ACS7 gene in Arabidopsis, an acs7-1 loss-of-function mutant was isolated. The acs7-1 mutant exhibited less sensitivity to the inhibition of root gravitropism by treatment with the calcium chelator ethylene glycol tetraacetic acid (EGTA). Seedlings were treated with gradient concentrations of ACC. The results showed that a certain concentration of ethylene enhanced the gravity response. Moreover, the acs7-1 mutant was less sensitive to inhibition of the gravity response by treatment with the auxin polar transport inhibitor 1-naphthylphthalamic acid, but exogenous ACC application recovered root gravitropism. Altogether, the results indicate that AtACS7 is involved in root gravitropism in a calcium-dependent manner in Arabidopsis.

  20. Hyperinvasiveness of Salmonella enterica serovar Choleraesuis linked to hyperexpression of type III secretion systems in vitro

    PubMed Central

    Huang, Kuan-Yeh; Wang, Yi-Hsin; Chien, Kun-Yi; Janapatla, Rajendra Prasad; Chiu, Cheng-Hsun

    2016-01-01

    Salmonella enterica serovars Choleraesuis and Typhimurium are among the non-typhoid Salmonella serovars that are important zoonotic pathogens. In clinical observation, S. Typhimurium typically causes diarrheal diseases; however, S. Choleraesuis shows high predilection to cause bacteremia. The mechanism why S. Choleraesuis is more invasive to humans remains unknown. In this study, we compared the S. Typhimurium LT2 and S. Choleraesuis SC-B67 proteomes through stable isotope labeling of amino acid in cell culture (SILAC). In SILAC, the expression of many virulence proteins in two type III secretion systems (T3SSs) were significantly higher in S. Choleraesuis than in S. Typhimurium. Similar differences were also found at the transcriptional level. Compared to S. Typhimurium, S. Choleraesuis showed a higher penetration level to Caco-2 (>100-fold) and MDCK (>10-fold) monolayers. In mice after oral challenge, the invasion of spleen and liver was also higher in S. Choleraesuis than in S. Typhimurium. The transcription of hilD in S. Choleraesuis was increased in physiological (1 mM) or high (10 mM) concentrations of Mg2+, but not in low (8 μM) concentration. We conclude that S. Choleraesuis showed hyperinvasiveness in cellular as well as mouse models due to hyperexpression of T3SS genes. PMID:27886215

  1. Variation of Langmuir wave polarization with electron beam speed in type III radio bursts

    SciTech Connect

    Malaspina, David M.; Cairns, Iver H.; Ergun, Robert E.

    2013-06-13

    Observations by the twin STEREO spacecraft of in-situ electric field waveforms and radio signatures associated with type III radio bursts have demonstrated that the polarization of electron beam-driven waves near the local plasma frequency depends strongly on the speed of the driving electron beam. We expand upon a previous study by including all radio bursts with in-situ waveforms observed by STEREO in 2011. The expanded data set contains five times more radio bursts (35 up from 7) and three times as many Langmuir waves (663 up from 168). While this expanded study supports the results of the original study, that faster (slower) beam electrons drive waves with strong (weak) electric fields perpendicular to the local magnetic field, the larger data set emphasizes that the observation of strong perpendicular electric fields at high electron beam speeds is probabilistic rather than definite. This property supports the interpretation of wave polarization dependence on beam speed as Langmuir/z-mode waves shifted to small wave number through interaction with turbulent solar wind density fluctuations.

  2. Type III phosphatidylinositol 4 kinases: structure, function, regulation, signalling and involvement in disease.

    PubMed

    Dornan, Gillian L; McPhail, Jacob A; Burke, John E

    2016-02-01

    Many important cellular functions are regulated by the selective recruitment of proteins to intracellular membranes mediated by specific interactions with lipid phosphoinositides. The enzymes that generate lipid phosphoinositides therefore must be properly positioned and regulated at their correct cellular locations. Phosphatidylinositol 4 kinases (PI4Ks) are key lipid signalling enzymes, and they generate the lipid species phosphatidylinositol 4-phosphate (PI4P), which plays important roles in regulating physiological processes including membrane trafficking, cytokinesis and organelle identity. PI4P also acts as the substrate for the generation of the signalling phosphoinositides phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). PI4Ks also play critical roles in a number of pathological processes including mediating replication of a number of pathogenic RNA viruses, and in the development of the parasite responsible for malaria. Key to the regulation of PI4Ks is their regulation by a variety of both host and viral protein-binding partners. We review herein our current understanding of the structure, regulatory interactions and role in disease of the type III PI4Ks.

  3. Hfq negatively regulates type III secretion in EHEC and several other pathogens

    PubMed Central

    Shakhnovich, Elizabeth A.; Davis, Brigid M.; Waldor, Matthew K.

    2009-01-01

    Summary Hfq is a conserved RNA-binding protein that regulates diverse cellular processes through post-transcriptional control of gene expression, often by functioning as a chaperone for regulatory sRNAs. Here, we explored the role of Hfq in enterohaemorrhagic E. coli (EHEC), a group of non-invasive intestinal pathogens. EHEC virulence is dependent on a Type III secretion system encoded in the LEE pathogenicity island. The abundance of transcripts for all 41 LEE genes and more than half of confirmed non-LEE-encoded T3 effectors were elevated in an EHEC hfq deletion mutant. Thus, Hfq promotes coordinated expression of the LEE-encoded T3S apparatus and both LEE- and non-LEE-encoded effectors. Increased transcript levels led to the formation of functional secretion complexes capable of secreting high quantities of effectors into the supernatant. The increase in LEE-derived transcripts and proteins was dependent on Ler, the LEE-encoded transcriptional activator, and the ler transcript appears to be a direct target of Hfq-mediated negative regulation. Finally, we found that Hfq contributes to the negative regulation of T3SSs in several other pathogens, suggesting that Hfq, potentially along with species-specific sRNAs, underlies a common means to prevent unfettered expression of T3SSs. PMID:19703108

  4. Molecular Models for the Core Components of the Flagellar Type-III Secretion Complex

    PubMed Central

    Matthews-Palmer, Teige R. S.; Beeby, Morgan

    2016-01-01

    We show that by using a combination of computational methods, consistent three-dimensional molecular models can be proposed for the core proteins of the type-III secretion system. We employed a variety of approaches to reconcile disparate, and sometimes inconsistent, data sources into a coherent picture that for most of the proteins indicated a unique solution to the constraints. The range of difficulty spanned from the trivial (FliQ) to the difficult (FlhA and FliP). The uncertainties encountered with FlhA were largely the result of the greater number of helix packing possibilities allowed in a large protein, however, for FliP, there remains an uncertainty in how to reconcile the large displacement predicted between its two main helical hairpins and their ability to sit together happily across the bacterial membrane. As there is still no high resolution structural information on any of these proteins, we hope our predicted models may be of some use in aiding the interpretation of electron microscope images and in rationalising mutation data and experiments. PMID:27855178

  5. Complex Function for SicA, a Salmonella enterica Serovar Typhimurium Type III Secretion-Associated Chaperone

    PubMed Central

    Tucker, Stephanie C.; Galán, Jorge E.

    2000-01-01

    Salmonella enterica encodes a type III secretion system within a pathogenicity island located at centisome 63 that is essential for virulence. All type III secretion systems require the function of a family of low-molecular-weight proteins that aid the secretion process by acting as partitioning factors and/or secretion pilots. One such protein is SicA, which is encoded immediately upstream of the type III secreted proteins SipB and SipC. We found that the absence of SicA results in the degradation of both SipB and SipC. Interestingly, in the absence of SipC, SipB was not only stable but also secreted at wild-type levels in a sicA mutant background, indicating that SicA is not required for SipB secretion. We also found that SicA is capable of binding both SipB and SipC. These results are consistent with a SicA role as a partitioning factor for SipB and SipC, thereby preventing their premature association and degradation. We also found that introduction of a sicA null mutation results in the lack of expression of SopE, another type III-secreted protein. Such an effect was shown to be transcriptional. Introduction of a loss-of-function sipC mutation into the sicA mutant background rescued sopE expression. These results indicate that the effect of sicA on sopE expression is indirect and most likely exerted through a regulatory factor(s) partitioned by SicA from SipC. These studies therefore describe a surprisingly complex function for the Salmonella enterica type III secretion-associated chaperone SicA. PMID:10735870

  6. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    PubMed

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD.

  7. The thyroxine inactivating gene, type III deiodinase, suppresses multiple signaling centers in Dictyostelium discoideum.

    PubMed

    Singh, Shashi Prakash; Dhakshinamoorthy, Ranjani; Jaiswal, Pundrik; Schmidt, Stefanie; Thewes, Sascha; Baskar, Ramamurthy

    2014-12-15

    Thyroxine deiodinases, the enzymes that regulate thyroxine metabolism, are essential for vertebrate growth and development. In the genome of Dictyostelium discoideum, a single intronless gene (dio3) encoding type III thyroxine 5' deiodinase is present. The amino acid sequence of D. discoideum Dio3 shares 37% identity with human T4 deiodinase and is a member of the thioredoxin reductase superfamily. dio3 is expressed throughout growth and development and by generating a knockout of dio3, we have examined the role of thyroxine 5' deiodinase in D. discoideum. dio3(-) had multiple defects that affected growth, timing of development, aggregate size, cell streaming, and cell-type differentiation. A prominent phenotype of dio3(-) was the breaking of late aggregates into small signaling centers, each forming a fruiting body of its own. cAMP levels, its relay, photo- and chemo-taxis were also defective in dio3(-). Quantitative RT-PCR analyses suggested that expression levels of genes encoding adenylyl cyclase A (acaA), cAMP-receptor A (carA) and cAMP-phosphodiesterases were reduced. There was a significant reduction in the expression of CadA and CsaA, which are involved in cell-cell adhesion. The dio3(-) slugs had prestalk identity, with pronounced prestalk marker ecmA expression. Thus, Dio3 seems to have roles in mediating cAMP synthesis/relay, cell-cell adhesion and slug patterning. The phenotype of dio3(-) suggests that Dio3 may prevent the formation of multiple signaling centers during D. discoideum development. This is the first report of a gene involved in thyroxine metabolism that is also involved in growth and development in a lower eukaryote.

  8. Cross-Talk between the Aeromonas hydrophila Type III Secretion System and Lateral Flagella System

    PubMed Central

    Zhao, Yu-Hang; Shaw, Jonathan G.

    2016-01-01

    Aeromonas hydrophila is responsible for aeromonad septicaemia in fish, and gastroenteritis and wound infections in humans. The type III secretion system (T3SS) is utilized by aeromonads to inject protein effectors directly into host cells. One of the major genetic regulators of the T3SS in several bacterial species is the AraC-like protein ExsA. Previous studies have suggested a link between T3SS regulation and lateral flagella expression. The aim of this study was to determine the genetic regulation of the T3SS and its potential interaction with the lateral flagella system in A. hydrophila. To investigate the genes encoding the T3SS regulatory components exsA, exsD, exsC, and exsE were mutated and the activities of the T3SS promoters were measured in wild type and mutant backgrounds demonstrating a regulatory network. The Exs proteins were shown to interact with each other by BACTH assay and Far-Western Blot. The findings suggested a regulatory cascade in which ExsE was bound to the chaperone protein ExsC. When ExsC was free it sequestered the anti-activator ExsD thus stopping the inhibition of the T3SS master regulator ExsA allowing T3SS expression. The T3SS regulatory components were also shown to affect the expression of the lateral flagella system. The activities of the lateral flagella promoters were shown to be repressed by the absence of ExsD and ExsE, suggesting that the T3SS master regulator ExsA was a negative regulator of the lateral flagella system. PMID:27656180

  9. A self-consistent mechanism for electron cyclotron maser emission and its application to type III solar radio bursts

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

    Type III solar radio bursts (SRBs) produced by fast electron beams (FEBs) traveling along solar magnetic fields are the best known and the most important kind of SRBs because of their clearest association with FEBs as well as most frequent observations during solar activities. However, the physics of their emitting mechanism has been a controversial issue. Based on the electron cyclotron maser (ECM) instability driven directly by a magnetized FEB, whose physics is fairly well known from the Earth's auroral kilometric radiation, this paper proposes a self-consistent mechanism for type III SRBs, in which the Alfvén wave (AW) produced by the current instability of the beam-return current system associated with the FEB, called the self-generated AW, plays an important and crucial role. Taking into account the return-current effect of the FEB, the growth rate and the saturation intensity of the self-generated AW are estimated. Then the effects of the self-generated AW on the ECM emission via the ECM instability driven by the magnetized FEB are further investigated. The results show that the self-generated AW can significantly influence and change the physical properties of the ECM emission. In particular, this novel ECM emission mechanism can effectively overcome the main difficulties of the conventional ECM emission mechanism in application to type III SRBs and may potentially provide a self-consistent physics scenario for type III SRBs.

  10. Type III radio burst productivity of solar flares. I - Release of energetic electrons out of the flare site

    NASA Astrophysics Data System (ADS)

    Poquerusse, M.; McIntosh, P. S.

    1990-12-01

    The statistical relationship between type III radio bursts and optical flares, using the comprehensive flare data base at the NOAA National Geophysical Data Center (Boulder, Colorado), and the radio observations obtained with the ARTEMIS multichannel spectrograph in Nancay (France), operating at 500-100 MHz are presented. At variance with previous results, it is seen that type III probability of occurrence depends only weakly upon the spatial extension of the flare observed in H-alpha, but strongly upon its brightness. It is confirmed that the type III probability increases with proximity to sunspots and with mass motions (surges and prominence activity); in addition, statistical data are consistent with both relations holding at fixed flare brightness. Thus, some of the conditions favorable to type III occurrence are characteristic of compact flares, while others are characteristic of large and long-duration flares, which are often related to mass ejections. This apparent paradox suggests that particle acceleration and magnetic expansion are at work simultaneously in the ejection of electron streams out of faring sites.

  11. Die another day: molecular mechanisms of effector-triggered immunity elicited by type III secreted effector proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial pathogens inject type III secreted effector (T3SE) proteins into their hosts where they display dual roles depending on the host genotype. T3SEs promote bacterial virulence in susceptible hosts, and elicit immunity in resistant hosts. T3SEs are typically recognized when they modify a host ...

  12. Functional and computational analysis of amino acid patterns predictive of type III secretion system substrates in Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial type III secretion systems (T3SSs) deliver proteins called effectors into eukaryotic cells. Although N-terminal amino acid sequences are required for translocation, the mechanism of substrate recognition by the T3SS is unknown. Almost all actively deployed T3SS substrates in the plant path...

  13. Identification and functional study of type III-A CRISPR-Cas systems in clinical isolates of Staphylococcus aureus.

    PubMed

    Cao, Linyan; Gao, Chun-Hui; Zhu, Jiade; Zhao, Liping; Wu, Qingfa; Li, Min; Sun, Baolin

    2016-12-01

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR associated proteins [Cas]) system can provide prokaryote with immunity against invading mobile genetic elements (MGEs) such as phages and plasmids, which are the main sources of staphylococcal accessory genes. To date, only a few Staphylococcus aureus strains containing CRISPR-Cas systems have been identified, but no functional study in these strains has been reported. In this study, 6 clinical isolates of S. aureus with type III-A CRISPR-Cas systems were identified, and whole-genome sequencing and functional study were conducted subsequently. Genome sequence analysis revealed a close linkage between the CRISPR-Cas system and the staphylococcal cassette chromosome mec (SCCmec) element in five strains. Comparative sequence analysis showed that the type III-A repeats are conserved within staphylococci, despite of the decreased conservation in trailer-end repeats. Highly homologous sequences of some spacers were identified in staphylococcal MGEs, and partially complementary sequences of spacers were mostly found in the coding strand of lytic regions in staphylococcal phages. Transformation experiments showed that S. aureus type III-A CRISPR-Cas system can specifically prevent plasmid transfer in a transcription-dependent manner. Base paring between crRNA and target sequence, the endoribonuclease, and the Csm complex were proved to be necessary for type III-A CRISPR-Cas immunity.

  14. Talents and Type Iiis: The Effects of the Talents Unlimited Model on Creative Productivity in Gifted Youngsters

    ERIC Educational Resources Information Center

    Newman, Jane L.

    2005-01-01

    This study examined a set of lessons that integrate the Talents Unlimited Model (TU; C. L. Schlichter, 1986) with the 10 steps of completing a Type III activity (J. S. Renzulli & S. M. Reis, 1985) to determine the effects of these lessons on the quality of students' creative products and on the number of students who completed their products.…

  15. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (L...

  16. Spatiotemporal Patterns of a Predator-Prey System with an Allee Effect and Holling Type III Functional Response

    NASA Astrophysics Data System (ADS)

    Li, Yuanyuan; Wang, Jinfeng

    A diffusive Gause type predator-prey system with Allee effect in prey growth and Holling type III response subject to Neumann boundary conditions is investigated. Existence of nonconstant positive steady state solutions is proved by Leray-Schauder degree theory and bifurcation theory. Global stability of the positive equilibrium of the system is also investigated. Moreover, bifurcations of spatially homogeneous and nonhomogeneous periodic solutions are analyzed. Our rigorous results justify some recent ecological observations.

  17. Manganese(III)-containing Wells-Dawson sandwich-type polyoxometalates: comparison with their manganese(II) counterparts.

    PubMed

    Lebrini, Mounim; Mbomekallé, Israël M; Dolbecq, Anne; Marrot, Jérôme; Berthet, Patrick; Ntienoue, Joseline; Sécheresse, Francis; Vigneron, Jacky; Etcheberry, Arnaud

    2011-07-18

    We present the synthesis and structural characterization, assessed by various techniques (FTIR, TGA, UV-vis, elemental analysis, single-crystal X-ray diffraction for three compounds, magnetic susceptibility, and electrochemistry) of five manganese-containing Wells-Dawson sandwich-type (WDST) complexes. The dimanganese(II)-containing complex, [Na(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](18-) (1), was obtained by reaction of MnCl(2) with 1 equiv of [As(2)W(15)O(56)](12-) in acetate medium (pH 4.7). Oxidation of 1 by Na(2)S(2)O(8) in aqueous solution led to the dimanganese(III) complex [Na(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](16-) (2), while its trimanganese(II) homologue, [Na(H(2)O)(2)Mn(II)(H(2)O)Mn(II)(2)(As(2)W(15)O(56))(2)](17-) (3), was obtained by addition of ca. 1 equiv of MnCl(2) to a solution of 1 in 1 M NaCl. The trimanganese(III) and tetramanganese(III) counterparts, [Mn(III)(H(2)O)Mn(III)(2)(As(2)W(15)O(56))(2)](15-) (4) and [Mn(III)(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](12-) (6), are, respectively, obtained by oxidation of aqueous solutions of 3 and [Mn(II)(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](16-) (5) by Na(2)S(2)O(8). Single-crystal X-ray analyses were carried out on 2, 3, and 4. BVS calculations and XPS confirmed that the oxidation state of Mn centers is +II for complexes 1, 3, and 5 and +III for 2, 4, and 6. A complete comparative electrochemical study was carried out on the six compounds cited above, and it was possible to observe the distinct redox steps Mn(IV/III) and Mn(III/II). Magnetization measurements, as a function of temperature, confirm the presence of antiferromagnetic interactions between the Mn ions in these compounds in all cases with the exception of compound 2.

  18. Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-{beta} responsiveness

    SciTech Connect

    Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew; Lyons, Karen M.

    2008-03-10

    Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-{beta} (TGF-{beta}) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-{beta}, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-{beta}. To explore this notion, we characterized TGF-{beta}-induced activation of fibroblasts from CCN2-null (CCN2{sup -/-}) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-{beta} signal transduction and regulation of collagen gene expression were examined in CCN2{sup -/-} MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2{sup -/-} MEFs was markedly reduced compared to wild type MEFs, TGF-{beta}-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2{sup -/-} MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-{beta}-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts.

  19. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    PubMed Central

    da Silva, Danielle Cristina Tomaz; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; de Campos, Dijon Henrique Salomé; do Nascimento, André Ferreira; de Oliveira, Sílvio Assis; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Background Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Objective Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Methods Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive weeks. Obesity was determined by adiposity index. Results The Ob15 group was similar to the C15 group regarding the expression of myocardial collagen type I; however, expression in the Ob30 group was less than C30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob30 when compared with Ob15. Obesity did not affect collagen type III expression. Conclusion This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression. PMID:24676371

  20. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Using Microwave Type-III Pairs

    NASA Astrophysics Data System (ADS)

    Tan, B. L.; Karlický, M.; Mészárosová, H.; Kashapova, L.; Huang, J.; Yan, Y.; Kontar, E. P.

    2016-10-01

    We report a peculiar and interesting train of microwave Type-III pair bursts in the impulsive rising phase of a solar flare on 26 September 2011. The observations include radio spectrometers at frequencies of 0.80 - 2.00 GHz from the Ondřejov radiospectrograph in the Czech Republic (ORSC), hard X-ray from the Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) and Gamma-Ray Burst Monitor onboard the Fermi Space Telescope ( Fermi/GRB), EUV images from the Sun Watcher using APS detectors and image Processing instrument onboard the Project for Onboard Autonomy 2 (SWAP/PROBA2), and magnetograms from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory (SDO/HMI). By using a recently developed method (Tan et al., Res. Astron. Astrophys. 16, 82, 2016a), we diagnosed the plasma density, temperature, plasma-β, magnetic field near the source region, the energy of energetic electrons, and the distance between the acceleration region and the emission start sites of Type-III bursts. From the diagnostics, we find that i) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites have almost no obvious variations during the period of Type-III pair trains, while the energy of electrons has an obvious peak value that is consistent with the hard X-ray emission. ii) The plasma-β is much higher than unity, showing a highly dynamic process near the emission start site of Type-III bursts. iii) Although the reversed-slope Type-III branches drift more slowly by one order of magnitude than that of the normal Type-IIIs, the related descending and ascending electrons still could have energy of the same order of magnitude. These facts indicate that both the ascending and descending electrons are possibly accelerated by a similar mechanism and in a small source region. These diagnostics can help us to understand the physics in the source region of solar bursts.

  1. The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse

    PubMed Central

    Eriksson, Krister S; Zhang, Shengwen; Lin, Ling; Larivière, Roxanne C; Julien, Jean-Pierre; Mignot, Emmanuel

    2008-01-01

    Background Peripherin, a type III neuronal intermediate filament, is widely expressed in neurons of the peripheral nervous system and in selected central nervous system hindbrain areas with projections towards peripheral structures, such as cranial nerves and spinal cord neurons. Peripherin appears to play a role in neurite elongation during development and axonal regeneration, but its exact function is not known. We noticed high peripherin expression in the posterior hypothalamus of mice, and decided to investigate further the exact location of expression and function of peripherin in the mouse posterior hypothalamus. Results In situ hybridization indicated expression of peripherin in neurons with a distribution reminiscent of the histaminergic neurons, with little signal in any other part of the forebrain. Immunocytochemical staining for histidine decarboxylase and peripherin revealed extensive colocalization, showing that peripherin is produced by histaminergic neurons in all parts of the tuberomammillary nucleus. We next used histamine immunostaining in peripherin knockout, overexpressing and wild type mice to study if altered peripherin expression affects these neurons, but could not detect any visible difference in the appearance of these neurons or their axons. Peripherin knockout mice and heterozygotic littermates were used for measurement of locomotor activity, feeding, drinking, and energy expenditure. Both genotypes displayed diurnal rhythms with all the parameters higher during the dark period. The respiratory quotient, an indicator of the type of substrate being utilized, also exhibited a significant diurnal rhythm in both genotypes. The diurnal patterns and the average values of all the recorded parameters for 24 h, daytime and night time were not significantly different between the genotypes, however. Conclusion In conclusion, we have shown that peripherin is expressed in the tuberomammillary neurons of the mouse hypothalamus. Monitoring of locomotor

  2. Lazarevicite-type short-range ordering in ternary III-V nanowires

    NASA Astrophysics Data System (ADS)

    Schnedler, M.; Lefebvre, I.; Xu, T.; Portz, V.; Patriarche, G.; Nys, J.-P.; Plissard, S. R.; Caroff, P.; Berthe, M.; Eisele, H.; Dunin-Borkowski, R. E.; Ebert, Ph.; Grandidier, B.

    2016-11-01

    Stabilizing ordering instead of randomness in alloy semiconductor materials is a powerful means to change their physical properties. We used scanning tunneling and transmission electron microscopies to reveal the existence of an unrecognized ordering in ternary III-V materials. The lazarevicite short-range order, found in the shell of InAs1 -xSbx nanowires, is driven by the strong Sb-Sb repulsion along <110 > atomic chains during their incorporation on unreconstructed {110 } sidewalls. Its spontaneous formation under group-III-rich conditions of growth offers the prospect to broaden the limited classes of ordered structures occurring in III-V semiconductor alloys.

  3. Design, expression, and stability of a diverse protein library based on the human fibronectin type III domain

    PubMed Central

    Olson, C. Anders; Roberts, Richard W.

    2007-01-01

    Protein libraries based on natural scaffolds enable the generation of novel molecular tools and potential therapeutics by directed evolution. Here, we report the design and construction of a high complexity library (30 × 1013 sequences) based on the 10th fibronectin type III domain of human fibronectin (10FnIII). We examined the bacterial expression characteristics and stability of this library using a green fluorescent protein (GFP)-reporter screen, SDS-PAGE analysis, and chemical denaturation, respectively. The high throughput GFP reporter screen demonstrates that a large fraction of our library expresses significant levels of soluble protein in bacteria. However, SDS-PAGE analysis of expression cultures indicates the ratio of soluble to insoluble protein expressed varies greatly for randomly chosen library members. We also tested the stabilities of several representative variants by guanidinium chloride denaturation. All variants tested displayed cooperative unfolding transitions similar to wild-type, and two exhibited free energies of unfolding equal to wild-type 10FnIII. This work demonstrates the utility of GFP-based screening as a tool for analysis of high-complexity protein libraries. Our results indicate that a vast amount of protein sequence space surrounding the 10FnIII scaffold is accessible for the generation of novel functions by directed as well as natural evolution. PMID:17322532

  4. T346Hunter: a novel web-based tool for the prediction of type III, type IV and type VI secretion systems in bacterial genomes.

    PubMed

    Martínez-García, Pedro Manuel; Ramos, Cayo; Rodríguez-Palenzuela, Pablo

    2015-01-01

    T346Hunter (Type Three, Four and Six secretion system Hunter) is a web-based tool for the identification and localisation of type III, type IV and type VI secretion systems (T3SS, T4SS and T6SS, respectively) clusters in bacterial genomes. Non-flagellar T3SS (NF-T3SS) and T6SS are complex molecular machines that deliver effector proteins from bacterial cells into the environment or into other eukaryotic or prokaryotic cells, with significant implications for pathogenesis of the strains encoding them. Meanwhile, T4SS is a more functionally diverse system, which is involved in not only effector translocation but also conjugation and DNA uptake/release. Development of control strategies against bacterial-mediated diseases requires genomic identification of the virulence arsenal of pathogenic bacteria, with T3SS, T4SS and T6SS being major determinants in this regard. Therefore, computational methods for systematic identification of these specialised machines are of particular interest. With the aim of facilitating this task, T346Hunter provides a user-friendly web-based tool for the prediction of T3SS, T4SS and T6SS clusters in newly sequenced bacterial genomes. After inspection of the available scientific literature, we constructed a database of hidden Markov model (HMM) protein profiles and sequences representing the various components of T3SS, T4SS and T6SS. T346Hunter performs searches of such a database against user-supplied bacterial sequences and localises enriched regions in any of these three types of secretion systems. Moreover, through the T346Hunter server, users can visualise the predicted clusters obtained for approximately 1700 bacterial chromosomes and plasmids. T346Hunter offers great help to researchers in advancing their understanding of the biological mechanisms in which these sophisticated molecular machines are involved. T346Hunter is freely available at http://bacterial-virulence-factors.cbgp.upm.es/T346Hunter.

  5. Cruciate Paralysis in a 20- year -old Male with an Undisplaced Type III Odontoid Fracture

    PubMed Central

    A, Mansukhani Sameer; V, Tuteja Sanesh; B, Dhar Sanjay

    2016-01-01

    Introduction: Cruciate Paralysis is a rare incomplete spinal cord syndrome presenting as brachial diplegia with minimal or no involvement of the lower extremities. It occurs as a result of trauma to the cervical spine and is associated with fractures of the axis and/or atlas. Diagnosis is confirmed on MRI and is managed by treatment of the underlying pathology. Prognosis depends on the extent of spinal cord injury and the exact cause. Case Presentation: A 20-year-old male presented to the casualty with a history of an injury to the back of the head as a result of a fall. He had severe pain in the neck and shoulder region and experienced difficulty in raising both arms and gripping objects. On examination, he had weakness of both arms, more on the right, involving the C5 to T1 distribution and brisk reflexes. There was no sensory deficit. Radiograph and a computed tomography (CT) scan of the cervical spine showed a type III undisplaced odontoid fracture. MRI showed a signal abnormality in the spinal cord at the level of the cervicomedullary junction extending up to the body of C2 vertebra. The patient was treated with traction in Gardner Wells tongs for six weeks and a sterno-occipital-mandibular immobilizer immobilizer (SOMI) brace thereafter. At three-month follow-up, he had attained complete neurological recovery. Conclusion: Cruciate Paralysis is an important cause of brachial diplegia and must be differentiated from Acute Central Cord syndrome which can have similar clinical features. PMID:28111622

  6. Characteristics of Metroxylon sagu resistant starch type III as prebiotic substance.

    PubMed

    Zi-Ni, Tan; Rosma, Ahmad; Napisah, Hussin; Karim, Alias A; Liong, Min-Tze

    2015-04-01

    Resistant starch type III (RS3 ) was produced from sago (Metroxylon sagu) and evaluated for its characteristics as a prebiotic. Two RS3 samples designated sago RS and HCl-sago RS contained 35.71% and 68.30% RS, respectively, were subjected to hydrolyses by gastric juice and digestive enzymes and to absorption. Both sago RS and HCl-sago RS were resistant to 180 min hydrolysis by gastric acidity at pH 1 to 4 with less than 0.85% hydrolyzed. Both samples were also resistant toward hydrolysis by gastrointestinal tract enzymes and intestinal absorption with 96.75% and 98.69% of RS3 were recovered respectively after 3.5 h digestion and overnight dialysis at 37 °C. Sago RS3 supported the growth of both beneficial (lactobacilli and Bifidobacteria) and pathogenic microbes (Escherichia coli, Campylobacter coli, and Clostridium perfringens) in the range of 2.60 to 3.91 log10 CFU/mL. Hence, prebiotic activity score was applied to describe the extent to which sago RS3 supports selective growth of the lactobacilli and bifidobacteria strains over pathogenic bacteria. The highest scores were obtained from Bifidobacterium sp. FTDC8943 grown on sago RS (+0.26) and HCl-sago RS (+0.24) followed by L. bulgaricus FTDC1511 grown on sago RS (+0.21). The findings had suggested that sago RS3 has the prebiotic partial characteristics and it is suggested to further assess the suitability of sago RS3 as a prebiotic material.

  7. Potassium transport of Salmonella is important for type III secretion and pathogenesis.

    PubMed

    Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C; Lu, Sangwei

    2013-08-01

    Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K(+)), sodium ion (Na(+)) and proton (H(+)) are involved in nearly all aspects of bacterial growth and survival. K(+) is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K(+) transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K(+) transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K(+) transport through deletion of K(+) transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K(+) transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K(+) transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria.

  8. Immunodominant regions of a Chlamydia trachomatis type III secretion effector protein, Tarp.

    PubMed

    Wang, Jie; Zhang, Yingqian; Yu, Ping; Zhong, Guangming

    2010-09-01

    We have previously shown that individuals infected with Chlamydia trachomatis can develop a robust antibody response to a Chlamydia type III secretion effector protein called Tarp and that immunization with Tarp induces protection against challenge infection in mice. The current study aimed to map the immunodominant regions of the Tarp protein by expressing 11 fragments of Tarp as glutathione S-transferase (GST) fusion proteins and detecting the reactivity of these fusion proteins with antisera from patients infected with C. trachomatis in the urogenital tract or in the ocular tissue and from rabbits immunized with C. trachomatis organisms. A major immunodominant region was strongly recognized by all antibodies. This region covers amino acids 152 to 302, consisting of three repeats (amino acids 152 to 201, 202 to 251, and 252 to 302). Each of the repeats contains multiple tyrosine residues that are phosphorylated by host cell kinases when Tarp is injected into host cells. Several other minor immunodominant regions were also identified, including those comprising amino acids 1 to 156, 310 to 431, and 582 to 682 (recognized by antisera from both humans and rabbits), that comprising amino acids 425 to 581 (recognized only by human antisera), and that comprising amino acids 683 to 847 (preferentially recognized by rabbit antisera). This immunodominance was also confirmed by the observations that six out of the nine monoclonal antibodies (MAbs) bound to the major immunodominant region and that the other three each bound to one of the minor fragments, comprising amino acids 1 to 119, 120 to 151, and 310 to 431. The antigenicity analyses have provided important information for further understanding the structure and function of Tarp.

  9. The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi.

    PubMed

    Johnson, Rebecca; Byrne, Alexander; Berger, Cedric N; Klemm, Elizabeth; Crepin, Valerie F; Dougan, Gordon; Frankel, Gad

    2017-02-15

    Strains of the various Salmonella enterica serovars cause gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (Salmonella pathogenicity island 1 [SPI-1] and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton postinfection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S. enterica serovar Typhimurium and S Typhi; direct comparison of the protein sequences revealed that S Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S Typhi and S. Typhimurium strains demonstrated that, unlike SptP in S. Typhimurium, SptP in S Typhi was not involved in invasion or cytoskeletal recovery postinfection. Investigation of whether the observed amino acid changes within SptP of S Typhi affected its function revealed that S Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that while S. Typhimurium SptP is stable intracellularly within S Typhi, S Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S. Typhimurium. Direct assessment of the strength of the interaction between SptP and SicP of both serovars via bacterial two-hybrid analysis demonstrated that S Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S. Typhimurium. Taken together, our results suggest that changes within the chaperone-binding domain of SptP in S Typhi hinder binding to its chaperone, resulting in instability, preventing translocation, and therefore restricting the intracellular activity of this effector.

  10. Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome

    PubMed Central

    Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres

    2013-01-01

    Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging. PMID:24324434

  11. Spiky Fine Structure of Type III-like Radio Bursts in Absorption

    NASA Astrophysics Data System (ADS)

    Chernov, G. P.; Yan, Y. H.; Tan, C. M.; Chen, B.; Fu, Q. J.

    2010-03-01

    An uncommon fine structure in the radio spectrum consisting of bursts in absorption was observed with the Chinese Solar Broadband Radiospectrometer (SBRS) in the frequency range of 2.6 - 3.8 GHz during an X3.4/4B flare on 13 December 2006 in active region NOAA 10930 (S05W33). Usual fine structures in emission such as spikes, zebra stripes, and drifting fibers were observed at the peak of every new flare brightening. Within an hour at the decay phase of the event we observed bursts consisting of spikes in absorption, which pulsated periodically in frequency. Their instantaneous frequency bandwidths were found to be in the 75 MHz range. Moreover, in the strongest Type III-like bursts in absorption, the spikes showed stripes of the zebra-pattern (ZP) that drifted to higher frequencies. All spikes had the duration as short as down to the limit of the instrument resolution of ≈8 ms. The TRACE 195 Å images indicate that the magnetic reconnection at this moment occurred in the western edge of the flare loop arcade. Taking into account the presence of the reverse-drifting bursts in emission, in the course of the restoration of the magnetic structures in the corona, the acceleration of the beams of fast particles must have occurred both upward and downward at different heights. The upward beams will be captured by the magnetic trap, where the loss-cone distribution of fast particles (responsible for the emission of continuum and ZP) were formed. An additional injection of fast particles will fill the loss-cone later, breaking the loss-cone distribution. Therefore, the generation of continuum will be quenched at these moments, which was evidenced by the formation of bursts in absorption.

  12. A type III effector antagonises death receptor signalling during bacterial gut infection

    PubMed Central

    Pearson, Jaclyn S; Giogha, Cristina; Ong, Sze Ying; Kennedy, Catherine L; Kelly, Michelle; Robinson, Keith S; Wong, Tania; Mansell, Ashley; Riedmaier, Patrice; Oates, Clare VL; Zaid, Ali; Mühlen, Sabrina; Crepin, Valerie F; Marches, Olivier; Ang, Ching-Seng; Williamson, Nicholas A; O’Reilly, Lorraine A; Bankovacki, Aleksandra; Nachbur, Ueli; Infusini, Giuseppe; Webb, Andrew I; Silke, John; Strasser, Andreas; Frankel, Gad; Hartland, Elizabeth L

    2013-01-01

    Successful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonise the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic E. coli (EPEC and EHEC), utilise a type III secretion system (T3SS) to deliver virulence effector proteins into host cells during infection that promote colonisation and interfere with antimicrobial host responses 1-3. Here we report that the T3SS effector NleB1 from EPEC binds to host cell death domain containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death receptor induced apoptosis. This inhibition depended on the N-GlcNAc transferase activity of NleB1, which specifically modified Arg117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing (A/E) pathogens antagonise death receptor induced apoptosis of infected cells, thereby blocking a major antimicrobial host response. PMID:24025841

  13. Alterations in Fibronectin Type III Domain Containing 1 Protein Gene Are Associated with Hypertension

    PubMed Central

    Deng, Alan Y.; Chauvet, Cristina; Ménard, Annie

    2016-01-01

    Multiple quantitative trait loci (QTLs) for blood pressure (BP) have been detected in rat models of human polygenic hypertension. Great challenges confronting us include molecular identifications of individual QTLs. We first defined the chromosome region harboring C1QTL1 to a segment of 1.9 megabases that carries 9 genes. Among them, we identified the gene encoding the fibronectin type III domain containing 1 protein (Fndc1)/activator of G protein signaling 8 (Ags8) to be the strongest candidate for C1QTL1, since numerous non-synonymous mutations are found. Moreover, the 5’ Fndc1/Ags8 putative promoter contains numerous mutations that can account for its differential expression in kidneys and the heart, prominent organs in modulating BP, although the Fndc1/Ags8 protein was not detectable in these organs under our experimental conditions. This work has provided the premier evidence that Fndc1/Ags8 is a novel and strongest candidate gene for C1QTL1 without completely excluding other 8 genes in the C1QTL1-residing interval. If proven true by future in vivo function studies such as single-gene Fndc1/Ags8 congenics, transgenesis or targeted-gene modifications, it might represent a part of the BP genetic architecture that operates in the upstream position distant from the end-phase physiology of BP control, since it activates a Gbetagamma component in a signaling pathway. Its functional role could validate the concept that a QTL in itself can influence BP ‘indirectly’ by regulating other genes downstream in a pathway. The elucidation of the mechanisms initiated by Fndc/Ags8 variations will reveal novel insights into the BP modulation via a regulatory hierarchy. PMID:27064407

  14. Yeast as a Heterologous Model System to Uncover Type III Effector Function

    PubMed Central

    Popa, Crina; Coll, Núria S.; Valls, Marc; Sessa, Guido

    2016-01-01

    Type III effectors (T3E) are key virulence proteins that are injected by bacterial pathogens inside the cells of their host to subvert cellular processes and contribute to disease. The budding yeast Saccharomyces cerevisiae represents an important heterologous system for the functional characterisation of T3E proteins in a eukaryotic environment. Importantly, yeast contains eukaryotic processes with low redundancy and are devoid of immunity mechanisms that counteract T3Es and mask their function. Expression in yeast of effectors from both plant and animal pathogens that perturb conserved cellular processes often resulted in robust phenotypes that were exploited to elucidate effector functions, biochemical properties, and host targets. The genetic tractability of yeast and its amenability for high-throughput functional studies contributed to the success of this system that, in recent years, has been used to study over 100 effectors. Here, we provide a critical view on this body of work and describe advantages and limitations inherent to the use of yeast in T3E research. “Favourite” targets of T3Es in yeast are cytoskeleton components and small GTPases of the Rho family. We describe how mitogen-activated protein kinase (MAPK) signalling, vesicle trafficking, membrane structures, and programmed cell death are also often altered by T3Es in yeast and how this reflects their function in the natural host. We describe how effector structure–function studies and analysis of candidate targeted processes or pathways can be carried out in yeast. We critically analyse technologies that have been used in yeast to assign biochemical functions to T3Es, including transcriptomics and proteomics, as well as suppressor, gain-of-function, or synthetic lethality screens. We also describe how yeast can be used to select for molecules that block T3E function in search of new antibacterial drugs with medical applications. Finally, we provide our opinion on the limitations of S

  15. Functional Characterization of Two Type III Secretion Systems of Vibrio parahaemolyticus

    PubMed Central

    Park, Kwon-Sam; Ono, Takahiro; Rokuda, Mitsuhiro; Jang, Myoung-Ho; Okada, Kazuhisa; Iida, Tetsuya; Honda, Takeshi

    2004-01-01

    Vibrio parahaemolyticus, a gram-negative marine bacterium, is a worldwide cause of food-borne gastroenteritis. Recent genome sequencing of the clinical V. parahaemolyticus strain RIMD2210633 identified two sets of genes for the type III secretion system (TTSS), TTSS1 and TTSS2. Here, we constructed a series of mutant strains from RIMD2210633 to determine whether the two putative TTSS apparatus are functional. The cytotoxic activity of mutant strains having a deletion in one of the TTSS1 genes was significantly decreased compared with that of the parent and TTSS2-related mutant strains. In an enterotoxicity assay with the rabbit ileal loop test, intestinal fluid accumulation was diminished by deletion of the TTSS2-related genes while TTSS1-related mutants caused a level of fluid accumulation similar to that of the parent. VopD, a protein encoded in the proximity of the TTSS1 region and a homologue of the Yersinia YopD, was secreted in a TTSS1-dependent manner. In contrast, VopP, which is encoded by a pathogenicity island on chromosome 2 and is homologous to the Yersinia YopP, was secreted via the TTSS2 pathway. These results provide evidence that V. parahaemolyticus TTSSs function as secretion systems and may have a role in the pathogenicity of the organism. This is the first report of functional TTSSs in Vibrio species. The presence of TTSS apparatus gene homologues was demonstrated in other vibrios, such as Vibrio alginolyticus, Vibrio harveyi, and Vibrio tubiashii, suggesting that some other vibrios also contain TTSS and that the TTSS has a role in protein secretion in those organisms during interaction with eukaryotic cells. PMID:15501799

  16. Exercise intolerance in Glycogen Storage Disease Type III: weakness or energy deficiency?

    PubMed

    Preisler, Nicolai; Pradel, Agnès; Husu, Edith; Madsen, Karen Lindhardt; Becquemin, Marie-Hélène; Mollet, Alix; Labrune, Philippe; Petit, Francois; Hogrel, Jean-Yves; Jardel, Claude; Maillot, Francois; Vissing, John; Laforêt, Pascal

    2013-05-01

    Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO 2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70% of VO 2peak with either a saline or a glucose infusion. VO 2peak was below normal. Glucose improved the work capacity by lowering the heart rate, and increasing the peak work rate by 30% (108 W with glucose vs. 83 W with placebo, p=0.018). The block in muscle glycogenolytic capacity, combined with the liver involvement caused exercise intolerance with dynamic skeletal muscle symptoms (excessive fatigue and muscle pain), and hypoglycemia in 4 subjects. In this study we combined anaerobic and aerobic exercise to systematically study skeletal muscle metabolism and exercise tolerance in patients with GSD IIIa. Exercise capacity was significantly reduced, and our results indicate that this was due to a block in muscle glycogenolytic capacity. Our findings suggest that the general classification of GSD III as a glycogenosis characterized by fixed symptoms related to muscle wasting should be modified to include dynamic exercise-related symptoms of muscle fatigue. A proportion of the skeletal muscle symptoms in GSD IIIa, i.e. weakness and fatigue, may be related to insufficient energy production in muscle.

  17. SOS Regulation of the Type III Secretion System of Enteropathogenic Escherichia coli▿

    PubMed Central

    Mellies, Jay L.; Haack, Kenneth R.; Galligan, Derek C.

    2007-01-01

    Genomes of bacterial pathogens contain and coordinately regulate virulence-associated genes in order to cause disease. Enteropathogenic Escherichia coli (EPEC), a major cause of watery diarrhea in infants and a model gram-negative pathogen, expresses a type III secretion system (TTSS) that is encoded by the locus of enterocyte effacement (LEE) and is necessary for causing attaching and effacing intestinal lesions. Effector proteins encoded by the LEE and in cryptic prophage are injected into the host cell cytoplasm by the TTTS apparatus, ultimately leading to diarrhea. The LEE is comprised of multiple polycistronic operons, most of which are controlled by the global, positive regulator Ler. Here we demonstrated that the LEE2 and LEE3 operons also responded to SOS signaling and that this regulation