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Sample records for anomalous type iv

  1. An Anomalous Type IV Secretion System in Rickettsia Is Evolutionarily Conserved

    PubMed Central

    Gillespie, Joseph J.; Ammerman, Nicole C.; Dreher-Lesnick, Sheila M.; Rahman, M. Sayeedur; Worley, Micah J.; Setubal, Joao C.; Sobral, Bruno S.; Azad, Abdu F.

    2009-01-01

    Background Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known. Results Superimposition of T4SS structural/functional information over previously identified Rickettsia components implicate a functional Rickettsia T4SS. virB4, virB8 and virB9 are duplicated, yet only one copy of each has the conserved features of similar genes in other T4SSs. An extraordinarily duplicated VirB6 gene encodes five hydrophobic proteins conserved only in a short region known to be involved in DNA transfer in A. tumefaciens. virB1, virB2 and virB7 are newly identified, revealing a Rickettsia T4SS lacking only virB5 relative to the vir archetype. Phylogeny estimation suggests vertical inheritance of all components, despite gene rearrangements into an archipelago of five islets. Similarities of Rickettsia VirB7/VirB9 to ComB7/ComB9 proteins of ε-proteobacteria, as well as phylogenetic affinities to the Legionella lvh T4SS, imply the Rickettsiales ancestor acquired a vir-like locus from distantly related bacteria, perhaps while residing in a protozoan host. Modern modifications of these systems likely reflect diversification with various eukaryotic host cells. Conclusion We present the rvh (Rickettsiales vir homolog) T4SS, an evolutionary conserved transporter with an unknown role in rickettsial biology. This work lays the foundation for future laboratory characterization of this system, and also identifies the Legionella lvh T4SS as a suitable genetic model. PMID:19279686

  2. Anomalous C IV and Si IV resonance lines in 36 Lyncis

    SciTech Connect

    Sadakane, K.

    1984-03-01

    Of the anomalously strong C IV and Si IV resonance lines found in the UV spectrum of the chemically peculiar star 36 Lyncis, the C IV lines near 1550 A are noted to be absent in about 40 other middle or late B-type main sequence stars. Also found is a peculiar intensity ratio between C IV and Si IV lines, where the former are stronger. The continuous energy distribution of 36 Lyn in the UV region fits with those of late B-type stars, and the presence of a hot, chromospheric or coronal gas is suggested. 14 references.

  3. Interplanetary Type IV Bursts

    NASA Astrophysics Data System (ADS)

    Hillaris, A.; Bouratzis, C.; Nindos, A.

    2016-08-01

    We study the characteristics of moving type IV radio bursts that extend to hectometric wavelengths (interplanetary type IV or type {IV}_{{IP}} bursts) and their relationship with energetic phenomena on the Sun. Our dataset comprises 48 interplanetary type IV bursts observed with the Radio and Plasma Wave Investigation (WAVES) instrument onboard Wind in the 13.825 MHz - 20 kHz frequency range. The dynamic spectra of the Radio Solar Telescope Network (RSTN), the Nançay Decametric Array (DAM), the Appareil de Routine pour le Traitement et l' Enregistrement Magnetique de l' Information Spectral (ARTEMIS-IV), the Culgoora, Hiraso, and the Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (IZMIRAN) Radio Spectrographs were used to track the evolution of the events in the low corona. These were supplemented with soft X-ray (SXR) flux-measurements from the Geostationary Operational Environmental Satellite (GOES) and coronal mass ejections (CME) data from the Large Angle and Spectroscopic Coronagraph (LASCO) onboard the Solar and Heliospheric Observatory (SOHO). Positional information of the coronal bursts was obtained by the Nançay Radioheliograph (NRH). We examined the relationship of the type IV events with coronal radio bursts, CMEs, and SXR flares. The majority of the events (45) were characterized as compact, their duration was on average 106 minutes. This type of events was, mostly, associated with M- and X-class flares (40 out of 45) and fast CMEs, 32 of these events had CMEs faster than 1000 km s^{-1}. Furthermore, in 43 compact events the CME was possibly subjected to reduced aerodynamic drag as it was propagating in the wake of a previous CME. A minority (three) of long-lived type {IV}_{{IP}} bursts was detected, with durations from 960 minutes to 115 hours. These events are referred to as extended or long duration and appear to replenish their energetic electron content, possibly from electrons escaping from the corresponding coronal

  4. Mucolipidosis Type IV: an Update

    PubMed Central

    Wakabayashi, Kazuyo; Gustafson, Ann Marie; Sidransky, Ellen; Goldin, Ehud

    2011-01-01

    Mucolipidosis type IV (MLIV) is a neurodevelopmental as well as neurodegenerative disorder with severe psychomotor developmental delay, progressive visual impairment, and achlorydria. It is characterized by the presence of lysosomal inclusions in many cell types in patients. MLIV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1, a member of the transient receptor potential (TRP) cation channel family. Although approximately 70-80% of patients identified are Ashkenazi Jewish, MLIV is a pan-ethnic disorder. Importantly, while MLIV is thought to be a rare disease, its frequency may be greater than currently appreciated, for its common presentation as a cerebral palsy-like encephalopathy can lead to misdiagnosis. Moreover, patients with milder variants are often not recognized as having MLIV. This review provides an update on the ethnic distribution, clinical manifestations, laboratory findings, methods of diagnosis, molecular genetics, differential diagnosis, and treatment of patients with MLIV. An enhanced awareness of the manifestations of this disorder may help to elucidate the true frequency and range of symptoms associated with MLIV, providing insight into the pathogenesis of this multi-system disease. PMID:21763169

  5. Fe II fluorescence and anomalous C IV doublet intensities in symbiotic novae

    NASA Technical Reports Server (NTRS)

    Michalitsianos, A. G.; Kafatos, M.; Meier, S. R.

    1992-01-01

    The variation of absolute intensities of Bowen-excited Fe II emission in the symbiotic stars RR Tel, RX Pup, and AG Peg is examined. The C IV doublet intensity ratios in RR Tel were not anomalous between 1979 and 1989, and the ratio had typical values within the optically thin range. The intensity of individual Fe II Bowen-excited lines is correlated with the C IV 1548.2 A flux, suggesting the presence of a foreground Fe II region in which fluorescent-excited material responds to flux variations of C IV 1548.2 A. In RX Pup the combined fluxes of Fe II Bowen-pumped lines can account for an appreciable fraction of the flux deficit in the C IV 1548.2 A line when the C IV doublet ratio is less than the optically thick limit of unity. The Fe II Bowen lines in RX Pup exhibit a velocity range from 0 to 80 km/s, where several strong Fe II emission lines correspond to deep absorption structure in the C IV 1548.2 A line profile. In AG Peg and C IV 1548.2 A flux deficit cannot be explained by Fe II fluorescent absorption alone when the C IV doublet ratio anomaly is at an extreme.

  6. Compositions of Normal and Anomalous Eucrite-Type Mafic Achondrites

    NASA Technical Reports Server (NTRS)

    Mittlefehldt, D. W.; Peng, Z. X.; Mertzman, S. A.

    2016-01-01

    The most common asteroidal igneous meteorites are eucrite-type mafic achondrites - basalts and gabbros composed of ferroan pigeonite, ferroan augite, calcic plagioclase, silica, ilmenite, troilite, Ca-phosphate, chromite and Fe-metal. These rocks are thought to have formed on a single asteroid along with howardites and diogenites. However, high precision O-isotopic analyses have shown that some mafic achondrites have small, well-resolved, non-mass-dependent differences that have been interpreted as indicating derivation from different asteroids. Some of these O-anomalous mafic achondrites also have anomalous petrologic characteristics, strengthening the case that they hail from distinct parent asteroids. We present the results of bulk compositional studies of a suite of normal and anomalous eucrite-type basalts and cumulate gabbros.

  7. [Type IV of hypersensitivity and its subtypes].

    PubMed

    Czarnobilska, Ewa; Obtułowicz, Krystyna; Wsołek, Katarzyna

    2007-01-01

    Type IV of hypersensitivity reaction is usually manifested in the skin in different clinical pattern. According to traditional Gell and Coombs classification, the mechanism of IV type of allergic reaction has been associated with contact allergy with the activity of lymphocytes Th1 secreting interferon gamma. Now, this vision seems to be too simplified. In the last years there were publications, which can throw a new light on these complicated mechanisms leading to the development of the type IV of allergy, especially to drugs, nickel and other haptens and also can explain the differentiation of clinical pattern in respective patients. The skin symptoms in type IV of hypersensitivity are triggered by activation of specific T-cell CD4+ and CD8+. Immunohistochemical and functional analysis of reactive T-cell has shown that the delayed hypersensitivity reaction depends on the secreted cytokines. For example maculo-papular exanthema may be either triggered by Th1 or Th2 in nature and cytokines interferon gamma, tumor necrosis factor alfa or interleukin-4, 5 and 13. Bullous reactions (i.e. Stevens-Johnsons Syndrome or toxic epidermal necrolysis) are characterized by widespread keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema reactions are stimulated via the T-cell release of 11-8 and granulocyte-monocyte colony-stimulatig factor (GM-CSF). For the better understanding of these inflammatory cascades deleted type IV of hypersensitivity reactions have been re-classified into four main subtypes: 1. IVa with Th1 and monocyte directed and cytokines: IFNgamma, IL-1, IL-2, 2. IVb with Th2 and eosinophils directed and cytokines: L-5, IL-4, IL-13, 3. IVc with T CD8+ directed and cytokines: perforin, granzyme B, Fas Ligand, 4. IVd with T CD4+, CD8+ and neutrophil directed and cytokines: IL8, GM-CSF. Clinically delayed hypersensitivity eruptions are often an overlap of cytokine

  8. Type IV Pilin Proteins: Versatile Molecular Modules

    PubMed Central

    Giltner, Carmen L.; Nguyen, Ylan

    2012-01-01

    Summary: Type IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin, and structurally related proteins are found as components of the type II secretion (T2S) system, where they are called pseudopilins; of DNA uptake/competence systems in both Gram-negative and Gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. This broad distribution of a single protein family implies both a common evolutionary origin and a highly adaptable functional plan. The type IV pilin is a remarkably versatile architectural module that has been adopted widely for a variety of functions, including motility, attachment to chemically diverse surfaces, electrical conductance, acquisition of DNA, and secretion of a broad range of structurally distinct protein substrates. In this review, we consider recent advances in this research area, from structural revelations to insights into diversity, posttranslational modifications, regulation, and function. PMID:23204365

  9. Ratchet model for type IV pilus retraction

    NASA Astrophysics Data System (ADS)

    Lindén, Martin; Tuohimaa, Tomi; Jonsson, Ann-Beth; Wallin, Mats

    2004-03-01

    Type IV pilus rectraction is required for twitching motility in a wide range of bacteriae, including Neisseria gonorrhoeae, Myxococcus xanthus and Pseudomonas aeruginosa. The mechanism of retraction is believed to be filament disassembly mediated by PilT, a member of the AAA family of motor proteins. Recent laser tweezer measurements of the force-velocity relation of PilT in N. gonorrhoeae, reveal that single PilT complexes generate forces of over 100 pN. We assume that PilT forms a cyclic ATPase surrounding the base of the pilus and formulate a model of retraction in terms of coupled flashing ratchets. We obtain a force-velocity relation by numerical simulation of the model which is in qualitative agreement with the experimental results.

  10. Isolation of Bacterial Type IV Machine Subassemblies

    PubMed Central

    Sarkar, Mayukh K.; Husnain, Seyyed I.; Jakubowski, Simon J.; Christie, Peter J.

    2012-01-01

    The bacterial type IV secretion systems (T4SSs) deliver DNA and protein substrates to bacterial and eukaryotic target cells generally by a mechanism requiring direct contact between donor and target cells. Recent advances in defining the architectures of T4SSs have been made through isolation of machine sub-assemblies for further biochemical and ultrastructural analysis. Here, we describe a protocol for isolation and characterization of VirB protein complexes from the paradigmatic VirB/VirD4 T4SS of Agrobacterium tumefaciens. This protocol can be adapted for isolation of T4SS subassemblies from other gram-negative bacteria as well as gram-positive bacteria. The biological importance of isolated T4SS subcomplexes can be assessed by assaying for copurification of trapped or cross-linked substrates. This can be achieved with a modified form of the chromatin immunoprecipitation (ChIP) assay termed transfer DNA immunoprecipitation (TrIP). Here, a TrIP protocol is described for recovery of formaldehyde-cross-linked DNA substrate–channel subunit complexes from cells employing T4SSs for conjugative DNA transfer. PMID:23299736

  11. Structure of a Type IV Secretion System

    PubMed Central

    Rivera-Calzada, Angel; Braun, Nathalie; Connery, Sarah; Dujeancourt, Annick; Lu, Fang; Redzej, Adam; Fronzes, Rémi; Orlova, Elena V.; Waksman, Gabriel

    2014-01-01

    Bacterial type IV secretion (T4S) systems translocate virulence factors into eukaryotic cells1,2, distribute genetic material between bacteria, and have shown potential as a tool for the genetic modification of human cells3. Given the complex choreography of the substrate through the secretion apparatus4, the molecular mechanism of the T4S system has proven difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy (EM) to reconstruct the T4S system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form a ~3 megadalton (MDa) nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex1 connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of twelve VirB4 ATPase subunits organised as side by side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems1,4-6. PMID:24670658

  12. Genetics Home Reference: mucopolysaccharidosis type IV

    MedlinePlus

    ... enzymes, GAGs accumulate within cells, specifically inside the lysosomes . Lysosomes are compartments in the cell that break down ... that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. In MPS IV, ...

  13. Control of melanoma cell invasion by type IV collagen.

    PubMed

    Pasco, Sylvie; Brassart, Bertrand; Ramont, Laurent; Maquart, François-Xavier; Monboisse, Jean-Claude

    2005-01-01

    Malignant melanoma is the leading cause of death from diseases of the skin. This review summarizes the data from the literature and our laboratory addressing the effects of type IV collagen on melanoma progression. Many different sequences from type IV collagen promote melanoma cell adhesion, migration and invasion. The triple helical conformation of the collagenous domain plays a critical role in some of these interactions. However, recent studies from our group demonstrated that a sequence from the alpha3(IV) NC1 domain inhibits melanoma cell proliferation, migration and invasion by decreasing MMP production and activation. Peptide sequences from the alpha1(IV), alpha2(IV) and alpha3(IV) chains named arresten, canstatin and tumstatin, respectively were shown to inhibit angiogenesis. Further investigations regarding the inhibitory effects of the alpha(IV) NC1 domains will have a paramount relevance for the design of efficient strategies to limit melanoma development. PMID:15936594

  14. Non-helical type IV collagen polypeptides in human placenta.

    PubMed

    Kajimura, Daisuke; Takahashi, Seiichiro; Yoshikawa, Kiwamu; Hattori, Shunji; Sado, Yoshikazu; Imamura, Yasutada; Hayashi, Toshihiko

    2004-01-30

    Our previous reports showed that cultured human cells secrete non-disulfide-bonded non-helical alpha1(IV) and alpha2(IV) chains under physiological conditions. In the present report we show that the alpha(IV) chains in non-helical form were reactive to lectin ABA (Agaricus bisporus agglutinin), whereas the alpha(IV) chains secreted in triple-helical form were not. These results indicate that ABA could be used to distinguish the two conformational isomers of type IV collagen polypeptides. An alpha1(IV) chain isolated from human placenta with an antibody-coupled column showed a positive reaction to ABA, indicating that gelatin form of the type IV collagen alpha1(IV) chain is produced and retained in the tissue in vivo. A possible significance of the gelatin form is discussed from the finding that the non-helical alpha1(IV) chain purified with EDTA-free buffer contained degraded polypeptides including NC1-size domain and showed an apparent inhibition against activated pro-MMP-9. This is the first report to show that a gelatin form of protein exists in vivo. PMID:14715239

  15. Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

    PubMed Central

    Abrahamson, Dale R.; Hudson, Billy G.; Stroganova, Larysa; Borza, Dorin-Bogdan; St. John, Patricia L.

    2009-01-01

    Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen α1α2α1(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen α3α4α5(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen α3α4α5(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen α5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen α3α4α5(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type. PMID:19423686

  16. Cellular origins of type IV collagen networks in developing glomeruli.

    PubMed

    Abrahamson, Dale R; Hudson, Billy G; Stroganova, Larysa; Borza, Dorin-Bogdan; St John, Patricia L

    2009-07-01

    Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen alpha 1 alpha 2 alpha1(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen alpha 3 alpha 4 alpha 5(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen alpha 3 alpha 4 alpha 5(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen alpha 5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen alpha 3 alpha 4 alpha 5(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type. PMID:19423686

  17. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

    PubMed Central

    Persat, Alexandre; Inclan, Yuki F.; Engel, Joanne N.; Stone, Howard A.; Gitai, Zemer

    2015-01-01

    Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity. PMID:26041805

  18. [Mucolipidoses type IV in a patient with mapuche ancestry].

    PubMed

    Hernández Ch, Marta; Méndez C, José Ignacio; Concha G, María José; Huete L, Isidro; González B, Sergio; Durán S, Gloria P

    2008-07-01

    We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at 3 years of age. At 5 years of age, a slow neurological deterioration started, associated to visual impairment. Optic atrophy was added to the typical neurological exam of ataxic cerebral palsy and the diagnosis was re-considered. Neuroimaging showed a slow and progressive atrophy of intracerebral structures and ultramicroscopy revealed intracytoplasmatic inclusions in conjunctiva and skin, compatible with mucolipidoses type IV (ML-IV). ML-IV must be included in the differential diagnosis of cerebral palsy associated with loss of acquired skills and progressive visual impairment. Electron microscopy of skin or conjunctiva is a useful diagnostic test. Suspicion of ML-IV must not be restricted to Ashkenazi Jewish population. PMID:18949166

  19. Ehlers-Danlos Syndrome Type IV with Bilateral Pneumothorax.

    PubMed

    Nakagawa, Hiroaki; Wada, Hiroshi; Hajiro, Takashi; Nagao, Taishi; Ogawa, Emiko; Hatamochi, Atsushi; Tanaka, Toshihiro; Nakano, Yasutaka

    2015-01-01

    A 17-year-old teen was hospitalized with bilateral pneumothorax. After the bilateral lungs were expanded using catheter tubes, he fully recovered and he was discharged from our hospital. He had a history of colon perforation. Ehlers-Danlos syndrome (EDS) was suspected due to the combination of colon perforation and pneumothorax, and EDS type IV was confirmed after a genetic study identified a c.1511g>a mutation in the COL3A1 gene. This is the first report of bilateral pneumothorax caused by EDS type IV. Clinicians should consider EDS type IV in the differential diagnosis for bilateral pneumothorax in conjunction with distinct previous histories and radiological findings. PMID:26666608

  20. Archaeal type IV pili and their involvement in biofilm formation

    PubMed Central

    Pohlschroder, Mechthild; Esquivel, Rianne N.

    2015-01-01

    Type IV pili are ancient proteinaceous structures present on the cell surface of species in nearly all bacterial and archaeal phyla. These filaments, which are required for a diverse array of important cellular processes, are assembled employing a conserved set of core components. While type IV pilins, the structural subunits of pili, share little sequence homology, their signal peptides are structurally conserved allowing for in silico prediction. Recently, in vivo studies in model archaea representing the euryarchaeal and crenarchaeal kingdoms confirmed that several of these pilins are incorporated into type IV adhesion pili. In addition to facilitating surface adhesion, these in vivo studies also showed that several predicted pilins are required for additional functions that are critical to biofilm formation. Examples include the subunits of Sulfolobus acidocaldarius Ups pili, which are induced by exposure to UV light and promote cell aggregation and conjugation, and a subset of the Haloferax volcanii adhesion pilins, which play a critical role in microcolony formation while other pilins inhibit this process. The recent discovery of novel pilin functions such as the ability of haloarchaeal adhesion pilins to regulate swimming motility may point to novel regulatory pathways conserved across prokaryotic domains. In this review, we will discuss recent advances in our understanding of the functional roles played by archaeal type IV adhesion pili and their subunits, with particular emphasis on their involvement in biofilm formation. PMID:25852657

  1. The first genetically confirmed Japanese patient with mucolipidosis type IV.

    PubMed

    Saijo, Harumi; Hayashi, Masaharu; Ezoe, Takanori; Ohba, Chihiro; Saitsu, Hirotomo; Kurata, Kiyoko; Matsumoto, Naomichi

    2016-05-01

    Mucolipidosis type IV (MLIV) is a rare neurodegenerative disorder characterized by severe psychomotor delay and visual impairment. We report the brain pathology in the first Japanese patient of MLIV with a novel homozygous missense mutation in MCOLN1. We detected the localized increase in p62-reactive astrocytes in the basal ganglia. PMID:27190617

  2. Space Telescope and Optical Reverberation Mapping Project. IV. Anomalous Behavior of the Broad Ultraviolet Emission Lines in NGC 5548

    NASA Astrophysics Data System (ADS)

    Goad, M. R.; Korista, K. T.; De Rosa, G.; Kriss, G. A.; Edelson, R.; Barth, A. J.; Ferland, G. J.; Kochanek, C. S.; Netzer, H.; Peterson, B. M.; Bentz, M. C.; Bisogni, S.; Crenshaw, D. M.; Denney, K. D.; Ely, J.; Fausnaugh, M. M.; Grier, C. J.; Gupta, A.; Horne, K. D.; Kaastra, J.; Pancoast, A.; Pei, L.; Pogge, R. W.; Skielboe, A.; Starkey, D.; Vestergaard, M.; Zu, Y.; Anderson, M. D.; Arévalo, P.; Bazhaw, C.; Borman, G. A.; Boroson, T. A.; Bottorff, M. C.; Brandt, W. N.; Breeveld, A. A.; Brewer, B. J.; Cackett, E. M.; Carini, M. T.; Croxall, K. V.; Dalla Bontà, E.; De Lorenzo-Cáceres, A.; Dietrich, M.; Efimova, N. V.; Evans, P. A.; Filippenko, A. V.; Flatland, K.; Gehrels, N.; Geier, S.; Gelbord, J. M.; Gonzalez, L.; Gorjian, V.; Grupe, D.; Hall, P. B.; Hicks, S.; Horenstein, D.; Hutchison, T.; Im, M.; Jensen, J. J.; Joner, M. D.; Jones, J.; Kaspi, S.; Kelly, B. C.; Kennea, J. A.; Kim, M.; Kim, S. C.; Klimanov, S. A.; Lee, J. C.; Leonard, D. C.; Lira, P.; MacInnis, F.; Manne-Nicholas, E. R.; Mathur, S.; McHardy, I. M.; Montouri, C.; Musso, R.; Nazarov, S. V.; Norris, R. P.; Nousek, J. A.; Okhmat, D. N.; Papadakis, I.; Parks, J. R.; Pott, J.-U.; Rafter, S. E.; Rix, H.-W.; Saylor, D. A.; Schimoia, J. S.; Schnülle, K.; Sergeev, S. G.; Siegel, M.; Spencer, M.; Sung, H.-I.; Teems, K. G.; Treu, T.; Turner, C. S.; Uttley, P.; Villforth, C.; Weiss, Y.; Woo, J.-H.; Yan, H.; Young, S.; Zheng, W.-K.

    2016-06-01

    During an intensive Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) UV monitoring campaign of the Seyfert 1 galaxy NGC 5548 performed from 2014 February to July, the normally highly correlated far UV continuum and broad emission line variations decorrelated for ∼60–70 days, starting ∼75 days after the first HST/COS observation. Following this anomalous state, the flux and variability of the broad emission lines returned to a more normal state. This transient behavior, characterized by significant deficits in flux and equivalent width of the strong broad UV emission lines, is the first of its kind to be unambiguously identified in an active galactic nucleus reverberation mapping campaign. The largest corresponding emission line flux deficits occurred for the high ionization, collisionally excited lines C iv and Si iv(+O iv]), and also He ii(+O iii]), while the anomaly in Lyα was substantially smaller. This pattern of behavior indicates a depletion in the flux of photons with {E}{{ph}}\\gt 54 {{eV}} relative to those near 13.6 eV. We suggest two plausible mechanisms for the observed behavior: (i) temporary obscuration of the ionizing continuum incident upon broad line region (BLR) clouds by a moving veil of material lying between the inner accretion disk and inner (BLR), perhaps resulting from an episodic ejection of material from the disk, or (ii) a temporary change in the intrinsic ionizing continuum spectral energy distribution resulting in a deficit of ionizing photons with energies >54 eV, possibly due to a transient restructuring of the Comptonizing atmosphere above the disk. Current evidence appears to favor the latter explanation.

  3. Respiratory complications of Ehlers-Danlos syndrome type IV.

    PubMed

    Hatake, Katsuhiko; Morimura, Yoshifumi; Kudo, Risa; Kawashima, Wataru; Kasuda, Shogo; Kuniyasu, Hiroki

    2013-01-01

    We describe a case of Ehlers-Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient's death because of pulmonary hemorrhage. Because this syndrome resulted in the patient's death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death. PMID:22940417

  4. Expression cloning of a candidate gene for Mucolipidosis type IV

    SciTech Connect

    Gama Sosa, M.A.; De Gasperi, R.; Battistini, S.

    1994-09-01

    Mucolipidosis IV is an autosomal recessive lysosomal storage disease characterized by progressive psychomotor retardation and opthalmological abnormalities, namely corneal opacity and retinal degeneration. Biochemically, it is characterized by the lysosomal accumulation of diverse compounds such as gangliosides, phospholipids and acidic mucopolysaccharides. To date, the basic biochemical defect causing this storage disease is still unknown and the relevant gene has also not been identified. An expression cloning strategy was used to identify human kidney cDNA clones capable of reverting in transient gene expression assays the PAS+ phenotype typical of Mucolipidosis IV cells to the normal PAS- phenotype. By this method, a candidate cDNA clone (Mu cDNA) capable of clearing Mucolipidosis IV fibroblasts of their PAS+ positive storage material was isolated. Nucleotide sequence analysis indicated the presence of 2 open reading frames. In vitro translation of T7 transcribed Mu RNA showed protein products of 7,000 and 6,000 mw. Altered expression of the Mu gene may result in the onset of Mucolipidosis type IV.

  5. Terminal ileum gangrene secondary to a type IV paraesophageal hernia

    PubMed Central

    Hsu, Ching Tsai; Hsiao, Po Jen; Chiu, Chih Chien; Chan, Jenq Shyong; Lin, Yee Fung; Lo, Yuan Hung; Hsiao, Chia Jen

    2016-01-01

    Type IV paraesophageal hernia (PEH) is very rare, and is characterized by the intrathoracic herniation of the abdominal viscera other than the stomach into the chest. We describe a 78-year-old woman who presented at our emergency department because of epigastric pain that she had experienced over the past 24 h. On the day after admission, her pain became severe and was accompanied by right chest pain and dyspnea. Chest radiography revealed an intrathoracic intestinal gas bubble occupying the right lower lung field. Emergency explorative laparotomy identified a type IV PEH with herniation of only the terminal ileum through a hiatal defect into the right thoracic cavity. In this report, we also present a review of similar cases in the literature published between 1980 and 2015 in PubMed. There were four published cases of small bowel herniation into the thoracic cavity during this period. Our patient represents a rare case of an individual diagnosed with type IV PEH with incarceration of only the terminal ileum. PMID:26937153

  6. Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis.

    PubMed Central

    Kalluri, R; Shield, C F; Todd, P; Hudson, B G; Neilson, E G

    1997-01-01

    Normal glomerular capillaries filter plasma through a basement membrane (GBM) rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now show that these latter isoforms are absent biochemically from the glomeruli in patients with X-linked Alport syndrome (XAS). Their GBM instead retain a fetal distribution of alpha1(IV) and alpha2(IV) isoforms because they fail to developmentally switch their alpha-chain use. The anomalous persistence of these fetal isoforms of type IV collagen in the GBM in XAS also confers an unexpected increase in susceptibility to proteolytic attack by collagenases and cathepsins. The incorporation of cysteine-rich alpha3(IV), alpha4(IV), and alpha5(IV) chains into specialized basement membranes like the GBM may have normally evolved to protectively enhance their resistance to proteolytic degradation at the site of glomerular filtration. The relative absence of these potentially protective collagen IV isoforms in GBM from XAS may explain the progressive basement membrane splitting and increased damage as these kidneys deteriorate. PMID:9153291

  7. Bacteria turn on surfaces by oversteering with Type IV pili

    NASA Astrophysics Data System (ADS)

    Jin, Fan; Conrad, Jacinta C.; Gibiansky, Maxsim L.; Wong, Gerard C. L.

    2011-03-01

    Type-IV pili (TFP) are linear nano-actuators that enable bacteria to crawl on surfaces. Analysis of TFP-mediated crawling in P. aeruginosa reveals that it always alternates between two types of distinct movements: a linear translation of constant velocity is followed by a combined translation-rotation that is ~ 10 x faster in instantaneous velocity. The latter process can turn the cell body by over-steering so that the rear of the cell loses traction with the surface. Orientational distributions of these movements suggest that the former is due to pulling by multiple TFP, whereas the latter is mostly due to release by single TFP.

  8. Adult presentation of Bartter syndrome type IV with erythrocytosis

    PubMed Central

    Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

    2015-01-01

    Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis. PMID:26537508

  9. Anomalous Elastic Behavior in hcp- and Sm-Type Dysprosium

    SciTech Connect

    Tschauner, Oliver; Grubor-Urosevic, Ognjen; Dera, Przemyslaw; Mulcahy, Sean R.

    2012-04-11

    The compression behavior of elemental dysprosium in the hcp- and the Sm-type phases has been examined under hydrostatic pressure. Sm-type Dy has been found about 1% denser than the hcp phase. This increase in density is due to c-axis contraction in Sm-type Dy, whereas the a-axis even expands compared with the hcp-phase. Both the hcp- and the Sm-type phases show an inversion in the pressure derivative of the c/a ratio. For hcp-Dy this inversion is very sharp with minimal c/a at 2.5 GPa. At the same pressure, the compression behavior of hcp-Dy changes abruptly from dominantly c-axis compression to almost isotropic compression with slightly softer S{sub 11}. The bulk modulus increases at this point by a factor of {approx}2. Both hcp- and Sm-type Dy exhibit a crossover from highly anisotropic compression mostly along the c-axis to almost isotropic compression. We discuss these anomalies with respect to a possible Lifshitz transition and structural soft modes.

  10. Anomalous absorption in a-type asymmetric top molecules in cosmic objects

    NASA Astrophysics Data System (ADS)

    Chandra, Suresh

    Since the detection of the first molecule OH in cosmic objects in 1963, scientists got interested in identification of molecules in the cosmic objects. By now more than 170 molecules have been identified. In order to know about the physical conditions prevailing in the cool cosmic objects and about the chemical reactions going on there, scientists are interested in identification of as many molecules as possible. In some molecular clouds, the kinetic temperature is very low, 10 - 20 K. For such objects, anomalous absorption, i.e., the absorption against the cosmic microwave background, may play an important role for identification of molecules. The transition 111 - 110 at 4.829 GHz of H_2CO was the first one showing the anomalous absorption in the cosmic objects. The molecule H_2CS also has been identified in the cosmic objects. We have discussed about the anomalous absorption of 111 - 110 transition in a-type asymmetric top molecules. For the investigation, the required parameters are the radiative and collisional transition probabilities. We can calculate radiative transition probabilities between the rotational levels. Calculation of collisional rates is a tedious job. In absence of accurate collisional rates, we can investigated the anomalous absorption in a qualitative manner by using the scaled values for collisional rates. We find that anomalous absorption of 111 - 110 transition is possible, provided collisional rates satisfy the required condition.

  11. Mechanical stability study of type IV cryomodule (ILC prototype)

    SciTech Connect

    McGee, M.W.; Doremus, R.; Wands, C.R.; /Fermilab

    2007-06-01

    An ANSYS modal and harmonic finite element analysis (FEA) was performed in order to investigate cryomodule design mechanical stability for the proposed International Linear Collider (ILC). The current cryomodule, designated Type IV or (T4CM), closely follows the Type III TESLA Test Facility (TTF) version used at DESY, with the exception of a proposed location of the superconducting (SC) quadrupole at the center. This analysis considered the stringent stability criteria established for the ILC, where vertical motion for the SC quadrupole is limited to the micron range at a few Hz. Model validation was achieved through Type III cryomodule vibration measurement studies performed at DESY. The effect of support location, support stiffness and other important parameters were considered in a parametric sensitivity study. FEA results, fast motion investigations and stabilization techniques are discussed.

  12. Named entity recognition for bacterial Type IV secretion systems.

    PubMed

    Ananiadou, Sophia; Sullivan, Dan; Black, William; Levow, Gina-Anne; Gillespie, Joseph J; Mao, Chunhong; Pyysalo, Sampo; Kolluru, Balakrishna; Tsujii, Junichi; Sobral, Bruno

    2011-01-01

    Research on specialized biological systems is often hampered by a lack of consistent terminology, especially across species. In bacterial Type IV secretion systems genes within one set of orthologs may have over a dozen different names. Classifying research publications based on biological processes, cellular components, molecular functions, and microorganism species should improve the precision and recall of literature searches allowing researchers to keep up with the exponentially growing literature, through resources such as the Pathosystems Resource Integration Center (PATRIC, patricbrc.org). We developed named entity recognition (NER) tools for four entities related to Type IV secretion systems: 1) bacteria names, 2) biological processes, 3) molecular functions, and 4) cellular components. These four entities are important to pathogenesis and virulence research but have received less attention than other entities, e.g., genes and proteins. Based on an annotated corpus, large domain terminological resources, and machine learning techniques, we developed recognizers for these entities. High accuracy rates (>80%) are achieved for bacteria, biological processes, and molecular function. Contrastive experiments highlighted the effectiveness of alternate recognition strategies; results of term extraction on contrasting document sets demonstrated the utility of these classes for identifying T4SS-related documents. PMID:21468321

  13. A force-dependent switch reverses type IV pilus retraction.

    PubMed

    Maier, Berenike; Koomey, Michael; Sheetz, Michael P

    2004-07-27

    Type IV pilus dynamics is important for virulence, motility, and DNA transfer in a wide variety of prokaryotes. The type IV pilus system constitutes a very robust and powerful molecular machine that transports pilus polymers as well as DNA through the bacterial cell envelope. In Neisseria gonorrhoeae, pilus retraction is a highly irreversible process that depends on PilT, an AAA ATPase family member. However, when levels of PilT are reduced, the application of high external forces (F = 110 +/- 10 pN) induces processive pilus elongation. At forces of >50 pN, single pili elongate at a rate of v = 350 +/- 50 nm/s. For forces of <50 pN, elongation velocity depends strongly on force and relaxation causes immediate retraction. Both pilus retraction and force-induced elongation can be modeled by chemical kinetics with same step length for the rate-limiting translocation step. The model implies that a force-dependent molecular switch can induce pilus elongation by reversing the retraction mechanism. PMID:15256598

  14. F-Area Type IV Tank Liner Life Estimation

    SciTech Connect

    Wiersman, B. J.

    2005-10-01

    The Savannah River Site (SRS) is proceeding with closure of the Type IV waste tanks that are located in F-area. These tanks are underground concrete vaults and have been in service since the early 1960's. The interior of the concrete vault is lined with carbon steel plate. The time necessary for the carbon steel plate to disintegrate was estimated. These calculations assumed that the concrete structure was degraded and therefore the exterior of the liner is exposed to the soil conditions. Two corrosion mechanisms were examined: pitting and general corrosion. Data from soil corrosion studies performed by the National Bureau of Standards (NBS) was utilized to estimate the corrosion rate of the carbon steel liner. The following conclusions were made: (1) Cecil Clay Loam in Atlanta, Georgia, a soil tested by the NBS, is representative of the SRS soil conditions near the F-Area Type IV tanks. (2) The time to tank wall disintegration due to general corrosion only was estimated to be 770 years after concrete vault failure. (3) The time to tank wall disintegration due to pitting corrosion was estimated to be 675 years after concrete vault failure. (4) The lower bound estimate for the time to tank wall disintegration is 675 years.

  15. Ehlers-Danlos Syndrome Type IV: A Case Report.

    PubMed

    Soo-Hoo, Sarah; Porten, Brandon R; Engstrom, Bjorn I; Skeik, Nedaa

    2016-04-01

    Ehlers-Danlos syndrome (EDS) encompasses a group of rare genetic connective tissue disorders. The vascular type (type IV) poses the most serious risk to patients. Diagnosis is usually difficult, especially if patients lack a family history. Life-threatening vascular emergency such as dissection or rupture can be the first presenting symptom. Management of the disease can pose a clinical challenge due to the emergency of presentation, tissue friability, and lack of clear management recommendations. We report a unique case of a 40-year-old man who presented with a ruptured celiac artery and a strong family history of EDS. This case highlights the difficulties and complications associated with treating this uncommon and serious disease. PMID:26975607

  16. Identification of mutations in Type IV glycogen storage disease

    SciTech Connect

    Bao, Y.; Kishnani, P.; Chen, Y.T.

    1994-09-01

    Type IV glycogen storage disease (GSD IV, Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE) activity, which results in the accumulation of glycogen with unbranched, long, outer chains in the tissues. The molecular basis of the disease is not known. We studied four patients with the disease; three with typical presentation of progressive liver cirrhosis and failure, and one with severe and fatal neonatal hypotonia and cardiomyopathy. Southern blot analysis with EcoRI or MspI did not detect gross DNA rearrangement, deletion or duplication in patients` glycogen branching enzyme genes. Northern analysis with total cellular RNAs isolated from skin fibroblast MI strains of three patients with typical clinical presentation showed a normal level and size (2.95 kb) of GBE mRNA hybridization band in two and absent mRNA hybridization band in the remaining one. The patient with atypical severe neonatal hypotonia demonstrated a less intense and smaller size (2.75 kb) of mRNA hybridization band. A 210 hp deletion from nucleotide sequence 873 to 1082 which causes 70 amino acids missing from amino acid sequence 262 to 331 was detected in all 17 clones sequenced from the fatal hypotonia patient. This deletion is located in the region which is highly conserved between prokaryotic, yeast and human GBE polypeptide sequences, and also includes the first of the four regions which constitute the catalytic active sites of most of amylolytic enzymes. A point mutation C-T (1633) which changes the amino acid from Arginine to Cystine was found in 19 of 20 cDNA clones from a patient with classical clinical presentation. This point mutation was unique to this patient and was not observed in three other patients or normal controls. This is the first report on the molecular basis of GSD IV and our data indicated the presence of extensive genetic heterogeneity in the disease.

  17. Identification of Anaplasma marginale Type IV Secretion System Effector Proteins

    PubMed Central

    Brayton, Kelly A.; Beare, Paul A.; Brown, Wendy C.; Heinzen, Robert A.; Broschat, Shira L.

    2011-01-01

    Background Anaplasma marginale, an obligate intracellular alphaproteobacterium in the order Rickettsiales, is a tick-borne pathogen and the leading cause of anaplasmosis in cattle worldwide. Complete genome sequencing of A. marginale revealed that it has a type IV secretion system (T4SS). The T4SS is one of seven known types of secretion systems utilized by bacteria, with the type III and IV secretion systems particularly prevalent among pathogenic Gram-negative bacteria. The T4SS is predicted to play an important role in the invasion and pathogenesis of A. marginale by translocating effector proteins across its membrane into eukaryotic target cells. However, T4SS effector proteins have not been identified and tested in the laboratory until now. Results By combining computational methods with phylogenetic analysis and sequence identity searches, we identified a subset of potential T4SS effectors in A. marginale strain St. Maries and chose six for laboratory testing. Four (AM185, AM470, AM705 [AnkA], and AM1141) of these six proteins were translocated in a T4SS-dependent manner using Legionella pneumophila as a reporter system. Conclusions The algorithm employed to find T4SS effector proteins in A. marginale identified four such proteins that were verified by laboratory testing. L. pneumophila was shown to work as a model system for A. marginale and thus can be used as a screening tool for A. marginale effector proteins. The first T4SS effector proteins for A. marginale have been identified in this work. PMID:22140462

  18. Role of Type IV Pili in Predation by Bdellovibrio bacteriovorus

    PubMed Central

    Chanyi, Ryan M.; Koval, Susan F.

    2014-01-01

    Bdellovibrio bacteriovorus, as an obligate predator of Gram-negative bacteria, requires contact with the surface of a prey cell in order to initiate the life cycle. After attachment, the predator penetrates the prey cell outer membrane and enters the periplasmic space. Attack phase cells of B. bacteriovorus have polar Type IV pili that are required for predation. In other bacteria, these pili have the ability to extend and retract via the PilT protein. B. bacteriovorus has two pilT genes, pilT1 and pilT2, that have been implicated in the invasion process. Markerless in-frame deletion mutants were constructed in a prey-independent mutant to assess the role of PilT1 and PilT2 in the life cycle. When predation was assessed using liquid cocultures, all mutants produced bdelloplasts of Escherichia coli. These results demonstrated that PilT1 and PilT2 are not required for invasion of prey cells. Predation of the mutants on biofilms of E. coli was also assessed. Wild type B. bacteriovorus 109JA and the pilT1 mutant decreased the mass of the biofilm to 35.4% and 27.9% respectively. The pilT1pilT2 mutant was able to prey on the biofilm, albeit less efficiently with 50.2% of the biofilm remaining. The pilT2 mutant was unable to disrupt the biofilm, leaving 92.5% of the original biofilm after predation. The lack of PilT2 function may impede the ability of B. bacteriovorus to move in the extracellular polymeric matrix and find a prey cell. The role of Type IV pili in the life cycle of B. bacteriovorus is thus for initial recognition of and attachment to a prey cell in liquid cocultures, and possibly for movement within the matrix of a biofilm. PMID:25409535

  19. Bacterial Type IV Secretion Systems: Versatile Virulence Machines

    PubMed Central

    Voth, Daniel E.; Broederdorf, Laura J.; Graham, Joseph G.

    2013-01-01

    Many bacterial pathogens employ multicomponent protein complexes to deliver macromolecules directly into their eukaryotic host cell to promote infection. Some Gram-negative pathogens use a versatile type IV secretion system (T4SS) that can translocate DNA or proteins into host cells. T4SSs represent major bacterial virulence determinants and have recently been the focus of intense research efforts designed to better understand and combat infectious diseases. Interestingly, although the two major classes of T4SSs function in a similar manner to secrete proteins, the translocated “effectors” vary substantially from one organism to another. In fact, differing effector repertoires likely contribute to organism-specific host cell interactions and disease outcomes. In this review, we discuss the current state of T4SS research, with an emphasis on intracellular bacterial pathogens of humans and the diverse array of translocated effectors used to manipulate host cells. PMID:22324993

  20. Type IV pili promote early biofilm formation by Clostridium difficile.

    PubMed

    Maldarelli, Grace A; Piepenbrink, Kurt H; Scott, Alison J; Freiberg, Jeffrey A; Song, Yang; Achermann, Yvonne; Ernst, Robert K; Shirtliff, Mark E; Sundberg, Eric J; Donnenberg, Michael S; von Rosenvinge, Erik C

    2016-08-01

    Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile growing in a biofilm has a distinct RNA expression profile, with significant differences in T4P gene expression. Microscopy of T4P-expressing and T4P-deficient strains suggests that T4P play an important role in early biofilm formation. A non-piliated pilA1 mutant forms an initial biofilm of significantly reduced mass and thickness in comparison to the wild type. Complementation of the pilA1 mutant strain leads to formation of a biofilm which resembles the wild-type biofilm. These findings suggest that T4P play an important role in early biofilm formation. Novel strategies for confronting biofilm infections are emerging; our data suggest that similar strategies should be investigated in CDI. PMID:27369898

  1. Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

    PubMed Central

    Xiao, Qian; Jiang, Yan; Liu, Qingbo; Yue, Jiao; Liu, Chunying; Zhao, Xiaotong; Qiao, Yuemei; Ji, Hongbin; Chen, Jianfeng; Ge, Gaoxiang

    2015-01-01

    Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. PMID:25992553

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

    PubMed

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-01-01

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

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

    PubMed Central

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-01-01

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

  4. Type IV Pili in Gram-Positive Bacteria

    PubMed Central

    Craig, Lisa

    2013-01-01

    SUMMARY Type IV pili (T4P) are surface-exposed fibers that mediate many functions in bacteria, including locomotion, adherence to host cells, DNA uptake (competence), and protein secretion and that can act as nanowires carrying electric current. T4P are composed of a polymerized protein, pilin, and their assembly apparatuses share protein homologs with type II secretion systems in eubacteria and the flagella of archaea. T4P are found throughout Gram-negative bacterial families and have been studied most extensively in certain model Gram-negative species. Recently, it was discovered that T4P systems are also widespread among Gram-positive species, in particular the clostridia. Since Gram-positive and Gram-negative bacteria have many differences in cell wall architecture and other features, it is remarkable how similar the T4P core proteins are between these organisms, yet there are many key and interesting differences to be found as well. In this review, we compare the two T4P systems and identify and discuss the features they have in common and where they differ to provide a very broad-based view of T4P systems across all eubacterial species. PMID:24006467

  5. Heterogeneity among specific phobia types in DSM-IV.

    PubMed

    Antony, M M; Brown, T A; Barlow, D H

    1997-12-01

    Recently, it has been suggested that situational specific phobias (e.g., phobias of driving, flying, enclosed places) are more closely related to agoraphobia than are other specific phobia types. The present study investigated this hypothesis by examining heterogeneity among the four main DSM-IV specific phobia types, particularly with respect to variables believed to be associated with agoraphobia. Using interviews and behavioral testing, 60 patients with specific phobias of animals, heights, blood/injections, or driving were compared with respect to etiology, age of onset, physiological response, predictability of panic attacks, and focus of apprehension. Fifteen patients suffering from panic disorder with agoraphobia served as a comparison group for some measures. Relative to the other specific phobias, driving phobias were most strongly associated with a later age of onset, similar to that of individuals with agoraphobia. Height phobias were also associated with a late age of onset as well as a more internal focus of apprehension, relative to other groups. Finally, individuals in the blood/injection phobia group reported a more internal focus of apprehension than those in other groups and were the only group to report a history of fainting in the phobic situation. Overall, the results did not support the hypothesis that situational phobias are a variant of agoraphobia. In fact, on several of the variables for which groups did differ, individuals with height phobias (a phobia from the natural environment type) showed a pattern most similar to individuals with agoraphobia. The implications of these results for the classification of specific phobias are discussed. PMID:9465442

  6. Type IV Pilus Secretins Have Extracellular C Termini

    PubMed Central

    Lieberman, Joshua A.; Petro, Courtney D.; Thomas, Stefani; Yang, Austin

    2015-01-01

    ABSTRACT Type IV pili (T4Ps) are surface appendages used by Gram-negative and Gram-positive pathogens for motility and attachment to epithelial surfaces. In Gram-negative bacteria, such as the important pediatric pathogen enteropathogenic Escherichia coli (EPEC), during extension and retraction, the pilus passes through an outer membrane (OM) pore formed by the multimeric secretin complex. The secretin is common to Gram-negative assemblies, including the related type 2 secretion (T2S) system and the type 3 secretion (T3S) system. The N termini of the secretin monomers are periplasmic and in some systems have been shown to mediate substrate specificity. In this study, we mapped the topology of BfpB, the T4P secretin from EPEC, using a combination of biochemical and biophysical techniques that allowed selective identification of periplasmic and extracellular residues. We applied rules based on solved atomic structures of outer membrane proteins (OMPs) to generate our topology model, combining the experimental results with secondary structure prediction algorithms and direct inspection of the primary sequence. Surprisingly, the C terminus of BfpB is extracellular, a result confirmed by flow cytometry for BfpB and a distantly related T4P secretin, PilQ, from Pseudomonas aeruginosa. Keeping with prior evidence, the C termini of two T2S secretins and one T3S secretin were not detected on the extracellular surface. On the basis of our data and structural constraints, we propose that BfpB forms a beta barrel with 16 transmembrane beta strands. We propose that the T4P secretins have a C-terminal segment that passes through the center of each monomer. PMID:25805731

  7. Structure of Clostridium difficile PilJ Exhibits Unprecedented Divergence from Known Type IV Pilins*

    PubMed Central

    Piepenbrink, Kurt H.; Maldarelli, Grace A.; de la Peña, Claudia F. Martinez; Mulvey, George L.; Snyder, Greg A.; De Masi, Leon; von Rosenvinge, Erik C.; Günther, Sebastian; Armstrong, Glen D.; Donnenberg, Michael S.; Sundberg, Eric J.

    2014-01-01

    Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, cellular adhesion, and colonization. Recently, there has been an increased appreciation of the ability of Gram-positive species, including Clostridium difficile, to produce Type IV pili. Here we report the first three-dimensional structure of a Gram-positive Type IV pilin, PilJ, demonstrate its incorporation into Type IV pili, and offer insights into how the Type IV pili of C. difficile may assemble and function. PilJ has several unique structural features, including a dual-pilin fold and the incorporation of a structural zinc ion. We show that PilJ is incorporated into Type IV pili in C. difficile and present a model in which the incorporation of PilJ into pili exposes the C-terminal domain of PilJ to create a novel interaction surface. PMID:24362261

  8. Mechanical Properties of Type IV Pili in P. Aeruginosa

    NASA Astrophysics Data System (ADS)

    Lu, Shun; Touhami, Ahmed; Scheurwater, Edie; Harvey, Hanjeong; Burrows, Lori; Dutcher, John

    2009-03-01

    Type IV pili (Tfp) are thin flexible protein filaments that extend from the cell membrane of bacteria such as Pseudomonas aeruginosa and Neisseria gonorrhoeae. The mechanical properties of Tfp are of great importance since they allow bacteria to interact with and colonize various surfaces. In the present study, we have used atomic force microscopy (AFM) for both imaging and pulling on Tfp from P. aeruginosa (PAO1) and from its PilA, PilT, and FliC mutants. A single pilus filament was mechanically stretched and the resulting force-extension profiles were fitted using the worm-like-chain (WLC) model. The statistical distributions obtained for contour length, persistence length, and number of pili per bacteria pole, were used to evaluate the mechanical properties of a single pilus and the biogenesis functions of different proteins (PilA, PilT) involved in its assembly and disassembly. Importantly, the persistence length value of ˜ 1 μm measured in the present study, which is consistent with the curvature of the pili observed in our AFM images, is significantly lower than the value of 5 μm reported earlier by Skerker et al. (1). Our results shed new light on the role of mechanical forces that mediate bacteria-surface interactions and biofilm formation. 1- J.M. Skerker and H.C. Berg, Proc. Natl. Acad. Sci. USA, 98, 6901-6904 (2001).

  9. Narrowband frequency-drift structures in solar type IV bursts

    NASA Astrophysics Data System (ADS)

    Nishimura, Yukio; Ono, Takayuki; Tsuchiya, Fuminori; Misawa, Hiroaki; Kumamoto, Atsushi; Katoh, Yuto; Masuda, Satoshi; Miyoshi, Yoshizumi

    2013-12-01

    We have established the Zao Solar Radiospectrograph (ZSR), a new solar radio observation system, at the Zao observatory of Tohoku University, Japan. We observed narrowband fine structures with type IV bursts with ZSR on 2 and 3 November 2008. The observed fine structures are similar to fiber bursts in terms of the drift rates and the existence of emission and absorption stripes. Statistical analysis of the drift rates, however, shows that the observed fine structures are different from the ordinary fiber bursts as regards the sense and the magnitude of their drift rates. First, the observed drift rates include both positive and negative rates, whereas ordinary fiber bursts are usually characterized by negative drift rates. Second, the absolute values of the observed drift rates are tens of MHz s-1, whereas the typical drift rate of fiber bursts at 325 MHz is approximately -9 MHz s-1. In addition, all fine structures analyzed have narrow emission bands of less than 17 MHz. We also show that the observed narrowband emission features with drift rates of approximately 40 MHz s-1 can be interpreted as the propagation of whistler-mode waves, which is the same process as that underlying fiber bursts.

  10. Characteristics of unsteady type IV shock/shock interaction

    NASA Astrophysics Data System (ADS)

    Chu, Y.-B.; Lu, X.-Y.

    2012-05-01

    Characteristics of the unsteady type IV shock/shock interaction of hypersonic blunt body flows are investigated by solving the Navier-Stokes equations with high-order numerical methods. The intrinsic relations of flow structures to shear, compression, and heating processes are studied and the physical mechanisms of the unsteady flow evolution are revealed. It is found that the instantaneous surface-heating peak is caused by the fluid in the "hot spot" generated by an oscillating and deforming jet bow shock (JBS) just ahead of the body surface. The features of local shock/boundary layer interaction and vortex/boundary layer interaction are clarified. Based on the analysis of flow evolution, it is identified that the upstream-propagating compression waves are associated with the interaction of the JBS and the shear layers formed by a supersonic impinging jet, and then the interaction of the freestream bow shocks and the compression waves results in entropy and vortical waves propagating to the body surface. Further, the feedback mechanism of the inherent unsteadiness of the flow field is revealed to be related to the impinging jet. A feedback model is proposed to reliably predict the dominant frequency of flow evolution. The results obtained in this study provide physical insight into the understanding of the mechanisms relevant to this complex flow.

  11. Characterization of the Francisella tularensis subsp. novicida type IV pilus.

    PubMed

    Zogaj, Xhavit; Chakraborty, Subhra; Liu, Jirong; Thanassi, David G; Klose, Karl E

    2008-07-01

    Francisella tularensis causes the disease tularaemia. Type IV pili (Tfp) genes are present in the genomes of all F. tularensis subspecies. We show that the wild-type F. tularensis subsp. novicida expresses pilus fibres on its surface, and mutations in the Tfp genes pilF and pilT disrupt pilus biogenesis. Mutations in other Tfp genes (pilQ and pilG) do not eliminate pilus expression. A mutation in pilE4 eliminates pilus expression, whereas mutations in the other pilin subunits pilE1-3 and pilE5 do not, suggesting that pilE4 is the major pilus structural subunit. The virulence regulator MglA is required for pilus expression, and it regulates the transcription of a putative Tfp glycosylation gene (FTN0431). However, MglA does not regulate transcription of pilF, pilT or pilE4, and a strain lacking FTN0431 still expresses pili; thus, it is unclear how MglA regulates pilus expression. Only pilF was also required for protein secretion, while pilE4 and pilT were not, indicating that there is very little overlap of the protein secretion/Tfp functions of the pil genes. The protein secretion component pilE1 was more important for in vitro intramacrophage growth and mouse virulence than the Tfp component pilE4. Our results provide the first genetic characterization of the novel Tfp system of F. tularensis. PMID:18599841

  12. An Unusual Type of Totally Anomalous Pulmonary Venous Connection to the Superior Cavoatrial Junction.

    PubMed

    Shamsuddin, Ahmad Mahir; Wong, Abdul Rahim; Anderson, Robert H; Corno, Antonio F

    2016-07-01

    A neonate with cyanosis at birth was found to have a rare type of totally anomalous pulmonary venous connection. The pulmonary veins entered a confluence posterior to the left atrial wall, which drained into the right superior cavoatrial junction. There were no other major structural defects and no evidence of isomerism. Because of the severe cyanosis, and the restrictive nature of the interatrial communication, we performed balloon atrioseptostomy to improve oxygenation. We then achieved successful surgical repair when the baby was aged 7 months. PMID:26795906

  13. Structural Characterization of Novel Pseudomonas aeruginosa Type IV Pilins

    SciTech Connect

    Nguyen, Y.; Jackson, S; Aidoo, F; Junop, M; Burrows, L

    2010-01-01

    Pseudomonas aeruginosa type IV pili, composed of PilA subunits, are used for attachment and twitching motility on surfaces. P. aeruginosa strains express one of five phylogenetically distinct PilA proteins, four of which are associated with accessory proteins that are involved either in pilin posttranslational modification or in modulation of pilus retraction dynamics. Full understanding of pilin diversity is crucial for the development of a broadly protective pilus-based vaccine. Here, we report the 1.6-{angstrom} X-ray crystal structure of an N-terminally truncated form of the novel PilA from strain Pa110594 (group V), which represents the first non-group II pilin structure solved. Although it maintains the typical T4a pilin fold, with a long N-terminal {alpha}-helix and four-stranded antiparallel {beta}-sheet connected to the C-terminus by a disulfide-bonded loop, the presence of an extra helix in the {alpha}{beta}-loop and a disulfide-bonded loop with helical character gives the structure T4b pilin characteristics. Despite the presence of T4b features, the structure of PilA from strain Pa110594 is most similar to the Neisseria gonorrhoeae pilin and is also predicted to assemble into a fiber similar to the GC pilus, based on our comparative pilus modeling. Interactions between surface-exposed areas of the pilin are suggested to contribute to pilus fiber stability. The non-synonymous sequence changes between group III and V pilins are clustered in the same surface-exposed areas, possibly having an effect on accessory protein interactions. However, based on our high-confidence model of group III PilA{sub PA14}, compensatory changes allow for maintenance of a similar shape.

  14. Diversity and Evolution of Type IV pili Systems in Archaea

    PubMed Central

    Makarova, Kira S.; Koonin, Eugene V.; Albers, Sonja-Verena

    2016-01-01

    Many surface structures in archaea including various types of pili and the archaellum (archaeal flagellum) are homologous to bacterial type IV pili systems (T4P). The T4P consist of multiple proteins, often with poorly conserved sequences, complicating their identification in sequenced genomes. Here we report a comprehensive census of T4P encoded in archaeal genomes using sensitive methods for protein sequence comparison. This analysis confidently identifies as T4P components about 5000 archaeal gene products, 56% of which are currently annotated as hypothetical in public databases. Combining results of this analysis with a comprehensive comparison of genomic neighborhoods of the T4P, we present models of organization of 10 most abundant variants of archaeal T4P. In addition to the differentiation between major and minor pilins, these models include extra components, such as S-layer proteins, adhesins and other membrane and intracellular proteins. For most of these systems, dedicated major pilin families are identified including numerous stand alone major pilin genes of the PilA family. Evidence is presented that secretion ATPases of the T4P and cognate TadC proteins can interact with different pilin sets. Modular evolution of T4P results in combinatorial variability of these systems. Potential regulatory or modulating proteins for the T4P are identified including KaiC family ATPases, vWA domain-containing proteins and the associated MoxR/GvpN ATPase, TFIIB homologs and multiple unrelated transcription regulators some of which are associated specific T4P. Phylogenomic analysis suggests that at least one T4P system was present in the last common ancestor of the extant archaea. Multiple cases of horizontal transfer and lineage-specific duplication of T4P loci were detected. Generally, the T4P of the archaeal TACK superphylum are more diverse and evolve notably faster than those of euryarchaea. The abundance and enormous diversity of T4P in hyperthermophilic archaea

  15. Diversity and Evolution of Type IV pili Systems in Archaea.

    PubMed

    Makarova, Kira S; Koonin, Eugene V; Albers, Sonja-Verena

    2016-01-01

    Many surface structures in archaea including various types of pili and the archaellum (archaeal flagellum) are homologous to bacterial type IV pili systems (T4P). The T4P consist of multiple proteins, often with poorly conserved sequences, complicating their identification in sequenced genomes. Here we report a comprehensive census of T4P encoded in archaeal genomes using sensitive methods for protein sequence comparison. This analysis confidently identifies as T4P components about 5000 archaeal gene products, 56% of which are currently annotated as hypothetical in public databases. Combining results of this analysis with a comprehensive comparison of genomic neighborhoods of the T4P, we present models of organization of 10 most abundant variants of archaeal T4P. In addition to the differentiation between major and minor pilins, these models include extra components, such as S-layer proteins, adhesins and other membrane and intracellular proteins. For most of these systems, dedicated major pilin families are identified including numerous stand alone major pilin genes of the PilA family. Evidence is presented that secretion ATPases of the T4P and cognate TadC proteins can interact with different pilin sets. Modular evolution of T4P results in combinatorial variability of these systems. Potential regulatory or modulating proteins for the T4P are identified including KaiC family ATPases, vWA domain-containing proteins and the associated MoxR/GvpN ATPase, TFIIB homologs and multiple unrelated transcription regulators some of which are associated specific T4P. Phylogenomic analysis suggests that at least one T4P system was present in the last common ancestor of the extant archaea. Multiple cases of horizontal transfer and lineage-specific duplication of T4P loci were detected. Generally, the T4P of the archaeal TACK superphylum are more diverse and evolve notably faster than those of euryarchaea. The abundance and enormous diversity of T4P in hyperthermophilic archaea

  16. Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

    PubMed Central

    Öhlund, D; Lundin, C; Ardnor, B; Öman, M; Naredi, P; Sund, M

    2009-01-01

    Background: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. Methods: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. Results: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. Conclusion: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context. PMID:19491897

  17. Clinical significance of serum laminin and type-IV collagen levels in cutaneous melanoma patients

    PubMed Central

    TAS, FARUK; BILGIN, ELIF; KARABULUT, SENEM; DURANYILDIZ, DERYA

    2016-01-01

    Laminin and type-IV collagen constitute a significant portion of the extracellular matrix. The objective of the present study was to evaluate whether the serum concentrations of laminin and type-IV collagen may serve as biomarkers for cutaneous melanoma. Sixty pathologically confirmed melanoma patients were enrolled in the study. Serum laminin and type-IV collagen levels were assessed using an ELISA. Thirty healthy controls were also examined. No significant differences in the baseline serum levels of laminin were identified between melanoma patients and healthy controls (P=0.45). However, the baseline serum levels of type-IV collagen were significantly elevated in melanoma patients compared with those in the control group (P<0.001). Clinical parameters, including patient age, gender, localization of lesion, histopathology, stage of disease, serum lactate dehydrogenase concentrations and responsiveness to chemotherapy were found not to be associated with the serum levels of laminin and type-IV collagen (P>0.05). Furthermore, the serum levels of laminin and type-IV collagen had no prognostic value regarding the outcome for melanoma patients (P=0.36 and P=0.26, respectively). While laminin levels showed no diagnostic value, the serum concentrations of type-IV collagen were indicated to serve as a diagnostic marker in patients with cutaneous melanoma. In conclusion, type-IV collagen levels may be used as a diagnostic marker for cutaneous melanoma, while being void of any prognostic value. PMID:27330797

  18. Non-existence of perfect dark energy fluid in Bianchi type-IV space time

    NASA Astrophysics Data System (ADS)

    Mishra, B.; Sahoo, P. K.; Suresh, Srikanth

    2015-07-01

    In this paper, non-diagonal Bianchi type-IV space-time is investigated in Einstein general theory of relativity. The matter field is considered in the form of perfect dark energy fluid. It is interesting to observe that in this case, Bianchi type IV perfect dark energy fluid cosmological model does not exist. The space-time reduces to Minkowskian geometry.

  19. Middle ear mechanics of type IV and type V tympanoplasty: II. Clinical analysis and surgical implications.

    PubMed

    Merchant, S N; Rosowski, J J; Ravicz, M E

    1995-09-01

    Type IV and type V tympanoplasty operations are simple, robust, and well-established techniques to reconstruct middle ears that have been severely altered by chronic otitis media. In a previous paper, the authors developed a simple four-block physiologic model to describe hearing results after these procedures. This paper presents a comparison of model predictions to hearing results obtained from a detailed retrospective clinical review of 30 type IV and type V procedures. Audiograms predicted by the model and those observed clinically show good agreement over a wide frequency range (500-4000 Hz) and for many different clinical conditions. Thus, this model reliably predicts postsurgical hearing results. The application of quantitative analyses provided by this model permits the formation of a few simple surgical rules that may improve postoperative hearing results. (1) The footplate should be left as mobile as possible (e.g., by covering it with a very thin split-thickness skin graft, as opposed to a fascia graft, which will tend to stiffen it). If the footplate is ankylosed, it should be removed and replaced with a compliant tissue graft, such as fat. (2) The round window acoustic graft shield should be made as stiff as possible. If the shield material used is temporalis fascia, then one should consider using more than one layer, or reinforcing it with cartilage. (3) An attempt should be made to create an aerated cavum minor containing at least 0.03 cc of air. PMID:8588661

  20. 10 CFR Appendix IV to Part 960 - Types of Information for the Nomination of Sites as Suitable for Characterization

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Types of Information for the Nomination of Sites as Suitable for Characterization IV Appendix IV to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. IV Appendix IV to Part 960—Types of Information for...

  1. Type IV collagen is a novel DEJ biomarker that is reduced by radiotherapy.

    PubMed

    McGuire, J D; Gorski, J P; Dusevich, V; Wang, Y; Walker, M P

    2014-10-01

    The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy--teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ

  2. Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Hagspiel, Klaus D.; Bonatti, Hugo; Sabri, Saher; Arslan, Bulent; Harthun, Nancy L.

    2011-04-15

    Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

  3. UNIFICATION OF LUMINOUS TYPE 1 QUASARS THROUGH C IV EMISSION

    SciTech Connect

    Richards, Gordon T.; Kruczek, Nicholas E.; Deo, Rajesh P.; Kratzer, Rachael M.; Gallagher, S. C.; Hall, Patrick B.; Hewett, Paul C.; Leighly, Karen M.; Shen, Yue

    2011-05-15

    Using a sample of {approx}30,000 quasars from the 7th Data Release of the Sloan Digital Sky Survey, we explore the range of properties exhibited by high-ionization, broad emission lines, such as C IV {lambda}1549. Specifically, we investigate the anti-correlation between continuum luminosity and emission-line equivalent width (the Baldwin Effect (BEff)) and the 'blueshifting' of the high-ionization emission lines with respect to low-ionization emission lines. Employing improved redshift determinations from Hewett and Wild, the blueshift of the C IV emission line is found to be nearly ubiquitous, with a mean shift of {approx}810 km s{sup -1} for radio-quiet (RQ) quasars and {approx}360 km s{sup -1} for radio-loud (RL) quasars. The BEff is present in both RQ and RL samples. We consider these phenomena within the context of an accretion disk-wind model that is modulated by the nonlinear correlation between ultraviolet and X-ray continuum luminosity. Composite spectra are constructed as a function of C IV emission-line properties in an attempt to reveal empirical relationships between different line species and the continuum. Within a two-component disk+wind model of the broad emission-line region (BELR), where the wind filters the continuum seen by the disk component, we find that RL quasars are consistent with being dominated by the disk component, while broad absorption line quasars are consistent with being dominated by the wind component. Some RQ objects have emission-line features similar to RL quasars; they may simply have insufficient black hole (BH) spin to form radio jets. Our results suggest that there could be significant systematic errors in the determination of L{sub bol} and BH mass that make it difficult to place these findings in a more physical context. However, it is possible to classify quasars in a paradigm where the diversity of BELR parameters is due to differences in an accretion disk wind between quasars (and over time); these differences are

  4. Type IV congenital laryngeal web: Case report and 15 year follow up.

    PubMed

    Sorichetti, Brendan; Moxham, John P; Kozak, Frederick K

    2016-01-01

    A five day old patient with mild VACTERL syndrome had repair of a type IV congenital laryngeal web with successful decannulation 76 days later. Voice and respiratory outcome is good with follow up 15 years later. This case presents a rare clinical finding of a type IV laryngeal web successfully repaired with a keel and subsequent long term follow up during an era when it was suggested that repair be delayed until 18 months of age at the earliest. PMID:26954872

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

    PubMed Central

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

    2014-01-01

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

  6. Complete primary structure of the triple-helical region and the carboxyl-terminal domain of a new type IV collagen chain, alpha 5(IV).

    PubMed

    Pihlajaniemi, T; Pohjolainen, E R; Myers, J C

    1990-08-15

    We have isolated and characterized overlapping cDNA clones which code for a previously unidentified human collagen chain. Although the cDNA-derived primary structure of this new polypeptide is very similar to the basement membrane collagen alpha 1(IV) and alpha 2(IV) chains, the carboxyl-terminal collagenous/non-collagenous junction sequence does not correspond to the junction sequence in either of the newly described alpha 3(IV) or alpha 4(IV) chains (Butkowski, R.J., Langeveld, J.P.M., Wieslander, J., Hamilton, J., and Hudson, B. G. (1987) J. Biol. Chem. 262, 7874-7877). Thus the protein presented here has been designated the alpha 5 chain of type IV collagen. Four clones encode an open reading frame of 1602 amino acids that cover about 95% of the entire chain including half of the amino-terminal 7S domain and all of the central triple-helical region and carboxyl-terminal NC1 domain. The collagenous region of the alpha 5(IV) chain contains 22 interruptions which are in most cases identical in distribution to those in both the alpha 1(IV) and alpha 2(IV) chains. Despite the relatively low degree of conservation among the amino acids in the triple-helical region of the three type IV collagen chains, analysis of the sequences clearly showed that alpha 5(IV) is more related to alpha 1(IV) than to alpha 2(IV). This similarity between the alpha 5(IV) and alpha 1(IV) chains is particularly evident in the NC1 domains where the two polypeptides are 83% identical in contrast to the alpha 5(IV) and alpha 2(IV) identity of 63%. In addition to greatly increasing the complexity of basement membranes, the alpha 5 chain of type IV collagen may be responsible for specialized functions of some of these extracellular matrices. In this regard, it is important to note that we have recently assigned the alpha 5(IV) gene to the region of the X chromosome containing the locus for a familial type of hereditary nephritis known as Alport syndrome (Myers, J.C., Jones, T.A., Pohjalainen, E

  7. Anomalous resistivity at the field null of the FRC: a quasi-linear expression based upon flute-type modes

    SciTech Connect

    Gerwin, R.

    1983-10-01

    In the Field-Reversed Theta Pinch (FRC) experiment, the poloidal flux is observed to be lost at a rate several times greater than classical resistivity would allow. Thus, there must be anomalous resistivity at the field null. Assuming that an electromagnetic microinstability of the flute mode type is responsible for this, we derived a general expression for the anomalous resistivity at the field null based upon a quasi-linear model of the microturbulence. This general expression does not depend upon the details of the ion-species model, for example, whether the ions are fluid or kinetic.

  8. Rat 17 beta-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene.

    PubMed

    Corton, J C; Bocos, C; Moreno, E S; Merritt, A; Marsman, D S; Sausen, P J; Cattley, R C; Gustafsson, J A

    1996-11-01

    To better understand the molecular mechanisms of the pleiotropic responses induced by exposure to peroxisome proliferator chemicals (PPCs), we conducted a systematic search for genes whose mRNA levels are modulated by the PPC WY-14,643 (WY) in rat liver. The sequence of one up-regulated cDNA (2480 bp) was predicted to encode a protein of 735 aa with 82% identity to the porcine 17 beta-hydroxysteroid dehydrogenase type IV (HSD IV). Like the porcine enzyme, the rat HSD IV contains' a region homologous to yeast hydratase-dehydrogenase-epimerases and to sterol carrier proteins, indicating that the rat HSD IV has broad substrate specificity and contributes to cholesterol metabolism. The rat HSD IV was regulated by diverse PPCs via two distinct mechanisms. Induction of HSD IV and acyl-CoA oxidase (ACO) proteins in rat liver at different treatment times and concentrations of gemfibrozil and di-n-butyl phthalate were almost identical, indicating that HSD IV mRNA induction involves the peroxisome proliferator-activated receptor alpha, a regulator of ACO. In contrast, HSD IV protein levels were only weakly induced by WY, a strong inducer of ACO protein, even though the levels of HSD IV and ACO mRNA were strongly stimulated by WY and gemfibrozil. Thus, HSD IV protein levels were uniquely regulated pretranslationally by WY via a novel mechanism. Increased conversion of estradiol to the less-active estrone by HSD IV induction may explain how phthalate exposure leads to decreases in serum estradiol levels and suppression of ovulation. PMID:8913347

  9. Limited significance of curative surgery in Borrmann type IV gastric cancer.

    PubMed

    Kim, Eun Young; Yoo, Han Mo; Song, Kyo Young; Park, Cho Hyun

    2016-07-01

    Borrmann type IV advanced gastric cancer has a poor prognosis. Although surgical resection remains the only hope for a cure, the role of curative surgery is questionable in this type of cancer. This study defined the role of curative surgery in the prognosis of type IV gastric cancer. We analyzed 168 patients with Borrmann type IV undergoing surgery at Seoul St. Mary's Hospital from 1989 to 2010. We categorized the patients into curative (R0) and non-curative (R1, R2, and non-resection) groups. The curative and non-curative groups comprised 88 and 80 patients, respectively. The preoperative predictive value of Borrmann type IV was 50.5, and 8.9 % of the patients had microscopic resection margin involvement. The 3- to 5-year overall survival (OS) of patients in the curative group was significantly higher than that of in the non-curative group (p < 0.001). However, in a multivariate analysis, curability was not a significant predictor of survival (p = 0.187). In the curative group, the most frequent recurrence site was the peritoneum (85.7 %). Most recurrences occurred within 2 years. The role of surgery for Borrmann type IV is quite limited. Such cases have a poor prognosis even after curative surgery. In addition, microscopic resection margin involvement is frequent in type IV cancer because it is difficult to diagnose preoperatively. Therefore, multimodal diagnostic tools and treatment strategies should be developed for Borrmann type IV gastric cancer. PMID:27251378

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

    PubMed

    Yamatani, Hide; Mann, Aaron; Feit, Marvin

    2013-01-01

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

  11. Complete primary structure of the sixth chain of human basement membrane collagen, alpha 6(IV). Isolation of the cDNAs for alpha 6(IV) and comparison with five other type IV collagen chains.

    PubMed

    Zhou, J; Ding, M; Zhao, Z; Reeders, S T

    1994-05-01

    Basement membranes were previously believed to contain five distinct type IV collagen subunits. We have recently isolated part of the cDNA for a novel type IV collagen, alpha 6(IV), and shown that COL4A6, the gene encoding this new chain, is deleted in Alport syndrome-associated leiomyomatosis (Zhou, J., Mochizuki, T., Smeets, H., Antignac, C., Laurila, P., de Paepe, A., Tryggvason, K., and Reeders, S. T. (1993) Science 261, 1167-1169). Here, we describe the entire human alpha 6(IV) cDNA and show that the gene encodes a classical type IV collagen with homology throughout its length to all the other five chains. There is a 21-residue signal peptide, a 1417-residue collagenous domain interrupted at 25 points, and a 228-residue carboxyl-terminal non-collagenous domain. When the complete primary structure of this new chain was compared with all the other known chains, it became clear that alpha 6(IV) has the most resemblance to alpha 2(IV) and alpha 4(IV). The evolution of the six chains was deduced, allowing a new classification of the type IV collagen family. The alpha 6(IV) chain is a candidate gene for X-linked Alport syndrome; knowledge of the complete structure of the chain will permit us to screen systematically for mutations in patients and to generate recombinant proteins and synthetic peptides for further study of cell-matrix interactions involving the alpha 6(IV) chain. PMID:8175748

  12. Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage.

    PubMed

    Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

    2011-01-01

    Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332

  13. Endovascular repair of direct carotid-cavernous fistula in Ehlers-Danlos type IV.

    PubMed

    Linfante, Italo; Lin, Eugene; Knott, Eric; Katzen, Barry; Dabus, Guilherme

    2014-01-01

    Ehlers-Danlos syndrome (EDS) type IV is a collagen vascular disease with an autosomal dominant inheritance caused by COL3A1 mutation. Patients with EDS type IV can present with organ rupture, spontaneous arterial dissections and ruptured aneurysms. Because of their propensity to form arterial dissections, aneurysms and rupture, they can develop carotid-cavernous fistula (CCF) after minor trauma or spontaneously. In EDS, it has been reported that even conventional catheter diagnostic angiography may result in large artery dissections and vessel rupture. In addition, the treatment of CCF in EDS type IV can result in up to 59% mortality after initial treatment, of which 23% is attributed to direct complications of treatment. We present the case of a patient with EDS type IV who previously had spontaneous dissection and multiple pseudoaneurysms of both the iliac and femoral arteries and the distal abdominal aorta. Several years later the patient developed a direct type A CCF which was successfully treated with endovascular embolization using a transvenous approach with detachable coils. The literature pertaining to CCF in EDS type IV and its treatment is reviewed. PMID:24385391

  14. Endovascular repair of direct carotid-cavernous fistula in Ehlers-Danlos type IV.

    PubMed

    Linfante, Italo; Lin, Eugene; Knott, Eric; Katzen, Barry; Dabus, Guilherme

    2015-01-01

    Ehlers-Danlos syndrome (EDS) type IV is a collagen vascular disease with an autosomal dominant inheritance caused by COL3A1 mutation. Patients with EDS type IV can present with organ rupture, spontaneous arterial dissections and ruptured aneurysms. Because of their propensity to form arterial dissections, aneurysms and rupture, they can develop carotid-cavernous fistula (CCF) after minor trauma or spontaneously. In EDS, it has been reported that even conventional catheter diagnostic angiography may result in large artery dissections and vessel rupture. In addition, the treatment of CCF in EDS type IV can result in up to 59% mortality after initial treatment, of which 23% is attributed to direct complications of treatment. We present the case of a patient with EDS type IV who previously had spontaneous dissection and multiple pseudoaneurysms of both the iliac and femoral arteries and the distal abdominal aorta. Several years later the patient developed a direct type A CCF which was successfully treated with endovascular embolization using a transvenous approach with detachable coils. The literature pertaining to CCF in EDS type IV and its treatment is reviewed. PMID:24401479

  15. On the Directivity of Low-Frequency Type IV Radio Bursts

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Akiyama, S.; Makela, P.; Yashiro, S.; Cairns, I. H.

    2016-01-01

    An intense type IV radio burst was observed by the STEREO Behind (STB) spacecraft located about 144 deg. behind Earth. The burst was associated with a large solar eruption that occurred on the backside of the Sun (N05E151) close to the disk center in the STB view. The eruption was also observed by the STEREO Ahead (STA) spacecraft (located at 149 deg. ahead of Earth) as an eruption close to the west limb (N05W60) in that view. The type IV burst was complete in STB observations in that the envelope reached the lowest frequency and then receded to higher frequencies. The burst was partial viewed from STA, revealing only the edge coming down to the lowest frequency. The type IV burst was not observed at all near Earth because the source was 61 deg. behind the east limb. The eruption was associated with a low-frequency type II burst observed in all three views, although it was not very intense. Solar energetic particles were also observed at both STEREOs and at SOHO, suggesting that the shock was much extended, consistent with the very high speed of the CME (2048 km/s). These observations suggest that the type IV emission is directed along a narrow cone above the flare site. We confirm this result statistically using the type IV bursts of solar cycle 23.

  16. Endovascular repair of direct carotid–cavernous fistula in Ehlers–Danlos type IV

    PubMed Central

    Linfante, Italo; Lin, Eugene; Knott, Eric; Katzen, Barry; Dabus, Guilherme

    2014-01-01

    Ehlers–Danlos syndrome (EDS) type IV is a collagen vascular disease with an autosomal dominant inheritance caused by COL3A1 mutation. Patients with EDS type IV can present with organ rupture, spontaneous arterial dissections and ruptured aneurysms. Because of their propensity to form arterial dissections, aneurysms and rupture, they can develop carotid–cavernous fistula (CCF) after minor trauma or spontaneously. In EDS, it has been reported that even conventional catheter diagnostic angiography may result in large artery dissections and vessel rupture. In addition, the treatment of CCF in EDS type IV can result in up to 59% mortality after initial treatment, of which 23% is attributed to direct complications of treatment. We present the case of a patient with EDS type IV who previously had spontaneous dissection and multiple pseudoaneurysms of both the iliac and femoral arteries and the distal abdominal aorta. Several years later the patient developed a direct type A CCF which was successfully treated with endovascular embolization using a transvenous approach with detachable coils. The literature pertaining to CCF in EDS type IV and its treatment is reviewed. PMID:24385391

  17. Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis.

    PubMed

    Burnier, J V; Wang, N; Michel, R P; Hassanain, M; Li, S; Lu, Y; Metrakos, P; Antecka, E; Burnier, M N; Ponton, A; Gallinger, S; Brodt, P

    2011-09-01

    The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27(IGF-IR) murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen α1 and α2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/α2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by small-interfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases. PMID:21478904

  18. Binding of human plasminogen to basement-membrane (type IV) collagen.

    PubMed

    Stack, M S; Moser, T L; Pizzo, S V

    1992-05-15

    Plasminogen, the zymogen form of the serine proteinase plasmin, has been implicated in numerous physiological and pathological processes involving extracellular-matrix remodelling. We have previously demonstrated that the activation of plasminogen catalysed by tissue plasminogen activator is dramatically stimulated in the presence of basement-membrane-specific type IV collagen [Stack, Gonzalez-Gronow & Pizzo (1990) Biochemistry 29, 4966-4970]. The present paper describes the binding of plasminogen to type IV collagen. Plasminogen binds to both the alpha 1(IV) and alpha 2(IV) chains of basement-membrane collagen, with binding to the alpha 2(IV) chain preferentially inhibited by 6-aminohexanoic acid. This binding is specific and saturable, with Kd,app. values of 11.5 and 12.7 nM for collagen and gelatin respectively. Although collagen also binds to immobilized plasminogen, this interaction is unaffected by 6-aminohexanoic acid. Limited elastase proteolysis of plasminogen generated distinct collagen-binding fragments, which were identified as the kringle 1-3 and kringle 4 domains. No binding of collagen to mini-plasminogen was observed. These studies demonstrate a specific interaction between plasminogen and type IV collagen and provide further evidence for regulation of plasminogen activation by protein components of the extracellular matrix. PMID:1599390

  19. Perisigmoid Abscess Leading to a Diagnosis of Ehlers-Danlos Syndrome Type IV.

    PubMed

    Normatov, Inessa; Kesavan, Anil; Srikumar, Pillai B; McConnie, Randolph M

    2016-01-01

    The Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders characterized by triad of joint hypermobility, skin extensibility, and tissue fragility. Ehlers-Danlos syndrome type IV places patients at risk for life-threatening, spontaneous, vascular or visceral rupture due to reduced or abnormal secretion of type III collagen. We present an adolescent male who was found to have a perisigmoid abscess with a fistula connecting to adjacent sigmoid colon secondary to undiagnosed EDS type IV. Conservative management with antibiotics and bowel rest was pursued to allow for elective resection for his acute complicated diverticulitis at a safer time. PMID:26958560

  20. Perisigmoid Abscess Leading to a Diagnosis of Ehlers-Danlos Syndrome Type IV

    PubMed Central

    Kesavan, Anil; Srikumar, Pillai B.; McConnie, Randolph M.

    2016-01-01

    The Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders characterized by triad of joint hypermobility, skin extensibility, and tissue fragility. Ehlers-Danlos syndrome type IV places patients at risk for life-threatening, spontaneous, vascular or visceral rupture due to reduced or abnormal secretion of type III collagen. We present an adolescent male who was found to have a perisigmoid abscess with a fistula connecting to adjacent sigmoid colon secondary to undiagnosed EDS type IV. Conservative management with antibiotics and bowel rest was pursued to allow for elective resection for his acute complicated diverticulitis at a safer time. PMID:26958560

  1. Type IV Cracking Susceptibility in Weld Joints of Different Grades of Cr-Mo Ferritic Steel

    NASA Astrophysics Data System (ADS)

    Laha, K.; Chandravathi, K. S.; Parameswaran, P.; Bhanu Sankara Rao, K.

    2009-02-01

    Relative type-IV cracking susceptibility in 2.25Cr-1Mo, 9Cr-1Mo, and 9Cr-1MoVNb ferritic steel weld joint has been assessed. The type-IV cracking was manifested as preferential accumulation of creep deformation and cavitation in the relatively soft intercritical region of heat affected zone of the weld joint. The type-IV cracking susceptibility has been defined as the reduction in creep-rupture strength of weld joint compared to its base metal. The 2.25Cr-1Mo steel exhibited more susceptibility to type-IV cracking at relatively lower temperatures; whereas, at higher temperatures, 9Cr-1MoVNb steel was more susceptible. The relative susceptibility to type-IV cracking in the weld joint of the Cr-Mo steels has been rationalized on the basis of creep-strengthening mechanisms operating in the steels and their venerability to change on intercritical heating during weld thermal cycle, subsequent postweld heat treatment, and creep exposure.

  2. High resolution observations with Artemis-IV and the NRH. I. Type IV associated narrow-band bursts

    NASA Astrophysics Data System (ADS)

    Bouratzis, C.; Hillaris, A.; Alissandrakis, C. E.; Preka-Papadema, P.; Moussas, X.; Caroubalos, C.; Tsitsipis, P.; Kontogeorgos, A.

    2016-02-01

    Context. Narrow-band bursts appear on dynamic spectra from microwave to decametric frequencies as fine structures with very small duration and bandwidth. They are believed to be manifestations of small scale energy release through magnetic reconnection. Aims: We analyzed 27 metric type IV events with embedded narrow-band bursts, which were observed by the ARTEMIS-IV radio spectrograph from 30 June 1999 to 1 August 2010. We examined the morphological characteristics of isolated narrow-band structures (mostly spikes) and groups or chains of structures. Methods: The events were recorded with the SAO high resolution (10 ms cadence) receiver of ARTEMIS-IV in the 270-450 MHz range. We measured the duration, spectral width, and frequency drift of ~12 000 individual narrow-band bursts, groups, and chains. Spike sources were imaged with the Nançay radioheliograph (NRH) for the event of 21 April 2003. Results: The mean duration of individual bursts at fixed frequency was ~100 ms, while the instantaneous relative bandwidth was ~2%. Some bursts had measurable frequency drift, either positive or negative. Quite often spikes appeared in chains, which were closely spaced in time (column chains) or in frequency (row chains). Column chains had frequency drifts similar to type-IIId bursts, while most of the row chains exhibited negative frequently drifts with a rate close to that of fiber bursts. From the analysis of NRH data, we found that spikes were superimposed on a larger, slowly varying, background component. They were polarized in the same sense as the background source, with a slightly higher degree of polarization of ~65%, and their size was about 60% of their size in total intensity. Conclusions: The duration and bandwidth distributions did not show any clear separation in groups. Some chains tended to assume the form of zebra, lace stripes, fiber bursts, or bursts of the type-III family, suggesting that such bursts might be resolved in spikes when viewed with high

  3. Mutations in Type I and Type IV Pilus Biosynthetic Genes Affect Twitching Motility Rates in Xylella fastidiosa▿ †

    PubMed Central

    De La Fuente, Leonardo; Burr, Thomas J.; Hoch, Harvey C.

    2007-01-01

    Xylella fastidiosa possesses both type I and type IV pili at the same cell pole. By use of a microfluidic device, the speed of twitching movement by wild-type cells on a glass surface against the flow direction of media was measured as 0.86 (standard error [SE], 0.04) μm min−1. A type I pilus mutant (fimA) moved six times faster (4.85 [SE, 0.27] μm min−1) and a pilY1 mutant moved three times slower (0.28 [SE, 0.03] μm min−1) than wild-type cells. Type I pili slow the rate of movement, while the putative type IV pilus protein PilY1 is likely important for attachment to surfaces. PMID:17693510

  4. Success and failure rates of cylinder implants in type IV bone.

    PubMed

    Fugazzotto, P A; Wheeler, S L; Lindsay, J A

    1993-11-01

    It is well documented that implant success rates are much lower in Type IV bone than in Types I, II, and III. However, all of these studies have reported on the use of screw type implants. The present study demonstrates the efficacy of cylinder implant use in Type IV bone. A total of 513 cylinders were placed in Type IV bone and were followed for 0 to 60+ months in function. The absolute success rate was 95.7%. Of the 22 fixture failures encountered, 8 were discovered at the time of second stage surgery, 3 during the first year following uncovering, and 11 occurred after 24 to 36 months in function. A possible rationale for the higher success rate of cylinders as compared to that reported for screw type implants in Type IV bone is presented. Further well-controlled studies directly comparing various implant designs in a range of bony sites are needed to better understand and to fully document the differences suggested by the present study. PMID:8295096

  5. Clinical Application of Antenatal Genetic Diagnosis of Osteogenesis Imperfecta Type IV

    PubMed Central

    Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

    2015-01-01

    Background Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Material/Methods Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Results Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Conclusions Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families. PMID:25835785

  6. Exceptionally widespread nanomachines composed of type IV pilins: the prokaryotic Swiss Army knives

    PubMed Central

    Berry, Jamie-Lee; Pelicic, Vladimir

    2014-01-01

    Prokaryotes have engineered sophisticated surface nanomachines that have allowed them to colonize Earth and thrive even in extreme environments. Filamentous machineries composed of type IV pilins, which are associated with an amazing array of properties ranging from motility to electric conductance, are arguably the most widespread since distinctive proteins dedicated to their biogenesis are found in most known species of prokaryotes. Several decades of investigations, starting with type IV pili and then a variety of related systems both in bacteria and archaea, have outlined common molecular and structural bases for these nanomachines. Using type IV pili as a paradigm, we will highlight in this review common aspects and key biological differences of this group of filamentous structures. PMID:25793962

  7. Conservative management of small bowel perforation in Ehlers-Danlos syndrome type IV.

    PubMed

    Allaparthi, Satya; Verma, Himanshu; Burns, David L; Joyce, Ann M

    2013-08-16

    Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type IV, or vascular EDS, is caused by loss-of-function mutations in the type III pro-collagen gene (COL3A1). Common complications of EDS type IV include gastrointestinal bleeding and bowel perforations, posing diagnostic and therapeutic dilemmas for both surgeons and gastroenterologists. Here, we describe a complicated case of EDS type IV in a 35-year-old caucasian female who presented with overt gastrointestinal bleeding. The patient had a prior history of spontaneous colonic perforation, and an uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated early due to tachycardia and severe abdominal pain, and a subsequent computed tomography scan confirmed the diagnosis of ileal perforation. The patient was managed conservatively, and demonstrated daily improvement. At the time of hospital discharge, no further episodes of gastrointestinal blood loss had occurred. This case highlights the benefit of conservative management for EDS patients with gastrointestinal hemorrhage. It is recommended that surgical treatment should be reserved for patients who fail conservative treatment or in cases of hemodynamic instability. Finally, this case demonstrates the necessity for a higher threshold of operative or endoscopic interventions in EDS type IV patients. PMID:23951395

  8. Management of spontaneous colonic perforation in Ehlers-Danlos syndrome type IV.

    PubMed

    Fuchs, Julie R; Fishman, Steven J

    2004-02-01

    A 14-year-old girl with a family history of fatal colonic rupture, presented with a 2-day history of abdominal pain and signs of peritonitis. At laparotomy, a full-thickness perforation of the sigmoid colon was found, which was exteriorized as a loop colostomy. Subsequently, molecular studies of the patient's cultured fibroblasts found a point mutation in the COL3A1 gene, confirming a diagnosis of Ehlers-Danlos syndrome type IV (EDS-IV). Four and a half years later, a total abdominal colectomy and ileoproctostomy were performed, restoring intestinal continuity. At 5 years follow-up, the patient has had no further complications. Although spontaneous colonic perforation is a well-reported manifestation of EDS-IV, a consensus on the surgical management of this complication in EDS-IV has yet to be determined. Given the high rate of reperforation in EDS-IV when the colon is left in place and the low incidence of reported small bowel and rectal perforations, subtotal colectomy is a reasonable treatment. Primary anastomosis and avoidance of an end-ileostomy was possible in this young patient, with no evidence of anastomotic leakage nor reperforation to date. Lifelong close follow-up should be continued in these patients, because the natural history of this anatomy in EDS-IV is not known. PMID:14966763

  9. Dynamic Reorganization and Enzymatic Remodeling of Type IV Collagen at Cell-Biomaterial Interface.

    PubMed

    Coelho, N M; Llopis-Hernández, V; Salmerón-Sánchez, M; Altankov, G

    2016-01-01

    Vascular basement membrane remodeling involves assembly and degradation of its main constituents, type IV collagen (Col IV) and laminin, which is critical during development, angiogenesis, and tissue repair. Remodeling can also occur at cell-biomaterials interface altering significantly the biocompatibility of implants. Here we describe the fate of adsorbed Col IV in contact with endothelial cells adhering on positively charged NH2 or hydrophobic CH3 substrata, both based on self-assembly monolayers (SAMs) and studied alone or mixed in different proportions. AFM studies revealed distinct pattern of adsorbed Col IV, varying from single molecular deposition on pure NH2 to network-like assembly on mixed SAMs, turning to big globular aggregates on bare CH3. Human umbilical endothelial cells (HUVECs) interact better with Col IV adsorbed as single molecules on NH2 surface and readily rearrange it in fibril-like pattern that coincide with secreted fibronectin fibrils. The cells show flattened morphology and well-developed focal adhesion complexes that are rich on phosphorylated FAK while expressing markedly low pericellular proteolytic activity. Conversely, on hydrophobic CH3 substrata HUVECs showed abrogated spreading and FAK phosphorylation, combined with less reorganization of the aggregated Col IV and significantly increased proteolytic activity. The later involves both MMP-2 and MMP-9, as measured by zymography and FITC-Col IV release. The mixed SAMs support intermediate remodeling activity. Taken together these results show that chemical functionalization combined with Col IV preadsorption provides a tool for guiding the endothelial cells behavior and pericellular proteolytic activity, events that strongly affect the fate of cardiovascular implants. PMID:27567485

  10. Campylobacter fetus subspecies contain conserved type IV secretion systems on multiple genomic islands and plasmids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The features contributing to the differences in pathogenicity of the C. fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode type IV secretion system (T4SS) and fic-domain (filamentation induced by cyclic AMP) proteins. In the genomes of ...

  11. Multiwavelength Analysis of a Moving Type-IV Radio Burst on 4th March 2012

    NASA Astrophysics Data System (ADS)

    Veluchamy, V.; Chen, Y.; Feng, S.; Du, G.; Song, H.; Kong, X.

    2015-12-01

    We performed a multiwavelength analysis of a moving Type-IV radio burst on 4th march 2012. The Type-IV radio burst is observed between 10:39 - 11:00 UT in the frequency range of 300 - 20 MHz. From the radio heliographic observation, the radio source of the type-IV burst is traced and their sky plane speed is estimated as ~ 370 km/s. A plasmoid structure is ejected during the impulsive phase of the flare, at the same time of the type-IV burst and the structure is clearly observed at SDO/AIA 131 Å channel. From this, we find that the radio source moves with the plasmoid. The high brightness temperature profile in the range of 108 - 109 K and the moderate polarization between -50 - 30 % supports the plasma emission mechanism. Further the differential emission measure (DEM) analysis will be carried out and their results will be presented to provide more evidence of the emission mechanism.

  12. The extracellular matrix of hydra is a porous sheet and contains type IV collagen.

    PubMed

    Shimizu, Hiroshi; Aufschnaiter, Roland; Li, Li; Sarras, Michael P; Borza, Dorin-Bogdan; Abrahamson, Dale R; Sado, Yoshikazu; Zhang, Xiaoming

    2008-01-01

    Hydra, as an early diploblastic metazoan, has a well-defined extracellular matrix (ECM) called mesoglea. It is organized in a tri-laminar pattern with one centrally located interstitial matrix that contains type I collagen and two sub-epithelial zones that resemble a basal lamina containing laminin and possibly type IV collagen. This study used monoclonal antibodies to the three hydra mesoglea components (type I, type IV collagens and laminin) and immunofluorescent staining to visualize hydra mesoglea structure and the relationship between these mesoglea components. In addition, hydra mesoglea was isolated free of cells and studied with immunofluorescence and scanning electron microscopy (SEM). Our results show that type IV collagen co-localizes with laminin in the basal lamina whereas type I collagen forms a grid pattern of fibers in the interstitial matrix. The isolated mesoglea can maintain its structural stability without epithelial cell attachment. Hydra mesoglea is porous with multiple trans-mesoglea pores ranging from 0.5 to 1 microm in diameter and about six pores per 100 microm(2) in density. We think these trans-mesoglea pores provide a structural base for epithelial cells on both sides to form multiple trans-mesoglea cell-cell contacts. Based on these findings, we propose a new model of hydra mesoglea structure. PMID:18602803

  13. The extracellular matrix of hydra is a porous sheet and contains type IV collagen

    PubMed Central

    Shimizu, Hiroshi; Aufschnaiter, Roland; Li, Li; Sarras, Michael P.; Borza, Dorin-Bogdan; Abrahamson, Dale R.; Sado, Yoshikazu; Zhang, Xiaoming

    2008-01-01

    Hydra, as an early diploblastic metazoan, has a well defined extracellular matrix (ECM) called-mesoglea. It is organized in a tri-laminar pattern with one centrally located interstitial matrix that contains type I collagen and two sub-epithelial zones that resemble a basal lamina containing laminin and possibly type IV collagen. This study used monoclonal antibodies to the three hydra mesoglea components (type I, type IV collagens and laminin) and immunofluorescent staining to visualize hydra mesoglea structure and the relationship between these mesoglea components. In addition, hydra mesoglea was isolated free of cells and studied with immunofluorescence and SEM. Our results show that type IV collagen co-localizes with laminin in the basal lamina whereas type I collagen forms a grid pattern of fibers in the interstitial matrix. The isolated-mesoglea can maintain its structural stability without epithelial cell attachment. Hydra mesogleais porous with multiple trans-mesoglea pores ranging from 0.5 to 1 µm in diameter and about 6 pores per 100 µm2 in density. We think these trans-mesoglea pores provide a structural base for epithelial cells on both sides to form multiple trans-mesoglea cell-cell contacts. Based on these findings, we propose a new model of hydra mesoglea structure. PMID:18602803

  14. Secretion and assembly of type IV and VI collagens depend on glycosylation of hydroxylysines.

    PubMed

    Sipilä, Laura; Ruotsalainen, Heli; Sormunen, Raija; Baker, Naomi L; Lamandé, Shireen R; Vapola, Miia; Wang, Chunguang; Sado, Yoshikazu; Aszodi, Attila; Myllylä, Raili

    2007-11-16

    Most lysines in type IV and VI collagens are hydroxylated and glycosylated, but the functions of these unique galactosylhydroxylysyl and glucosylgalactosylhydroxylysyl residues are poorly understood. The formation of glycosylated hydroxylysines is catalyzed by multifunctional lysyl hydroxylase 3 (LH3) in vivo, and we have used LH3-manipulated mice and cells as models to study the function of these carbohydrates. These hydroxylysine-linked carbohydrates were shown recently to be indispensable for the formation of basement membranes (Ruotsalainen, H., Sipilä, L., Vapola, M., Sormunen, R., Salo, A. M., Uitto, L., Mercer, D. K., Robins, S. P., Risteli, M., Aszodi, A., Fässler, R., and Myllylä, R. (2006) J. Cell Sci. 119, 625-635). Analysis of LH3 knock-out embryos and cells in this work indicated that loss of glycosylated hydroxylysines prevents the intracellular tetramerization of type VI collagen and leads to impaired secretion of type IV and VI collagens. Mice lacking the LH activity of LH3 produced slightly underglycosylated type IV and VI collagens with abnormal distribution. The altered distribution and aggregation of type VI collagen led to similar ultrastructural alterations in muscle to those detected in collagen VI knockout and some Ullrich congenital muscular dystrophy patients. Our results provide new information about the function of hydroxylysine-linked carbohydrates of collagens, indicating that they play an important role in the secretion, assembly, and distribution of highly glycosylated collagen types. PMID:17873278

  15. Monoclonal antibodies to human type IV collagen: useful reagents to demonstrate the heterotrimeric nature of the molecule.

    PubMed Central

    Odermatt, B F; Lang, A B; Rüttner, J R; Winterhalter, K H; Trüeb, B

    1984-01-01

    Monoclonal antibodies (mAbs) have been prepared against type IV collagen isolated from human kidney. Two mAbs, designated CIV 22 and CIV 16, were extensively characterized. CIV 22 reacted only with native type IV collagen, whereas CIV 16 also bound to fragments derived from the alpha 1(IV) chain after reduction and alkylation of the molecule. Therefore, CIV 22 recognizes a conformational epitope on the triple helical type IV collagen, whereas CIV 16 binds to a sequential determinant in the carboxyl-terminal half of the alpha 1(IV) chain. By immunofluorescence, typical basement membrane structures were stained with both mAbs on frozen sections of different human organs. The mAbs were used to investigate the chain composition of type IV collagen. Radiolabeled type IV collagen bound to CIV 22, proving its triple helical configuration. These native probes, containing both the alpha 1(IV) and the alpha 2(IV) chains, also bound to CIV 16. Since CIV 16 does not react with the isolated alpha 2(IV) chain, both chains must be arranged in a single triple helical molecule (heterotrimer). Images PMID:6209713

  16. Searching algorithm for type IV secretion system effectors 1.0: a tool for predicting type IV effectors and exploring their genomic context.

    PubMed

    Meyer, Damien F; Noroy, Christophe; Moumène, Amal; Raffaele, Sylvain; Albina, Emmanuel; Vachiéry, Nathalie

    2013-11-01

    Type IV effectors (T4Es) are proteins produced by pathogenic bacteria to manipulate host cell gene expression and processes, divert the cell machinery for their own profit and circumvent the immune responses. T4Es have been characterized for some bacteria but many remain to be discovered. To help biologists identify putative T4Es from the complete genome of α- and γ-proteobacteria, we developed a Perl-based command line bioinformatics tool called S4TE (searching algorithm for type-IV secretion system effectors). The tool predicts and ranks T4E candidates by using a combination of 13 sequence characteristics, including homology to known effectors, homology to eukaryotic domains, presence of subcellular localization signals or secretion signals, etc. S4TE software is modular, and specific motif searches are run independently before ultimate combination of the outputs to generate a score and sort the strongest T4Es candidates. The user keeps the possibility to adjust various searching parameters such as the weight of each module, the selection threshold or the input databases. The algorithm also provides a GC% and local gene density analysis, which strengthen the selection of T4E candidates. S4TE is a unique predicting tool for T4Es, finding its utility upstream from experimental biology. PMID:23945940

  17. Spontaneous rupture of the spleen in type IV Ehlers-Danlos syndrome: report of a case.

    PubMed

    Privitera, Antonio; Milkhu, Chaz; Datta, Vivek; Sayegh, Mazim; Cohen, Richard; Windsor, Alastair

    2009-01-01

    The vascular type of Ehlers-Danlos syndrome, type IV, is associated with severe complications, including arterial rupture and visceral perforation. However, to our knowledge, there has been only one previous report of splenic rupture caused by a spontaneous hemorrhage in type IV Ehlers-Danlos syndrome. We report another case of this uncommon complication, occurring in a 35-year-old woman who presented after the sudden onset of acute abdominal pain. Patients should be stabilized quickly in the intensive care unit and the most timesaving surgical techniques used. Moreover, tissues must be handled with great care intraoperatively in view of their extreme fragility. Despite prompt and appropriate treatment, the prognosis is often dismal. PMID:19132469

  18. Type-IV Superconductivity: Can Superconductivity be more Exotic than Unconventional?

    NASA Astrophysics Data System (ADS)

    Lebed, A. G.

    2006-02-01

    Abrikosov vortex phase in s-wave layered superconductor in a parallel magnetic field is shown to be absolutely unstable with respect to the appearance of a triplet component which breaks inversion (parity) and spin-rotational symmetries of Cooper pairs. Symmetry breaking paramagnetic effects are demonstrated to be of the order of unity if the orbital upper critical field, Hc2 (0), is of the order of Clogston paramagnetic limiting field, Hp. We suggest a generic phase diagram of such type-IV superconductor, which is singlet one at H=0 and in the Meissner phase and characterized by mixed singlet triplet order parameter with broken symmetries of Copper pairs in vortex phase. A possibility to observe type-IV superconductivity in clean organic, high-Tc, and MgB2 superconductors is discussed.

  19. Type IV Sacrococcygeal Teratoma Displacing the Urinary Bladder: Unique Magnetic Resonance Imaging

    PubMed Central

    Eftekharzadeh, Sahar; Keihani, Sorena; Fareghi, Mehdi; Alamsahebpour, Alireza; Kajbafzadeh, Abdol-Mohammad

    2016-01-01

    Type IV sacrococcygeal teratoma is a rare pediatric tumor that is confined to the presacral area with no external component. The signs and symptoms often arise due to mass effect and compression of adjacent organs. Urinary retention is an uncommon presenting symptom in these patients. A wide spectrum of imaging findings may be encountered in cases with sacrococcygeal teratoma because of variability of tumor size and components. We hereby present a unique magnetic resonance urography finding in a type IV sacrococcygeal teratoma which caused bladder displacement. A meticulous and complete resection of tumor with special attention to the pelvic plexus led to preservation of normal voiding function and normal bowel function in this patient. PMID:27413571

  20. Glycogen Storage Disease Type IV: A Case With Histopathologic Findings in First-Trimester Placental Tissue.

    PubMed

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B; Lund, Allan M

    2016-01-01

    A 30-yr-old woman presented with 2 consecutive miscarriages within 7 mo. Histopathologic examination of the placental tissue showed intracytoplasmic inclusion vacuoles with a strong reaction in Periodic acid-Schiff staining and a slightly pallor reaction in alcian blue staining. Additional molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made on histopathologic examination. Genetic analysis is required to confirm the diagnosis and to offer prenatal genetic testing in future pregnancies. PMID:26166723

  1. A numerical study of the unsteady processes associated with the type IV shock interaction

    NASA Technical Reports Server (NTRS)

    Lind, Charles A.; Lewis, Mark J.

    1993-01-01

    A time-dependent ADI formulation of the two dimensional Navier-Stokes equations coupled with the total variation diminishing (TVD) scheme is used to examine the type IV shock interaction time accurately. The experimentally measured and computationally calculated unsteadiness of the type IV interaction is shown to be related to the formation and shedding of shear layers in the shock layer, and the frequency of oscillation of the jet is a strong function of the shedding rate of these shear layers. For one particular geometry, an oscillation frequency of 1.4 kHz was calculated. The effects of shock impingement angle and shock strength on the location and magnitude of the peak pressure are also identified. In one case it is shown that a 1-deg change in the impinging shock angle can alter the location of the associated jet by almost 11 deg with a change in the peak surface pressure of 32 percent.

  2. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    SciTech Connect

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  3. Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes

    PubMed Central

    LI, YONG-QIN; LIU, RUI; XUE, JIA-HONG; ZHANG, YAN; GAO, DENG-FENG; WU, XIAO-SAN; WANG, CONG-XIA; YANG, YU-BAI

    2015-01-01

    The adhesion of monocytes to endothelial cells is one of the early stages in the development of atherosclerosis. The expression of type IV collagenases, which include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized to play an important role in monocyte infiltration and transformation into foam cells. The aim of the present study was to examine the effects of monocyte-endothelium interactions on the expression levels of type IV collagenases and their specific inhibitors in monocytes, and to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in this process. Monocytes were single-cultured or co-cultured with endothelial cells. The expression of the type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined by immunohistochemistry followed by image analysis. The expression levels of MMP-2 and MMP-9 were found to be low in the single-culture monocytes, but increased significantly when the monocytes and endothelial cells were co-cultured. However, treatment with monoclonal TNF-α or IL-1β antibodies partially inhibited the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes. Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and a small increase in the expression levels was observed when the monocytes were co-cultured with endothelial cells. Therefore, monocyte-endothlium interactions were shown to increase the expression of type IV collagenases in monocytes, resulting in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF-α and IL-1β were demonstrated to play important roles in this process. PMID:25574228

  4. Microstructures and Type-IV Creep Damage of High Cr Steel Welds

    NASA Astrophysics Data System (ADS)

    Hongo, Hiromichi; Tabuchi, Masaaki; Takahashi, Yukio

    Creep strength of welded joints in high Cr steels decreases due to the formation of Type-IV creep damage in the heat-affected zone (HAZ) during long-term use at high temperatures. This paper aims to elucidate the processes and mechanisms of Type-IV failure. Creep tests for the welded joints with different groove configurations of Mod.9Cr-1Mo steel were conducted. Distributions of Type-IV creep damages in HAZ of these welds were measured quantitatively, and were compared with FEM computations using damage mechanics analysis. For the welded joints with double U groove, creep voids were observed mostly at 20% below the surface of the plate, and scarcely near surfaces and center of thickness. For the welded joints with single U groove, creep voids were observed inside the plate thickness more than 3mm below the surfaces. From the comparison of experimental damage distributions with FEM analysis, it is considered to be important to take the stress triaxiality into account for the prediction of damage location and fracture life of high Cr ferritic steel welds.

  5. Structure and function of the adhesive type IV pilus of Sulfolobus acidocaldarius

    PubMed Central

    Henche, Anna-Lena; Ghosh, Abhrajyoti; Yu, Xiong; Jeske, Torsten; Egelman, Edward; Albers, Sonja-Verena

    2014-01-01

    Archaea display a variety of type IV pili on their surface and employ them in different physiological functions. In the crenarchaeon Sulfolobus acidocaldarius the most abundant surface structure is the aap pilus (archaeal adhesive pilus). The construction of in frame deletions of the aap genes revealed that all the five genes (aapA, aapX, aapE, aapF, aapB) are indispensible for assembly of the pilus and an impact on surface motility and biofilm formation was observed. Our analyses revealed that there exists a regulatory cross-talk between the expression of aap genes and archaella (formerly archaeal flagella) genes during different growth phases. The structure of the aap pilus is entirely different from the known bacterial type IV pili as well as other archaeal type IV pili. An aap pilus displayed 3 stranded helices where there is a rotation per subunit of ~ 138° and a rise per subunit of ~ 5.7 Å. The filaments have a diameter of ~ 110 Å and the resolution was judged to be ~ 9 Å. We concluded that small changes in sequence might be amplified by large changes in higher-order packing. Our finding of an extraordinary stability of aap-pili possibly represents an adaptation to harsh environments that S. acidocaldarius encounters. PMID:23078543

  6. Functional Characterization of Type IV Pili Expressed on Diarrhea-Associated Isolates of Aeromonas species

    PubMed Central

    Kirov, Sylvia M.; O’Donovan, Lisa A.; Sanderson, Kevin

    1999-01-01

    Our past work has shown that long, flexible type IV pili (single or in bundles) are the predominant pili expressed on fecal isolates of diarrhea-associated species of Aeromonas (Aeromonas veronii biovar sobria and A. caviae). They represent a family of type IV pili which we have designated Bfp (for bundle-forming pili). Reports from Japan suggest that Bfp are intestinal colonization factors. This study presents compelling evidence to support this conclusion. Aeromonas bacteria and/or Bfp purified from a strain of A. veronii biovar sobria were shown to adhere to epithelial and intestinal cell lines, freshly isolated human enterocytes, and fresh and fixed human and rabbit intestinal tissues, as determined by light and electron microscopy and immunohistochemical detection. Removal of Bfp by mechanical means decreased adhesion to cell lines by up to 80%. Purified Bfp blocked adhesion of the test strain to intestinal cells in a dose-dependent manner. Adhesion was also blocked by the Fab fraction of anti-Bfp immunoglobulin G. Moreover, ultrastructural studies (ruthenium red staining and transmission and scanning electron microscopy) demonstrated for the first time that Aeromonas adhesion to human enterocytes is pilus mediated and suggested that Bfp may also promote colonization by forming bacterium-to-bacterium linkages. Bfp-positive isolates examined for type IV pilus-mediated twitching motility in agar and slide culture assays developed for Pseudomonas aeruginosa did not, however, exhibit this function. PMID:10496928

  7. Laminin and Type IV Collagen Isoform Substitutions Occur in Temporally and Spatially Distinct Patterns in Developing Kidney Glomerular Basement Membranes

    PubMed Central

    St. John, Patricia L.; Stroganova, Larysa; Zelenchuk, Adrian; Steenhard, Brooke M.

    2013-01-01

    Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin α1β1γ1 and collagen α1α2α1(IV), whereas mature glomeruli contain laminin α5β2γ1 and collagen α3α4α5(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newborn mouse GBMs. Our results show loss of laminin α1 from GBMs in early capillary loop stages and continuous linear deposition of laminin bearing the α5 chain thereafter. In contrast, collagen α1α2α1(IV) persisted in linear patterns into late capillary loop stages, when collagen α3α4α5(IV) first appeared in discontinuous, non-linear patterns. This patchy pattern for collagen α3α4α5(IV) continued into maturing glomeruli where there were lengths of linear, laminin α5-positive GBM entirely lacking either isoform of collagen IV. Relative abundance of laminin and collagen IV mRNAs in newborn and 5-week-old mouse kidneys also differed, with those encoding laminin α1, α5, β1, β2, and γ1, and collagen α1(IV) and α2(IV) chains all significantly declining at 5 weeks, but α3(IV) and α4(IV) were significantly upregulated. We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli. PMID:23896970

  8. Anomalous circulation patterns in association with two types of daily precipitation extremes over southeastern China during boreal summer

    NASA Astrophysics Data System (ADS)

    Li, Minggang; Guan, Zhaoyong; Jin, Dachao; Han, Jie; Zhang, Qian

    2016-04-01

    Based on the daily rainfall data from China Meteorological Administration, the tropical cyclone (TC) best track data from Japan Meteorological Agency, and the NCEP-NCAR reanalysis data from NOAA, regional mean daily precipitation extreme (RDPE) events over southeastern China (specifically, the Fujian-Jiangxi region (FJR)) and the associated circulation anomalies are investigated. For the summers of 1979-2011, a total of 105 RDPE events are identified, among which 35 are TC-influenced (TCIn-RDPE) and 70 are TC-free events (TCFr-RDPE). Distinct differences between these two types of RDPEs are found in both their statistical features and the related circulation patterns. TCFr-RDPEs usually occur in June, while TCIn-RDPEs mainly take place during July-August. When TCFr-RDPEs happen, a center of the anomalous cyclonic circulation is observed over the FJR, with an anomalous anticyclonic circulation to the south of this region. The warm/moist air flows from the South China Sea (SCS) and western Pacific meet with colder air from the north, forming a narrow convergent belt of water vapor over the FJR. Simultaneously, positive diabatic forcing anomalies are observed over the FJR, whereas negative anomalies appear over both its south and north sides, facilitating the formation and maintenance of the cyclonic circulation anomaly, as well as the upward motion of the atmosphere, over the FJR. When TCIn-RDPEs occur, southeastern China is dominated by a TC-related stronger anomalous cyclonic circulation. An anomalous anticyclonic circulation in the mid and high latitudes north of the FJR exists in the mid and upper troposphere, opposite to the situation during TCFr-RDPE events. Abundant warm/wet air is carried into the FJR from both the Indian Ocean and the SCS, leading to a large amount of latent heat release over the FJR and inducing strong ascending motion there. Furthermore, large differences are also found in the manifestation of Rossby wave energy propagation between these

  9. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV.

    PubMed

    Akman, H Orhan; Sheiko, Tatiana; Tay, Stacey K H; Finegold, Milton J; Dimauro, Salvatore; Craigen, William J

    2011-11-15

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic feature of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of disease onset. Absence of enzyme activity is lethal in utero or in infancy affecting primarily muscle and liver. However, residual enzyme activity (5-20%) leads to juvenile or adult onset of a disorder that primarily affects muscle as well as central and peripheral nervous system. Here, we describe two mouse models of GSD IV that reflect this spectrum of disease. Homologous recombination was used to insert flippase recognition target recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase-Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice bearing this mutation (Gbe1(neo/neo)) exhibit a phenotype similar to juvenile onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1(-/-)), leading to a phenotype of lethal early onset GSD IV, with significant in utero accumulation of PG. Adult mice with residual GBE exhibit progressive neuromuscular dysfunction and die prematurely. Differently from muscle, PG in liver is a degradable source of glucose and readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. PMID:21856731

  10. Dissemination of methicillin-resistant Staphylococcus aureus SCCmec type IV and SCCmec type V epidemic clones in a tertiary hospital: challenge to infection control.

    PubMed

    Dhawan, B; Rao, C; Udo, E E; Gadepalli, R; Vishnubhatla, S; Kapil, A

    2015-01-01

    Two-hundred MRSA strains from inpatients with healthcare-associated (HA) and 100 MRSA strains from outpatients with community-associated (CA) skin and soft tissue infections (SSTIs) were tested for antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine leucocidin (PVL) toxin, seh and arcA genes. Based on SCCmec typing, HA-MRSA isolates were further divided into HA-SCCmec I/II/III MRSA and HA-SCCmec IV/V MRSA, and CA-MRSA isolates into CA-SCCmec I/II/III MRSA and CA-SCCmec IV/V MRSA. SCCmec types were further characterized by pulsed-field gel electrophoresis, spa typing and multi-locus sequence typing. Seventy-five (37·5%) HA-MRSA isolates and 83/100 CA-MRSA isolates were SCCmec IV/V genotype. HA-SCCmec IV/V MRSA was associated with malignancy (P = 0·03) and bone fractures (P = 0·02) compared to CA-SCCmec IV/V MRSA. HA-SCCmec IV/V MRSA was associated with PVL gene carriage compared to HA-SCCmec I/II/III MRSA (P < 0·001). ST22-MRSA-IV (EMRSA-15), ST772-MRSA-V, and ST36-MRSA-IV and ST239:EMRSA-I:III were the major clones identified. Our study documents the emergence of SCCmec IV and SCCmec V MRSA clones in an Indian hospital. PMID:24690229

  11. Endovascular Treatment of a Carotid Dissecting Pseudoaneurysm in a Patient with Ehlers-Danlos Syndrome Type IV with Fatal Outcome

    SciTech Connect

    Lim, Siok Ping Duddy, Martin J.

    2008-01-15

    We present a patient with Ehlers-Danlos syndrome type IV (EDS IV) with a carotid dissecting pseudoaneurysm causing severe carotid stenosis. This lesion was treated endovascularly. Unfortunately, the patient died of remote vascular catastrophes (intracranial hemorrhage and abdominal aortic rupture). This unique case illustrates the perils of endovascular treatment of EDS IV patients and the need for preoperative screening for concomitant lesions. It also shows that a dissecting pseudoaneurysm can feasibly be treated with a covered stent and that closure is effective using Angioseal in patients with EDS IV.

  12. Alternative Neisseria spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue.

    PubMed

    Chamot-Rooke, Julia; Rousseau, Benoit; Lanternier, Fanny; Mikaty, Guillain; Mairey, Emilie; Malosse, Christian; Bouchoux, Guy; Pelicic, Vladimir; Camoin, Luc; Nassif, Xavier; Duménil, Guillaume

    2007-09-11

    The importance of protein glycosylation in the interaction of pathogenic bacteria with their host is becoming increasingly clear. Neisseria meningitidis, the etiological agent of cerebrospinal meningitis, crosses cellular barriers after adhering to host cells through type IV pili. Pilin glycosylation genes (pgl) are responsible for the glycosylation of PilE, the major subunit of type IV pili, with the 2,4-diacetamido-2,4,6-trideoxyhexose residue. Nearly half of the clinical isolates, however, display an insertion in the pglBCD operon, which is anticipated to lead to a different, unidentified glycosylation. Here the structure of pilin glycosylation was determined in such a strain by "top-down" MS approaches. MALDI-TOF, nanoelectrospray ionization Fourier transform ion cyclotron resonance, and nanoelectrospray ionization quadrupole TOF MS analysis of purified pili preparations originating from N. meningitidis strains, either wild type or deficient for pilin glycosylation, revealed a glycan mass inconsistent with 2,4-diacetamido-2,4,6-trideoxyhexose or any sugar in the databases. This unusual modification was determined by in-source dissociation of the sugar from the protein followed by tandem MS analysis with collision-induced fragmentation to be a hexose modified with a glyceramido and an acetamido group. We further show genetically that the nature of the sugar present on the pilin is determined by the carboxyl-terminal region of the pglB gene modified by the insertion in the pglBCD locus. We thus report a previously undiscovered monosaccharide involved in posttranslational modification of type IV pilin subunits by a MS-based approach and determine the molecular basis of its biosynthesis. PMID:17804791

  13. Characterization of type IV pilus genes in plant growth-promoting Pseudomonas putida WCS358.

    PubMed Central

    de Groot, A; Heijnen, I; de Cock, H; Filloux, A; Tommassen, J

    1994-01-01

    In a search for factors that could contribute to the ability of the plant growth-stimulating Pseudomonas putida WCS358 to colonize plant roots, the organism was analyzed for the presence of genes required for pilus biosynthesis. The pilD gene of Pseudomonas aeruginosa, which has also been designated xcpA, is involved in protein secretion and in the biogenesis of type IV pili. It encodes a peptidase that processes the precursors of the pilin subunits and of several components of the secretion apparatus. Prepilin processing activity could be demonstrated in P. putida WCS358, suggesting that this nonpathogenic strain may contain type IV pili as well. A DNA fragment containing the pilD (xcpA) gene of P. putida was cloned and found to complement a pilD (xcpA) mutation in P. aeruginosa. Nucleotide sequencing revealed, next to the pilD (xcpA) gene, the presence of two additional genes, pilA and pilC, that are highly homologous to genes involved in the biogenesis of type IV pili. The pilA gene encodes the pilin subunit, and pilC is an accessory gene, required for the assembly of the subunits into pili. In comparison with the pil gene cluster in P. aeruginosa, a gene homologous to pilB is lacking in the P. putida gene cluster. Pili were not detected on the cell surface of P. putida itself, not even when pilA was expressed from the tac promoter on a plasmid, indicating that not all the genes required for pilus biogenesis were expressed under the conditions tested. Expression of pilA of P. putida in P. aeruginosa resulted in the production of pili containing P. putida PilA subunits. Images PMID:7905475

  14. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    NASA Astrophysics Data System (ADS)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  15. Ten tips for treating acne vulgaris in Fitzpatrick skin types IV-VI.

    PubMed

    Spann, Candace Thornton

    2011-06-01

    During the 21st century, people with skin of color will account for a large portion of the US population. According to race projections from the US Census Bureau, persons of African American, Hispanic, Asian and Native American descent will make up nearly half of the total US population by the year 2050. Because of our changing demographics, it is important that all dermatologists become comfortable in treating skin of color. This article provides 10 practical pearls for management of acne vulgaris in patients with Fitzpatrick skin types IV-VI. PMID:21637906

  16. Unveiling Cell Surface and Type IV Secretion Proteins Responsible for Archaeal Rudivirus Entry

    PubMed Central

    Deng, Ling; He, Fei; Bhoobalan-Chitty, Yuvaraj; Martinez-Alvarez, Laura; Guo, Yang

    2014-01-01

    Sulfolobus mutants resistant to archaeal lytic virus Sulfolobus islandicus rod-shaped virus 2 (SIRV2) were isolated, and mutations were identified in two gene clusters, cluster sso3138 to sso3141 and cluster sso2386 and sso2387, encoding cell surface and type IV secretion proteins, respectively. The involvement of the mutations in the resistance was confirmed by genetic complementation. Blocking of virus entry into the mutants was demonstrated by the lack of early gene transcription, strongly supporting the idea of a role of the proteins in SIRV2 entry. PMID:24965447

  17. Type IV acromioclavicular joint dislocation associated with a mid-shaft clavicle malunion.

    PubMed

    Mohammed, Khalid D; Stachiw, Danielle; Malone, Alex A

    2016-01-01

    This reports presents the case of a combined clavicle fracture malunion and chronic Type IV acromioclavicular (AC) joint dislocation. The patient was seen acutely in the emergency department following a mountain bike accident at which time the clavicle fracture was identified and managed conservatively however the AC dislocation was not diagnosed. The patient presented 25 months following the injury with persistent pain and disability and was treated with clavicle osteotomy and AC stabilization. We document the clinical details, surgical treatment and outcome. PMID:26980988

  18. Type IV acromioclavicular joint dislocation associated with a mid-shaft clavicle malunion

    PubMed Central

    Mohammed, Khalid D.; Stachiw, Danielle; Malone, Alex A.

    2016-01-01

    This reports presents the case of a combined clavicle fracture malunion and chronic Type IV acromioclavicular (AC) joint dislocation. The patient was seen acutely in the emergency department following a mountain bike accident at which time the clavicle fracture was identified and managed conservatively however the AC dislocation was not diagnosed. The patient presented 25 months following the injury with persistent pain and disability and was treated with clavicle osteotomy and AC stabilization. We document the clinical details, surgical treatment and outcome. PMID:26980988

  19. DSMC Simulation of Shock/Shock Interactions: Emphasis on Type IV Interactions

    NASA Technical Reports Server (NTRS)

    Moss, J. N.; Pot, T.; Chanetz, B.; Lefebvre, M.

    1999-01-01

    This paper presents the results of a numerical study of shock/shock interactions that include both the Edney type IV and type III interactions, with emphasis on the type IV interactions. Computations are made using the direct simulation Monte Carlo (DSMC) method of Bird for Mach 10 air flow, as produced in the ONERA R5Ch low-density wind tunnel. The simulations include the flow about a shock generator which creates a relatively weak oblique shock that impinges on a much stronger cylinder bow shock. The sensitivity and characteristics of the interactions are examined by varying the horizontal distance separating the shock generator leading edge and cylinder. Results of the simulation for one separation distance are compared with wind tunnel measurements. Comparisons are made for surface heating and pressure and for flow-field values of density and rotational temperatures, as obtained with the Dual-line Coherent Anti-Stokes Scattering (DL-CARS) technique. The comparisons between experiment and calculation yield a consistent description of the shock interaction features and a consistent description of the surface heating and pressure distributions, with the exception of the peak values-the computed values being greater than the measured values.

  20. Collagen type IV of Drosophila is stockpiled in the growing oocyte and differentially located during early stages of embryogenesis.

    PubMed

    Knibiehler, B; Mirre, C; Le Parco, Y

    1990-05-01

    We have developed and characterized a battery of specific polyclonal antibodies directed against specific portions of the alpha-chain of collagen type IV synthesized in Drosophila by the gene DCg1. Here, we describe the use of these antibodies together with in situ hybridization experiments in an attempt to study the expression and localization of collagen type IV during Drosophila oogenesis and early embryogenesis. The results clearly demonstrate that DCg1 is maternally expressed by follicle cells and that the collagen type IV chain produced is stockpiled in the growing oocyte. During the gastrulation stages, this component of Drosophila basement membranes concentrated on cells involved in the gradual invaginations leading to morphogenetic furrows. The presence of collagen type IV, which is an RGD-bearing molecule, during early stages of Drosophila development is discussed in comparison with the crucial, active role its vertebrate counterpart is supposed to play in morphogenetic processes. PMID:2117479

  1. Sequence analyses of type IV pili from Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus.

    PubMed

    Aagesen, Alisha M; Häse, Claudia C

    2012-08-01

    Bacterial surface structures called pili have been studied extensively for their role as possible colonization factors. Most sequenced Vibrio genomes predict a variety of pili genes in these organisms, including several types of type IV pili. In particular, the mannose-sensitive hemagglutinin (MSHA) and the PilA pili, also known as the chitin-regulated pilus (ChiRP), are type IVa pili commonly found in Vibrio genomes and have been shown to play a role in the colonization of Vibrio species in the environment and/or host tissue. Here, we report sequence comparisons of two type IVa pilin subunit genes, mshA and pilA, and their corresponding amino acid sequences, for several strains from the three main human pathogenic Vibrio species, V. cholerae, V. parahaemolyticus, and V. vulnificus. We identified specific groupings of these two genes in V. cholerae, whereas V. parahaemolyticus and V. vulnificus strains had no apparent allelic clusters, and these genes were strikingly divergent. These results were compared with other genes from the MSHA and PilA operons as well as another Vibrio pili from the type IVb group, the toxin co-regulated pilus (TCP) from V. cholerae. Our data suggest that a selective pressure exists to cause these strains to vary their MSHA and PilA pilin subunits. Interestingly, V. cholerae strains possessing TCP have the same allele for both mshA and pilA. In contrast, V. cholerae isolates without TCP have polymorphisms in their mshA and pilA sequences similar to what was observed for both V. parahaemolyticus and V. vulnificus. This data suggests a possible linkage between host interactions and maintaining a highly conserved type IV pili sequence in V. cholerae. Although the mechanism underlying this intriguing diversity has yet to be elucidated, our analyses are an important first step towards gaining insights into the various aspects of Vibrio ecology. PMID:22383120

  2. Galactose recognition by a tetrameric C-type lectin, CEL-IV, containing the EPN carbohydrate recognition motif.

    PubMed

    Hatakeyama, Tomomitsu; Kamiya, Takuro; Kusunoki, Masami; Nakamura-Tsuruta, Sachiko; Hirabayashi, Jun; Goda, Shuichiro; Unno, Hideaki

    2011-03-25

    CEL-IV is a C-type lectin isolated from a sea cucumber, Cucumaria echinata. This lectin is composed of four identical C-type carbohydrate-recognition domains (CRDs). X-ray crystallographic analysis of CEL-IV revealed that its tetrameric structure was stabilized by multiple interchain disulfide bonds among the subunits. Although CEL-IV has the EPN motif in its carbohydrate-binding sites, which is known to be characteristic of mannose binding C-type CRDs, it showed preferential binding of galactose and N-acetylgalactosamine. Structural analyses of CEL-IV-melibiose and CEL-IV-raffinose complexes revealed that their galactose residues were recognized in an inverted orientation compared with mannose binding C-type CRDs containing the EPN motif, by the aid of a stacking interaction with the side chain of Trp-79. Changes in the environment of Trp-79 induced by binding to galactose were detected by changes in the intrinsic fluorescence and UV absorption spectra of WT CEL-IV and its site-directed mutants. The binding specificity of CEL-IV toward complex oligosaccharides was analyzed by frontal affinity chromatography using various pyridylamino sugars, and the results indicate preferential binding to oligosaccharides containing Galβ1-3/4(Fucα1-3/4)GlcNAc structures. These findings suggest that the specificity for oligosaccharides may be largely affected by interactions with amino acid residues in the binding site other than those determining the monosaccharide specificity. PMID:21247895

  3. Fine Structure in Type IV Solar Radio Bursts during three major Solar Events of October-November 2003 observed by Artemis IV.

    NASA Astrophysics Data System (ADS)

    Tsitsipis, P.; Kontogeorgos, A.; Caroubalos, C.; Moussas, X.; Hillaris, A.; Preka-Papadema, P.; Bougeret, J.-L.; Alissandrakis, C.; Dumas, G.; Polygiannakis, J.

    The fine structure in three solar type IV radio bursts was studied using the French-Greek ARTEMIS-IV multichannel radio spectrograph. The bursts were recorded during three major solar events, on the 26 and 28 October.and 3 Nov. 2003; these we associated with intense flares and CMEs. The observed fine structure includes intermediate drift bursts (fibers) and pulsations. The complexity and overlapping of the various spectral characteristics necessitated the utilization of certain, 2D-FFT based, filtering processes, aiming firstly at structure detection in the frequency-time plane (ie the dynamic spectrum) and secondly in the separation of fibers and pulsations and the suppression of the type IV continuum. This methodology results also to the fibers frequency drift rate distributions and their evolution in time. These fiber frequency drift distributions may be interpreted as the exciter velocity distributions, using a Newkirk coronal density model; the latter may be used as diagnostics of the magnetic field restructuring and energy release during a solar energetic event (flare and/or CME). Artemis IV will provide complementary data to the STEREO/WAVES experiment.

  4. Glycosylation Modulates Melanoma Cell α2β1 and α3β1 Integrin Interactions with Type IV Collagen*

    PubMed Central

    Stawikowski, Maciej J.; Aukszi, Beatrix; Stawikowska, Roma; Cudic, Mare; Fields, Gregg B.

    2014-01-01

    Although type IV collagen is heavily glycosylated, the influence of this post-translational modification on integrin binding has not been investigated. In the present study, galactosylated and nongalactosylated triple-helical peptides have been constructed containing the α1(IV)382–393 and α1(IV)531–543 sequences, which are binding sites for the α2β1 and α3β1 integrins, respectively. All peptides had triple-helical stabilities of 37 °C or greater. The galactosylation of Hyl393 in α1(IV)382–393 and Hyl540 and Hyl543 in α1(IV)531–543 had a dose-dependent influence on melanoma cell adhesion that was much more pronounced in the case of α3β1 integrin binding. Molecular modeling indicated that galactosylation occurred on the periphery of α2β1 integrin interaction with α1(IV)382–393 but right in the middle of α3β1 integrin interaction with α1(IV)531–543. The possibility of extracellular deglycosylation of type IV collagen was investigated, but no β-galactosidase-like activity capable of collagen modification was found. Thus, glycosylation of collagen can modulate integrin binding, and levels of glycosylation could be altered by reduction in expression of glycosylation enzymes but most likely not by extracellular deglycosylation activity. PMID:24958723

  5. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation.

    PubMed Central

    Adès, L. C.; Waltham, R. D.; Chiodo, A. A.; Bateman, J. F.

    1995-01-01

    Ehlers-Danlos syndrome encompasses a group of inherited disorders of connective tissue, some of which are characterised by abnormalities of collagen metabolism. The chromosomal location, identified genes and biochemical defects, inheritance pattern, and clinical features for the various known subtypes are outlined. Prenatal diagnosis is possible for types IV, VI, VIIA1, and VIIA2. An unusual presentation of type IV Ehlers-Danlos syndrome in a 16 year old boy with an anterior myocardial infarction resulting from dissection of the left anterior descending coronary artery is reported here. A clinical diagnosis of type IV Ehlers-Danlos syndrome was made subsequently and confirmed by the reduced production, impaired secretion, and abnormally slow electrophoretic migration of type III collagen, indicating an underlying mutation in the COL3A1 gene. This patient represents the first case of type IV Ehlers-Danlos syndrome with symptomatic coronary artery dissection. Images PMID:7546986

  6. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane

    PubMed Central

    Morrissey, Meghan A.; Jayadev, Ranjay; Miley, Ginger R.; Blebea, Catherine A.; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R.

    2016-01-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  7. Characterization of adhesion threads of Deinococcus geothermalis as type IV pili.

    PubMed

    Saarimaa, C; Peltola, M; Raulio, M; Neu, T R; Salkinoja-Salonen, M S; Neubauer, P

    2006-10-01

    Deinococcus geothermalis E50051 forms tenuous biofilms on paper machine surfaces. Field emission electron microscopy analysis revealed peritrichous appendages which mediated cell-to-surface and cell-to-cell interactions but were absent in planktonically grown cells. The major protein component of the extracellular extract of D. geothermalis had an N-terminal sequence similar to the fimbrial protein pilin annotated in the D. geothermalis DSM 11300 draft sequence. It also showed similarity to the type IV pilin sequence of D. radiodurans and several gram-negative pathogenic bacteria. Other proteins in the extract had N-terminal sequences identical to D. geothermalis proteins with conservative motifs for serine proteases, metallophosphoesterases, and proteins whose function is unknown. Periodic acid-Schiff staining for carbohydrates indicated that these extracellular proteins may be glycosylated. A further confirmation for the presence of glycoconjugates on the cell surface was obtained by confocal laser scanning imaging of living D. geothermalis cells stained with Amaranthus caudatus lectin, which specifically binds to galactose residues. The results indicate that the thread-like appendages of D. geothermalis E50051 are glycosylated type IV pili, bacterial attachment organelles which have thus far not been described for the genus Deinococcus. PMID:16980504

  8. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.

    PubMed

    Morrissey, Meghan A; Jayadev, Ranjay; Miley, Ginger R; Blebea, Catherine A; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R

    2016-02-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  9. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

    PubMed Central

    Mitra, Arijit; Ramakrishnan, R.; Kader, Mohideen Abdul

    2014-01-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

  10. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

    PubMed

    Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul

    2014-08-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

  11. A novel GBE1 gene variant in a child with glycogen storage disease type IV.

    PubMed

    Said, Samar M; Murphree, Marine I; Mounajjed, Taofic; El-Youssef, Mounif; Zhang, Lizhi

    2016-08-01

    Glycogen storage disease type IV is an autosomal recessive disorder of carbohydrates caused by deficiency of amylo-1-4-glycanoglycosyltransferase, which leads to accumulation of amylopectin-like polysaccharides in tissues including liver, heart and neuromuscular system. More than 40 different mutations in the glycogen branching enzyme gene (GBE1) have been described. In this study, we report a 2-year-old boy who presented with developmental delay and muscle weakness. He subsequently was diagnosed with glycogen storage disease type IV based on a liver biopsy histology and electron microscopy. Glycogen branching enzyme activity was in the low range. Genetic analysis demonstrated a novel heterozygous variant (c.760A>G; p.Thr254Ala) in exon 6 of the GBE1 gene, which is believed to be pathogenic. This variant was inherited from the patient's mother who was asymptomatic with normal glycogen branching enzyme activity. Whole-exome sequencing failed to reveal additional variations in the GBE1 gene. PMID:27107456

  12. Identification, Immunogenicity and Crossreactivity of Type IV Pilin and Pilin-like Proteins from Clostridium difficile

    PubMed Central

    Maldarelli, Grace A.; De Masi, Leon; von Rosenvinge, Erik C.; Carter, Mihaela; Donnenberg, Michael S.

    2014-01-01

    The Gram-positive anaerobe Clostridium difficile is the major cause of nosocomial diarrhea; manifestations of infection include diarrhea, pseudomembranous colitis, and death. Genes for type IV pili, a bacterial nanofiber often involved in colonization and until relatively recently described only in Gram-negatives, are present in all members of the Clostridiales. We hypothesized that any pilins encoded in the C. difficile genome would be immunogenic, as has been shown with pilins from Gram-negative organisms. We describe nine pilin or pilin-like protein genes, for which we introduce a coherent nomenclature, in the C. difficile R20291 genome. The nine predicted pilin or pilin-like proteins have relatively conserved N-terminal hydrophobic regions, but diverge at their C-termini. Analysis of synonymous and nonsynonymous substitutions revealed evidence of diversifying selective pressure in two pilin genes. Six of the nine identified proteins were purified and used to immunize mice. Immunization of mice with each individual protein generated antibody responses that varied in titer and crossreactivity, a notable result given the low amino acid sequence identity among the pilins. Further studies in other small mammals mirrored our results in mice. Our results illuminate components of the C. difficile type IV pilus, and help identify targets for an anti-C. difficile vaccine. PMID:24550179

  13. Motion of the sources for type II and type IV radio bursts and flare-associated interplanetary disturbances

    NASA Technical Reports Server (NTRS)

    Sakurai, K.; Chao, J. K.

    1974-01-01

    Shock waves are indirectly observed as the source of type II radio bursts, whereas magnetic bottles are identified as the source of moving metric type IV radio bursts. The difference between the expansion speeds of these waves and bottles is examined during their generation and propagation near the flare regions. It is shown that, although generated in the explosive phase of flares, the bottles behave quite differently from the waves and that the bottles are generally much slower than the waves. It has been suggested that the waves are related to flare-associated interplanetary disturbances which produce SSC geomagnetic storms. These disturbances may, therefore, be identified as interplanetary shock waves. The relationship among magnetic bottles, shock waves near the sun, and flare-associated disturbances in interplanetary space is briefly discussed.

  14. Structure of a type IV pilus machinery in the open and closed state

    PubMed Central

    Gold, Vicki AM; Salzer, Ralf; Averhoff, Beate; Kühlbrandt, Werner

    2015-01-01

    Proteins of the secretin family form large macromolecular complexes, which assemble in the outer membrane of Gram-negative bacteria. Secretins are major components of type II and III secretion systems and are linked to extrusion of type IV pili (T4P) and to DNA uptake. By electron cryo-tomography of whole Thermus thermophilus cells, we determined the in situ structure of a T4P molecular machine in the open and the closed state. Comparison reveals a major conformational change whereby the N-terminal domains of the central secretin PilQ shift by ∼30 Å, and two periplasmic gates open to make way for pilus extrusion. Furthermore, we determine the structure of the assembled pilus. DOI: http://dx.doi.org/10.7554/eLife.07380.001 PMID:25997099

  15. Bright but slow - Type II supernovae from OGLE-IV - implications for magnitude-limited surveys

    NASA Astrophysics Data System (ADS)

    Poznanski, D.; Kostrzewa-Rutkowska, Z.; Wyrzykowski, L.; Blagorodnova, N.

    2015-05-01

    We study a sample of 11 Type II supernovae (SNe) discovered by the OGLE-IV survey. All objects have well-sampled I-band light curves, and at least one spectrum. We find that two or three of the 11 SNe have a declining light curve, and spectra consistent with other SNe II-L, while the rest have plateaus that can be as short as 70 d, unlike the 100 d typically found in nearby galaxies. The OGLE SNe are also brighter, and show that magnitude-limited surveys find SNe that are different than usually found in nearby galaxies. We discuss this sample in the context of understanding Type II SNe as a class and their suggested use as standard candles.

  16. Fine Structure of Metric Type IV Radio Bursts Observed with the ARTEMIS-IV Radio-Spectrograph: Association with Flares and Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Bouratzis, C.; Hillaris, A.; Alissandrakis, C. E.; Preka-Papadema, P.; Moussas, X.; Caroubalos, C.; Tsitsipis, P.; Kontogeorgos, A.

    2015-01-01

    Fine structures embedded in type IV burst continua may be used as diagnostics of the magnetic-field restructuring and the corresponding energy release associated with the low-corona development of flare or coronal mass ejection (CME) events. A catalog of 36 type IV bursts observed with the SAO receiver of the ARTEMIS-IV solar radio-spectrograph in the 450 - 270 MHz range at high cadence (0.01 sec) was compiled; the fine structures were classified into five basic classes with two or more subclasses each. The time of fine-structure emission was compared with the injection of energetic electrons as recorded by hard X-ray and microwave emission, the soft X-ray (SXR) light curves and the CME onset time. Our results indicate a very tight temporal association between energy release episodes and pulsations, spikes, narrow-band bursts of the type III family, and zebra bursts. Of the remaining categories, the featureless broadband continuum starts near the time of the first energy release, between the CME onset and the SXR peak, but extends for several tens of minutes after that, covering almost the full extent of the flare-CME event. The intermediate drift bursts, fibers in their majority, mostly follow the first energy release, but have a wider distribution than other fine structures.

  17. On the source of the dust extinction in type Ia supernovae and the discovery of anomalously strong Na I absorption

    SciTech Connect

    Phillips, M. M.; Morrell, Nidia; Hsiao, E. Y.; Campillay, Abdo; Contreras, Carlos; Simon, Joshua D.; Burns, Christopher R.; Persson, Sven E.; Thompson, I. B.; Freedman, Wendy L.; Cox, Nick L. J.; Foley, Ryan J.; Karakas, Amanda I.; Patat, F.; Sternberg, A.; Williams, R. E.; Gal-Yam, A.; Leonard, D. C.; Stritzinger, Maximilian; Folatelli, Gastón; and others

    2013-12-10

    High-dispersion observations of the Na I D λλ5890, 5896 and K I λλ7665, 7699 interstellar lines, and the diffuse interstellar band at 5780 Å in the spectra of 32 Type Ia supernovae are used as an independent means of probing dust extinction. We show that the dust extinction of the objects where the diffuse interstellar band at 5780 Å is detected is consistent with the visual extinction derived from the supernova colors. This strongly suggests that the dust producing the extinction is predominantly located in the interstellar medium of the host galaxies and not in circumstellar material associated with the progenitor system. One quarter of the supernovae display anomalously large Na I column densities in comparison to the amount of dust extinction derived from their colors. Remarkably, all of the cases of unusually strong Na I D absorption correspond to 'Blueshifted' profiles in the classification scheme of Sternberg et al. This coincidence suggests that outflowing circumstellar gas is responsible for at least some of the cases of anomalously large Na I column densities. Two supernovae with unusually strong Na I D absorption showed essentially normal K I column densities for the dust extinction implied by their colors, but this does not appear to be a universal characteristic. Overall, we find the most accurate predictor of individual supernova extinction to be the equivalent width of the diffuse interstellar band at 5780 Å, and provide an empirical relation for its use. Finally, we identify ways of producing significant enhancements of the Na abundance of circumstellar material in both the single-degenerate and double-degenerate scenarios for the progenitor system.

  18. An extracellular protease of Streptococcus gordonii hydrolyzes type IV collagen and collagen analogues.

    PubMed

    Juarez, Z E; Stinson, M W

    1999-01-01

    Streptococcus gordonii is a frequent cause of infective bacterial endocarditis, but its mechanisms of virulence are not well defined. In this study, streptococcal proteases were recovered from spent chemically defined medium (CDM) and fractionated by ammonium sulfate precipitation and by ion-exchange and gel filtration column chromatography. Three proteases were distinguished by their different solubilities in ammonium sulfate and their specificities for synthetic peptides. One of the enzymes cleaved collagen analogs Gly-Pro 4-methoxy-beta-naphthylamide, 2-furanacryloyl-Leu-Gly-Pro-Ala (FALGPA), and p-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-Arg (pZ-peptide) and was released from the streptococci while complexed to peptidoglycan fragments. Treatment of this protease with mutanolysin reduced its 180- to 200-kDa mass to 98 kDa without loss of enzymatic activity. The purified protease cleaved bovine gelatin, human placental type IV collagen, and the Aalpha chain of fibrinogen but not albumin, fibronectin, laminin, or myosin. Enzyme activity was inhibited by phenylmethylsulfonyl fluoride, indicating that it is a serine-type protease. Maximum production of the 98-kDa protease occurred during growth of S. gordonii CH1 in CDM containing 0.075% total amino acids at pH 7.0 with minimal aeration. Higher initial concentrations of amino acids prevented the release of the protease without reducing cell-associated enzyme levels, and the addition of an amino acid mixture to an actively secreting culture stopped further enzyme release. The purified protease was stored frozen at -20 degreesC for several months or heated at 50 degreesC for 10 min without loss of activity. These data indicate that S. gordonii produces an extracellular gelatinase/type IV collagenase during growth in medium containing minimal concentrations of free amino acids. Thus, the extracellular enzyme is a potential virulence factor in the amino acid-stringent, thrombotic, valvular lesions of bacterial

  19. Structural characterization of ribosome recruitment and translocation by type IV IRES.

    PubMed

    Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

    2016-01-01

    Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts tvhe otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. PMID:27159451

  20. Classification of bulimic-type eating disorders: from DSM-IV to DSM-5.

    PubMed

    Mond, Jonathan M

    2013-01-01

    Proposed changes to the classification of bulimic-type eating disorders in the lead up to the publication of DSM-5 are reviewed. Several of the proposed changes, including according formal diagnostic status to binge eating disorder (BED), removing the separation of bulimia nervosa (BN) into purging and non-purging subtypes, and reducing the binge frequency threshold from twice per week to once per week for both BN and (BED), have considerable empirical evidence to support them and will likely have the effect of facilitating clinical practice, improving access to care, improving public and professional awareness and understanding of these disorders and stimulating the additional research needed to address at least some problematic issues. However, the omission of any reference to variants of BN characterized by subjective, but not objective, binge eating episodes, and to the undue influence of weight or shape on self-evaluation or similar cognitive criterion in relation to the diagnosis of BED, is regrettable, given their potential to inform clinical and research practice and given that there is considerable evidence to support specific reference to these distinctions. Other aspects of the proposed criteria, such as retention of behavioral indicators of impaired control associated with binge eating and the presence of marked distress regarding binge eating among the diagnostic for BED, appear anomalous in that there is little or no evidence to support their validity or clinical utility. It is hoped that these issues will be addressed in final phase of the DSM-5 development process. PMID:24999412

  1. Classification of bulimic-type eating disorders: from DSM-IV to DSM-5

    PubMed Central

    2013-01-01

    Proposed changes to the classification of bulimic-type eating disorders in the lead up to the publication of DSM-5 are reviewed. Several of the proposed changes, including according formal diagnostic status to binge eating disorder (BED), removing the separation of bulimia nervosa (BN) into purging and non-purging subtypes, and reducing the binge frequency threshold from twice per week to once per week for both BN and (BED), have considerable empirical evidence to support them and will likely have the effect of facilitating clinical practice, improving access to care, improving public and professional awareness and understanding of these disorders and stimulating the additional research needed to address at least some problematic issues. However, the omission of any reference to variants of BN characterized by subjective, but not objective, binge eating episodes, and to the undue influence of weight or shape on self-evaluation or similar cognitive criterion in relation to the diagnosis of BED, is regrettable, given their potential to inform clinical and research practice and given that there is considerable evidence to support specific reference to these distinctions. Other aspects of the proposed criteria, such as retention of behavioral indicators of impaired control associated with binge eating and the presence of marked distress regarding binge eating among the diagnostic for BED, appear anomalous in that there is little or no evidence to support their validity or clinical utility. It is hoped that these issues will be addressed in final phase of the DSM-5 development process. PMID:24999412

  2. Crucial role for the VWF A1 domain in binding to type IV collagen.

    PubMed

    Flood, Veronica H; Schlauderaff, Abraham C; Haberichter, Sandra L; Slobodianuk, Tricia L; Jacobi, Paula M; Bellissimo, Daniel B; Christopherson, Pamela A; Friedman, Kenneth D; Gill, Joan Cox; Hoffmann, Raymond G; Montgomery, Robert R

    2015-04-01

    Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed. We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain. We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis. PMID:25662333

  3. Crucial role for the VWF A1 domain in binding to type IV collagen

    PubMed Central

    Schlauderaff, Abraham C.; Haberichter, Sandra L.; Slobodianuk, Tricia L.; Jacobi, Paula M.; Bellissimo, Daniel B.; Christopherson, Pamela A.; Friedman, Kenneth D.; Gill, Joan Cox; Hoffmann, Raymond G.; Montgomery, Robert R.; Abshire, T.; Dunn, A.; Bennett, C.; Lusher, J.; Rajpurkar, M.; Brown, D.; Shapiro, A.; Lentz, S.; Gill, J.; Leissinger, C.; Ragni, M.; Hord, J.; Manco-Johnson, M.; Strouse, J.; Ma, A.; Valentino, L.; Boggio, L.; Sharathkumar, A.; Gruppo, R.; Kerlin, B.; Journeycake, J.; Kulkarni, R.; Green, D.; Mahoney, D.; Mathias, L.; Bedros, A.; Diamond, C.; Neff, A.; DiMichele, D.; Giardina, P.; Cohen, A.; Paidas, M.; Werner, E.; Matsunaga, A.; Tarantino, M.; Shafer, F.; Konkle, B.; Cuker, A.; Kouides, P.; Stein, D.

    2015-01-01

    Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed. We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF–collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain. We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis. PMID:25662333

  4. Hip resurfacing after iliofemoral distraction for type IV developmental dysplasia of the hip a case report.

    PubMed

    Sambri, A; Cadossi, M; Mazzotti, A; Faldini, C; Giannini, S

    2015-01-01

    Osteoarthritis secondary to developmental dysplasia of the hip is a surgical challenge because of the modified anatomy of the acetabulum which is deficient in its shape with poor bone quality, torsional deformities of the femur and the altered morphology of femoral head. Particularly in Crowe type III and IV, additional surgical challenges are present, such as limb-length discrepancy and adductor muscle contractures. This is a bilateral hip dysplasia case where bilateral hip replacement was indicated, on the left side with a resurfacing one and on the other side a two stage procedure using a iliofemoral external fixator to restore equal leg length with a lower risk of complications. This case report shows both the negative clinical outcome of the left and the excellent one of the right hip where the dysplasia was much more severe. Patient selection and implant positioning are crucial in determining long-term results. PMID:27218252

  5. Thompson and Hamilton type IV Freiberg's disease with involvement of multiple epiphyses of both feet.

    PubMed

    Lui, Tun Hing

    2015-01-01

    A 17-year-old boy reported left second and third toe pain after axial loading injury to his left foot. Radiographs showed collapse of the second metatarsal heads and epiphysial irregularities of the fifth metatarsal heads and the condyle of the proximal phalanx of the hallux of both feet. The patient was diagnosed to have Thompson and Hamilton type IV Freiberg's disease. He was screened for epiphysial dysplasia of the other sites. He had on and off bilateral hip and knee pain. Radiographs showed bilateral symmetrical epiphysial abnormalities with morphological change as focal concavity in bilateral femoral heads and fragmentation of the patellar articular surface with preservation of the patellofemoral joint space. PMID:25721826

  6. Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation.

    PubMed

    Ripoll-Rozada, Jorge; García-Cazorla, Yolanda; Getino, María; Machón, Cristina; Sanabria-Ríos, David; de la Cruz, Fernando; Cabezón, Elena; Arechaga, Ignacio

    2016-06-01

    Bacterial conjugation is the main mechanism responsible for the dissemination of antibiotic resistance genes. Hence, the search for specific conjugation inhibitors is paramount in the fight against the spread of these genes. In this pursuit, unsaturated fatty acids have been found to specifically inhibit bacterial conjugation. Despite the growing interest on these compounds, their mode of action and their specific target remain unknown. Here, we identified TrwD, a Type IV secretion traffic ATPase, as the molecular target for fatty acid-mediated inhibition of conjugation. Moreover, 2-alkynoic fatty acids, which are also potent inhibitors of bacterial conjugation, are also powerful inhibitors of the ATPase activity of TrwD. Characterization of the kinetic parameters of ATPase inhibition has led us to identify the catalytic mechanism by which fatty acids exert their activity. These results open a new avenue for the rational design of inhibitors of bacterial conjugation in the fight against the dissemination of antibiotic resistance genes. PMID:26915347

  7. New type IV pili-related genes involved in early stages of Ralstonia solanacearum potato infection.

    PubMed

    Siri, María Inés; Sanabria, Analía; Boucher, Christian; Pianzzola, María Julia

    2014-07-01

    This study provides insights into the pathogenesis of Ralstonia solanacearum, in particular with regards to strains belonging to phylotype IIB, sequevar 1 (IIB-1) and their interaction with potato, its natural host. We performed a comparative genomic analysis among IIB-1 R. solanacearum strains with different levels of virulence in order to identify candidate virulence genes. With this approach, we identified a 33.7-kb deletion in a strain showing reduced virulence on potato. This region contains a cluster of six genes putatively involved in type IV pili (Tfp) biogenesis. Functional analysis suggests that these proteins contribute to several Tfp-related functions such as twitching motility and biofilm formation. In addition, this genetic cluster was found to contribute to early bacterial wilt pathogenesis and colonization fitness of potato roots. PMID:24625029

  8. Type IV FDP avulsion: lessons learned clinically and through review of the literature.

    PubMed

    Henry, Steven L; Katz, Mark A; Green, David P

    2009-12-01

    The type IV flexor digitorum profundus avulsion is a rare injury involving fracture of the volar base of the distal phalanx and separation of the tendon from the fracture fragment. Recommendations for management are sparse and are substantiated only by a few isolated case reports. We recently encountered two of these injuries, both of which proved challenging, particularly with regard to joint incongruity and tendon adhesions. In reviewing the literature, it is apparent that no consensus exists regarding surgical strategies. However, based on our experience and that of other authors, we can suggest the following: (1) high index of suspicion of this potentially deceptive injury, with use of magnetic resonance imaging or ultrasound if preoperative confirmation is needed; (2) rigid bony fixation that prevents dorsal subluxation of the distal phalanx; (3) tendon repair that is independent of the bony fixation; and (4) early range of motion therapy. PMID:19399559

  9. Type IV pilus retraction in pathogenic Neisseria is regulated by the PilC proteins

    PubMed Central

    Morand, Philippe C; Bille, Emmanuelle; Morelle, Sandrine; Eugène, Emmanuel; Beretti, Jean-Luc; Wolfgang, Matthew; Meyer, Thomas F; Koomey, Michael; Nassif, Xavier

    2004-01-01

    Pathogenic Neisseria express type IV pili (tfp), which have been shown to play a central role in the interactions of bacteria with their environment. The regulation of piliation thus constitutes a central element in bacterial life cycle. The PilC proteins are outer membrane-associated proteins that have a key role in tfp biogenesis since PilC-null mutants appear defective for fibre expression. Moreover, tfp are also subjected to retraction, which is under the control of the PilT nucleotide-binding protein. In this work, we bring evidence that fibre retraction involves the translocation of pilin subunits to the cytoplasmic membrane. Furthermore, by engineering meningococcal strains that harbour inducible pilC genes, and with the use of meningococcus–cell interaction as a model for the sequential observation of fibre expression and retraction, we show that the PilC proteins regulate PilT-mediated fibre retraction. PMID:15103324

  10. Widespread distribution and structural diversity of Type IV IRESs in members of Picornaviridae

    PubMed Central

    Asnani, Mukta; Kumar, Parimal; Hellen, Christopher U. T.

    2015-01-01

    Picornavirus genomes contain internal ribosomal entry sites (IRESs) that promote end-independent translation initiation. Five structural classes of picornavirus IRES have been identified, but numerous IRESs remain unclassified. Here, previously unrecognized Type IV IRESs were identified in members of three proposed picornavirus genera (Limnipivirus, Pasivirus, Rafivirus) and four recognized genera (Kobuvirus, Megrivirus, Sapelovirus, Parechovirus). These IRESs are ∼230–420 nucleotides long, reflecting heterogeneity outside a common structural core. Closer analysis yielded insights into evolutionary processes that have shaped contemporary IRESs. The presence of related IRESs in diverse genera supports the hypothesis that they are heritable genetic elements that spread by horizontal gene transfer. Recombination likely also accounts for the exchange of some peripheral subdomains, suggesting that IRES evolution involves incremental addition of elements to a pre-existing core. Nucleotide conservation is concentrated in ribosome-binding sites, and at the junction of helical domains, likely to ensure orientation of subdomains in an active conformation. PMID:25726971

  11. A phage protein that inhibits the bacterial ATPase required for type IV pilus assembly.

    PubMed

    Chung, In-Young; Jang, Hye-Jeong; Bae, Hee-Won; Cho, You-Hee

    2014-08-01

    Type IV pili (TFPs) are required for bacterial twitching motility and for phage infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as Tip, representing twitching inhibitory protein), whose expression is necessary and sufficient to mediate the inhibition of twitching motility. Tip interacts with and blocks the activity of bacterial-encoded PilB, the TFP assembly/extension ATPase, at an internal 40-aa region unique to PilB. Tip expression results in the loss of surface piliation. Based on these observations and the fact that many P. aeruginosa phages require TFPs for infection, Tip-mediated twitching inhibition may represent a generalized strategy for superinfection exclusion. Moreover, because TFPs are required for full virulence, PilB may be an attractive target for the development of novel antiinfectives. PMID:25049409

  12. Shipment and Disposal of Solidified Organic Waste (Waste Type IV) to the Waste Isolation Pilot Plant (WIPP)

    SciTech Connect

    D'Amico, E. L; Edmiston, D. R.; O'Leary, G. A.; Rivera, M. A.; Steward, D. M.

    2006-07-01

    In April of 2005, the last shipment of transuranic (TRU) waste from the Rocky Flats Environmental Technology Site to the WIPP was completed. With the completion of this shipment, all transuranic waste generated and stored at Rocky Flats was successfully removed from the site and shipped to and disposed of at the WIPP. Some of the last waste to be shipped and disposed of at the WIPP was waste consisting of solidified organic liquids that is identified as Waste Type IV in the Contact-Handled Transuranic Waste Authorized Methods for Payload Control (CH-TRAMPAC) document. Waste Type IV waste typically has a composition, and associated characteristics, that make it significantly more difficult to ship and dispose of than other Waste Types, especially with respect to gas generation. This paper provides an overview of the experience gained at Rocky Flats for management, transportation and disposal of Type IV waste at WIPP, particularly with respect to gas generation testing. (authors)

  13. Expression of Cellulosome Components and Type IV Pili within the Extracellular Proteome of Ruminococcus flavefaciens 007

    PubMed Central

    Vodovnik, Maša; Duncan, Sylvia H.; Reid, Martin D.; Cantlay, Louise; Turner, Keith; Parkhill, Julian; Lamed, Raphael; Yeoman, Carl J.; Miller, Margret E. Berg.; White, Bryan A.; Bayer, Edward A.; Marinšek-Logar, Romana; Flint, Harry J.

    2013-01-01

    Background Ruminococcus flavefaciens is an important fibre-degrading bacterium found in the mammalian gut. Cellulolytic strains from the bovine rumen have been shown to produce complex cellulosome structures that are associated with the cell surface. R. flavefaciens 007 is a highly cellulolytic strain whose ability to degrade dewaxed cotton, but not Avicel cellulose, was lost following initial isolation in the variant 007S. The ability was recovered after serial subculture to give the cotton-degrading strain 007C. This has allowed us to investigate the factors required for degradation of this particularly recalcitrant form of cellulose. Methodology/Principal Findings The major proteins associated with the bacterial cell surface and with the culture supernatant were analyzed for R. flavefaciens 007S and 007C grown with cellobiose, xylan or Avicel cellulose as energy sources. Identification of the proteins was enabled by a draft genome sequence obtained for 007C. Among supernatant proteins a cellulosomal GH48 hydrolase, a rubrerthyrin-like protein and a protein with type IV pili N-terminal domain were the most strongly up-regulated in 007C cultures grown on Avicel compared with cellobiose. Strain 007S also showed substrate-related changes, but supernatant expression of the Pil protein and rubrerythrin in particular were markedly lower in 007S than in 007C during growth on Avicel. Conclusions/Significance This study provides new information on the extracellular proteome of R. flavefaciens and its regulation in response to different growth substrates. Furthermore it suggests that the cotton cellulose non-degrading strain (007S) has altered regulation of multiple proteins that may be required for breakdown of cotton cellulose. One of these, the type IV pilus was previously shown to play a role in adhesion to cellulose in R. albus, and a related pilin protein was identified here for the first time as a major extracellular protein in R. flavefaciens. PMID:23750253

  14. A Decameter Stationary Type IV Burst in Imaging Observations on 2014 September 6

    NASA Astrophysics Data System (ADS)

    Koval, Artem; Stanislavsky, Aleksander; Chen, Yao; Feng, Shiwei; Konovalenko, Aleksander; Volvach, Yaroslav

    2016-08-01

    First-of-its-kind radio imaging of a decameter solar stationary type IV radio burst has been presented in this paper. On 2014 September 6 the observations of type IV burst radio emission were carried out with the two-dimensional heliograph based on the Ukrainian T-shaped radio telescope (UTR-2), together with other telescope arrays. Starting at ˜09:55 UT and for ˜3 hr, the radio emission was kept within the observational session of UTR-2. The interesting observation covered the full evolution of this burst, “from birth to death.” During the event lifetime, two C-class solar X-ray flares with peak times 11:29 UT and 12:24 UT took place. The time profile of this burst in radio has a double-humped shape that can be explained by injection of energetic electrons, accelerated by the two flares, into the burst source. According to the heliographic observations, we suggest that the burst source was confined within a high coronal loop, which was part of a relatively slow coronal mass ejection. The latter has been developed for several hours before the onset of the event. Through analysis of about 1.5 × 106 heliograms (3700 temporal frames with 4096 images in each frame that correspond to the number of frequency channels), the radio burst source imaging shows a fascinating dynamical evolution. Both space-based (GOES, SDO, SOHO, STEREO) data and various ground-based instrumentation (ORFEES, NDA, RSTO, NRH) records have been used for this study.

  15. Type IV Creep Damage Behavior in Gr.91 Steel Welded Joints

    NASA Astrophysics Data System (ADS)

    Hongo, Hiromichi; Tabuchi, Masaaki; Watanabe, Takashi

    2012-04-01

    Modified 9Cr-1Mo steel (ASME Grade 91 steel) is used as a key structural material for boiler components in ultra-supercritical (USC) thermal power plants at approximately 873 K (600 °C). The creep strength of welded joints of this steel decreases as a result of Type IV creep cracking that forms in the heat-affected zone (HAZ) under long-term use at high temperatures. The current article aims to elucidate the damage processes and microstructural degradations that take place in the HAZ of these welded joints. Long-term creep tests for base metal, simulated HAZ, and welded joints were conducted at 823 K, 873 K, and 923 K (550 °C, 600 °C, and 650 °C). Furthermore, creep tests of thick welded joint specimens were interrupted at several time steps at 873 K (600 °C) and 90 MPa, after which the distribution and evolution of creep damage inside the plates were measured quantitatively. It was found that creep voids are initiated in the early stages (0.2 of life) of creep rupture life, which coalesce to form a crack at a later stage (0.8 of life). In a fine-grained HAZ, creep damage is concentrated chiefly in an area approximately 20 pct below the surface of the plate. The experimental creep damage distributions coincide closely with the computed results obtained by damage mechanics analysis using the creep properties of a simulated fine-grained HAZ. Both the concentration of creep strain and the high multiaxial stress conditions in the fine-grained HAZ influence the distribution of Type IV creep damage.

  16. Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation.

    PubMed

    Gault, Joseph; Ferber, Mathias; Machata, Silke; Imhaus, Anne-Flore; Malosse, Christian; Charles-Orszag, Arthur; Millien, Corinne; Bouvier, Guillaume; Bardiaux, Benjamin; Péhau-Arnaudet, Gérard; Klinge, Kelly; Podglajen, Isabelle; Ploy, Marie Cécile; Seifert, H Steven; Nilges, Michael; Chamot-Rooke, Julia; Duménil, Guillaume

    2015-09-01

    The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences. PMID:26367394

  17. Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation

    PubMed Central

    Gault, Joseph; Ferber, Mathias; Machata, Silke; Imhaus, Anne-Flore; Malosse, Christian; Charles-Orszag, Arthur; Millien, Corinne; Bouvier, Guillaume; Bardiaux, Benjamin; Péhau-Arnaudet, Gérard; Klinge, Kelly; Podglajen, Isabelle; Ploy, Marie Cécile; Seifert, H. Steven; Nilges, Michael; Chamot-Rooke, Julia; Duménil, Guillaume

    2015-01-01

    The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences. PMID:26367394

  18. A Decameter Stationary Type IV Burst in Imaging Observations on 2014 September 6

    NASA Astrophysics Data System (ADS)

    Koval, Artem; Stanislavsky, Aleksander; Chen, Yao; Feng, Shiwei; Konovalenko, Aleksander; Volvach, Yaroslav

    2016-08-01

    First-of-its-kind radio imaging of a decameter solar stationary type IV radio burst has been presented in this paper. On 2014 September 6 the observations of type IV burst radio emission were carried out with the two-dimensional heliograph based on the Ukrainian T-shaped radio telescope (UTR-2), together with other telescope arrays. Starting at ∼09:55 UT and for ∼3 hr, the radio emission was kept within the observational session of UTR-2. The interesting observation covered the full evolution of this burst, “from birth to death.” During the event lifetime, two C-class solar X-ray flares with peak times 11:29 UT and 12:24 UT took place. The time profile of this burst in radio has a double-humped shape that can be explained by injection of energetic electrons, accelerated by the two flares, into the burst source. According to the heliographic observations, we suggest that the burst source was confined within a high coronal loop, which was part of a relatively slow coronal mass ejection. The latter has been developed for several hours before the onset of the event. Through analysis of about 1.5 × 106 heliograms (3700 temporal frames with 4096 images in each frame that correspond to the number of frequency channels), the radio burst source imaging shows a fascinating dynamical evolution. Both space-based (GOES, SDO, SOHO, STEREO) data and various ground-based instrumentation (ORFEES, NDA, RSTO, NRH) records have been used for this study.

  19. Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126.

    PubMed

    Paavola, Kevin J; Sidik, Harwin; Zuchero, J Bradley; Eckart, Michael; Talbot, William S

    2014-08-12

    GPR126 is an orphan heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) that is essential for the development of diverse organs. We found that type IV collagen, a major constituent of the basement membrane, binds to Gpr126 and activates its signaling function. Type IV collagen stimulated the production of cyclic adenosine monophosphate in rodent Schwann cells, which require Gpr126 activity to differentiate, and in human embryonic kidney (HEK) 293 cells expressing exogenous Gpr126. Type IV collagen specifically bound to the extracellular amino-terminal region of Gpr126 containing the CUB (complement, Uegf, Bmp1) and pentraxin domains. Gpr126 derivatives lacking the entire amino-terminal region were constitutively active, suggesting that this region inhibits signaling and that ligand binding relieves this inhibition to stimulate receptor activity. A new zebrafish mutation that truncates Gpr126 after the CUB and pentraxin domains disrupted development of peripheral nerves and the inner ear. Thus, our findings identify type IV collagen as an activating ligand for GPR126, define its mechanism of activation, and highlight a previously unrecognized signaling function of type IV collagen in basement membranes. PMID:25118328

  20. Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter.

    PubMed Central

    Bian, J; Sun, Y

    1997-01-01

    p53, a tumor suppressor and a transcription factor, has been shown to transcriptionally activate the expression of a number of important genes involved in the regulation of cell growth, DNA damage, angiogenesis, and apoptosis. In a computer search for other potential p53 target genes, we identified a perfect p53 binding site in the promoter of the human type IV collagenase (also called 72-kDa gelatinase or matrix metalloproteinase 2 [MMP-2]) gene. This p53 binding site was found to specifically bind to p53 protein in a gel shift assay. Transcription assays with luciferase reporters driven by the promoter or enhancer of the type IV collagenase gene revealed that (i) activation of the promoter activity is p53 binding site dependent in p53-positive cells but not in p53-negative cells and (ii) wild-type p53, but not p53 mutants commonly found in human cancers, transactivates luciferase expression driven by the type IV collagenase promoter as well as by a p53 site-containing enhancer element in the promoter. Significantly, expression of the endogenous type IV collagenase is also under the control of p53. Treatment of U2-OS cells, a wild-type p53-containing osteogenic sarcoma line, with a common p53 inducer, etoposide, induced p53 DNA binding and transactivation activities in a time-dependent manner. Induction of type IV collagenase expression followed the p53 activation pattern. No induction of type IV collagenase expression can be detected under the same experimental conditions in p53-negative Saos-2 cells. All these in vitro and in vivo assays strongly suggest that the type IV collagenase gene is a p53 target gene and that its expression is subject to p53 regulation. Our finding links p53 to a member of the MMP genes, a family of genes implicated in trophoblast implantation, wound healing, angiogenesis, arthritis, and tumor cell invasion. p53 may regulate these processes by upregulating expression of type IV collagenase. PMID:9343394

  1. Structural characterization of ribosome recruitment and translocation by type IV IRES

    PubMed Central

    Murray, Jason; Savva, Christos G; Shin, Byung-Sik; Dever, Thomas E; Ramakrishnan, V; Fernández, Israel S

    2016-01-01

    Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. DOI: http://dx.doi.org/10.7554/eLife.13567.001 PMID:27159451

  2. Agrobacterium VirB10 domain requirements for type IV secretion and T pilus biogenesis

    PubMed Central

    Jakubowski, Simon J.; Kerr, Jennifer E.; Garza, Isaac; Krishnamoorthy, Vidhya; Bayliss, Richard; Waksman, Gabriel; Christie, Peter J.

    2013-01-01

    Summary Agrobacterium tumefaciens VirB10 couples inner membrane (IM) ATP energy consumption to substrate transfer through the VirB/D4 type IV secretion (T4S) channel and also mediates biogenesis of the virB-encoded T pilus. Here, we determined the functional importance of VirB10 domains denoted as the: (i) N-terminal cytoplasmic region, (ii) transmembrane (TM) α-helix, (iii) proline-rich region (PRR) and (iv) C-terminal β-barrel domain. Mutations conferring a transfer- and pilus-minus (Tra−, Pil−) phenotype included PRR deletion and β-barrel substitution mutations that prevented VirB10 interaction with the outer membrane (OM) VirB7–VirB9 channel complex. Mutations permissive for substrate transfer but blocking pilus production (Tra+, Pil−) included a cytoplasmic domain deletion and TM domain insertion mutations. Another class of Tra+ mutations also selectively disrupted pilus biogenesis but caused release of pilin monomers to the milieu; these mutations included deletions of α-helical projections extending from the β-barrel domain. Our findings, together with results of Cys accessibility studies, indicate that VirB10 stably integrates into the IM, extends via its PRR across the periplasm, and interacts via its β-barrel domain with the VirB7–VirB9 channel complex. The data further support a model that distinct domains of VirB10 regulate formation of the secretion channel or the T pilus. PMID:19054325

  3. Positive Regulatory Domain I-Binding Factor 1 mediates repression of the MHC Class II Transactivator (CIITA) type IV promoter

    PubMed Central

    Chen, Han; Gilbert, Carolyn A.; Hudson, John A.; Bolick, Sophia C.; Wright, Kenneth L.; Piskurich, Janet F.

    2006-01-01

    MHC class II transactivator (CIITA), a co-activator that controls MHC class II (MHC II) transcription, functions as the master regulator of MHC II expression. Persistent activity of the CIITA type III promoter (pIII), one of the four potential promoters of this gene, is responsible for constitutive expression of MHC II by B lymphocytes. In addition, IFN-γ induces expression of CIITA in these cells through the type IV promoter (pIV). Positive regulatory domain 1-binding factor 1 (PRDI-BF1), called B lymphocyte-induced maturation protein 1 (Blimp-1) in mice, represses the expression of CIITA pIII in plasma and multiple myeloma cells. To investigate regulation of CIITA pIV expression by PRDI-BF1 in the B lymphocyte lineage, protein/DNA binding studies, and functional promoter analyses were performed. PRDI-BF1 bound to the IRF-E site in CIITA pIV. Ectopic expression of either PRDI-BF1 or Blimp-1 repressed this promoter in B lymphocytes. In vitro binding and functional analyses of CIITA pIV demonstrated that the IFN regulatory factor-element (IRF-E) is the target of this repression. In vivo genomic footprint analysis demonstrated protein binding at the IRF-E site of CIITA pIV in U266 myeloma cells, which express PRDI-BF1. PRDI-BF1β, a truncated form of PRDI-BF1 that is co-expressed in myeloma cells, also bound to the IRF-E site and repressed CIITA pIV. These findings demonstrate for the first time that, in addition to silencing expression of CIITA pIII in B lymphocytes, PRDI-BF1 is capable of binding and suppressing CIITA pIV. PMID:16765445

  4. AN ASSESSMENT OF THE SERVICE HISTORY AND CORROSION SUSCEPTIBILITY OF TYPE IV WASTE TANKS

    SciTech Connect

    Wiersma, B

    2008-09-18

    Type IV waste tanks were designed and built to store waste that does not require auxiliary cooling. Each Type IV tank is a single-shell tank constructed of a steel-lined pre-stressed concrete tank in the form of a vertical cylinder with a concrete domed roof. There are four such tanks in F-area, Tanks 17-20F, and four in H-Area, Tanks 21-24H. Leak sites were discovered in the liners for Tanks 19 and 20F in the 1980's. Although these leaks were visually observed, the investigation to determine the mechanism by which the leaks had occurred was not completed at that time. Therefore, a concern was raised that the same mechanism which caused the leak sites in the Tanks in F-area may also be operable in the H-Area tanks. Data from the construction of the tanks (i.e., certified mill test reports for the steel, no stress-relief), the service history (i.e., waste sample data, temperature data), laboratory tests on actual wastes and simulants (i.e., electrochemical testing), and the results of the visual inspections were reviewed. The following observations and conclusions were made: (1) Comparison of the compositional and microstructural features indicate that the A212 material utilized for construction of the H-Area tanks are far more resistant to SCC than the A285 materials used for construction of the F-Area tanks. (2) A review of the materials of construction, temperature history, service histories concluded that F-Area tanks likely failed by caustic stress corrosion cracking. (3) The environment in the F-Area tanks was more aggressive than that experienced by the H-Area tanks. (4) Based on a review of the service history, the H-Area tanks have not been exposed to an environment that would render the tanks susceptible to either nitrate stress corrosion cracking (i.e., the cause of failures in the Type I and II tanks) or caustic stress corrosion cracking. (5) Due to the very dilute and uninhibited solutions that have been stored in Tank 23H, vapor space corrosion has

  5. Community-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 80 Type IV (CC80-MRSA-IV) Isolated from the Middle East: A Heterogeneous Expanding Clonal Lineage

    PubMed Central

    Harastani, Houda H.; Tokajian, Sima T.

    2014-01-01

    Background The emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has caused a change in MRSA epidemiology worldwide. In the Middle East, the persistent spread of CA-MRSA isolates that were associated with multilocus sequence type (MLST) clonal complex 80 and with staphylococcal cassette chromosome mec (SCCmec) type IV (CC80-MRSA-IV), calls for novel approaches for infection control that would limit its spread. Methodology/Principal Findings In this study, the epidemiology of CC80-MRSA-IV was investigated in Jordan and Lebanon retrospectively covering the period from 2000 to 2011. Ninety-four S. aureus isolates, 63 (67%) collected from Lebanon and 31 (33%) collected from Jordan were included in this study. More than half of the isolates (56%) were associated with skin and soft tissue infections (SSTIs), and 73 (78%) were Panton-Valentine Leukocidin (PVL) positive. Majority of the isolates (84%) carried the gene for exofoliative toxin d (etd), 19% had the Toxic Shock Syndrome Toxin-1 gene (tst), and seven isolates from Jordan had a rare combination being positive for both tst and PVL genes. spa typing showed the prevalence of type t044 (85%) and pulsed-field gel electrophoresis (PFGE) recognized 21 different patterns. Antimicrobial susceptibility testing showed the prevalence (36%) of a unique resistant profile, which included resistance to streptomycin, kanamycin, and fusidic acid (SKF profile). Conclusions The genetic diversity among the CC80 isolates observed in this study poses an additional challenge to infection control of CA-MRSA epidemics. CA-MRSA related to ST80 in the Middle East was distinguished in this study from the ones described in other countries. Genetic diversity observed, which may be due to mutations and differences in the antibiotic regimens between countries may have led to the development of heterogeneous strains. Hence, it is difficult to maintain “the European CA-MRSA clone” as a uniform clone and it

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

    PubMed Central

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

    1994-01-01

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

  7. Altered stress fibers and integrin expression in the Malpighian epithelium of Drosophila type IV collagen mutants

    PubMed Central

    Kiss, András A.; Popovics, Nikoletta; Szabó, Gábor; Csiszár, Katalin; Mink, Mátyás

    2016-01-01

    Basement membranes (BMs) are highly specialized extracellular matrices (ECMs) that provide support and polarization cues for epithelial cells. Proper adhesion to the BM is pivotal in epithelial cell function and survival. Type IV collagens are the predominant components of all types of BMs, that form an irregular, polygonal lattice and serve as a scaffold for numerous other BM components and BM-associated cells. Mutations in the ubiquitous human BM components COL4A1 and COL4A2 cause a multisystem disorder involving nephropathy. Affected patients develop renal dysfunction and chronic kidney failure with or without hematuria. Mouse Col4a1 and Col4a2 mutants recapitulate the human symptoms. In vertebrates, excretion is accomplished by the kidneys and by the Malpighian tubules in insects, including the fruit fly Drosophila. Our present results with dominant, temperature-sensitive mutation of the Drosophila col4a1 gene demonstrate altered integrin expression and amplified effects of mechanical stress on the Malpighian epithelial cytoskeleton. PMID:27077087

  8. Hereditary Sensory and Autonomic Neuropathy Type IV in 9 Year Old Boy: A Case Report.

    PubMed

    Azadvari, Mohaddeseh; Emami Razavi, Seyedeh Zahra; Kazemi, Shahrbanoo

    2016-01-01

    Objective The Hereditary Sensory and Autonomic neuropathy (HSAN) is a rare group of neuropathies that affects the Sensory and Autonomic nervous system. The patients do not have the ability of sensing different sensations such as pain and temperature, which tends to lead to different injuries. In addition, due to autonomic involvement, the patients suffer from fluctuation in body temperature periodically and lack of precipitation. HSAN is divided into 5 types according to the age of onset, clinical features, and inheritance. Our case was a 9-yr old boy from cousin parents. He had some developmental delay and history of recurrent fever and convulsion in the first year of his life. Gradually, other symptoms added to patient' feature such as multiple painless skin ulcers, tooth loss, destruction of toes and fingers. In electrodiagnostic study, we found decreased amplitude of sensory nerves, while the other studies were normal. Laboratory test and imaging studies were also normal. All clinical and paraclinical findings were in favor of HSAN type IV. There is no cure for such patients; as a result, these patients and their families need receiving appropriate education and timely rehabilitation services. PMID:27247588

  9. 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.

  10. Delay between the Circularly Polarized Components in Fine Structures during Solar Type IV Events

    NASA Astrophysics Data System (ADS)

    Chernov, G. P.; Zlobec, P.

    1995-08-01

    We analyzed intermediately polarized (20 80%) fine structures (pulsations, sudden reductions, fiber bursts and zebras) that were recorded in type IV events. The mean polarization degree was practically the same for all the fine structures recorded in an interval lasting a few minutes and it was similar to the polarization of the continuum. A detailed analysis during the evolution of single structures reveals changes in polarization (in particular an ‘undulation’ at flux density minima) even stronger than 20%. They were caused by a delay, up to 0.1 s, between the two circularly polarized components. The weaker polarimetric component was delayed in 2 sets and the stronger one in 1 set. In the event of April 24, 1985 different types of fine structures were sporadically detected in more than one hour long time interval. Short delays of the stronger or of the weaker component were sometimes observed. The events characterized by fine structures are generally totally polarized in the ordinary mode. We assume that this holds also for the phenomena studied here. The observed intermediate polarization therefore requires a depolarization due to propagation effects. We discuss the mode coupling and the reflection of the original radio signal that could also generate the delay of the weaker and the stronger component respectively. The possibility of polarization variation due to the change of the angle between the direction of the propagation and the magnetic field in a quasi-transversal region and in a low intensity magnetic field in a current sheet is also given.

  11. Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IV.

    PubMed

    Venugopal, Bhuvarahamurthy; Browning, Marsha F; Curcio-Morelli, Cyntia; Varro, Andrea; Michaud, Norman; Nanthakumar, Nanda; Walkley, Steven U; Pickel, James; Slaugenhaupt, Susan A

    2007-11-01

    Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV. The Mcoln1(-/-) mice present with numerous dense inclusion bodies in all cell types in brain and particularly in neurons, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. Neurobehavioral assessments, including analysis of gait and clasping, confirm the presence of a neurological defect. Gait deficits progress to complete hind-limb paralysis and death at age ~8 mo. The Mcoln1(-/-) mice are born in Mendelian ratios, and both male and female Mcoln1(-/-) mice are fertile and can breed to produce progeny. The creation of the first murine model for human MLIV provides an excellent system for elucidating disease pathogenesis. In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder. PMID:17924347

  12. Hereditary Sensory and Autonomic Neuropathy Type IV in 9 Year Old Boy: A Case Report

    PubMed Central

    AZADVARI, Mohaddeseh; EMAMI RAZAVI, Seyedeh Zahra; KAZEMI, Shahrbanoo

    2016-01-01

    Objective The Hereditary Sensory and Autonomic neuropathy (HSAN) is a rare group of neuropathies that affects the Sensory and Autonomic nervous system. The patients do not have the ability of sensing different sensations such as pain and temperature, which tends to lead to different injuries. In addition, due to autonomic involvement, the patients suffer from fluctuation in body temperature periodically and lack of precipitation. HSAN is divided into 5 types according to the age of onset, clinical features, and inheritance. Our case was a 9-yr old boy from cousin parents. He had some developmental delay and history of recurrent fever and convulsion in the first year of his life. Gradually, other symptoms added to patient’ feature such as multiple painless skin ulcers, tooth loss, destruction of toes and fingers. In electrodiagnostic study, we found decreased amplitude of sensory nerves, while the other studies were normal. Laboratory test and imaging studies were also normal. All clinical and paraclinical findings were in favor of HSAN type IV. There is no cure for such patients; as a result, these patients and their families need receiving appropriate education and timely rehabilitation services. PMID:27247588

  13. High-Force Generation Is a Conserved Property of Type IV Pilus Systems▿

    PubMed Central

    Clausen, Martin; Jakovljevic, Vladimir; Søgaard-Andersen, Lotte; Maier, Berenike

    2009-01-01

    The type IV pilus (T4P) system of Neisseria gonorrhoeae is the strongest linear molecular motor reported to date, but it is unclear whether high-force generation is conserved between bacterial species. Using laser tweezers, we found that the average stalling force of single-pilus retraction in Myxococcus xanthus of 149 ± 14 pN exceeds the force generated by N. gonorrhoeae. Retraction velocities including a bimodal distribution were similar between M. xanthus and N. gonorrhoeae, but force-dependent directional switching was not. Force generation by pilus retraction is energized by the ATPase PilT. Surprisingly, an M. xanthus mutant lacking PilT apparently still retracted T4P, although at a reduced frequency. The retraction velocity was comparable to the high-velocity mode in the wild type at low forces but decreased drastically when the force increased, with an average stalling force of 70 ± 10 pN. Thus, M. xanthus harbors at least two different retraction motors. Our results demonstrate that the major physical properties are conserved between bacteria that are phylogenetically distant and pursue very different lifestyles. PMID:19429611

  14. Xanthomonas citri subsp. citri type IV Pilus is required for twitching motility, biofilm development, and adherence.

    PubMed

    Dunger, German; Guzzo, Cristiane R; Andrade, Maxuel O; Jones, Jeffrey B; Farah, Chuck S

    2014-10-01

    Bacterial type IV pili (T4P) are long, flexible surface filaments that consist of helical polymers of mostly pilin subunits. Cycles of polymerization, attachment, and depolymerization mediate several pilus-dependent bacterial behaviors, including twitching motility, surface adhesion, pathogenicity, natural transformation, escape from immune system defense mechanisms, and biofilm formation. The Xanthomonas citri subsp. citri strain 306 genome codes for a large set of genes involved in T4P biogenesis and regulation and includes several pilin homologs. We show that X. citri subsp. citri can exhibit twitching motility in a manner similar to that observed in other bacteria such as Pseudomonas aeruginosa and Xylella fastidiosa and that this motility is abolished in Xanthomonas citri subsp. citri knockout strains in the genes coding for the major pilin subunit PilAXAC3241, the ATPases PilBXAC3239 and PilTXAC2924, and the T4P biogenesis regulators PilZXAC1133 and FimXXAC2398. Microscopy analyses were performed to compare patterns of bacterial migration in the wild-type and knockout strains and we observed that the formation of mushroom-like structures in X. citri subsp. citri biofilm requires a functional T4P. Finally, infection of X. citri subsp. citri cells by the bacteriophage (ΦXacm4-11 is T4P dependent. The results of this study improve our understanding of how T4P influence Xanthomonas motility, biofilm formation, and susceptibility to phage infection. PMID:25180689

  15. Altered stress fibers and integrin expression in the Malpighian epithelium of Drosophila type IV collagen mutants.

    PubMed

    Kiss, András A; Popovics, Nikoletta; Szabó, Gábor; Csiszár, Katalin; Mink, Mátyás

    2016-06-01

    Basement membranes (BMs) are highly specialized extracellular matrices (ECMs) that provide support and polarization cues for epithelial cells. Proper adhesion to the BM is pivotal in epithelial cell function and survival. Type IV collagens are the predominant components of all types of BMs, that form an irregular, polygonal lattice and serve as a scaffold for numerous other BM components and BM-associated cells. Mutations in the ubiquitous human BM components COL4A1 and COL4A2 cause a multisystem disorder involving nephropathy. Affected patients develop renal dysfunction and chronic kidney failure with or without hematuria. Mouse Col4a1 and Col4a2 mutants recapitulate the human symptoms. In vertebrates, excretion is accomplished by the kidneys and by the Malpighian tubules in insects, including the fruit fly Drosophila. Our present results with dominant, temperature-sensitive mutation of the Drosophila col4a1 gene demonstrate altered integrin expression and amplified effects of mechanical stress on the Malpighian epithelial cytoskeleton. PMID:27077087

  16. c-Type Cytochrome-Dependent Formation of U(IV) Nanoparticles by Shewanella oneidensis

    SciTech Connect

    Marshall, Matthew J.; Beliaev, Alex S.; Dohnalkova, Alice; Kennedy, David W.; Shi, Liang; Wang, Zheming; Boyanov, Maxim I.; Lai, Barry; Kemner, Kenneth M.; Mclean, Jeffrey S.; Reed, Samantha B.; Culley, David E.; Bailey, Vanessa L.; Simonson, Cody J.; Saffarini, Daad; Romine, Margaret F.; Zachara, John M.; Fredrickson, Jim K.

    2006-08-08

    Modern approaches for bioremediation of radionuclide contaminated environments are based on the ability of microorganisms to effectively catalyze changes in the oxidation states of metals that in turn influence their solubility. Although microbial metal reduction has been identified as an effective means for immobilizing highly-soluble uranium(VI) complexes in situ, the biomolecular mechanisms of U(VI) reduction are not well understood. Here, we show that c-type cytochromes of a dissimilatory metal reducing bacterium, Shewanella oneidensis MR-1 are essential for the reduction of U(VI) and formation of extracelluar UO2 nanoparticles. In particular, the outer membrane (OM) decaheme cytochrome MtrC, previously implicated in Mn(IV) and Fe(III) reduction, directly transferred electrons to U(VI). Additionally, deletions of mtrC and/or omcA significantly affected the in vivo U(VI) reduction rate relative to wild type MR-1. Similar to the wild type, the mutants accumulated UO2 nanoparticles extracellularly to high densities in association with an exopolymeric substance (EPS). In wild type cells, this UO2-EPS matrix exhibited glycocalyx-like properties, contained multiple elements of the OM, polysaccharide, and heme containing proteins. Using a novel combination of methods including synchrotron-based X-ray fluorescence microscopy and high resolution immune-electron microscopy, we demonstrate a close association of the extracellular UO2 nanoparticles with MtrC and OmcA. This is the first study to directly localize the OM-associated cytochromes with EPS, which contains biogenic UO2 nanoparticles. In the environment, such association of UO2 nanoparticles with biopolymers may exert a strong influence on subsequent behavior including susceptibility to oxidation by O2 or transport in soils and sediments.

  17. c-Type Cytochrome-Dependent Formation of U(IV) Nanoparticles by Shewanella oneidensis

    PubMed Central

    Marshall, Matthew J; Dohnalkova, Alice C; Kennedy, David W; Shi, Liang; Wang, Zheming; Boyanov, Maxim I; Lai, Barry; Kemner, Kenneth M; McLean, Jeffrey S; Reed, Samantha B; Culley, David E; Bailey, Vanessa L; Simonson, Cody J; Saffarini, Daad A; Romine, Margaret F; Zachara, John M

    2006-01-01

    Modern approaches for bioremediation of radionuclide contaminated environments are based on the ability of microorganisms to effectively catalyze changes in the oxidation states of metals that in turn influence their solubility. Although microbial metal reduction has been identified as an effective means for immobilizing highly-soluble uranium(VI) complexes in situ, the biomolecular mechanisms of U(VI) reduction are not well understood. Here, we show that c-type cytochromes of a dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1, are essential for the reduction of U(VI) and formation of extracelluar UO 2 nanoparticles. In particular, the outer membrane (OM) decaheme cytochrome MtrC (metal reduction), previously implicated in Mn(IV) and Fe(III) reduction, directly transferred electrons to U(VI). Additionally, deletions of mtrC and/or omcA significantly affected the in vivo U(VI) reduction rate relative to wild-type MR-1. Similar to the wild-type, the mutants accumulated UO 2 nanoparticles extracellularly to high densities in association with an extracellular polymeric substance (EPS). In wild-type cells, this UO 2-EPS matrix exhibited glycocalyx-like properties and contained multiple elements of the OM, polysaccharide, and heme-containing proteins. Using a novel combination of methods including synchrotron-based X-ray fluorescence microscopy and high-resolution immune-electron microscopy, we demonstrate a close association of the extracellular UO 2 nanoparticles with MtrC and OmcA (outer membrane cytochrome). This is the first study to our knowledge to directly localize the OM-associated cytochromes with EPS, which contains biogenic UO 2 nanoparticles. In the environment, such association of UO 2 nanoparticles with biopolymers may exert a strong influence on subsequent behavior including susceptibility to oxidation by O 2 or transport in soils and sediments. PMID:16875436

  18. ANOMALOUS SILICATE DUST EMISSION IN THE TYPE 1 LINER NUCLEUS OF M81

    SciTech Connect

    Smith, Howard A.; Ashby, M. L. N.; Fazio, G. G.; Huang, J.-S.; Marengo, M.; Wang, Z.; Willner, S.; Zezas, A.; Li, Aigen; Li, M. P.; Koehler, M.; Spinoglio, L.; Wu, Y. L. E-mail: lia@missouri.ed

    2010-06-10

    We report the detection and successful modeling of the unusual 9.7 {mu}m Si-O stretching silicate emission feature in the type 1 (i.e., face-on) LINER nucleus of M81. Using the Infrared Spectrograph (IRS) instrument on Spitzer, we determine the feature in the central 230 pc of M81 to be in strong emission, with a peak at {approx}10.5 {mu}m. This feature is strikingly different in character from the absorption feature of the galactic interstellar medium, and from the silicate absorption or weak emission features typical of galaxies with active star formation. We successfully model the high signal-to-noise ratio IRS spectra with porous silicate dust using laboratory-acquired mineral spectra. We find that the most probable fit uses micron-sized, porous grains of amorphous silicate and amorphous carbon. In addition to silicate dust, there is weak polycyclic aromatic hydrocarbon (PAH) emission present (particularly at 11.3 {mu}m, arising from the C-H out-of-plane bending vibration of relatively large PAHs of {approx}500-1000 C atoms) whose character reflects the low-excitation active galactic nucleus environment, with some evidence that small PAHs of {approx}100-200 C atoms (responsible for the 7.7 {mu}m C-C stretching band) in the immediate vicinity of the nucleus have been preferentially destroyed. Analysis of the infrared fine structure lines confirms the LINER character of the M81 nucleus. Four of the infrared H{sub 2} rotational lines are detected and fit to an excitation temperature of T {approx} 800 K. Spectral maps of the central 230 pc in the [Ne II] 12.8 {mu}m line, the H{sub 2} 17 {mu}m line, and the 11.3 {mu}m PAH C-H bending feature reveal arc- or spiral-like structures extending from the core. We also report on epochal photometric and spectroscopic observations of M81, whose nuclear intensity varies in time across the spectrum due to what is thought to be inefficient, sub-Eddington accretion onto its central black hole. We find that, contrary to the

  19. Relationship between serum and hepatic 7S fragments of type IV collagen in chronic liver disease.

    PubMed

    Suou, T; Yamada, S; Hosho, K; Yoshikawa, N; Kawasaki, H

    1996-05-01

    We evaluated the mechanism of increased serum concentrations of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in chronic liver disease. We measured the concentrations of hepatic-free and deposited 7S collagens after extraction with Tris-HCl buffer and bacterial collagenase, then compared them with the serum levels in 8 normal controls and 48 patients with chronic liver disease. The hepatic 7S collagen levels extracted with Tris-HCl buffer and collagenase accounted for 7% and 93%, respectively, of the total 7S collagen levels in normal controls. Both hepatic 7S collagen levels as well as serum levels increased in accordance with the progress of liver disease. Serum levels of 7S collagen showed a closer correlation with the hepatic 7S collagen levels extracted with Tris-HCl buffer (r = .822), compared with those extracted with collagenase (r = .382). On the other hand, the histological degrees of liver fibrosis were highly correlated with the hepatic collagenase-extracted 7S collagen levels (r = .822), compared with serum and the hepatic Tris-HCl buffer-extracted levels (r = .478 and r = .537, respectively). Although there was no difference in serum and hepatic 7S collagen levels between B and C viral patients, the serum and hepatic Tris-HCl buffer-extracted 7S collagen levels were higher in patients with alcoholic cirrhosis than patients with viral cirrhosis. However, the hepatic collagenase-extracted levels were similar in both groups. Gel filtration demonstrated that the serum and hepatic Tris-HCl buffer-extracted 7S collagens were mainly eluted in the macromolecular 7S collagen-reactive fraction in cirrhosis, whereas the hepatic collagenase-extracted 7S collagen was eluted in the authentic 7S collagen-reactive fraction. The results suggest that serum 7S collagen levels are not a particularly reliable measure of hepatic fibrosis but reflect the enhanced metabolism, especially synthesis of type IV collagen in the liver. PMID:8621148

  20. Expression of CD26 and its association with dipeptidyl peptidase IV activity in lymphocytes of type 2 diabetes patients.

    PubMed

    Bellé, Luziane Potrich; Bitencourt, Paula Eliete Rodrigues; de Bona, Karine Santos; Zanette, Régis Adriel; Moresco, Rafael Noal; Moretto, Maria Beatriz

    2011-11-01

    Immune response and inflammation were suggested to play certain roles in the development and complications of type 2 diabetes mellitus. The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. These parameters were assessed in 25 T2DM patients and 20 control subjects. We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. Meanwhile, a significant negative correlation was observed between CD26 expression and DPP-IV activity in lymphocytes of T2DM patients. Moreover, a positive correlation was found between DPPIV and ADA activities. The results suggest that the reduction of CD26 expression may be associated in the regulation of DPP-IV in T2DM patients. PMID:21614532

  1. Outside-In Assembly Pathway of the Type IV Pilus System in Myxococcus xanthus

    PubMed Central

    Friedrich, Carmen; Bulyha, Iryna

    2014-01-01

    Type IV pili (T4P) are ubiquitous bacterial cell surface structures that undergo cycles of extension, adhesion, and retraction. T4P function depends on a highly conserved envelope-spanning macromolecular machinery consisting of 10 proteins that localizes polarly in Myxococcus xanthus. Using this localization, we investigated the entire T4P machinery assembly pathway by systematically profiling the stability of all and the localization of eight of these proteins in the absence of other T4P machinery proteins as well as by mapping direct protein-protein interactions. Our experiments uncovered a sequential, outside-in pathway starting with the outer membrane (OM) PilQ secretin ring. PilQ recruits a subcomplex consisting of the inner membrane (IM) lipoprotein PilP and the integral IM proteins PilN and PilO by direct interaction with the periplasmic domain of PilP. The PilP/PilN/PilO subcomplex recruits the cytoplasmic PilM protein, by direct interaction between PilN and PilM, and the integral IM protein PilC. The PilB/PilT ATPases that power extension/retraction localize independently of other T4P machinery proteins. Thus, assembly of the T4P machinery initiates with formation of the OM secretin ring and continues inwards over the periplasm and IM to the cytoplasm. PMID:24187092

  2. N. elongata produces type IV pili that mediate interspecies gene transfer with N. gonorrhoeae.

    PubMed

    Higashi, Dustin L; Biais, Nicolas; Weyand, Nathan J; Agellon, Al; Sisko, Jennifer L; Brown, Lewis M; So, Magdalene

    2011-01-01

    The genus Neisseria contains at least eight commensal and two pathogenic species. According to the Neisseria phylogenetic tree, commensals are basal to the pathogens. N. elongata, which is at the opposite end of the tree from N. gonorrhoeae, has been observed to be fimbriated, and these fimbriae are correlated with genetic competence in this organism. We tested the hypothesis that the fimbriae of N. elongata are Type IV pili (Tfp), and that Tfp functions in genetic competence. We provide evidence that the N. elongata fimbriae are indeed Tfp. Tfp, as well as the DNA Uptake Sequence (DUS), greatly enhance N. elongata DNA transformation. Tfp allows N. elongata to make intimate contact with N. gonorrhoeae and to mediate the transfer of antibiotic resistance markers between these two species. We conclude that Tfp functional for genetic competence is a trait of a commensal member of the Neisseria genus. Our findings provide a mechanism for the horizontal gene transfer that has been observed among Neisseria species. PMID:21731720

  3. Force-dependent polymorphism in type IV pili reveals hidden epitopes.

    PubMed

    Biais, Nicolas; Higashi, Dustin L; Brujic, Jasna; So, Magdalene; Sheetz, Michael P

    2010-06-22

    Through evolution, nature has produced exquisite nanometric structures, with features unrealized in the most advanced man-made devices. Type IV pili (Tfp) represent such a structure: 6-nm-wide retractable filamentous appendages found in many bacteria, including human pathogens. Whereas the structure of Neisseria gonorrhoeae Tfp has been defined by conventional structural techniques, it remains difficult to explain the wide spectrum of functions associated with Tfp. Here we uncover a previously undescribed force-induced quaternary structure of the N. gonorrhoeae Tfp. By using a combination of optical and magnetic tweezers, atomic force microscopy, and molecular combing to apply forces on purified Tfp, we demonstrate that Tfp subjected to approximately 100 pN of force will transition into a new conformation. The new structure is roughly 3 times longer and 40% narrower than the original structure. Upon release of the force, the Tfp fiber regains its original form, indicating a reversible transition. Equally important, we show that the force-induced conformation exposes hidden epitopes previously buried in the Tfp fiber. We postulate that this transition provides a means for N. gonorrhoeae to maintain attachment to its host while withstanding intermittent forces encountered in the environment. Our findings demonstrate the need to reassess our understanding of Tfp dynamics and functions. They could also explain the structural diversity of other helical polymers while presenting a unique mechanism for polymer elongation and exemplifying the extreme structural plasticity of biological polymers. PMID:20534431

  4. Genes Required for Assembly of Pili Associated with the Helicobacter pylori cag Type IV Secretion System

    PubMed Central

    Johnson, Elizabeth M.; Gaddy, Jennifer A.; Voss, Bradley J.; Hennig, Ewa E.

    2014-01-01

    Helicobacter pylori causes numerous alterations in gastric epithelial cells through processes that are dependent on activity of the cag type IV secretion system (T4SS). Filamentous structures termed “pili” have been visualized at the interface between H. pylori and gastric epithelial cells, and previous studies suggested that pilus formation is dependent on the presence of the cag pathogenicity island (PAI). Thus far, there has been relatively little effort to identify specific genes that are required for pilus formation, and the role of pili in T4SS function is unclear. In this study, we selected 7 genes in the cag PAI that are known to be required for T4SS function and investigated whether these genes were required for pilus formation. cagT, cagX, cagV, cagM, and cag3 mutants were defective in both T4SS function and pilus formation; complemented mutants regained T4SS function and the capacity for pilus formation. cagY and cagC mutants were defective in T4SS function but retained the capacity for pilus formation. These results define a set of cag PAI genes that are required for both pilus biogenesis and T4SS function and reveal that these processes can be uncoupled in specific mutant strains. PMID:24891108

  5. Cag Type IV Secretion System: CagI Independent Bacterial Surface Localization of CagA

    PubMed Central

    Kumar, Navin; Shariq, Mohd; Kumari, Rajesh; Tyagi, Rakesh K.; Mukhopadhyay, Gauranga

    2013-01-01

    Helicobacter pylori Cag type IV secretion system (Cag-T4SS) is a multi-component transporter of oncoprotein CagA across the bacterial membranes into the host epithelial cells. To understand the role of unique Cag-T4SS component CagI in CagA translocation, we have characterized it by biochemical and microscopic approaches. We observed that CagI is a predominantly membrane attached periplasmic protein partially exposed to the bacterial surface especially on the pili. The association of the protein with membrane appeared to be loose as it could be easily recovered in soluble fraction. We documented that the stability of the protein is dependent on several key components of the secretion system and it has multiple interacting partners including a non-cag-PAI protein HP1489. Translocation of CagA across the bacterial membranes to cell surface is CagI-independent process. The observations made herein are expected to assist in providing an insight into the substrate translocation by the Cag-T4SS system and Helicobacter pylori pathogenesis. PMID:24040297

  6. Theoretical studies of organotin(IV) complexes derived from ONO-donor type schiff base ligands.

    PubMed

    Şirikci, Gökhan; Ancın, Nilgün Ataünal; Öztaş, Selma Gül

    2015-09-01

    In this work a molecular modeling study was carried out based on a series of organotin(IV) derivatives which were complexed with ONO-Donor type Schiff base ligands to build up a statistical data pool for researchers. For this purpose, various properties of the selected complexes such as energies, band gaps, chemical reactivity descriptors, polarizabilities, geometric parameters, (1)H-NMR, (13)C-NMR chemical shifting values were obtained through density functional theory using B3LYP, CAM-B3LYP, TPSSTPSS, TPSSh, HCTH, wB97XD, and MN12SX functionals. Empirical dispersion corrections were incorporated for some functionals and solvent effects were also taken into account through applying polarizable continuum model (PCM). (1)H-NMR, (13)C-NMR chemical shifts were calculated via linear regression analysis using either gauge invariant atomic orbital (GIAO) or continuous set of gauge transformations (CSGT) methods. While structural properties were being explored, quantitative effects of utilized functionals and empirical dispersion corrections over calculated properties were shown in detail. PMID:26245450

  7. Cyclic Di-GMP Riboswitch-Regulated Type IV Pili Contribute to Aggregation of Clostridium difficile

    PubMed Central

    Bordeleau, Eric; Purcell, Erin B.; Lafontaine, Daniel A.; Fortier, Louis-Charles; Tamayo, Rita

    2014-01-01

    Clostridium difficile is an anaerobic Gram-positive bacterium that causes intestinal infections with symptoms ranging from mild diarrhea to fulminant colitis. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that typically regulates the switch from motile, free-living to sessile and multicellular behaviors in Gram-negative bacteria. Increased intracellular c-di-GMP concentration in C. difficile was recently shown to reduce flagellar motility and to increase cell aggregation. In this work, we investigated the role of the primary type IV pilus (T4P) locus in c-di-GMP-dependent cell aggregation. Inactivation of two T4P genes, pilA1 (CD3513) and pilB1 (CD3512), abolished pilus formation and significantly reduced cell aggregation under high c-di-GMP conditions. pilA1 is preceded by a putative c-di-GMP riboswitch, predicted to be transcriptionally active upon c-di-GMP binding. Consistent with our prediction, high intracellular c-di-GMP concentration increased transcript levels of T4P genes. In addition, single-round in vitro transcription assays confirmed that transcription downstream of the predicted transcription terminator was dose dependent and specific to c-di-GMP binding to the riboswitch aptamer. These results support a model in which T4P gene transcription is upregulated by c-di-GMP as a result of its binding to an upstream transcriptionally activating riboswitch, promoting cell aggregation in C. difficile. PMID:25512308

  8. Preparation and characterization of resistant starch type IV nanoparticles through ultrasonication and miniemulsion cross-linking.

    PubMed

    Ding, Yongbo; Zheng, Jiong; Xia, Xuejuan; Ren, Tingyuan; Kan, Jianquan

    2016-05-01

    This study aimed to assess the properties of resistant starch type IV (chemically modified starch, RS4) prepared from a new and convenient synthesis route by using ultrasonication combined with water-in-oil miniemulsion cross-linking technique. A three-factor Box-Behnken design and optimization was used to minimize particle size through the developed RS4 nanoparticles. The predicted minimized Z-Avel (576.1nm) under the optimum conditions of the process variables (ultrasonic power, 214.57W; sonication time, 114.73min; and oil/water ratio, 10.54:1) was very close to the experimental value (651.0nm) determined in a batch experiment. After preparing the RS4 nanoparticles, morphological, physical, chemical, and functional properties were assessed. Results revealed that RS4 nanoparticle size reached about 600nm. Scanning electron microscopy images showed that ultrasonication induced notches and grooves on the surface. Under polarized light, the polarized cross was impaired. X-ray diffraction results revealed that the crystalline structure was disrupted. Smaller or no endotherms were exhibited in DSC analysis. In the FTIR graph, new peaks at 1532.91 and 1451.50cm(-1) were observed, and pasting properties were reduced. Amylose content, solubility, and SP increased, but RS content decreased. Anti-digestibility remained after ultrasonication. The prepared RS4 nanoparticles could be extensively used in biomedical applications and in the development of new medical materials. PMID:26877007

  9. Mechanism and function of type IV secretion during infection of the human host

    PubMed Central

    Gonzalez-Rivera, Christian; Bhatty, Minny; Christie, Peter J.

    2015-01-01

    Bacterial pathogens employ type IV secretion systems (T4SSs) for various purposes to aid in survival and proliferation in eukaryotic host. One large T4SS subfamily, the conjugation systems, confers a selective advantage to the invading pathogen in clinical settings through dissemination of antibiotic resistance genes and virulence traits. Besides their intrinsic importance as principle contributors to the emergence of multiply drug-resistant ‘superbugs’, detailed studies of these highly tractable systems have generated important new insights into the mode of action and architectures of paradigmatic T4SSs as a foundation for future efforts aimed at suppressing T4SS machine function. Over the past decade, extensive work on the second large T4SS subfamily, the effector translocators, has identified a myriad of mechanisms employed by pathogens to subvert, subdue, or bypass cellular processes and signaling pathways of the host cell. An overarching theme in the evolution of many effectors is that of molecular mimicry. These effectors carry domains similar to those of eukaryotic proteins and exert their effects through stealthy interdigitation of cellular pathways, often with the outcome not of inducing irreversible cell damage but rather of reversibly modulating cellular functions. This chapter summarizes the major developments for the actively studied pathogens with an emphasis on the structural and functional diversity of the T4SSs and the emerging common themes surrounding effector function in the human host. PMID:27337453

  10. Flexibility of bacterial type IV pili determined using atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Mogyoros, Josh; Lu, Shun; Harvey, Hanjeong; Burrows, Lori; Wickham, Robert; Dutcher, John

    Type IV pili (T4P) are very thin protein filaments extended and retracted from the surface of certain Gram-negative bacteria. Pili play a major role in processes such as adhesion, twitching motility and biofilm formation. We used atomic force microscopy (AFM) to perform force spectroscopy measurements on T4P of P. aeruginosa. Bacteria were adhered to the end of an AFM cantilever that was brought into contact with a substrate, allowing the pili to adhere. Force-separation curves were collected by retracting the cantilever, corresponding to the stretching of the T4P that was well described by the worm-like chain (WLC) model. Distinct peaks were observed in the distributions of the best-fit values of the persistence length Lp on two different surfaces, providing strong evidence for close-packed bundling of very flexible T4P. Surprisingly, the most prominent value of Lp ~ 1 nm is significantly less than the ~ 8 nm length of the PilA subunit. We have investigated this intriguing result by refining our protocol to combine AFM with fluorescence microscopy to isolate a single bacterium on a colloidal probe, as well as critically examining the applicability of the WLC model.

  11. Type IV Pilus Proteins Form an Integrated Structure Extending from the Cytoplasm to the Outer Membrane

    PubMed Central

    Li, Chengyun; Wallace, Regina A.; Black, Wesley P.; Li, Yue-zhong; Yang, Zhaomin

    2013-01-01

    The bacterial type IV pilus (T4P) is the strongest biological motor known to date as its retraction can generate forces well over 100 pN. Myxococcus xanthus, a δ-proteobacterium, provides a good model for T4P investigations because its social (S) gliding motility is powered by T4P. In this study, the interactions among M. xanthus T4P proteins were investigated using genetics and the yeast two-hybrid (Y2H) system. Our genetic analysis suggests that there is an integrated T4P structure that crosses the inner membrane (IM), periplasm and the outer membrane (OM). Moreover, this structure exists in the absence of the pilus filament. A systematic Y2H survey provided evidence for direct interactions among IM and OM proteins exposed to the periplasm. For example, the IM lipoprotein PilP interacted with its cognate OM protein PilQ. In addition, interactions among T4P proteins from the thermophile Thermus thermophilus were investigated by Y2H. The results indicated similar protein-protein interactions in the T4P system of this non-proteobacterium despite significant sequence divergence between T4P proteins in T. thermophilus and M. xanthus. The observations here support the model of an integrated T4P structure in the absence of a pilus in diverse bacterial species. PMID:23922942

  12. Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA

    PubMed Central

    Cunha, Larissa D.; Ribeiro, Juliana M.; Fernandes, Talita D.; Massis, Liliana M.; Khoo, Chen Ai; Moffatt, Jennifer H.; Newton, Hayley J.; Roy, Craig R.; Zamboni, Dario S.

    2015-01-01

    Coxiella burnetii is a highly infectious bacterium that promotes its own replication in macrophages by inhibiting several host cell responses. Here, we show that C. burnetii inhibits caspase-1 activation in primary mouse macrophages. By using co-infection experiments, we determine that the infection of macrophages with C. burnetii inhibits the caspase-11-mediated non-canonical activation of the NLRP3 inflammasome induced by subsequent infection with Escherichia coli or Legionella pneumophila. Genetic screening using flagellin mutants of L. pneumophila as a surrogate host, reveals a novel C. burnetii gene (IcaA) involved in the inhibition of caspase activation. Expression of IcaA in L. pneumophila inhibited the caspase-11 activation in macrophages. Moreover, icaA- mutants of C. burnetii failed to suppress the caspase-11-mediated inflammasome activation induced by L. pneumophila. Our data reveal IcaA as a novel C. burnetii effector protein that is secreted by the Dot/Icm type IV secretion system and interferes with the caspase-11-induced, non-canonical activation of the inflammasome. PMID:26687278

  13. Stage IV intramucosal gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type.

    PubMed

    Ohtaka, Masahiko; Sato, Tadashi; Kobayashi, Shouji; Sueki, Ryouta; Yamaguchi, Tatsuya; Uetake, Tomoyoshi; Ohtsuka, Hiroyuki; Iwao, Noriaki; Kirito, Keita; Enomoto, Nobuyuki

    2013-04-01

    A 45-year-old woman with no symptoms underwent upper gastrointestinal endoscopy. A discolored area was noted at the greater curvature of the gastric upper body. Endoscopic ultrasonography demonstrated thickening of the second sonographic layer indicating that the depth of invasion was confined to the mucosa. A urea breath test and anti-Helicobacter pylori antibody test were negative. A computed tomography scan showed a consolidation at the right lung. Gastric biopsy and transbronchial lung biopsy (TBLB) demonstrated a monotonous proliferation of atypical small lymphocytes. A diagnosis of gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) was made. The clinical stage was stage IV. A genetic analysis showed rearrangement of the joining region of the immunoglobulin heavy chain gene and identical clones in both lesions. An API2-MALT1 fusion gene was detected in the gastric lesion. After H. pylori eradication treatment, combination treatment with rituximab plus CHOP (R-CHOP) was performed; 6 months later an endoscopy revealed complete disappearance of the lesion. Multiple gastric biopsies showed no infiltrating atypical lymphocytes. Similarly, the lesion in the lung showed complete remission (CR) on CT and TBLB. This report shows that a gastric MALT lymphoma located in the mucosa and disseminated to the lung maintained CR by R-CHOP. PMID:26181449

  14. Frequency Dependence of Polarization of Zebra Pattern in Type-IV Solar Radio Bursts

    NASA Astrophysics Data System (ADS)

    Kaneda, Kazutaka; Misawa, H.; Iwai, K.; Tsuchiya, F.; Obara, T.

    2015-08-01

    We investigated the polarization characteristics of a zebra pattern (ZP) in a type-IV solar radio burst observed with AMATERAS on 2011 June 21 for the purpose of evaluating the generation processes of ZPs. Analyzing highly resolved spectral and polarization data revealed the frequency dependence of the degree of circular polarization and the delay between two polarized components for the first time. The degree of circular polarization was 50%-70% right-handed and it varied little as a function of frequency. Cross-correlation analysis determined that the left-handed circularly polarized component was delayed by 50-70 ms relative to the right-handed component over the entire frequency range of the ZP and this delay increased with the frequency. We examined the obtained polarization characteristics by using pre-existing ZP models and concluded that the ZP was generated by the double-plasma-resonance process. Our results suggest that the ZP emission was originally generated in a completely polarized state in the O-mode and was partly converted into the X-mode near the source. Subsequently, the difference between the group velocities of the O-mode and X-mode caused the temporal delay.

  15. Molecular organization of type IV collagen: polymer liquid crystal-like aspects.

    PubMed

    Gathercole, L J; Barnard, K; Atkins, E D

    1989-12-01

    A new X-ray diffraction pattern from type IV collagen is described, which can be interpreted on the basis of crystalline and liquid crystalline origins of the reflections. Bovine anterior lens capsules extracted with 1 M NaCl and oriented by extension of 60% under constant load gave medium angle X-ray diffraction patterns showing many of the characteristics typical of liquid crystals. Prominent features, apart from those wide angle features attributable to the collagen triple helix, are (1) a four-point pattern of broad reflections at d-spacing 3.9 nm, and layer line spacing near 5 nm. (2) A broad intense equatorial peak centred at 1.24 nm, indicative of liquid-like lateral molecular associations. (3) A set of five sharp, streaked meridional reflections (previously obscured by the broad peak near 5 nm in unextracted capsules). (4) A further six higher angle reflections of a diffuse, arced and broad appearance on the meridian. The sharp streaked meridional reflections emanate from a long-range periodicity of units 8-9 nm in diameter. These features form a self-consistent system if interpreted on the basis of a staggered liquid crystal-like array of collagen molecules, in which case the first five meridionals and remaining broad reflections, sampled on the meridian, can all be indexed as orders of 21 nm. PMID:2489101

  16. Late onset pityriasis rubra pilaris type IV treated with low-dose acitretin.

    PubMed

    Mota, Fernando; Carvalho, Sandrina; Sanches, Madalena; Selores, Manuela

    2016-01-01

    Pityriasis rubra pilaris is a chronic inflammatory dermatosis of unknown etiology and great clinical variability. It has been divided into six categories. Types III, IV, and V occur in childhood and are distinguished by their clinical presentation, age of onset, and course. We report a 19-year-old male patient with a 2-week history of pruritic, scaling dermatosis of the hands, feet, elbows, and knees. He had no family history of skin disease. On physical examination, we observed circumscribed, reddish-orange, scaling plaques affecting the elbows and knees and a waxy palmoplantar keratoderma. The skin biopsy showed acanthosis, alternating orthokeratosis, parakeratosis, and follicular plugging suggestive of pityriasis rubra pilaris. The patient started treatment with oral acitretin, 25 mg every other day. The treatment was tolerated well, and after 6 months the lesions had resolved completely. Pityriasis rubra pilaris is a chronic papulosquamous disorder of unknown pathogenesis, characterized by reddish-orange scaly plaques, palmoplantar keratoderma, and keratotic follicular papules. There is still no consensus regarding the treatment, but therapeutic options include systemic retinoids, particularly acitretin in the recommended dose of 0.5 to 0.75 mg/kg/day. In our case, the patient was treated with a low-dose regimen of acitretin, which was effective and well tolerated. PMID:27014774

  17. Transthoracic Collis-Nissen repair for massive type IV paraesophageal hernia.

    PubMed

    Itano, Hideki; Okamoto, Shiroh; Kodama, Kanji; Horita, Naokatsu

    2008-09-01

    An 80-year-old woman presented with type IV massive hiatal hernia with intrathoracic upside-down stomach and transverse colon. She was dyspneic and vomited upon consuming food or water. Consequently, she developed aspiration pneumonia. Both esophagoscopy and upper gastrointestinal series demonstrated significant cephalad displacement of the gastroesophageal junction. A Collis-Nissen hernial repair by muscle-sparing mini-thoracotomy was performed successfully. To date, 3 years after surgery, the patient is enjoying normal oral intake, has an excellent activities of daily living level, and there is no hernia recurrence. Cases of massive paraesophageal hernia are frequently associated with esophageal shortening that causes tension on the repairs and late failure. Advantages of the transthoracic approach in such cases include feasibility of direct esophageal mobilization, accurate assessment of esophageal tension, and facilitation of Collis gastroplasty. The true indication for transthoracic Collis-Nissen repair among cases of paraesophageal hiatal hernia with a short esophagus should be acknowledged more in the era of laparoscopy. PMID:18791669

  18. Aggressive change of a carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV.

    PubMed

    Kojima, Atsuhiro; Saga, Isako; Tomio, Ryosuke; Kosho, Tomoki; Hatamochi, Atsushi

    2015-06-01

    The authors report a rare case of a carotid-cavernous fistula (CCF) secondary to Ehlers-Danlos syndrome (EDS) type IV which showed an aggressive angiographical change.A 59-year-old woman presented with headache, right pulsatile tinnitus, and diplopia on the right side. The diagnostic angiography demonstrated a right CCF. Accordingly transarterial embolization of the fistula was attempted 5 days later. The initial right internal carotid angiography showed an aneurysm on the petrous portion of the internal carotid artery (ICA) which was not recognized in the diagnostic angiography. Spontaneous reduction of the shunt flow and long dissection of the ICA were also revealed. The aneurysm was successfully occluded with coils, and only minor shunt flow was shown on the final angiogram. EDS type IV was diagnosed with a skin biopsy for a collagen abnormality. After the operation, the stenosis of the right ICA gradually progressed, although there was no recurrence of the CCF.Interventional treatment for patients with EDS can cause devastating vascular complication. We should be aware of the possibility of EDS type IV when a spontaneous CCF shows unusual angiographical change because early diagnosis of EDS type IV is crucial for determination of the optimum treatment option. PMID:26015525

  19. Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.

    PubMed

    Deng, Yao; Wei, Shijie; Hu, Shijun; Chen, Jinlan; Tan, Zhiping; Yang, Yifeng

    2015-07-01

    Ehlers-Danlos syndrome type IV is an autosomal dominant connective tissue disease. Mutations in COL3A1 have been identified to underlie this disease; however, to the best of our knowledge, no COL3A1 mutations have been reported in Ehlers-Danlos syndrome type IV patients with an ascending aortic aneurysm. In order to develop further understanding of COL3A1 mutations, an Ehlers-Danlos syndrome type IV patient diagnosed with an ascending aortic aneurysm and a familial history of sudden mortality was analyzed. Genomic DNA was isolated from the peripheral blood of the patient and his family members. All coding exons of eight aneurysm-related genes (FBN1, TGFBR1, TGFBR 2, MYH11, ACTA2, SLC2A10, NOTCH1 and COL3A1) were amplified using polymerase chain reaction (PCR). The PCR products were sequenced with the ABI 3100 Genetic Analyzer, and a mutation was predicted and identified using Polyphen-2, SIFT and Mutation Taster. The novel mutation was identified as c.2950G>A in COL3A1, which results in p.G984R. All three programs predicted this mutation to be deleterous to the protein function. The novel mutation identified in this study is potentially responsible for Ehlers-Danlos syndrome type IV in this patient, and expands the spectrum of COL3A1 mutations. PMID:25776230

  20. [Mucopolysaccharidosis. A case report of Morquio's type-A disease (MPS IV-A)].

    PubMed

    Pagni, L; Bartolozzi, L; Giacchetti, D

    1992-11-01

    The mucopolysaccharidosis represent a broad spectrum of disorders due to the deficiency of one of a group of enzymes which degrade three classes of mucopolysaccharides: heparan sulfate, dermatan-sulfate and keratan sulfate. The general phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, joint stiffness, hernias, dysostosis multiplex, mucopolysaccharides excretion in the urine and metachromatic staining in peripheral leukocytes and bone marrow. Various components of the MPS phenotype are also found in the mucolipidoses, glycoprotein storage diseases. Detailed clinical and radiologic evaluation and identification of the type of MPS excreted in the urine help to narrow the diagnosis possibilities. Definitive diagnosis requires assay of specific enzymes in various tissues such as cultured skin fibroblasts. For the moment there are 14 types of known mucopolysaccharidoses, including several subtypes. They are classified into Hurler's syndrome (MPS I-H); Scheie's syndrome (MPS I-S); Hurler-Scheie's syndrome (MPS I-H/S); Hunter's syndrome A, B (MPS II-A, B); Sanfilippo's syndrome A,B,C,D (MPS II-A,B,C,D); Morquio's syndrome A,B,C (MSP IV-A,B,C); Maroteaux-Lamy's syndrome (MPS VI) and Sly's syndrome MPS VII). The mucopolysaccharidosis incidence is around 0.04-0.3% of the newborn and they are 1.5% of all congenital disorders. All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive. Patient suffering of MPS, usually, don't show clinical sign from their birth in fact they develop later their characteristics. The average surviving of this patients is around 20-30 years old, and the exitus is due to cardiac failure or to infections to the gastrointestinal tract or to instability of atlantoaxial joint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1294876

  1. Pseudomonas aeruginosa d-Arabinofuranose Biosynthetic Pathway and Its Role in Type IV Pilus Assembly*

    PubMed Central

    Harvey, Hanjeong; Kus, Julianne V.; Tessier, Luc; Kelly, John; Burrows, Lori L.

    2011-01-01

    Pseudomonas aeruginosa strains PA7 and Pa5196 glycosylate their type IVa pilins with α1,5-linked d-arabinofuranose (d-Araf), a rare sugar configuration identical to that found in cell wall polymers of the Corynebacterineae. Despite this chemical identity, the pathway for biosynthesis of α1,5-d-Araf in Gram-negative bacteria is unknown. Bioinformatics analyses pointed to a cluster of seven P. aeruginosa genes, including homologues of the Mycobacterium tuberculosis genes Rv3806c, Rv3790, and Rv3791, required for synthesis of a polyprenyl-linked d-ribose precursor and its epimerization to d-Araf. Pa5196 mutants lacking the orthologues of those genes had non-arabinosylated pilins, poor twitching motility, and significantly fewer surface pili than the wild type even in a retraction-deficient (pilT) background. The Pa5196 pilus system assembled heterologous non-glycosylated pilins efficiently, demonstrating that it does not require post-translationally modified subunits. Together the data suggest that pilins of group IV strains need to be glycosylated for productive subunit-subunit interactions. A recombinant P. aeruginosa PAO1 strain co-expressing the genes for d-Araf biosynthesis, the pilin modification enzyme TfpW, and the acceptor PilAIV produced arabinosylated pili, confirming that the Pa5196 genes identified are both necessary and sufficient. A P. aeruginosa epimerase knock-out could be complemented with the corresponding Mycobacterium smegmatis gene, demonstrating conservation between the systems of the Corynebacterineae and Pseudomonas. This work describes a novel Gram-negative pathway for biosynthesis of d-Araf, a key therapeutic target in Corynebacterineae. PMID:21676874

  2. The Host Protein Calprotectin Modulates the Helicobacter pylori cag Type IV Secretion System via Zinc Sequestration

    PubMed Central

    Gaddy, Jennifer A.; Radin, Jana N.; Loh, John T.; Piazuelo, M. Blanca; Kehl-Fie, Thomas E.; Delgado, Alberto G.; Ilca, Florin T.; Peek, Richard M.; Cover, Timothy L.; Chazin, Walter J.; Skaar, Eric P.; Scott Algood, Holly M.

    2014-01-01

    Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters essential nutrient metals away from invading pathogenic bacteria. Neutrophils participate in this process by producing several metal chelating proteins, including lactoferrin and calprotectin (CP). As neutrophils are an important component of the inflammatory response directed against the bacterium Helicobacter pylori, a major risk factor for gastric cancer, it was hypothesized that CP plays a role in the host response to H. pylori. Utilizing a murine model of H. pylori infection and gastric epithelial cell co-cultures, the role CP plays in modifying H. pylori -host interactions and the function of the cag Type IV Secretion System (cag T4SS) was investigated. This study indicates elevated gastric levels of CP are associated with the infiltration of neutrophils to the H. pylori-infected tissue. When infected with an H. pylori strain harboring a functional cag T4SS, calprotectin-deficient mice exhibited decreased bacterial burdens and a trend toward increased cag T4SS -dependent inflammation compared to wild-type mice. In vitro data demonstrate that culturing H. pylori with sub-inhibitory doses of CP reduces the activity of the cag T4SS and the biogenesis of cag T4SS-associated pili in a zinc-dependent fashion. Taken together, these data indicate that zinc homeostasis plays a role in regulating the proinflammatory activity of the cag T4SS. PMID:25330071

  3. [Reactivity of antibodies to collagen types I to IV and antibodies to chondroitin sulfate in the spleen].

    PubMed

    Galbavý, S; Ruzicková, M; Surmíková, E; Danihel, L; Porubský, J; Papincák, J; Holesa, S; Trnka, J

    1996-02-01

    Antibodies to collagen type I and III reacted negatively, antibodies to collagen type IV positively with reticulin, trabeculae and circumferent reticulum of lymphatic sheaths, poorly positively with capsula, strongly positively with subcapsular zone. Antibodies to collagen type II reacted positively with capsula, poorly with subcapsular zone, strongly with sinus wall and poorly with trabeculae. They did not react with circumferent reticulum of periarterial lymphoid sheaths. Antibodies to collagen type II and IV reacted positively with central arteries. Antibodies to chondroitinsulphate C reacted poorly and antibodies to chondroitinsulphate B strongly positively with sinus walls and oval cells spread in the white and red pulpa. Antibodies to chondroitin sulphate A reacted similarly as antibodies to chondroitinsulphate B. PMID:9560890

  4. Assessing Adhesion Forces of Type I and Type IV Pili of Xylella fastidiosa Bacteria by Use of a Microfluidic Flow Chamber▿ †

    PubMed Central

    De La Fuente, Leonardo; Montanes, Emilie; Meng, Yizhi; Li, Yaxin; Burr, Thomas J.; Hoch, H. C.; Wu, Mingming

    2007-01-01

    Xylella fastidiosa, a bacterium responsible for Pierce's disease in grapevines, possesses both type I and type IV pili at the same cell pole. Type IV pili facilitate twitching motility, and type I pili are involved in biofilm development. The adhesiveness of the bacteria and the roles of the two pili types in attachment to a glass substratum were evaluated using a microfluidic flow chamber in conjunction with pilus-defective mutants. The average adhesion force necessary to detach wild-type X. fastidiosa cells was 147 ± 11 pN. Mutant cells possessing only type I pili required a force of 204 ± 22 pN for removal, whereas cells possessing only type IV pili required 119 ± 8 pN to dislodge these cells. The experimental results demonstrate that microfluidic flow chambers are useful and convenient tools for assessing the drag forces necessary for detaching bacterial cells and that with specific pilus mutants, the role of the pilus type can be further assessed. PMID:17293518

  5. Expression of the MHC Class II Transactivator (CIITA) type IV promoter in B lymphocytes and regulation by IFN-γ

    PubMed Central

    Piskurich, Janet F.; Gilbert, Carolyn A.; Ashley, Brittany D.; Zhao, Mojun; Chen, Han; Wu, Jian; Wright, Kenneth L.

    2006-01-01

    The MHC class II transactivator (CIITA), the master regulator of MHC class II (MHC II) expression, is a co-activator that controls MHC II transcription. Human B lymphocytes express MHC II constitutively due to persistent activity of CIITA promoter III (pIII), one of the four potential promoters (pI-pIV) of this gene. Although increases in MHC II expression in B cells in response to cytokines have been observed and induction of MHC II and CIITA by IFN-γ has been studied in a number of different cell types, the specific effects of IFN-γ on CIITA expression in B cells have not been studied. To investigate the regulation of CIITA expression by IFN-γ in B cells, RT-PCR, in vivo and in vitro protein/DNA binding studies, and functional promoter analyses were performed. Both MHC II and CIITA type IV-specific RNAs increased in human B lymphocytes in response to IFN-γ treatment. CIITA promoter analysis confirmed that pIV is IFN-γ inducible in B cells and that the GAS and IRF-E sites are necessary for full induction. DNA binding of IRF-1 and IRF-2, members of the IFN regulatory factor family, was up-regulated in B cells in response to IFN-γ and increased the activity of CIITA pIV. In vivo genomic footprint analysis demonstrated proteins binding at the GAS, IRF-E and E box sites of CIITA pIV. Although CIITA pIII is considered to be the hematopoietic-specific promoter of CIITA, these findings demonstrate that pIV is active in B lymphocytes and potentially contributes to the expression of CIITA and MHC II in these cells. PMID:15950283

  6. Functional divergence of FimX in PilZ binding and type IV pilus regulation.

    PubMed

    Qi, Yaning; Xu, Linghui; Dong, Xueming; Yau, Yin Hoe; Ho, Chun Loong; Koh, Siew Lee; Shochat, Susana Geifman; Chou, Shan-Ho; Tang, Kai; Liang, Zhao-Xun

    2012-11-01

    Type IV pili (T4P) are polar surface structures that play important roles in bacterial motility, biofilm formation, and pathogenicity. The protein FimX and its orthologs are known to mediate T4P formation in the human pathogen Pseudomonas aeruginosa and some other bacterial species. It was reported recently that FimX(XAC2398) from Xanthomonas axonopodis pv. citri interacts with PilZ(XAC1133) directly through the nonenzymatic EAL domain of FimX(XAC2398). Here we present experimental data to reveal that the strong interaction between FimX(XAC2398) and PilZ(XAC1133) is not conserved in P. aeruginosa and likely other Pseudomonas species. In vitro and in vivo binding experiments showed that the interaction between FimX and PilZ in P. aeruginosa is below the measurable limit. Surface plasmon resonance assays further confirmed that the interaction between the P. aeruginosa proteins is at least more than 3 orders of magnitude weaker than that between the X. axonopodis pv. citri pair. The N-terminal lobe region of FimX(XAC2398) was identified as the binding surface for PilZ(XAC1133) by amide hydrogen-deuterium exchange and site-directed mutagenesis studies. Lack of several key residues in the N-terminal lobe region of the EAL domain of FimX is likely to account for the greatly reduced binding affinity between FimX and PilZ in P. aeruginosa. All together, the results suggest that the interaction between PilZ and FimX in Xanthomonas species is not conserved in P. aeruginosa due to the evolutionary divergence among the FimX orthologs. The precise roles of FimX and PilZ in bacterial motility and T4P biogenesis are likely to vary among bacterial species. PMID:22942245

  7. Type IV pili interactions promote intercellular association and moderate swarming of Pseudomonas aeruginosa.

    PubMed

    Anyan, Morgen E; Amiri, Aboutaleb; Harvey, Cameron W; Tierra, Giordano; Morales-Soto, Nydia; Driscoll, Callan M; Alber, Mark S; Shrout, Joshua D

    2014-12-16

    Pseudomonas aeruginosa is a ubiquitous bacterium that survives in many environments, including as an acute and chronic pathogen in humans. Substantial evidence shows that P. aeruginosa behavior is affected by its motility, and appendages known as flagella and type IV pili (TFP) are known to confer such motility. The role these appendages play when not facilitating motility or attachment, however, is unclear. Here we discern a passive intercellular role of TFP during flagellar-mediated swarming of P. aeruginosa that does not require TFP extension or retraction. We studied swarming at the cellular level using a combination of laboratory experiments and computational simulations to explain the resultant patterns of cells imaged from in vitro swarms. Namely, we used a computational model to simulate swarming and to probe for individual cell behavior that cannot currently be otherwise measured. Our simulations showed that TFP of swarming P. aeruginosa should be distributed all over the cell and that TFP-TFP interactions between cells should be a dominant mechanism that promotes cell-cell interaction, limits lone cell movement, and slows swarm expansion. This predicted physical mechanism involving TFP was confirmed in vitro using pairwise mixtures of strains with and without TFP where cells without TFP separate from cells with TFP. While TFP slow swarm expansion, we show in vitro that TFP help alter collective motion to avoid toxic compounds such as the antibiotic carbenicillin. Thus, TFP physically affect P. aeruginosa swarming by actively promoting cell-cell association and directional collective motion within motile groups to aid their survival. PMID:25468980

  8. A type IV translocated Legionella cysteine phytase counteracts intracellular growth restriction by phytate.

    PubMed

    Weber, Stephen; Stirnimann, Christian U; Wieser, Mara; Frey, Daniel; Meier, Roger; Engelhardt, Sabrina; Li, Xiaodan; Capitani, Guido; Kammerer, Richard A; Hilbi, Hubert

    2014-12-01

    The causative agent of Legionnaires' pneumonia, Legionella pneumophila, colonizes diverse environmental niches, including biofilms, plant material, and protozoa. In these habitats, myo-inositol hexakisphosphate (phytate) is prevalent and used as a phosphate storage compound or as a siderophore. L. pneumophila replicates in protozoa and mammalian phagocytes within a unique "Legionella-containing vacuole." The bacteria govern host cell interactions through the Icm/Dot type IV secretion system (T4SS) and ∼300 different "effector" proteins. Here we characterize a hitherto unrecognized Icm/Dot substrate, LppA, as a phytate phosphatase (phytase). Phytase activity of recombinant LppA required catalytically essential cysteine (Cys(231)) and arginine (Arg(237)) residues. The structure of LppA at 1.4 Å resolution revealed a mainly α-helical globular protein stabilized by four antiparallel β-sheets that binds two phosphate moieties. The phosphates localize to a P-loop active site characteristic of dual specificity phosphatases or to a non-catalytic site, respectively. Phytate reversibly abolished growth of L. pneumophila in broth, and growth inhibition was relieved by overproduction of LppA or by metal ion titration. L. pneumophila lacking lppA replicated less efficiently in phytate-loaded Acanthamoeba castellanii or Dictyostelium discoideum, and the intracellular growth defect was complemented by the phytase gene. These findings identify the chelator phytate as an intracellular bacteriostatic component of cell-autonomous host immunity and reveal a T4SS-translocated L. pneumophila phytase that counteracts intracellular bacterial growth restriction by phytate. Thus, bacterial phytases might represent therapeutic targets to combat intracellular pathogens. PMID:25339170

  9. The Coxiella burnetii Cryptic Plasmid Is Enriched in Genes Encoding Type IV Secretion System Substrates▿ †

    PubMed Central

    Voth, Daniel E.; Beare, Paul A.; Howe, Dale; Sharma, Uma M.; Samoilis, Georgios; Cockrell, Diane C.; Omsland, Anders; Heinzen, Robert A.

    2011-01-01

    The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a phagolysosome-like parasitophorous vacuole (PV), in which it replicates. The organism encodes a Dot/Icm type IV secretion system (T4SS) predicted to deliver to the host cytosol effector proteins that mediate PV formation and other cellular events. All C. burnetii isolates carry a large, autonomously replicating plasmid or have chromosomally integrated plasmid-like sequences (IPS), suggesting that plasmid and IPS genes are critical for infection. Bioinformatic analyses revealed two candidate Dot/Icm substrates with eukaryotic-like motifs uniquely encoded by the QpH1 plasmid from the Nine Mile reference isolate. CpeC, containing an F-box domain, and CpeD, possessing kinesin-related and coiled-coil regions, were secreted by the closely related Legionella pneumophila Dot/Icm T4SS. An additional QpH1-specific gene, cpeE, situated in a predicted operon with cpeD, also encoded a secreted effector. Further screening revealed that three hypothetical proteins (CpeA, CpeB, and CpeF) encoded by all C. burnetii plasmids and IPS are Dot/Icm substrates. By use of new genetic tools, secretion of plasmid effectors by C. burnetii during host cell infection was confirmed using β-lactamase and adenylate cyclase translocation assays, and a C-terminal secretion signal was identified. When ectopically expressed in HeLa cells, plasmid effectors trafficked to different subcellular sites, including autophagosomes (CpeB), ubiquitin-rich compartments (CpeC), and the endoplasmic reticulum (CpeD). Collectively, these results suggest that C. burnetii plasmid-encoded T4SS substrates play important roles in subversion of host cell functions, providing a plausible explanation for the absolute maintenance of plasmid genes by this pathogen. PMID:21216993

  10. Type IV pili interactions promote intercellular association and moderate swarming of Pseudomonas aeruginosa

    PubMed Central

    Anyan, Morgen E.; Amiri, Aboutaleb; Harvey, Cameron W.; Tierra, Giordano; Morales-Soto, Nydia; Driscoll, Callan M.; Alber, Mark S.; Shrout, Joshua D.

    2014-01-01

    Pseudomonas aeruginosa is a ubiquitous bacterium that survives in many environments, including as an acute and chronic pathogen in humans. Substantial evidence shows that P. aeruginosa behavior is affected by its motility, and appendages known as flagella and type IV pili (TFP) are known to confer such motility. The role these appendages play when not facilitating motility or attachment, however, is unclear. Here we discern a passive intercellular role of TFP during flagellar-mediated swarming of P. aeruginosa that does not require TFP extension or retraction. We studied swarming at the cellular level using a combination of laboratory experiments and computational simulations to explain the resultant patterns of cells imaged from in vitro swarms. Namely, we used a computational model to simulate swarming and to probe for individual cell behavior that cannot currently be otherwise measured. Our simulations showed that TFP of swarming P. aeruginosa should be distributed all over the cell and that TFP−TFP interactions between cells should be a dominant mechanism that promotes cell−cell interaction, limits lone cell movement, and slows swarm expansion. This predicted physical mechanism involving TFP was confirmed in vitro using pairwise mixtures of strains with and without TFP where cells without TFP separate from cells with TFP. While TFP slow swarm expansion, we show in vitro that TFP help alter collective motion to avoid toxic compounds such as the antibiotic carbenicillin. Thus, TFP physically affect P. aeruginosa swarming by actively promoting cell−cell association and directional collective motion within motile groups to aid their survival. PMID:25468980

  11. A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate

    PubMed Central

    Weber, Stephen; Stirnimann, Christian U.; Wieser, Mara; Frey, Daniel; Meier, Roger; Engelhardt, Sabrina; Li, Xiaodan; Capitani, Guido; Kammerer, Richard A.; Hilbi, Hubert

    2014-01-01

    The causative agent of Legionnaires' pneumonia, Legionella pneumophila, colonizes diverse environmental niches, including biofilms, plant material, and protozoa. In these habitats, myo-inositol hexakisphosphate (phytate) is prevalent and used as a phosphate storage compound or as a siderophore. L. pneumophila replicates in protozoa and mammalian phagocytes within a unique “Legionella-containing vacuole.” The bacteria govern host cell interactions through the Icm/Dot type IV secretion system (T4SS) and ∼300 different “effector” proteins. Here we characterize a hitherto unrecognized Icm/Dot substrate, LppA, as a phytate phosphatase (phytase). Phytase activity of recombinant LppA required catalytically essential cysteine (Cys231) and arginine (Arg237) residues. The structure of LppA at 1.4 Å resolution revealed a mainly α-helical globular protein stabilized by four antiparallel β-sheets that binds two phosphate moieties. The phosphates localize to a P-loop active site characteristic of dual specificity phosphatases or to a non-catalytic site, respectively. Phytate reversibly abolished growth of L. pneumophila in broth, and growth inhibition was relieved by overproduction of LppA or by metal ion titration. L. pneumophila lacking lppA replicated less efficiently in phytate-loaded Acanthamoeba castellanii or Dictyostelium discoideum, and the intracellular growth defect was complemented by the phytase gene. These findings identify the chelator phytate as an intracellular bacteriostatic component of cell-autonomous host immunity and reveal a T4SS-translocated L. pneumophila phytase that counteracts intracellular bacterial growth restriction by phytate. Thus, bacterial phytases might represent therapeutic targets to combat intracellular pathogens. PMID:25339170

  12. Campylobacter fetus Subspecies Contain Conserved Type IV Secretion Systems on Multiple Genomic Islands and Plasmids

    PubMed Central

    van der Graaf–van Bloois, Linda; Miller, William G.; Yee, Emma; Gorkiewicz, Gregor; Forbes, Ken J.; Zomer, Aldert L.; Wagenaar, Jaap A.; Duim, Birgitta

    2016-01-01

    The features contributing to differences in pathogenicity of the Campylobacter fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode a type IV secretion system (T4SS) and fic domain (filamentation induced by cyclic AMP) proteins, which may disrupt host cell processes. In the genomes of 27 C. fetus strains, three phylogenetically-different T4SS-encoding regions (T4SSs) were identified: one was located in both the chromosome and in extra-chromosomal plasmids; one was located exclusively in the chromosome; and one exclusively in extra-chromosomal plasmids. We observed that C. fetus strains can contain multiple T4SSs and that homologous T4SSs can be present both in chromosomal genomic islands (GI) and on plasmids in the C. fetus strains. The GIs of the chromosomally located T4SS differed mainly by the presence of fic genes, insertion sequence elements and phage-related or hypothetical proteins. Comparative analysis showed that T4SS sequences, inserted in the same locations, were conserved in the studied C. fetus genomes. Using phylogenetic analysis of the T4SSs, it was shown that C. fetus may have acquired the T4SS regions from other Campylobacter species by horizontal gene transfer. The identified T4SSs and fic genes were found in Cff and Cfv strains, although the presence of T4SSs and fic genes were significantly associated with Cfv strains. The T4SSs and fic genes could not be associated with S-layer serotypes or geographical origin of the strains. PMID:27049518

  13. Functional analysis of an unusual type IV pilus in the Gram‐positive Streptococcus sanguinis

    PubMed Central

    Gurung, Ishwori; Spielman, Ingrid; Davies, Mark R.; Lala, Rajan; Gaustad, Peter; Biais, Nicolas

    2015-01-01

    Summary Type IV pili (Tfp), which have been studied extensively in a few Gram‐negative species, are the paradigm of a group of widespread and functionally versatile nano‐machines. Here, we performed the most detailed molecular characterisation of Tfp in a Gram‐positive bacterium. We demonstrate that the naturally competent S treptococcus sanguinis produces retractable Tfp, which like their Gram‐negative counterparts can generate hundreds of piconewton of tensile force and promote intense surface‐associated motility. Tfp power ‘train‐like’ directional motion parallel to the long axis of chains of cells, leading to spreading zones around bacteria grown on plates. However, S . sanguinis  Tfp are not involved in DNA uptake, which is mediated by a related but distinct nano‐machine, and are unusual because they are composed of two pilins in comparable amounts, rather than one as normally seen. Whole genome sequencing identified a locus encoding all the genes involved in Tfp biology in S . sanguinis. A systematic mutational analysis revealed that Tfp biogenesis in S . sanguinis relies on a more basic machinery (only 10 components) than in Gram‐negative species and that a small subset of four proteins dispensable for pilus biogenesis are essential for motility. Intriguingly, one of the piliated mutants that does not exhibit spreading retains microscopic motility but moves sideways, which suggests that the corresponding protein controls motion directionality. Besides establishing S . sanguinis as a useful new model for studying Tfp biology, these findings have important implications for our understanding of these widespread filamentous nano‐machines. PMID:26435398

  14. Functional analysis of an unusual type IV pilus in the Gram-positive Streptococcus sanguinis.

    PubMed

    Gurung, Ishwori; Spielman, Ingrid; Davies, Mark R; Lala, Rajan; Gaustad, Peter; Biais, Nicolas; Pelicic, Vladimir

    2016-01-01

    Type IV pili (Tfp), which have been studied extensively in a few Gram-negative species, are the paradigm of a group of widespread and functionally versatile nano-machines. Here, we performed the most detailed molecular characterisation of Tfp in a Gram-positive bacterium. We demonstrate that the naturally competent Streptococcus sanguinis produces retractable Tfp, which like their Gram-negative counterparts can generate hundreds of piconewton of tensile force and promote intense surface-associated motility. Tfp power 'train-like' directional motion parallel to the long axis of chains of cells, leading to spreading zones around bacteria grown on plates. However, S. sanguinis Tfp are not involved in DNA uptake, which is mediated by a related but distinct nano-machine, and are unusual because they are composed of two pilins in comparable amounts, rather than one as normally seen. Whole genome sequencing identified a locus encoding all the genes involved in Tfp biology in S. sanguinis. A systematic mutational analysis revealed that Tfp biogenesis in S. sanguinis relies on a more basic machinery (only 10 components) than in Gram-negative species and that a small subset of four proteins dispensable for pilus biogenesis are essential for motility. Intriguingly, one of the piliated mutants that does not exhibit spreading retains microscopic motility but moves sideways, which suggests that the corresponding protein controls motion directionality. Besides establishing S. sanguinis as a useful new model for studying Tfp biology, these findings have important implications for our understanding of these widespread filamentous nano-machines. PMID:26435398

  15. The Rickettsia type IV secretion system: unrealized complexity mired by gene family expansion.

    PubMed

    Gillespie, Joseph J; Phan, Isabelle Q H; Driscoll, Timothy P; Guillotte, Mark L; Lehman, Stephanie S; Rennoll-Bankert, Kristen E; Subramanian, Sandhya; Beier-Sexton, Magda; Myler, Peter J; Rahman, M Sayeedur; Azad, Abdu F

    2016-08-01

    Many prokaryotes utilize type IV secretion systems (T4SSs) to translocate substrates (e.g. nucleoprotein, DNA, protein) across the cell envelope, and/or to elaborate surface structures (i.e. pili or adhesins). Among eight distinct T4SS classes, P-T4SSs are typified by the Agrobacterium tumefaciens vir T4SS, which is comprised of 12 scaffold components (VirB1-VirB11, VirD4). While most P-T4SSs include all 12 Vir proteins, some differ from the vir archetype by either containing additional scaffold components not analogous to Vir proteins or lacking one or more of the Vir proteins. In a special case, the Rickettsiales vir homolog (rvh) P-T4SS comprises unprecedented gene family expansion. rvh contains three families of gene duplications (rvhB9, rvhB8, rvhB4): RvhB9,8,4-I are conserved relative to equivalents in other P-T4SSs, while RvhB9,8,4-II have evolved atypical features that deviate substantially from other homologs. Furthermore, rvh contains five VirB6-like genes (rvhB6a-e), which are tandemly arrayed and contain large N- and C-terminal extensions. Our work herein focuses on the complexity underpinned by rvh gene family expansion. Furthermore, we describe an RvhB10 insertion, which occurs in a region that forms the T4SS pore. The significance of these curious properties to rvh structure and function is evaluated, shedding light on a highly complex T4SS. PMID:27307105

  16. Prediction of bacterial type IV secreted effectors by C-terminal features

    PubMed Central

    2014-01-01

    Background Many bacteria can deliver pathogenic proteins (effectors) through type IV secretion systems (T4SSs) to eukaryotic cytoplasm, causing host diseases. The inherent property, such as sequence diversity and global scattering throughout the whole genome, makes it a big challenge to effectively identify the full set of T4SS effectors. Therefore, an effective inter-species T4SS effector prediction tool is urgently needed to help discover new effectors in a variety of bacterial species, especially those with few known effectors, e.g., Helicobacter pylori. Results In this research, we first manually annotated a full list of validated T4SS effectors from different bacteria and then carefully compared their C-terminal sequential and position-specific amino acid compositions, possible motifs and structural features. Based on the observed features, we set up several models to automatically recognize T4SS effectors. Three of the models performed strikingly better than the others and T4SEpre_Joint had the best performance, which could distinguish the T4SS effectors from non-effectors with a 5-fold cross-validation sensitivity of 89% at a specificity of 97%, based on the training datasets. An inter-species cross prediction showed that T4SEpre_Joint could recall most known effectors from a variety of species. The inter-species prediction tool package, T4SEpre, was further used to predict new T4SS effectors from H. pylori, an important human pathogen associated with gastritis, ulcer and cancer. In total, 24 new highly possible H. pylori T4S effector genes were computationally identified. Conclusions We conclude that T4SEpre, as an effective inter-species T4SS effector prediction software package, will help find new pathogenic T4SS effectors efficiently in a variety of pathogenic bacteria. PMID:24447430

  17. Phylogenomics Reveals a Diverse Rickettsiales Type IV Secretion System▿ † ‡

    PubMed Central

    Gillespie, Joseph J.; Brayton, Kelly A.; Williams, Kelly P.; Quevedo Diaz, Marco A.; Brown, Wendy C.; Azad, Abdu F.; Sobral, Bruno W.

    2010-01-01

    With an obligate intracellular lifestyle, Alphaproteobacteria of the order Rickettsiales have inextricably coevolved with their various eukaryotic hosts, resulting in small, reductive genomes and strict dependency on host resources. Unsurprisingly, large portions of Rickettsiales genomes encode proteins involved in transport and secretion. One particular transporter that has garnered recent attention from researchers is the type IV secretion system (T4SS). Homologous to the well-studied archetypal vir T4SS of Agrobacterium tumefaciens, the Rickettsiales vir homolog (rvh) T4SS is characterized primarily by duplication of several of its genes and scattered genomic distribution of all components in several conserved islets. Phylogeny estimation suggests a single event of ancestral acquirement of the rvh T4SS, likely from a nonalphaproteobacterial origin. Bioinformatics analysis of over 30 Rickettsiales genome sequences illustrates a conserved core rvh scaffold (lacking only a virB5 homolog), with lineage-specific diversification of several components (rvhB1, rvhB2, and rvhB9b), likely a result of modifications to cell envelope structure. This coevolution of the rvh T4SS and cell envelope morphology is probably driven by adaptations to various host cells, identifying the transporter as an important target for vaccine development. Despite the genetic intractability of Rickettsiales, recent advancements have been made in the characterization of several components of the rvh T4SS, as well as its putative regulators and substrates. While current data favor a role in effector translocation, functions in DNA uptake and release and/or conjugation cannot at present be ruled out, especially considering that a mechanism for plasmid transfer in Rickettsia spp. has yet to be proposed. PMID:20176788

  18. An Agrobacterium VirB10 Mutation Conferring a Type IV Secretion System Gating Defect▿

    PubMed Central

    Banta, Lois M.; Kerr, Jennifer E.; Cascales, Eric; Giuliano, Meghan E.; Bailey, Megan E.; McKay, Cedar; Chandran, Vidya; Waksman, Gabriel; Christie, Peter J.

    2011-01-01

    Agrobacterium VirB7, VirB9, and VirB10 form a “core complex” during biogenesis of the VirB/VirD4 type IV secretion system (T4SS). VirB10 spans the cell envelope and, in response to sensing of ATP energy consumption by the VirB/D4 ATPases, undergoes a conformational change required for DNA transfer across the outer membrane (OM). Here, we tested a model in which VirB10 regulates substrate passage by screening for mutations that allow for unregulated release of the VirE2 secretion substrate to the cell surface independently of target cell contact. One mutation, G272R, conferred VirE2 release and also rendered VirB10 conformationally insensitive to cellular ATP depletion. Strikingly, G272R did not affect substrate transfer to target cells (Tra+) but did block pilus production (Pil−). The G272R mutant strain displayed enhanced sensitivity to vancomycin and SDS but did not nonspecifically release periplasmic proteins or VirE2 truncated of its secretion signal. G272 is highly conserved among VirB10 homologs, including pKM101 TraF, and in the TraF X-ray structure the corresponding Gly residue is positioned near an α-helical domain termed the antenna projection (AP), which is implicated in formation of the OM pore. A partial AP deletion mutation (ΔAP) also confers a Tra+ Pil− phenotype; however, this mutation did not allow VirE2 surface exposure but instead allowed the release of pilin monomers or short oligomers to the milieu. We propose that (i) G272R disrupts a gating mechanism in the core chamber that regulates substrate passage across the OM and (ii) the G272R and ΔAP mutations block pilus production at distinct steps of the pilus biogenesis pathway. PMID:21421757

  19. Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex

    PubMed Central

    Frick-Cheng, Arwen E.; Pyburn, Tasia M.; Voss, Bradley J.; McDonald, W. Hayes

    2016-01-01

    ABSTRACT Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori. Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δcag3 or ΔcagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. PMID:26758182

  20. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

    PubMed Central

    Shaffer, Carrie L.; Good, James A. D.; Kumar, Santosh; Krishnan, K. Syam; Gaddy, Jennifer A.; Loh, John T.; Chappell, Joseph; Almqvist, Fredrik

    2016-01-01

    ABSTRACT Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs. PMID:27118587

  1. EFFICACY OF PULSED DYE LASER IN COSMETICALLY DISTRESSING FACIAL DERMATOSES IN SKIN TYPES IV AND V

    PubMed Central

    Khandpur, Sujay; Sharma, Vinod K

    2008-01-01

    Background: Pulsed dye laser (PDL) has revolutionized treatment of vascular dermatoses. It has been successfully employed to treat several non-vascular conditions in fair skinned individuals without producing significant pigmentary and textural complications. Aim: A preliminary study was undertaken to assess its efficacy in cosmetically distressing facial, vascular and non-vascular dermatoses in Indian patients with skin types IV and V. Materials and Methods: Nine patients of ages 7 to 55 years, with facial verruca plana (VP- 4 cases), angiofibromas (AF- 4 cases) and multiple pyogenic granulomas (PG- one case) were recruited. They had no systemic complaints. Laser parameters used were (spot size/fluence/wavelength/pulse duration):VP- 5mm/5.5-7.5J/585nm/0.45ms; AF-5mm/6-8.5J/585nm/0.45ms;PG- 5mm/7J/585 and 595nm alternately/1.5ms. Response was assessed clinically and photographically. Results and Conclusions: All VP lesions completely resolved after 2-4 sessions (mean 3.25 sessions), AF showed 50% regression in all cases after 2-3 sessions (mean 2.5 sessions) and ≥75% subsidence after 3-7 sessions (mean 5.5 sessions) and in PG, after 3 sessions, there was complete subsidence of small satellite lesions with moderate shrinkage of larger papules and complete resolution after 5 sessions. Complications included transient hyperpigmentation/hypopigmentation only. There was no recurrence during next 6 months. PDL offers significant cosmetic improvement in facial dermatoses in Indian patients. PMID:19882031

  2. Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism

    PubMed Central

    Sticchi, Elena; Magi, Alberto; Kamstrup, Pia R.; Marcucci, Rossella; Prisco, Domenico; Martinelli, Ida; Mannucci, Pier Mannuccio; Abbate, Rosanna; Giusti, Betti

    2016-01-01

    In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6–17) vs 15(9–25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. PMID:26900838

  3. Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

    PubMed

    Sticchi, Elena; Magi, Alberto; Kamstrup, Pia R; Marcucci, Rossella; Prisco, Domenico; Martinelli, Ida; Mannucci, Pier Mannuccio; Abbate, Rosanna; Giusti, Betti

    2016-01-01

    In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. PMID:26900838

  4. The initial stage of development of type IV radio bursts and the relation to expanding magnetic bottles

    NASA Technical Reports Server (NTRS)

    Sakurai, K.

    1973-01-01

    Using the observed data for wideband type IV solar radio bursts, the onset time differences between the microwave and metric frequencies and the peak flux intensities of the metric component are analyzed as a function of the longitudinal position of the associated flares on the solar disk. It is shown that this time difference is dependent on the position of the associated flare and that the peak flux intensity reaches maximum when a flare occurs in the region from 10 to 40 deg west of the central meridian of the solar disk. These results are explained by taking into account the eastward expansion of magnetic bottles which trap mildly relativistic electrons responsible for type IV bursts. The relation between these magnetic bottles and shock waves which excite type II radio bursts is discussed.

  5. The Optical Gravitational Lensing Experiment. The OGLE-III Catalog of Variable Stars. II.Type II Cepheids and Anomalous Cepheids in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Soszyński, I.; Udalski, A.; Szymański, M. K.; Kubiak, M.; Pietrzyński, G.; Wyrzykowski, Ł.; Szewczyk, O.; Ulaczyk, K.; Poleski, R.

    2008-12-01

    In the second part of the OGLE-III Catalog of Variable Stars (OIII-CVS) we present 197 type II Cepheids and 83 anomalous Cepheids in the Large Magellanic Cloud (LMC). The sample of type II Cepheids consists of 64 BL Her stars, 96 W Vir stars and 37 RV Tau stars. Anomalous Cepheids are divided into 62 fundamental-mode and 21 first-overtone pulsators. These are the largest samples of such types of variable stars detected anywhere outside the Galaxy. We present the period-luminosity and color-magnitude diagrams of stars in the sample. If the boundary period between BL Her and W Vir stars is adopted at 4 days, both groups differ significantly in (V-I) colors. We identify a group of 16 peculiar W Vir stars with different appearance of the light curves, brighter and bluer than ordinary stars of that type. Four of these peculiar W Vir stars show additional eclipsing modulation superimposed on the pulsation light curves. Four other stars of that type show long-period secondary variations which may be ellipsoidal modulations. It suggests that peculiar W Vir subgroup may be related to binarity. In total, we identified seven type II Cepheids simultaneously exhibiting eclipsing variations which is a very large fraction compared to classical Cepheids in the LMC. We discuss diagrams showing Fourier parameters of the light curve decomposition against periods. Three sharp features interpreted as an effect of resonances between radial modes are detectable in these diagrams for type II Cepheids.

  6. Enterococcus faecalis adhesin, ace, mediates attachment to extracellular matrix proteins collagen type IV and laminin as well as collagen type I.

    PubMed

    Nallapareddy, S R; Qin, X; Weinstock, G M; Höök, M; Murray, B E

    2000-09-01

    Adhesin-mediated binding to extracellular matrix (ECM) proteins is thought to be a crucial step in the pathogenic process of many bacterial infections. We have previously reported conditional adherence of most Enterococcus faecalis isolates, after growth at 46 degrees C, to ECM proteins collagen types I and IV and laminin; identified an E. faecalis-specific gene, ace, whose encoded protein has characteristics of a bacterial adhesin; and implicated Ace in binding to collagen type I. In this study, we constructed an ace disruption mutant from E. faecalis strain OG1RF that showed marked reduction in adherence to collagen types I and IV and laminin when compared to the parental OG1RF strain after growth at 46 degrees C. Polyclonal immune serum raised against the OG1RF-derived recombinant Ace A domain reacted with a single approximately 105-kDa band of mutanolysin extracts from OG1RF grown at 46 degrees C, while no band was detected in extracts from OG1RF grown at 37 degrees C, nor from the OG1RF ace mutant grown at 37 or 46 degrees C. IgGs purified from the anti-Ace A immune serum inhibited adherence of 46 degrees C-grown E. faecalis OG1RF to immobilized collagen type IV and laminin as well as collagen type I, at a concentration as low as 1 microg/ml, and also inhibited the 46 degrees C-evoked adherence of two clinical isolates tested. We also showed in vitro interaction of collagen type IV with Ace from OG1RF mutanolysin extracts on a far-Western blot. Binding of recombinant Ace A to immobilized collagen types I and IV and laminin was demonstrated in an enzyme-linked immunosorbent assay and was shown to be concentration dependent. These results indicate that Ace A mediates the conditional binding of E. faecalis OG1RF to collagen type IV and laminin in addition to collagen type I. PMID:10948147

  7. Undiagnosed Borrmann type IV gastric cancer despite repeated endoscopic biopsies and PET-CT examination: A case report

    PubMed Central

    Zhu, Fang-Qing; Chu, Hong-Jin; Gong, Zhao-Hua; Du, Feng-Cai; Chen, Jian; Jiang, Li-Xin

    2016-01-01

    Borrmann type IV gastric cancer is a particular histological type of carcinoma, which has the characteristic of diffused infiltration that invades the entire stomach, resulting in the thickening and stiffness of the stomach wall. Borrmann type IV gastric cancer is known for the difficulty of detecting tumor cells in endoscopic biopsy specimens. This is crucial in obtaining the pathological results to make a therapeutic decision. The case reported in the present study was highly suspected to be Borrmann type IV gastric cancer according to the clinical manifestations and gastrointestinal barium meal examinations, but demonstrated negative results in multiple endoscopic biopsies and positron emission tomography-computed tomography (PET-CT) examination. The patient was discharged as no affirmative diagnosis was specified. Two weeks after discharge, the patient was administered to another hospital under emergency treatment due to frequent urination. Cystoscopy examination revealed marked thickening of the right bladder wall over a large area. Biopsy specimens were sampled. Pathological consultation suggested a gastrointestinal original of the lesion, which was most likely poorly differentiated gastric adenocarcinoma with neuroendocrine metastasis to the bladder. PMID:27446457

  8. The determination of PCBs in Rocky Flats Type IV waste sludge by gas chromatography/electron capture detection. Part 2

    SciTech Connect

    Parish, K.J.; Applegate, D.V.; Postlethwait, P.D.; Boparai, A.S.; Reedy, G.T.

    1994-12-01

    Before disposal, radioactive sludge (Type IV) from Rocky Flats Plant (RFP) must be evaluated for polychlorinated biphenyl (PCB) content. The Type IV sludge consists of organic solvents, degreasers, cutting oils, and transuranic (TRU) waste mixed with calcium silicate (MicroCel E{reg_sign} and Oil Dri{reg_sign} to form a grease or paste-like material. For laboratory testing, a nonradioactive simulated Type 17V RFP sludge was prepared at Argonne National Laboratory-East (ANL-E). This sludge has a composition similar to that expected from field samples. In an earlier effort, a simplified method was developed for extraction, cleanup of extract, and determination of PCBs in samples of simulated sludge spiked with Aroclors 1254 and 1260. The simplified method has now been used to determine the presence and quantities of other Aroclors in the simulated sludge, namely, Aroclors 10 1 6, 1221, 1232, 1242, and 1248. The accuracy and precision of the data for these Aroclors were found to be similar to the data for sludges spiked with Aroclors 1254 and 1260. Since actual sludges may vary in composition, the method was also verified by analyzing another source of Type IV simulated sludge, prepared by Argonne National Laboratory-West (ANL-W).

  9. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report

    PubMed Central

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-01-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  10. Placement of ¹²⁵I seed strands and stents for a type IV Klatskin tumor.

    PubMed

    Zhang, Wen; Yang, Zheng-Qiang; Shi, Hai-Bin; Liu, Shen; Zhou, Wei-Zhong; Zhao, Lin-Bo

    2015-01-01

    Herein, we report a new technique that consists of placing two (125)I seed strands and two stents in the right and left intrahepatic bile ducts for the treatment of hilar cholangiocarcinoma. A 75-year-old man presented with jaundice and was diagnosed with Bismuth type IV Klatskin tumor. Abdominal computed tomography (CT) showed intrahepatic and extrahepatic bile duct dilatation and a soft tissue mass in the hepatic hilum. Because curative surgical resection was not possible, we placed (125)I seed strands and stents in the right and left intrahepatic bile ducts. Three months later, abdominal CT showed less intrahepatic and extrahepatic bile duct dilatation than before the procedure. This technique was feasible and could be considered for the treatment of patients with Bismuth type IV tumors. PMID:25574114

  11. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report.

    PubMed

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-05-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  12. A Comparative Structure/Function Analysis of Two Type IV Pilin DNA Receptors Defines a Novel Mode of DNA Binding.

    PubMed

    Berry, Jamie-Lee; Xu, Yingqi; Ward, Philip N; Lea, Susan M; Matthews, Stephen J; Pelicic, Vladimir

    2016-06-01

    DNA transformation is a widespread process allowing bacteria to capture free DNA by using filamentous nano-machines composed of type IV pilins. These proteins can act as DNA receptors as demonstrated by the finding that Neisseria meningitidis ComP minor pilin has intrinsic DNA-binding ability. ComP binds DNA better when it contains the DNA-uptake sequence (DUS) motif abundant in this species genome, playing a role in its trademark ability to selectively take up its own DNA. Here, we report high-resolution structures for meningococcal ComP and Neisseria subflava ComPsub, which recognize different DUS motifs. We show that they are structurally identical type IV pilins that pack readily into filament models and display a unique DD region delimited by two disulfide bonds. Functional analysis of ComPsub defines a new mode of DNA binding involving the DD region, adapted for exported DNA receptors. PMID:27161979

  13. New type of blue ternary complex of arsenazo I with plutonium (IV) in the presence of hydrogen peroxide: preliminary investigations.

    PubMed

    Pérez-Bustamante, J A

    1974-12-01

    The preparation and spectrophotometric properties of a new type of complex compound of arsenazo I with Pu(IV) in the presence of H(2)O(2) are described. The new compound has a blue colour, derived from a wide absorption band with a maximum at 610 nm. and a corresponding molar absorptivity of 4 x 10(4) l. mole(-1).cm(-1). From 2 hr after its preparation this curious new compound undergoes for several days a steady decomposition accompanied by decolorization. The formation of similar peroxy Pu(IV) complexes has not so far been shown to take place with arsenazo III or with any other "arsenazo-type" reagent. PMID:18961599

  14. Cyclic Di-GMP Regulates Type IV Pilus-Dependent Motility in Myxococcus xanthus

    PubMed Central

    Skotnicka, Dorota; Petters, Tobias; Heering, Jan; Hoppert, Michael; Kaever, Volkhard

    2015-01-01

    ABSTRACT The nucleotide-based second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. Myxococcus xanthus undergoes major lifestyle changes in response to nutrient availability, with the formation of spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. Here, we investigated the function of c-di-GMP in M. xanthus and show that this bacterium synthesizes c-di-GMP during growth. Manipulation of the c-di-GMP level by expression of either an active, heterologous diguanylate cyclase or an active, heterologous phosphodiesterase correlated with defects in type IV pilus (T4P)-dependent motility, whereas gliding motility was unaffected. An increased level of c-di-GMP correlated with reduced transcription of the pilA gene (which encodes the major pilin of T4P), reduced the assembly of T4P, and altered cell agglutination, whereas a decreased c-di-GMP level correlated with altered cell agglutination. The systematic inactivation of the 24 genes in M. xanthus encoding proteins containing GGDEF, EAL, or HD-GYP domains, which are associated with c-di-GMP synthesis, degradation, or binding, identified three genes encoding proteins important for T4P-dependent motility, whereas all mutants had normal gliding motility. Purified DmxA had diguanylate cyclase activity, whereas the hybrid histidine protein kinases TmoK and SgmT, each of which contains a GGDEF domain, did not have diguanylate cyclase activity. These results demonstrate that c-di-GMP is important for T4P-dependent motility in M. xanthus. IMPORTANCE We provide the first direct evidence that M. xanthus synthesizes c-di-GMP and demonstrate that c-di-GMP is important for T4P-dependent motility, whereas we did not obtain evidence that c-di-GMP regulates gliding motility. The data presented uncovered a novel mechanism for regulation of T4P

  15. Truncation of type IV pilin induces mucoidy in Pseudomonas aeruginosa strain PAO579

    PubMed Central

    Ryan Withers, T; Heath Damron, F; Yin, Yeshi; Yu, Hongwei D

    2013-01-01

    Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP causing the conversion to mucoidy. Pseudomonas aeruginosa strain PAO579, a derivative of the nonmucoid strain PAO1, is mucoid due to an unidentified mutation (muc-23). Using whole genome sequencing, we identified 16 nonsynonymous and 15 synonymous single nucleotide polymorphisms (SNP). We then identified three tandem single point mutations in the pilA gene (PA4525), as the cause of mucoidy in PAO579. These tandem mutations generate a premature stop codon resulting in a truncated version of PilA (PilA108), with a C-terminal motif of phenylalanine-threonine-phenylalanine (FTF). Inactivation of pilA108 confirmed it was required for mucoidy. Additionally, algW and algU were also required for mucoidy of PAO579. Western blot analysis indicated that MucA was less stable in PAO579 than nonmucoid PAO1 or PAO381. The mucoid phenotype and high PalgU and PalgD promoter activities of PAO579 require pilA108, algW, algU, and rpoN encoding the alternative sigma factor σ54. We also observed that RpoN regulates expression of algW and pilA in PAO579. Together, these results suggest that truncation in type IV pilin in P. aeruginosa strain PAO579 can induce mucoidy through an AlgW/AlgU-dependent pathway. PMID:23533140

  16. Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems

    PubMed Central

    Phan, Isabelle Q. H.; Scheib, Holger; Subramanian, Sandhya; Edwards, Thomas E.; Lehman, Stephanie S.; Piitulainen, Hanna; Sayeedur Rahman, M.; Rennoll-Bankert, Kristen E.; Staker, Bart L.; Taira, Suvi; Stacy, Robin; Myler, Peter J.; Azad, Abdu F.

    2015-01-01

    ABSTRACT Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species (vir, vbh, and trw). In a unique case, most rickettsial species encode a T4SS (rvh) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably, while RvhB8-I dimerizes and is structurally similar to other VirB8 proteins, the RvhB8-II dimer interface deviates substantially from other VirB8 structures, potentially preventing RvhB8-I/RvhB8-II heterodimerization. For the rvh T4SS, the evolution of divergent VirB8 paralogs implies a functional diversification that is unknown in other T4SSs. Collectively, our data identify two different constraints (spatiotemporal for Bartonella trw and vir T4SSs and structural for rvh T4SSs) that mediate the functionality of multiple divergent T4SSs within a single bacterium. PMID:26646013

  17. Structure of the type IV secretion system in different strains of Anaplasma phagocytophilum

    PubMed Central

    2012-01-01

    Background Anaplasma phagocytophilum is an intracellular organism in the Order Rickettsiales that infects diverse animal species and is causing an emerging disease in humans, dogs and horses. Different strains have very different cell tropisms and virulence. For example, in the U.S., strains have been described that infect ruminants but not dogs or rodents. An intriguing question is how the strains of A. phagocytophilum differ and what different genome loci are involved in cell tropisms and/or virulence. Type IV secretion systems (T4SS) are responsible for translocation of substrates across the cell membrane by mechanisms that require contact with the recipient cell. They are especially important in organisms such as the Rickettsiales which require T4SS to aid colonization and survival within both mammalian and tick vector cells. We determined the structure of the T4SS in 7 strains from the U.S. and Europe and revised the sequence of the repetitive virB6 locus of the human HZ strain. Results Although in all strains the T4SS conforms to the previously described split loci for vir genes, there is great diversity within these loci among strains. This is particularly evident in the virB2 and virB6 which are postulated to encode the secretion channel and proteins exposed on the bacterial surface. VirB6-4 has an unusual highly repetitive structure and can have a molecular weight greater than 500,000. For many of the virs, phylogenetic trees position A. phagocytophilum strains infecting ruminants in the U.S. and Europe distant from strains infecting humans and dogs in the U.S. Conclusions Our study reveals evidence of gene duplication and considerable diversity of T4SS components in strains infecting different animals. The diversity in virB2 is in both the total number of copies, which varied from 8 to 15 in the herein characterized strains, and in the sequence of each copy. The diversity in virB6 is in the sequence of each of the 4 copies in the single locus and the

  18. Anomalous resistivity effect on multiple ion beam emission and hard x-ray generation in a Mather type plasma focus device

    SciTech Connect

    Behbahani, R. A.; Aghamir, F. M.

    2011-10-15

    Multi ion beam and hard x-ray emissions were detected in a high inductance (more than 100 nH) Mather type plasma focus (PF) device at different filling gas pressures and charging voltages. The signal analysis was performed through the current trace, as it is the fundamental signal from which all of the phenomena in a PF device can be extracted. Two different fitting processes were carried out according to Lee's computational (snow-plow) model. In the first process, only plasma dynamics and classical (Spitzer) resistances were considered as energy consumer parameters for plasma. This led to an unsuccessful fitting and did not answer the energy transfer mechanism into plasma. A second fitting process was considered through the addition of anomalous resistance, which provided the best fit. Anomalous resistance was the source of long decrease in current trace, and multi dips and multi peaks of high voltage probe. Multi-peak features were interpreted considering the second fitting process along with the mechanisms for ion beam production and hard x-ray emission. To show the important role of the anomalous resistance, the duration of the current drop was discussed.

  19. Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish.

    PubMed

    Takeuchi, Miki; Yamaguchi, Shingo; Yonemura, Shigenobu; Kakiguchi, Kisa; Sato, Yoshikatsu; Higashiyama, Tetsuya; Shimizu, Takashi; Hibi, Masahiko

    2015-10-01

    Granule cells (GCs) are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio) gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM) component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs). Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets. PMID:26451951

  20. Fatal Peritoneal Bleeding Following Embolization of a Carotid-Cavernous Fistula in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Usinskiene, Jurgita; Mazighi, Mikael; Bisdorff, Annouk; Houdart, Emmanuel

    2006-12-15

    We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed.

  1. Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish

    PubMed Central

    Takeuchi, Miki; Yamaguchi, Shingo; Yonemura, Shigenobu; Kakiguchi, Kisa; Sato, Yoshikatsu; Higashiyama, Tetsuya; Shimizu, Takashi; Hibi, Masahiko

    2015-01-01

    Granule cells (GCs) are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio) gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM) component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs). Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets. PMID:26451951

  2. Antimicrobial peptide inhibition of fungalysin proteases that target plant type 19 Family IV defense chitinases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal crops and other plants produce secreted seed chitinases that reduce pathogenic infection, most likely by targeting the fungal chitinous cell wall. We have shown that corn (Zea mays) produces three GH family 19, plant class IV chitinases, that help in protecting the plant against Fusarium and ...

  3. Anomalous law of cooling

    SciTech Connect

    Lapas, Luciano C.; Ferreira, Rogelma M. S.; Rubí, J. Miguel; Oliveira, Fernando A.

    2015-03-14

    We analyze the temperature relaxation phenomena of systems in contact with a thermal reservoir that undergoes a non-Markovian diffusion process. From a generalized Langevin equation, we show that the temperature is governed by a law of cooling of the Newton’s law type in which the relaxation time depends on the velocity autocorrelation and is then characterized by the memory function. The analysis of the temperature decay reveals the existence of an anomalous cooling in which the temperature may oscillate. Despite this anomalous behavior, we show that the variation of entropy remains always positive in accordance with the second law of thermodynamics.

  4. Anomalous law of cooling

    NASA Astrophysics Data System (ADS)

    Lapas, Luciano C.; Ferreira, Rogelma M. S.; Rubí, J. Miguel; Oliveira, Fernando A.

    2015-03-01

    We analyze the temperature relaxation phenomena of systems in contact with a thermal reservoir that undergoes a non-Markovian diffusion process. From a generalized Langevin equation, we show that the temperature is governed by a law of cooling of the Newton's law type in which the relaxation time depends on the velocity autocorrelation and is then characterized by the memory function. The analysis of the temperature decay reveals the existence of an anomalous cooling in which the temperature may oscillate. Despite this anomalous behavior, we show that the variation of entropy remains always positive in accordance with the second law of thermodynamics.

  5. Anomalous law of cooling.

    PubMed

    Lapas, Luciano C; Ferreira, Rogelma M S; Rubí, J Miguel; Oliveira, Fernando A

    2015-03-14

    We analyze the temperature relaxation phenomena of systems in contact with a thermal reservoir that undergoes a non-Markovian diffusion process. From a generalized Langevin equation, we show that the temperature is governed by a law of cooling of the Newton's law type in which the relaxation time depends on the velocity autocorrelation and is then characterized by the memory function. The analysis of the temperature decay reveals the existence of an anomalous cooling in which the temperature may oscillate. Despite this anomalous behavior, we show that the variation of entropy remains always positive in accordance with the second law of thermodynamics. PMID:25770525

  6. Determination of PCBs in Rocky Flats Type IV waste sludge by gas chromatography/electron capture detection

    SciTech Connect

    Parish, K.J.; Applegate, D.V.; Boparai, A.S.; Reedy, G.T.

    1993-12-01

    Type IV Rocky Flats Plant (RFP) radioactive sludge samples must be evaluated for polychlorinated biphenyl (PCB) content before disposal. The Type IV sludge consists of organic solvents, degreasers, cutting oils, and transuranic (TRU) waste mixed with calcium silicate (MicroCel E{reg_sign}) and Oil Dri{reg_sign} to form a grease or paste-like material. For laboratory studies a nonradioactive simulated Type IV RFP sludge was prepared having a composition similar to that expected from field samples. A simplified method was developed for extraction, purification and analysis of PCBs using samples of simulated sludge spiked with Aroclors 1254 and 1260 (reports provided to Argonne indicated Aroclors 1254 and 1260 as the most likely PCB contaminants in RFP sludge samples). The developed method was compared to the Environmental Protection Agency (EPA) accepted SW-846 method for analysis of PCBs (Method 8081). The accuracy and precision data were found to be similar for the two methods. The developed method was also tested with samples of simulated sludge spiked with Pu (in solid and solution forms). Reduction of radioactivity in final extract versus in the spike sample ranged from a factor of 10{sup 5} to 10{sup 7}.

  7. Glomerular basement membrane expansion in passive Heymann nephritis. Absence of increased synthesis of type IV collagen, laminin, or fibronectin.

    PubMed Central

    Fogel, M. A.; Boyd, C. D.; Leardkamolkarn, V.; Abrahamson, D. R.; Minto, A. W.; Salant, D. J.

    1991-01-01

    The distribution and synthetic rate of glomerular basement membrane components was examined in the Passive Heymann Nephritis model of experimental membranous nephropathy. The extensive tissue injury that developed included subepithelial electron-dense deposits, podocyte foot process effacement, and expansion of the glomerular basement membrane. Levels of mRNA for type IV collagen, laminin, and fibronectin from isolated glomeruli was quantitated by slot-blot analysis and showed no change in experimental animals as compared to controls at either 1 week, 3 weeks, or 3 months after disease induction. Immunoelectron microscopy with gold-labeled anti-laminin IgG revealed no difference in the number of particles bound to the glomerular basement membrane of experimental animals and controls. Immunofluorescence with both type IV collagen antisera and anti-laminin antibody showed no difference in the intensity or pattern of staining. Despite extensive glomerular damage and glomerular basement membrane thickening, no evidence was found for either an increase in the synthetic rate of type IV collagen, laminin, or fibronectin or for an accumulation of basement membrane laminin within the damaged glomeruli. Alternate processes, such as diminished density of matrix components or accumulation of other unmeasured matrix constituents, presumably account for the expansion of the glomerular basement membrane seen in experimental membranous nephropathy. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1992771

  8. Multiple strokes and bilateral carotid dissections: a fulminant case of newly diagnosed Ehlers-Danlos syndrome type IV.

    PubMed

    Dohle, C; Baehring, J M

    2012-07-15

    Ehlers-Danlos Syndrome is a rare group of inheritable disorders resulting in abnormal collagen production, leading to skin fragility, joint hypermobility and easy bruising. Six major subtypes have been identified, of which Type IV most often leads to neurovascular complications, may lead to inner organ rupture and overall has the worst prognosis. Early recognition followed by genetic testing is key, since this diagnosis will guide decision making in the management of complications, influence the choice of antiplatelet medications versus anticoagulants and allow for potentially affected family members to be identified, undergo genetic testing and reproductive counseling. We here report the case of a 50 year old woman with a fulminant presentation of Ehlers Danlos Syndrome Type IV, including bilateral carotid and vertebral artery dissection, multiple strokes and liver rupture. Of note, this patient did not have a known history or obvious clinical features of connective tissue disease. Genetic testing confirmed the diagnosis. Review of her family history revealed multiple family members with a history of aortic dissection or aneurysm rupture. This case illustrates that Ehlers Danlos Syndrome Type IV is an important differential diagnosis even in adult patients without a known history of connective tissue disease and no prior complications. PMID:22559935

  9. Genomic and Gene-Expression Comparisons among Phage-Resistant Type-IV Pilus Mutants of Pseudomonas syringae pathovar phaseolicola

    PubMed Central

    Sistrom, Mark; Park, Derek; O’Brien, Heath E.; Wang, Zheng; Guttman, David S.; Townsend, Jeffrey P.; Turner, Paul E.

    2015-01-01

    Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Φ6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Φ6 as a model system in evolutionary biology, Pph resistance to phage Φ6 remains poorly characterized. To investigate differences between phage Φ6 resistant Pph strains, we examined genomic and gene expression variation among three bacterial genotypes that differ in the number of type IV pili expressed per cell: ordinary (wild-type), non-piliated, and super-piliated. Genome sequencing of non-piliated and super-piliated Pph identified few mutations that separate these genotypes from wild type Pph–and none present in genes known to be directly involved in type IV pilus expression. Expression analysis revealed that 81.1% of gene ontology (GO) terms up-regulated in the non-piliated strain were down-regulated in the super-piliated strain. This differential expression is particularly prevalent in genes associated with respiration—specifically genes in the tricarboxylic acid cycle (TCA) cycle, aerobic respiration, and acetyl-CoA metabolism. The expression patterns of the TCA pathway appear to be generally up and down-regulated, in non-piliated and super-piliated Pph respectively. As pilus retraction is mediated by an ATP motor, loss of retraction ability might lead to a lower energy draw on the bacterial cell, leading to a different energy balance than wild type. The lower metabolic rate of the super-piliated strain is potentially a result of its loss of ability to retract. PMID:26670219

  10. A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions.

    PubMed

    Wang, Yong-Xin; Xue, Dan-Ting; Liu, Meng; Zhou, Zheng-Min; Shang, Jing

    2016-03-01

    The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions