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Sample records for cornea type iii

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

    SciTech Connect

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

    1988-05-01

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

  2. Heterogeneity of collagens in rabbit cornea: type VI collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.

    1988-05-01

    Normal adult rabbit corneas were digested with 5% pepsin and their collagens extracted with acetic acid. Collagen extracts were fractionated by differential salt precipitation. The 2.5 M NaCl fraction was then redissolved with tris buffer and precipitated with sodium acetate. The precipitate contained a high-molecular-weight disulfide-bonded aggregate which, upon reduction with mercaptoethanol, was converted into three distinct polypeptides having molecular weights between 45 and 66 Kd. These physical characteristics, together with the susceptibility of these polypeptides to collagenase and their amino acid composition, identified the high molecular weight aggregate as type VI collagen. Corneas from neonate rabbits and adult corneas containing 2-week-old scars were organ cultured in the presence of (/sup 14/C) glycine to incorporate radiolabel into collagen. Tissues were digested with 0.02% pepsin and their collagens extracted with formic acid. The total radioactivity of the extracts and tissue residues was determined before the collagens were separated by SDS-polyacrylamide slab gel electrophoresis. Radioactive collagen polypeptides bands were then stained with Coomassie blue, processed for fluorography, and analyzed by densitometry. The results show that: (1) type VI collagen is synthesized by neonate corneas and healing adult corneas; (2) it is not readily solubilized from either corneal tissue by 0.02% pepsin digestion and formic acid extraction; and (3) the proportion of type VI collagen deposited in scar tissue is markedly lower than that found in neonate corneas.

  3. Migration Type III

    NASA Astrophysics Data System (ADS)

    Artymowicz, Pawel

    2004-03-01

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

  4. Fueling type III secretion

    PubMed Central

    Lee, Pei-Chung

    2015-01-01

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

  5. Cranial mononeuropathy III - diabetic type

    MedlinePlus

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

  6. Type I Interferon and Lymphangiogenesis in the HSV-1 Infected Cornea – Are they Beneficial to the Host?

    PubMed Central

    Bryant-Hudson, Katie; Conrady, Christopher D.; Carr, Daniel J.J.

    2013-01-01

    Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that can result in significant human morbidity. Within the cornea, it was thought the initial recognition of the pathogen was through Toll-like receptors expressed on/in resident cells that then elicit pro-inflammatory cytokine production, activation of anti-viral pathways, and recruitment of leukocytes. However, our lab has uncovered a novel, TLR-independent innate sensor that supersedes TLR induction of anti-viral pathways following HSV-1 infection. In addition, we have also found HSV-1 induces the genesis of lymphatic vessels into the cornea proper by a mechanism independent of TLRs and unique in the field of neovascularization. This review will focus on these two innate immune events during acute HSV-1 infection of the cornea. PMID:23876483

  7. Cranial mononeuropathy III - diabetic type

    MedlinePlus

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

  8. Glycosaminoglycans and mucopolysaccharidosis type III.

    PubMed

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

    2016-01-01

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

  9. Cloudy cornea

    MedlinePlus

    ... Do you wear contact lenses? Is there any history of injury to the eye? Has there been any discomfort? If so, is there anything that helps? Tests may include: Biopsy of lid tissue Computer mapping of the cornea (corneal topography) Schirmer's test ...

  10. Dens invaginatus (Type III B)

    PubMed Central

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

    2012-01-01

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

  11. The structural and optical properties of type III human collagen biosynthetic corneal substitutes.

    PubMed

    Hayes, Sally; Lewis, Phillip; Islam, M Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M

    2015-10-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2-9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

  12. The structural and optical properties of type III human collagen biosynthetic corneal substitutes

    PubMed Central

    Hayes, Sally; Lewis, Phillip; Islam, M. Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M.

    2015-01-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2–9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

  13. Type III functional response in Daphnia.

    PubMed

    Sarnelle, Orlando; Wilson, Alan E

    2008-06-01

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

  14. Mucolipidosis Type III α/β

    PubMed Central

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

    2014-01-01

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

  15. Artificial corneas versus donor corneas for repeat corneal transplants

    PubMed Central

    Akpek, Esen K; Alkharashi, Majed; Hwang, Frank S; Ng, Sueko M; Lindsley, Kristina

    2014-01-01

    Background Individuals who have failed one or more full thickness penetrating keratoplasties (PKs) may be offered repeat corneal surgery using an artificial or donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis. Both donor and artificial corneal transplantations involve removal of the diseased and opaque recipient cornea (or the previously failed cornea) and replacement with another donor or prosthetic cornea. Objectives To assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 November 2013. Selection criteria Two review authors independently assessed reports from the electronic searches to identify randomized controlled trials (RCTs) or controlled clinical trials (CCTs). We resolved discrepancies by discussion or consultation with a third review author. Data collection and analysis For discussion purposes, we assessed findings from observational cohort studies and non-comparative case series. No data synthesis was performed. Main results We did not identify any RCTs or CCTs comparing artificial corneas with donor corneas for repeat corneal transplantations. Authors

  16. Energy source of flagellar type III secretion.

    PubMed

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

    2008-01-24

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

  17. Arthroscopic fixation of type III acromioclavicular dislocations.

    PubMed

    Somers, Jan F A; Van der Linden, Dietert

    2007-10-01

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

  18. Sources of type III solar microwave bursts

    NASA Astrophysics Data System (ADS)

    Zhdanov, Dmitriy; Lesovoi, Sergey; Tokhchukova, Susanna

    2016-06-01

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

  19. CD4+ T Cell Migration into the Cornea is Reduced in CXCL9 Deficient but not CXCL10 Deficient Mice following Herpes Simplex Virus Type 1 Infection1

    PubMed Central

    Wuest, Todd; Farber, Joshua; Luster, Andrew; Carr, Daniel J. J.

    2007-01-01

    The role of CXCL9 and CXCL10 in the ocular immune response to herpes simplex virus type 1 (HSV-1) infection was investigated using mice deficient in either CXCL9 or CXCL10. CXCL10 but not CXCL9 deficient mice showed an increase in sensitivity to ocular virus infection as measured by an elevation in virus titer recovered in the tear film and corneal tissue. The increase in virus was associated with an increase in the expression of the chemokine CCL2 but no significant change in the infiltration of CD4+ T cells or NK cells into the corneal stroma. In contrast, a significant reduction in CD4+ T cell infiltration into the cornea was found in CXCL9 deficient mice following HSV-1 infection consistent with the absence of CXCL9 expression and reduction in expression of other chemokines including CCL3, CCL5, CXCL1, and CXCL10. Collectively, the results suggest a non-redundant role for CXCL9 and CXCL10 in response to ocular HSV-1 infection in terms of controlling virus replication and recruitment of CD4+ T cells into the cornea. PMID:17296171

  20. DECIMETRIC TYPE III BURSTS: GENERATION AND PROPAGATION

    SciTech Connect

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

    2011-09-01

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

  1. Cornea and ocular surface treatment.

    PubMed

    De Miguel, Maria P; Alio, Jorge L; Arnalich-Montiel, Francisco; Fuentes-Julian, Sherezade; de Benito-Llopis, Laura; Amparo, Francisco; Bataille, Laurent

    2010-06-01

    In addition to being a protective shield, the cornea represents two thirds of the eye's refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach. PMID:19941445

  2. Type III Radio Bursts and Microflares

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

  3. Recurrent erosion of the cornea.

    PubMed Central

    Brown, N.; Bron, A.

    1976-01-01

    Altogether, 80 patients aged between 24 and 73 years with recurrent erosion of the cornea have been studied and compared with a control group of 200. The patients' erosions were divisible into macroform and microform types. The macroform occurred in 10%, the microform in 56%, and both types in the same patients in 31%. The macroform was more commonly related to trauma than the microform. However, many (40%) were spontaneous in origin. The most common cause of the initial trauma was a finger nail. The recurrences occurred at around the time of waking, either just before or just after. Difficulty in opening the eye occurred in 10%. There was little evidence of precipitating factors, but eye rubbing was admitted by 10% and barbiturates were implicated in 3%. The corneae were examined in the healed state, when a high incidence (59%) were found to have superficial corneal dystrophies of the fingerprint lines, bleb, and Bietti's lacunar (map-like) types. These are considered individually, particular attention being paid to the distinction between the various types of line resembling the fingerprint line. Epithelial microcysts were also a common finding (59%) and were sometimes of the Cogan type. In only 11% of patients were there no corneal signs in the healed state. The need for careful examination of the cornea by retroillumination, using both the iris and the fundus, is stressed. The control group, in contrast, showed a very low incidence of dystrophies and cysts. Treatment was given initially with either drops or ointment and no differences in healing were found. Debridement was performed in 12 eyes as an initial treatment and also in four eyes which were not healing on medical treatment. Debridement assisted healing, but did not prevent recurrence. One eye was treated with debridement and scarification and seven with carbolization. These procedures appeared to reduce the recurrence rate. Sodium chloride ointment 5% was found useful as a prophylactic taken at bedtime

  4. [Generation of bioartificial organs. The cornea as a model].

    PubMed

    Campos Muñoz, Antonio; Alaminos Mingorance, Miguel

    2011-01-01

    The development of bioartificial organs is a new target in the development of tissue engineering. It consists in the use of stem cells in a decellularized stroma of other organs. In this paper we present our previous experience in the construction of a complete artificial cornea using cell cultures and biomaterials and compare it with the construction of a bioartificial cornea using a decellularized porcine stroma. The results, in building this new type of cornea, showed that 1.5 M NaCl treatment of porcine corneas is able to generate an acellular corneal stroma with adequate histologic and optical properties and that human keratocytes are able to penetrate and spread within this scaffold with proper levels of cell differentiation. In contrast, 0.1% SDS treatment of porcine corneas resulted in high levels of fibril disorganization and poor optical behavior of these corneas. PMID:23350328

  5. Preservation of Human Cornea

    PubMed Central

    Armitage, W. John

    2011-01-01

    Summary The successful outcome of the majority of corneal transplants depends on the presence of a viable corneal endothelium. This monolayer of cells lines the inner surface of the cornea and its primary function is to maintain corneal transparency by controlling the hydration of the collagenous stromal layer. Since human corneal endothelial cells do not readily proliferate, preservation of the endothelium is a primary aim of methods of corneal storage. Although some cryopreserved corneas have been transplanted successfully, the complexity of the cryopreservation technique and its potential for causing endothelial damage have limited its application. Hypothermia (2–8 °C) is the most commonly applied method of storage, which allows storage for 7–14 days. Organ culture (28–37 °C), which extends storage time to 4 weeks, is used widely in European eye banks. Graft outcomes for corneas stored by these two techniques appear similar. PMID:21566714

  6. Gamma-Irradiated Sterile Cornea for Use in Corneal Transplants in a Rabbit Model

    PubMed Central

    Yoshida, Junko; Heflin, Thomas; Zambrano, Andrea; Pan, Qing; Meng, Huan; Wang, Jiangxia; Stark, Walter J.; Daoud, Yassine J.

    2015-01-01

    Purpose: Gamma irradiated corneas in which the donor keratocytes and endothelial cells are eliminated are effective as corneal lamellar and glaucoma patch grafts. In addition, gamma irradiation causes collagen cross inking, which stiffens collagen fibrils. This study evaluated gamma irradiated corneas for use in corneal transplantations in a rabbit model comparing graft clarity, corneal neovascularization, and edema. Methods: Penetrating keratoplasty was performed on rabbits using four types of corneal grafts: Fresh cornea with endothelium, gamma irradiated cornea, cryopreserved cornea, and fresh cornea without endothelium. Slit lamp examination was performed at postoperative week (POW) one, two, and four. Corneal clarity, edema, and vascularization were graded. Confocal microscopy and histopathological evaluation were performed. A P < 0.05 was statistically significant. Results: For all postoperative examinations, the corneal clarity and edema were statistically significantly better in eyes that received fresh cornea with endothelium compared to the other three groups (P < 0.05). At POW 1, gamma irradiated cornea scored better than the cryopreserved and fresh cornea without endothelium groups in clarity (0.9 vs. 1.5 and 2.6, respectively), and edema (0.6 vs. 0.8 and 2.0, respectively). The gamma irradiated corneas, cryopreserved corneas and the fresh corneas without endothelium, developed haze and edema after POW 2. Gamma irradiated cornea remained statistically significantly clearer than cryopreserved and fresh cornea without endothelium during the observation period (P < 0.05). Histopathology indicated an absence of keratocytes in gamma irradiated cornea. Conclusion: Gamma irradiated corneas remained clearer and thinner than the cryopreserved cornea and fresh cornea without endothelium. However, this outcome is transient. Gamma irradiated corneas are useful for lamellar and patch grafts, but cannot be used for penetrating keratoplasty. PMID:26180475

  7. Dendritic cell dysfunction and diabetic sensory neuropathy in the cornea.

    PubMed

    Gao, Nan; Yan, Chenxi; Lee, Patrick; Sun, Haijing; Yu, Fu-Shin

    2016-05-01

    Diabetic peripheral neuropathy (DPN) often leads to neurotrophic ulcerations in the cornea and skin; however, the underlying cellular mechanisms of this complication are poorly understood. Here, we used post-wound corneal sensory degeneration and regeneration as a model and tested the hypothesis that diabetes adversely affects DC populations and infiltration, resulting in disrupted DC-nerve communication and DPN. In streptozotocin-induced type 1 diabetic mice, there was a substantial reduction in sensory nerve density and the number of intraepithelial DCs in unwounded (UW) corneas. In wounded corneas, diabetes markedly delayed sensory nerve regeneration and reduced the number of infiltrating DCs, which were a major source of ciliary neurotrophic factor (CNTF) in the cornea. While CNTF neutralization retarded reinnervation in normal corneas, exogenous CNTF accelerated nerve regeneration in the wounded corneas of diabetic mice and healthy animals, in which DCs had been locally depleted. Moreover, blockade of the CNTF-specific receptor CNTFRα induced sensory nerve degeneration and retarded regeneration in normal corneas. Soluble CNTFRα also partially restored the branching of diabetes-suppressed sensory nerve endings and regeneration in the diabetic corneas. Collectively, our data show that DCs mediate sensory nerve innervation and regeneration through CNTF and that diabetes reduces DC populations in UW and wounded corneas, resulting in decreased CNTF and impaired sensory nerve innervation and regeneration. PMID:27064280

  8. Dendritic cell dysfunction and diabetic sensory neuropathy in the cornea

    PubMed Central

    Gao, Nan; Yan, Chenxi; Lee, Patrick; Sun, Haijing

    2016-01-01

    Diabetic peripheral neuropathy (DPN) often leads to neurotrophic ulcerations in the cornea and skin; however, the underlying cellular mechanisms of this complication are poorly understood. Here, we used post-wound corneal sensory degeneration and regeneration as a model and tested the hypothesis that diabetes adversely affects DC populations and infiltration, resulting in disrupted DC-nerve communication and DPN. In streptozotocin-induced type 1 diabetic mice, there was a substantial reduction in sensory nerve density and the number of intraepithelial DCs in unwounded (UW) corneas. In wounded corneas, diabetes markedly delayed sensory nerve regeneration and reduced the number of infiltrating DCs, which were a major source of ciliary neurotrophic factor (CNTF) in the cornea. While CNTF neutralization retarded reinnervation in normal corneas, exogenous CNTF accelerated nerve regeneration in the wounded corneas of diabetic mice and healthy animals, in which DCs had been locally depleted. Moreover, blockade of the CNTF-specific receptor CNTFRα induced sensory nerve degeneration and retarded regeneration in normal corneas. Soluble CNTFRα also partially restored the branching of diabetes-suppressed sensory nerve endings and regeneration in the diabetic corneas. Collectively, our data show that DCs mediate sensory nerve innervation and regeneration through CNTF and that diabetes reduces DC populations in UW and wounded corneas, resulting in decreased CNTF and impaired sensory nerve innervation and regeneration. PMID:27064280

  9. Extrapyramidal Symptoms and Medication Use in Mucopolysaccharidosis Type III

    ERIC Educational Resources Information Center

    Tchan, Michel C.; Sillence, David

    2009-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  11. Neuroanatomy and Neurochemistry of Mouse Cornea

    PubMed Central

    He, Jiucheng; Bazan, Haydee E. P.

    2016-01-01

    Purpose To investigate the entire nerve architecture and content of the two main sensory neuropeptides in mouse cornea to determine if it is a good model with similarities to human corneal innervation. Methods Mice aged 1 to 24 weeks were used. The corneas were stained with neuronal-class βIII-tubulin, calcitonin gene–related peptide (CGRP), and substance P (SP) antibodies; whole-mount images were acquired to build an entire view of corneal innervation. To test the origin of CGRP and SP, trigeminal ganglia (TG) were processed for immunofluorescence. Relative corneal nerve fiber densities or neuron numbers were assessed by computer-assisted analysis. Results Between 1 and 3 weeks after birth, mouse cornea was mainly composed of a stromal nerve network. At 4 weeks, a whorl-like structure (or vortex) appeared that gradually became more defined. By 8 weeks, anatomy of corneal nerves had reached maturity. Epithelial bundles converged into the central area to form the vortex. The number and pattern of whorl-like structures were different. Subbasal nerve density and nerve terminals were greater in the center than the periphery. Nerve fibers and terminals that were CGRP-positive were more abundant than SP-positive nerves and terminals. In trigeminal ganglia, the number of CGRP-positive neurons significantly outnumbered those positive for SP. Conclusions This is the first study to show a complete map of the entire corneal nerves and CGRP and SP sensory neuropeptide distribution in the mouse cornea. This finding shows mouse corneal innervation has many similarities to human cornea and makes the mouse an appropriate model to study pathologies involving corneal nerves. PMID:26906155

  12. Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study

    PubMed Central

    Sindt, Christine W; Grout, Trudy K; Critser, D Brice; Kern, Jami R; Meadows, David L

    2012-01-01

    Background The purpose of this study was to assess whether differences in central corneal dendritic immune cell densities associated with combinations of soft contact lenses and lens care solutions could be detected by in vivo confocal microscopy. Methods Participants were adults naïve to contact lens wear (n = 10) or who wore soft contact lenses habitually on a daily-wear schedule (n = 38) or on a study-assigned schedule for 30 days with daily disposable silicone hydrogel lenses (n = 15). Central corneas were scanned using an in vivo confocal microscope. Cell densities were compared among groups by demographic parameters, lens materials, and lens care solutions (polyhexamethylene biguanide [PHMB], polyquaternium-1 and myristamidopropyl dimethylamine [PQ/MAPD], peroxide, or blister pack solution [for daily disposable lenses]). Results Among lens wearers, no associations were observed between immune cell densities and age, gender, or years of lens-wearing experience. Mean cell density was significantly lower (P < 0.01) in nonwearers (29 ± 23 cells/mm2, n = 10) than in lens wearers (64 ± 71 cells/mm2, n = 53). Mean cell density was lower (P = 0.21) with traditional polymer lenses (47 ± 44 cells/mm2, n = 12) than with silicone hydrogel lenses (69 ± 77 cells/mm2, n = 41). Lowest to highest mean density of immune cells among lens wearers was as follows: PQ/MAPD solution (49 ± 28 cells/mm2), blister pack solution (63 ± 81 cells/mm2), PHMB solution (66 ± 44 cells/mm2), and peroxide solution (85 ± 112 cells/mm2). Conclusion In this pilot study, in vivo confocal microscopy was useful for detecting an elevated immune response associated with soft contact lenses, and for identifying lens-related and solution-related immune responses that merit further research. PMID:22536045

  13. Auroral Kilometric Radiation and Type III Solar Radio Bursts

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

  14. Assessment of Sleep in Children with Mucopolysaccharidosis Type III

    PubMed Central

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

    2014-01-01

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

  15. MMP-type endopeptidase activity in the cornea. Its evolution during organ culture storage at the Eye Bank. Effect of hyaluronan.

    PubMed

    Isnard, N; Sabatier, P; Robert, A M; Robert, L; Renard, G

    2005-09-01

    About 46% of total corneas obtained from donors in the French Eye Bank cannot be grafted for several reasons as loss of endothelium or other. Corneal cells express proteolytic enzymes, essentially matrix metallo-proteinase MMP-2 and MMP-9. In presence of hyaluronan and some other GAG-s their activity increases as could be shown on keratocyte cultures. Hyaluronan concentration increases during in vitro preservation and can represent a serious hazard for corneal conservation. The control of MMP-release and activation might well be one of the factors involved in graft deterioration. We could show however that only a slight fraction (< or =12%) of total, relatively high endopeptidase activity of the cornea is released in the media during storing. It appears therefore that most of the proteolytic activity determined in corneal extracts remains confined to the stroma and might not represent an important risk for preservation, at least for the endothelium. PMID:16085120

  16. The general solution of Bianchi type III vacuum cosmology

    NASA Astrophysics Data System (ADS)

    Christodoulakis, T.; Terzis, Petros A.

    2007-02-01

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

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

    PubMed

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

    2016-01-01

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

  18. Regenerative approaches for the cornea.

    PubMed

    Griffith, M; Alarcon, E I; Brunette, I

    2016-09-01

    The cornea is the transparent front part of the eye that transmits light to the back of the eye to generate vision. Loss of corneal transparency, if irreversible, leads to severe vision loss or blindness. For decades, corneal transplantation using human donor corneas has been the only option for treating corneal blindness. Despite recent improvement in surgical techniques, donor cornea transplantation remains plagued by risks of suboptimal optical results and visual acuity, immune rejection and eventually graft failure. Furthermore, the demand for suitable donor corneas is increasing faster than the number of donors, leaving thousands of curable patients untreated worldwide. Here, we critically review the state of the art of biomaterials for corneal regeneration. However, the lessons learned from the use of the cornea as a disease model will allow for extension of the biomaterials and techniques for regeneration of more complex organs such as the heart. PMID:27098482

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

    PubMed Central

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

    2014-01-01

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

  20. Microwave Type III Pair Bursts in Solar Flares

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  2. The position and polarization of Type III solar bursts

    NASA Technical Reports Server (NTRS)

    Dulk, G. A.; Suzuki, S.

    1980-01-01

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

  3. A Novel Antimicrobial Peptidoglycan Recognition Protein in the Cornea

    PubMed Central

    Ghosh, Amit; Lee, Seakwoo; Dziarski, Roman; Chakravarti, Shukti

    2011-01-01

    Purpose In an earlier gene expression study, the authors identified a novel antimicrobial gene, Peptidoglycan recognition protein 1 (Pglyrp1), in the mouse cornea. Here the expression of the Pglyrp1 transcript and the encoded protein, PGLYRP1, in the cornea was investigated. The role of PGLYRP1 in the cornea was further investigated using wild-type and Pglyrp1-deficient mice. This is the first report of this antimicrobial protein in the cornea. Methods PGLYRP1 was detected in the cornea and was further localized to the epithelium by immunohistology, confocal microscopy, immunoblotting, and real-time PCR. The role of PGLYRP1 in the cornea was investigated by comparing the response of wild-type and Pglyrp1–/– mice to corneal epithelial wounds and Pseudomonas aeruginosa–mediated corneal infections. The antibacterial effects of corneal PGLYRP1 were assayed by measuring bacterial growth in vitro, in the presence of wild-type corneal epithelial extracts, before and after antibody-mediated blocking of PGLYRP1. Results PGLYRP1 is expressed at high levels in the mouse corneal epithelium. PGLYRP1 was localized to the mouse corneal epithelium and the human corneal epithelium. The Pglyrp1–/– mouse shows delayed healing and poor clearing of bacterial keratitis; in vitro its epithelial protein extract shows reduced bacteriostatic activity compared with wild-type mice. Conclusions PGLYRP1 is a novel antimicrobial protein of the corneal epithelium and protects the ocular surface from bacterial infections. PMID:19387073

  4. Mechanical characterization of porcine corneas.

    PubMed

    Boschetti, F; Triacca, V; Spinelli, L; Pandolfi, A

    2012-03-01

    An experimental program has been carried out in order to investigate the mechanical behavior of porcine corneas. We report the results of inflation tests on the whole cornea and uniaxial tests on excised corneal strips, performed on 51 fresh porcine eyes. Uniaxial tests have been performed on specimens cut from previously inflated corneas. The cornea behavior is characterized by means of elastic stiffness, measured on both average pressure-apex displacement and average uniaxial stress-strain curves; and by means of transversal contraction coefficient, peak stress, and failure stress measured on uniaxial stress-strain curves. Uniaxial tests performed on excised strips allowed to measure the anisotropy in the corneal stiffness and to compare the stiffness of the cornea with the one of the sclera. Viscous properties of the cornea have been obtained through uniaxial relaxation curves on excised corneal strips. The relevant geometrical parameters have been measured and, with the aid of the elastic thin shell theory, a stress-strain curve has been derived from the average inflation test data and compared with similar data available in the literature. The experimental system has been developed in view of future applications to the mechanical testing of both porcine and human corneas. PMID:22482683

  5. A tiny event producing an interplanetary type III burst

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Winter, L. M.; Ledbetter, K.

    2015-08-01

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

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

    PubMed

    Meng, Xiangying; Huguet, Gemma; Rinzel, John

    2012-08-01

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

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

    PubMed

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

    2003-04-01

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

  9. Spatial trends in Pearson Type III statistical parameters

    USGS Publications Warehouse

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

    1995-01-01

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

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

    PubMed Central

    Tao, Matthew A.; Garrigues, Grant E.

    2015-01-01

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

  11. Assembly and function of type III secretory systems.

    PubMed

    Cornelis, G R; Van Gijsegem, F

    2000-01-01

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

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

    SciTech Connect

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

    2012-02-01

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

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

    PubMed

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

    2016-07-01

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

  14. Changing pattern of utilization of human donor cornea in India

    PubMed Central

    Gogia, Varun; Gupta, Shikha; Agarwal, Tushar; Pandey, Veena; Tandon, Radhika

    2015-01-01

    Purpose: To review the changing pattern of donor, corneal utilization in an eye bank at a Tertiary Care Center in Northern India by analyzing the trend in the years 2003, 2008, and 2011. Methods: A retrospective review of eye bank records for 3 years (2003, 2008, and 2011) was performed at the National Eye Bank. Details including a clinical grade of donor cornea, indication of corneal transplantation (therapeutic or optical), type of procedure (penetrating or lamellar keratoplasty [LK]), and clinical diagnosis of the graft recipients were recorded. Primary outcome measure was to observe any preference toward LK, judicious usage of donor corneal tissue, and impact of lamellar corneal transplant in the usage of donor corneas. Secondary outcomes included overall utilization rate and change in trend of indication for keratoplasty. Results: A total of 673, 745, and 864 corneas were retrieved in the years 2003, 2008, and 2011, respectively. The percentage of donor corneal utilization increased significantly over time with the rate being 65.08%, 70.06%, and 68.29%, respectively, in the years 2003, 2008, and 2011 (P = 0.014); however, this change was reflected only in the usage of nonoptical grade corneas and not for the optical grade corneas. There was an overall increase in lamellar corneal procedures for any clinical grade of cornea (P = 0.0019); number of Descemet's stripping automated endothelial keratoplasty (DSAEK) procedures increased significantly (P < 0.001), particularly for pseudophakic corneal edema (PCE) (P = 0.0085) and failed graft (P = 0.002). Significant increase in the utilization of nonoptical grade corneas was observed over the years (P = 0.005), though the utilization did not increase significantly for optical purposes viz., LK (P = 0.08). Conclusions: Utilization rate of donor corneas increased over the years, primarily due to increase in usage of nonoptical grade corneas for therapeutic purposes. There was a procedural shift toward DSAEK for PCE and

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-03-29

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

  18. A clinical study of canine collagen type III glomerulopathy

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    SciTech Connect

    Thejappa, G.; MacDowall, R. J.

    2014-02-11

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

  1. 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

  2. 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

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1998-02-01

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

  7. Surgical management of Mason type III radial head fractures

    PubMed Central

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

    2013-01-01

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

  8. Yersinia Type III Secretion System Master Regulator LcrF.

    PubMed

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

    2016-02-01

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

  9. Yersinia Type III Secretion System Master Regulator LcrF

    PubMed Central

    Schwiesow, Leah; Lam, Hanh

    2015-01-01

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

  10. High-Frequency Cutoff in Type III Bursts

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    2003-01-01

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

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

    SciTech Connect

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

    1992-01-01

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

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

    SciTech Connect

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

    1992-05-01

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

  14. A Raman scattering and FT-IR spectroscopic study on the effect of the solar radiation in Antarctica on bovine cornea

    NASA Astrophysics Data System (ADS)

    Yamamoto, Tatsuyuki; Murakami, Naoki; Yoshikiyo, Keisuke; Takahashi, Tetsuya; Yamamoto, Naoyuki

    2010-01-01

    The Raman scattering and FT-IR spectra of the corneas, transported to the Syowa station in Antarctica and exposed to the solar radiation of the mid-summer for four weeks, were studied to reveal that type IV collagen involved in corneas were fragmented. The amide I and III Raman bands were observed at 1660 and 1245 cm -1, respectively, and the amide I and II infrared bands were observed at 1655 and 1545 cm -1, respectively, for original corneas before exposure. The background of Raman signals prominently increased and the ratio of amide II infrared band versus amide I decreased by the solar radiation in Antarctica. The control experiment using an artificial UV lamp was also performed in laboratory. The decline rate of the amide II/amide I was utilized for estimating the degree of fragmentation of collagen, to reveal that the addition of vitamin C suppressed the reaction while the addition of sugars promoted it. The effect of the solar radiation in Antarctica on the corneas was estimated as the same as the artificial UV lamp of four weeks (Raman) or one week (FT-IR) exposure.

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

    PubMed

    Riedl, Marc A

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Three-Dimensional Ultrasonic Imaging Of The Cornea

    NASA Technical Reports Server (NTRS)

    Heyser, Rrichar C.; Rooney, James A.

    1988-01-01

    Proposed technique generates pictures of curved surfaces. Object ultrasonically scanned in raster pattern generated by scanning transmitter/receiver. Receiver turned on at frequent intervals to measure depth variations of scanned object. Used for medical diagnoses by giving images of small curved objects as cornea. Adaptable to other types of reflection measurementsystems such as sonar and radar.

  18. Polarization of human donor corneas.

    PubMed

    Parekh, Mohit; Ruzza, Alessandro; Ferrari, Stefano; Salvalaio, Gianni; Elbadawy, Hossein; Ponzin, Diego; Lipari, Eugenio

    2016-06-01

    To investigate the de-orientation effect of DSAEK grafts by observing the cross patterns and polarization power of human donor corneas using a polarizing device (Lumaxis(®)). Forty human donor corneas were placed in small petri-plates with epithelial side facing up. Polarizing power (arbitrary unit) and crosses were monitored and recorded by the software. The tissue was marked at 'Superior' position to ensure that the base and the polarizer are in alignment with each other after the cut. The anterior lamellar cut was performed using microkeratome. The lenticule was placed back in the same position as marked to mimic the alignment. The tissue was further rotated by 45° ensuring that the base of the cornea and the polarizer were in alignment. The polarization power and 'crosses' were identified at each step. The average of forty corneas from pre-cut to post-45° angular change showed statistically significant difference (p < 0.05) in terms of polarizing power. The cross-shaped pattern deformed and lost the sharpness towards 45° angle. However, multiple variances in terms of 'cross-patterns' were observed throughout the study. Lumaxis(®) was able to determine the worst quality tissue in terms of polarization (no black zone and crosses). Despite the quality of cross pattern which can be used as an additional objective parameter to evaluate the optical properties of the corneal tissue, this preliminary study needs to be further justified in terms of clinical relevance whether polarization changes with oriented or de-oriented grafts have any effects and consequences on the visual acuity. PMID:26920874

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

    PubMed

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

    1980-01-01

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

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

    SciTech Connect

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

    1998-03-01

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

  1. The Structure and Function of Type III Secretion Systems

    PubMed Central

    Notti, Ryan Q.; Stebbins, C. Erec

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Armentrout, Erin I.; Rietsch, Arne

    2016-01-01

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

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

    PubMed

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

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    2004-01-01

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

  6. Polarization and position measurements of Type III bursts

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  7. GOES Type III Loop Heat Pipe Life Test Results

    NASA Technical Reports Server (NTRS)

    Ottenstein, Laura

    2011-01-01

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

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

    SciTech Connect

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

    2012-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

  10. Type III secretion-dependent modulation of innate immunity as one of multiple factors regulated by Pseudomonas aeruginosa RetS.

    PubMed

    Zolfaghar, Irandokht; Evans, David J; Ronaghi, Reza; Fleiszig, Suzanne M J

    2006-07-01

    Mutation of retS (rtsM) of Pseudomonas aeruginosa strain PA103 reduces its virulence in both ocular and respiratory murine models of infection. In vitro, retS mutants exhibit loss of the ExsA-regulated type III secretion system (TTSS), reduced twitching motility, and a decrease in association with, invasion of, and survival within corneal epithelial cells. In addition, transcription of multiple other virulence genes is positively and negatively affected by retS mutation. Since our published data show that ExoU and ExoT, the two TTSS effectors encoded by strain PA103, each confer virulence in this corneal model, we hypothesized that loss of virulence of retS mutants follows loss of type III secretion. Corneal pathology, bacterial colonization, and phagocyte infiltration were compared for wild-type PA103, retS mutants, and various TTSS mutants after infection with approximately 10(6) CFU bacteria. Results showed that either a retS or an exsA (TTSS) mutation delayed disease progression, as illustrated by reduced severity scores and colonization levels during the first 48 h postinfection. Surprisingly, retS mutant infections then became more severe than those involving exsA mutants. By day 7, colonization levels of retS mutants even surpassed those of wild-type bacteria (more than twofold, P = 0.028). Although retS mutants caused more severe opacification of central corneas than both the wild type and the exsA mutants, neither mutant caused the peripheral ring opacity commonly associated with wild-type infection, suggesting that the TTSS was involved. Histological experiments with retS and various TTSS mutants showed that ring opacification required ExoU but not ExoT and that it consisted of dense polymorphonuclear phagocyte infiltration at the corneal periphery and the absence of any cell type in the central cornea. These data suggest that these P. aeruginosa TTSS effectors have different effects on innate immunity and that RetS influences virulence beyond its effects

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

    NASA Astrophysics Data System (ADS)

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

    1985-10-01

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

  12. The Importance of the Pseudomonas aeruginosa Type III Secretion System in Epithelium Traversal Depends upon Conditions of Host Susceptibility

    PubMed Central

    Sullivan, Aaron B.; Tam, K. P. Connie; Metruccio, Matteo M. E.; Evans, David J.

    2015-01-01

    Pseudomonas aeruginosa is invasive or cytotoxic to host cells, depending on the type III secretion system (T3SS) effectors encoded. While the T3SS is known to be involved in disease in vivo, how it participates remains to be clarified. Here, mouse models of superficial epithelial injury (tissue paper blotting with EGTA treatment) and immunocompromise (MyD88 deficiency) were used to study the contribution of the T3SS transcriptional activator ExsA to epithelial traversal. Corneas of excised eyeballs were inoculated with green fluorescent protein (GFP)-expressing PAO1 or isogenic exsA mutants for 6 h ex vivo before bacterial traversal and epithelial thickness were quantified by using imaging. In the blotting-EGTA model, exsA mutants were defective in capacity for traversal. Accordingly, an ∼16-fold variability in exsA expression among PAO1 isolates from three sources correlated with epithelial loss. In contrast, MyD88−/− epithelia remained susceptible to P. aeruginosa traversal despite exsA mutation. Epithelial lysates from MyD88−/− mice had reduced antimicrobial activity compared to those from wild-type mice with and without prior antigen challenge, particularly 30- to 100-kDa fractions, for which mass spectrometry revealed multiple differences, including (i) lower baseline levels of histones, tubulin, and lumican and (ii) reduced glutathione S-transferase, annexin, and dermatopontin, after antigen challenge. Thus, the importance of ExsA in epithelial traversal by invasive P. aeruginosa depends on the compromise enabling susceptibility, suggesting that strategies for preventing infection will need to extend beyond targeting the T3SS. The data also highlight the importance of mimicking conditions allowing susceptibility in animal models and the need to monitor variability among bacterial isolates from different sources, even for the same strain. PMID:25667266

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Minamino, Tohru

    2014-08-01

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

  15. Yersinia type III effectors perturb host innate immune responses

    PubMed Central

    Pha, Khavong; Navarro, Lorena

    2016-01-01

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

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

    PubMed

    Pha, Khavong; Navarro, Lorena

    2016-02-26

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

  17. Synthetic cornea: biocompatibility and optics

    NASA Astrophysics Data System (ADS)

    Parel, Jean-Marie A.; Kaminski, Stefan; Fernandez, Viviana; Alfonso, E.; Lamar, Peggy; Lacombe, Emmanuel; Duchesne, Bernard; Dubovy, Sander; Manns, Fabrice; Rol, Pascal O.

    2002-06-01

    Purpose. Experimentally find a method to provide a safe surgical technique and an inexpensive and long lasting mesoplant for the restoration of vision in patients with bilateral corneal blindness due to ocular surface and stromal diseases. Methods. Identify the least invasive and the safest surgical technique for synthetic cornea implantation. Identify the most compatible biomaterials and the optimal shape a synthetic cornea must have to last a long time when implanted in vivo. Results. Penetrating procedures were deemed too invasive, time consuming, difficult and prone to long term complications. Therefore a non-penetrating delamination technique with central trephination was developed to preserve the integrity of Descemet's membrane and the anterior segment. Even though this approach limits the number of indications, it is acceptable since the majority of patients only have opacities in the stroma. The prosthesis was designed to fit in the removed tissue plane with its skirt fitted under the delaminated stroma. To improve retention, the trephination wall was made conical with the smallest opening on the anterior surface and a hat-shaped mesoplant was made to fit. The skirt was perforated in its perimeter to allow passage of nutrients and tissues ingrowths. To simplify the fabrication procedure, the haptic and optic were made of the same polymer. The intrastromal biocompatibility of several hydrogels was found superior to current clinically used PMMA and PTFE materials. Monobloc mesoplants made of 4 different materials were implanted in rabbits and followed weekly until extrusion occurred. Some remained optically clear allowing for fundus photography. Conclusions. Hydrogel synthetic corneas can be made to survive for periods longer than 1 year. ArF excimer laser photoablation studies are needed to determine the refractive correction potential of these mesoplants. A pilot FDA clinical trial is needed to assess the mesoplant efficacy and very long-term stability.

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

    NASA Astrophysics Data System (ADS)

    Coley, A. A.; Hervik, S.

    2008-10-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. 77 FR 76382 - Payout Requirements for Type III Supporting Organizations That Are Not Functionally Integrated

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

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

  2. 46 CFR 171.082 - Damage stability standards for vessels with Type III subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Cytochrome P450 Activity in Ex Vivo Cornea Models and a Human Cornea Construct.

    PubMed

    Kölln, Christian; Reichl, Stephan

    2016-07-01

    The pharmacokinetic behaviors of novel ophthalmic drugs are often preliminarily investigated in preclinical studies using ex vivo animal cornea or corneal cell culture models. During transcorneal passage, topically applied drugs may be affected by drug metabolizing enzymes. The knowledge regarding the functional expression of metabolic enzymes in corneal tissue is marginal; thus, the aim of this study was to investigate cytochrome P450 activity in an organotypic three-dimensional human cornea construct and to compare it with porcine and rabbit corneas, which are commonly used ex vivo cornea models. The total cytochrome P450 activity was determined by measuring the transformation of 7-ethoxycoumarin. Furthermore, the expression of the cytochrome P450 enzyme 2D6 (CYP2D6) was investigated at the protein level using immunohistochemistry and western blotting. CYP2D6 activity measurements were performed using a d-luciferin-based assay. In summary, similar levels of the total cytochrome P450 activity were identified in all 3 cornea models. The protein expression of CYP2D6 was confirmed in the human cornea construct and porcine cornea, whereas the signals in the rabbit cornea were weak. The analysis of the CYP2D6 activity indicated similar values for the human cornea construct and porcine cornea; however, a distinctly lower activity was observed in the rabbit cornea. PMID:27212636

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

    PubMed Central

    Hueck, Christoph J.

    1998-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Nat; Makela, Pertti

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Gopalswamy, Nat; Maekelae, Pertti

    2010-09-20

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

  12. 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

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

    PubMed

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

    2014-01-01

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

  14. Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse Cornea

    PubMed Central

    Baba, Kenkichi; Davidson, Alec J.; Tosini, Gianluca

    2015-01-01

    Purpose Previous studies have reported the presence of a circadian rhythm in PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina, RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the eye and it is believed to be one of the key circadian signals within the eye. The aim of the present study was to investigate the regulation of the PER2::LUC circadian rhythm in mouse cornea and to determine the role played by MLT. Methods Corneas were obtained from PER2::LUC mice and cultured to measure bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera. To determine the time-dependent resetting of the corneal circadian clocks in response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to the cultured corneas at different times of the day. We also defined the location of the MT2 receptor within different corneal layers using immunohistochemistry. Results A long-lasting bioluminescence rhythm was recorded from cultured PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and endothelium. MLT administration in the early night delayed the cornea rhythm, whereas administration of MLT at late night to early morning advanced the cornea rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent with these results, MT2 immunoreactivity was localized to the corneal epithelium and endothelium. Conclusions Our work demonstrates that MLT entrains the PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea may represent a model to study the molecular mechanisms by which MLT affects the circadian clock. PMID:26207312

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

    PubMed Central

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

    1986-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

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

    NASA Technical Reports Server (NTRS)

    Calvert, W.

    1981-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

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

    SciTech Connect

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

    2008-07-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    PubMed

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  3. Excimer laser photorefractive surgery of the cornea

    NASA Astrophysics Data System (ADS)

    Gaster, Ronald N.

    1998-09-01

    The 193 nm argon fluoride (ArF) excimer laser can effectively be used to change the radius of curvature of the cornea and thus alter the refractive state of the eye. This change allows myopic (nearsighted) patients to see well with less dependence on glasses or contact lenses. The two major techniques of laser refractive surgery currently in effect in the United States are photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). This paper will discuss these refractive cornea surgical techniques.

  4. Hyperglycemia-Induced Abnormalities in Rat and Human Corneas: The Potential of Second Harmonic Generation Microscopy

    PubMed Central

    Latour, Gaël; Kowalczuk, Laura; Savoldelli, Michèle; Bourges, Jean-Louis; Plamann, Karsten; Behar-Cohen, Francine; Schanne-Klein, Marie-Claire

    2012-01-01

    Background Second Harmonic Generation (SHG) microscopy recently appeared as an efficient optical imaging technique to probe unstained collagen-rich tissues like cornea. Moreover, corneal remodeling occurs in many diseases and precise characterization requires overcoming the limitations of conventional techniques. In this work, we focus on diabetes, which affects hundreds of million people worldwide and most often leads to diabetic retinopathy, with no early diagnostic tool. This study then aims to establish the potential of SHG microscopy for in situ detection and characterization of hyperglycemia-induced abnormalities in the Descemet’s membrane, in the posterior cornea. Methodology/Principal Findings We studied corneas from age-matched control and Goto-Kakizaki rats, a spontaneous model of type 2 diabetes, and corneas from human donors with type 2 diabetes and without any diabetes. SHG imaging was compared to confocal microscopy, to histology characterization using conventional staining and transmitted light microscopy and to transmission electron microscopy. SHG imaging revealed collagen deposits in the Descemet’s membrane of unstained corneas in a unique way compared to these gold standard techniques in ophthalmology. It provided background-free images of the three-dimensional interwoven distribution of the collagen deposits, with improved contrast compared to confocal microscopy. It also provided structural capability in intact corneas because of its high specificity to fibrillar collagen, with substantially larger field of view than transmission electron microscopy. Moreover, in vivo SHG imaging was demonstrated in Goto-Kakizaki rats. Conclusions/Significance Our study shows unambiguously the high potential of SHG microscopy for three-dimensional characterization of structural abnormalities in unstained corneas. Furthermore, our demonstration of in vivo SHG imaging opens the way to long-term dynamical studies. This method should be easily generalized to

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

    PubMed Central

    Rice, Austin J.; Park, Aekyung

    2014-01-01

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

  6. 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

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

    PubMed

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

    2006-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Reid, Elizabeth; Charleston, Bryan

    2014-09-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  11. Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?

    PubMed Central

    Evans, David J.; Fleiszig, Suzanne M. J.

    2013-01-01

    Purpose To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas aeruginosa. Perspective We focus on our current understanding of the interplay between bacteria, tear fluid and the corneal epithelium that determine health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P. aeruginosa infection. Methods Use of “null-infection” in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P. aeruginosa survive at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Results and Discussion Tear fluid and the corneal epithelium combine to make a formidable defense against P. aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P. aeruginosa adaptation, expression of the type three secretion system, proteases, and P. aeruginosa biofilm formation on contact lenses. Conclusion After more than two decades of research focused on understanding how contact lens wear predisposes to P. aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens. PMID:23601656

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

    PubMed

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

    2011-02-01

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

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

    PubMed Central

    Acharya, Prashant; Arora, Bakul; Pinto, Nelson

    2015-01-01

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

  14. Ultraviolet laser effects on the cornea

    NASA Astrophysics Data System (ADS)

    Zuclich, Joseph A.

    1990-07-01

    Ultraviolet radiation in the ambient environment or from artificial sources may pose both acute and chronic hazards to the skin and the ocular tissues. In general terrestrial conditions have evolved such that there are only narrow safety margins between ambient UV levels and exposure levels harmful to the human. Obvious examples of acute consequences ofUV overexposure are sunburn and snowblindness as well as analogous conditions induced by artificial sources such as the welder''s arc mercury vapor lamps and UV-emitting lasers. Further chronic UV exposure is strongly implicated as a causative agent in certain types of cataract and skin cancer. This presentation will summarize a number of specific cases where UV radiation affected the primate cornea. Data presented will include the action spectra for far- and near-UV induced ocular damage the pulsewidth and total energy dependencies of ocular thresholds studies of cumulative effects of repeated UV exposures and quantitative determinations of tissue repair or recovery rates. Depending on the exposure parameters utilized photochemical thermal or photoablative damage mechanisms may prevail. 1.

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

    PubMed Central

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

    1985-01-01

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

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

    SciTech Connect

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

    2013-12-10

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2006-06-21

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

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

    SciTech Connect

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

    2014-07-20

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

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

    SciTech Connect

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

    1989-10-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    Rucks, Elizabeth A.; Olson, Joan C.

    2005-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

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

    PubMed

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

    2005-08-30

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

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

    PubMed

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

    2011-11-01

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

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

    PubMed Central

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

    2008-01-01

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

  11. A new method for reshaping the cornea

    NASA Astrophysics Data System (ADS)

    Littlefield, Timothy; Koepnick, Russell G.; Binder, Perry S.; Geggel, Harry S.

    1997-01-01

    The optical theory behind a new technique for reshaping the cornea to correct refractive errors of the eye is presented. This technique is capable of excising both positive and negative meniscus (lenticular)-shaped tissues of predetermined optical power from the anterior cornea. The optical lens bending theory routinely used by optical designers to reduce the amount of spherical and comatic aberrations in a lens system is employed in this technique. This technique uses a microkeratome to remove a planoconvex, or planoconcave-shaped tissue from the cornea while the eye is in a deformed state. When the eye returns to its natural, undeformed state, a lenticular tissue of predetermined optical power has been removed, correcting for myopic or hyperopic refractive errors, respectively. An elementary introduction to the current surgical techniques used for the correction of refractive errors is presented. Meniscus cross sections of the excised tissues are shown to demonstrate the optical theory discussed.

  12. Pediatric genetic disease of the cornea

    PubMed Central

    Fecarotta, Christopher M.; Huang, Wendy W.

    2014-01-01

    Our objective is to evaluate the literature regarding selected genetic diseases of the cornea, including megalocornea, keratoglobus, keratoconus, cystinosis, the mucopolysaccharidoses, sclerocornea, Peters' anomaly, familial dysautonomia, and various corneal dystrophies. The transparency of the cornea is a consequence of uniformity in both size and spacing of the collagen lamellae. The cornea's clarity depends on a delicate biochemical and structural balance; consequently, genetic disorders that disrupt either its metabolic or anatomic function can cause opacity and vision loss. Many childhood corneal diseases have a genetic etiology and are associated with known syndromes. Each disorder has unique associated set of possible complications. Prognosis often depends on the extent of opacity and disorganization of the anterior segment. Corneal transplantation has been performed for these disorders with variable success.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Alvarez, H.; Haddock, F. T.

    1973-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Sakurai, K.

    1974-01-01

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

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

    PubMed

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

    1976-10-01

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

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

    SciTech Connect

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

    2010-12-06

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

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

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

    1986-09-01

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

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

    PubMed

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

    2016-06-01

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

  3. Terahertz optical properties of the cornea

    NASA Astrophysics Data System (ADS)

    Liu, Wen-Quan; Lu, Yuan-Fu; Jiao, Guo-Hua; Chen, Xian-Feng; Li, Jin-Ying; Chen, Si-Hai; Dong, Yu-Ming; Lv, Jian-Cheng

    2016-01-01

    We present a study aimed at developing a terahertz time domain spectroscopy (THz-TDS) system for detection of the optical properties of ex vivo rabbit corneal tissues with different water content at terahertz frequencies (0.1-0.3 THz). The refractive index decreased with frequency while the absorption coefficient increased with frequency. Our experimental results matched the theoretical calculation very well revealing that both the absorption coefficient and the refractive index of a hydrated cornea were much larger than that of a dehydrated cornea and the terahertz properties depended on the hydrate conditions of the biosamples.

  4. Experimental quantification of the tactile spatial responsivity of human cornea.

    PubMed

    Beiderman, Yevgeny; Belkin, Michael; Rotenstreich, Ygal; Zalevsky, Zeev

    2015-01-01

    We present the first experimental quantification of the tactile spatial responsivity of the cornea and we teach a subject to recognize spatial tactile shapes that are stimulated on their cornea. PMID:26158088

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2006-09-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2008-01-22

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2013-01-01

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

  15. 33 CFR 159.12a - Certification of certain Type III devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    PubMed

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

    1990-03-01

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

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

    PubMed

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

    2012-05-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2013-06-28

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Derks, Terry G J; Smit, G Peter A

    2015-05-01

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

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

    SciTech Connect

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

    1992-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

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

    PubMed

    Nissen, Carl W; Chatterjee, Abhishek

    2007-02-01

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

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

    PubMed

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

    1998-07-24

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

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

    PubMed

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

    1999-05-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    1995-01-27

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

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

    PubMed

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

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

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

    PubMed

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

    2016-02-15

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

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

    NASA Astrophysics Data System (ADS)

    Inoue, M.; Yokoo, H.

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

  4. UVA system for human cornea irradiation

    NASA Astrophysics Data System (ADS)

    Pereira, Fernando R. A.; Stefani, Mario; Otoboni, José A.; Richter, Eduardo H.; Rossi, Giuliano; Mota, Alessandro D.; Ventura, Liliane

    2009-02-01

    According to recent studies, an increase in corneal stiffness is a promising alternative for avoiding ectasias and for stagnating keratoconus of grades 1 and 2. The clinical treatment consists essentially of instilling Riboflavin (vitamin B2), in the cornea and then irradiating the corneal tissue, with UVA (365nm) radiation at 3mW/cm2 for 30min. This procedure provides collagen cross-linking in the corneal surface, increasing its stiffness. This work presents a system for UVA irradiation of the corneas at a peak wavelength of 365nm with adjustable power up to 5mW. The system has closed loop electronics to control the emitted power with 20% precision from the sated power output. The system is a prototype for performing corneal cross-linking and has been clinically tested. The closed loop electronics is a differential from the equipments available on the market.

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

    PubMed

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

    2016-05-01

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

  6. Proteoglycans contain a 4.6 A repeat in muscular dystrophy corneas: x-ray diffraction evidence.

    PubMed Central

    Quantock, A J; Klintworth, G K; Schanzlin, D J; Capel, M S; Lenz, M E; Thonar, E J

    1996-01-01

    Synchrotron x-ray diffraction patterns from macular corneal dystrophy (MCD) corneas contain an unusual reflection that arises because of an undefined ultrastructure with a periodic repeat in the region of 4.6 A. In this study, we compared with wide-angle x-ray diffraction patterns obtained from four normal human corneas and four MCD corneas. Moreover, portions of two of the MCD corneas were pretreated with a specific glycosidase to shed light on the origin of the 4.6 A reflection. None of the normal corneas produced an x-ray reflection in the region of 4.6 A, whereas all four of the MCD corneas did (MCD type I at 4.65 A and 4.63 A, MCD type II at 4.63 A and 4.67 A). This reflection was diminished after incubation of the MCD tissues with either chondroitinase ABC or N-glycanase. The findings indicate that glycosaminoglycans or proteoglycans contribute to the unusual MCD x-ray reflection and hence most likely contain a periodic 4.6 A ultrastructure. Furthermore, the results imply that periodic 4.6 A MCD ultrastructures reside in either intact, unsulfated lumican molecules and regions of the CS/DS-containing molecules or in a region of a hybrid macromolecular aggregate formed by the interaction of the two molecules. PMID:8785355

  7. CD8+ T cells suppress viral replication in the cornea but contribute to VEGF-C-induced lymphatic vessel genesis.

    PubMed

    Conrady, Christopher D; Zheng, Min; Stone, Donald U; Carr, Daniel J J

    2012-07-01

    HSV-1 is the leading cause of infectious corneal blindness in the industrialized world. CD4(+) T cells are thought to be the major leukocyte population mediating immunity to HSV-1 in the cornea as well as the likely source of immunopathology that reduces visual acuity. However, the role of CD8(+) T cells in immune surveillance of the cornea is unclear. Thus, we sought to evaluate the role of CD8(+) T cells in ocular immunity using transgenic mice in which >98% of CD8(+) T cells are specific for the immunodominant HSV-1 epitope (gBT-I.1). We found a significant reduction in virus, elevation in HSV-specific CD8(+) T cell influx, and more CD8(+) T cells expressing CXCR3 in the cornea of transgenic mice compared with those in the cornea of wild-type controls yet similar acute corneal pathology. However, by day 30 postinfection, wild-type mice had drastically more blood and lymphatic vessel projections into the cornea compared with gBT-I.1 mice, in which only lymphatic vessel growth in response to VEGF-C could be appreciated. Taken together, these results show that CD8(+) T cells are required to eliminate virus more efficiently from the cornea but play a minimal role in immunopathology as a source of VEGF-C. PMID:22649204

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

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

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

    PubMed

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

    2009-06-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Abdulcadir, Jasmine; Dällenbach, Patrick

    2013-01-01

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

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

    PubMed

    Abdulcadir, Jasmine; Dällenbach, Patrick

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-10-01

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

  16. Klf4 Regulates the Expression of Slurp1, Which Functions as an Immunomodulatory Peptide in the Mouse Cornea

    PubMed Central

    Swamynathan, Sudha; Buela, Kristine-Ann; Kinchington, Paul; Lathrop, Kira L.; Misawa, Hidemi; Hendricks, Robert L.; Swamynathan, Shivalingappa K.

    2012-01-01

    Purpose. The secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here, we examine its corneal expression and functions. Methods. Gene expression was quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent staining. Effect of Kruppel-like factor 4 (Klf4) on Slurp1 promoter was evaluated by chromatin immunoprecipitation (ChIP) and transient transfections. Adenoviral vectors were used to express Slurp1 in corneas. Leukocytic infiltration in bacterial lipopolysaccharide (LPS)–, herpes simplex virus type 1 (HSV-1)–, or adenovirus (serotype 5)–treated mouse corneas was characterized by flow cytometry. Results. Corneal expression of Slurp1 increased sharply upon mouse eyelid opening, concurrent with the elevated expression of Klf4. Slurp1 was significantly decreased in Klf4 conditional null (Klf4CN) corneas that displayed elevated expression of cytokines and cytokine receptors, as well as neutrophil influx consistent with a proinflammatory environment. In additional models of corneal inflammation, Slurp1 expression was abrogated within 24 hours of LPS injection or HSV-1 or adenoviral infection, accompanied by a predominantly neutrophilic infiltrate. Neutrophilic infiltration was enhanced in HSV-1-infected Klf4CN corneas lacking Slurp1. SLURP1 promoter activity was stimulated by KLF4, suppressed by IL-4, IL-13, and TNFα, and unperturbed by IFN-γ. Slurp1 downregulation and neutrophil influx were comparable in HSV-1-infected wild-type (WT) and Ifng−/− mouse corneas. Mouse corneas infected with Slurp1-expressing adenoviral vectors displayed reduced signs of inflammation and restricted neutrophilic infiltration compared with those infected with control vectors. Conclusions. Klf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions. PMID:23139280

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

    PubMed Central

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

    1998-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Tian, Brian Wei Cheng Anthony

    2015-01-01

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

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Gene Therapy in the Cornea: 2005-present

    PubMed Central

    Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

    2011-01-01

    Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

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

    PubMed

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

    2012-01-27

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

  8. Decorin and biglycan of normal and pathologic human corneas

    NASA Technical Reports Server (NTRS)

    Funderburgh, J. L.; Hevelone, N. D.; Roth, M. R.; Funderburgh, M. L.; Rodrigues, M. R.; Nirankari, V. S.; Conrad, G. W.

    1998-01-01

    PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

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

    PubMed

    Kenyon, Brian J; Loos, Larry G

    2005-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Hamidi, Zety Sharizat Binti

    2013-11-01

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

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

    SciTech Connect

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

    2012-02-26

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

  12. Results of Operative and Nonoperative Treatment of Rockwood Types III and V Acromioclavicular Joint Dislocation

    PubMed Central

    Joukainen, Antti; Kröger, Heikki; Niemitukia, Lea; Mäkelä, E. Antero; Väätäinen, Urho

    2014-01-01

    Background: The optimal treatment of acute, complete dislocation of the acromioclavicular joint (ACJ) is still unresolved. Purpose: To determine the difference between operative and nonoperative treatment in acute Rockwood types III and V ACJ dislocation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: In the operative treatment group, the ACJ was reduced and fixed with 2 transarticular Kirschner wires and ACJ ligament suturing. The Kirschner wires were extracted after 6 weeks. Nonoperatively treated patients received a reduction splint for 4 weeks. At the 18- to 20-year follow-up, the Constant, University of California at Los Angeles Shoulder Rating Scale (UCLA), Larsen, and Simple Shoulder Test (SST) scores were obtained, and clinical and radiographic examinations of both shoulders were performed. Results: Twenty-five of 35 potential patients were examined at the 18- to 20-year follow-up. There were 11 patients with Rockwood type III and 14 with type V dislocations. Delayed surgical treatment for ACJ was used in 2 patients during follow-up: 1 in the operatively treated group and 1 in the nonoperatively treated group. Clinically, ACJs were statistically significantly less prominent or unstable in the operative group than in the nonoperative group (normal/prominent/unstable: 9/4/3 and 0/6/3, respectively; P = .02) and in the operative type III (P = .03) but not type V dislocation groups. In operatively and nonoperatively treated patients, the mean Constant scores were 83 and 85, UCLA scores 25 and 27, Larsen scores 11 and 11, and SST scores 11 and 12 at follow-up, respectively. There were no statistically significant differences in type III and type V dislocations. In the radiographic analysis, the ACJ was wider in the nonoperative than the operative group (8.3 vs 3.4 mm; P = .004), and in the type V dislocations (nonoperative vs operative: 8.5 vs 2.4 mm; P = .007). There was no statistically significant difference between study groups in

  13. Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients

    PubMed Central

    Buznyk, Oleksiy; Pasyechnikova, Nataliya; Islam, M Mirazul; Iakymenko, Stanislav; Fagerholm, Per; Griffith, May

    2015-01-01

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial. PMID:25996570

  14. Cornea procurement from very old donors: post organ culture cornea outcome and recipient graft outcome

    PubMed Central

    Gain, P; Thuret, G; Chiquet, C; Rizzi, P; Pugniet, J L; Acquart, S; Colpart, J J; Le Petit, J C; Maugery, J

    2002-01-01

    Aim: To study the suitability of corneas from very old donors for graft after banking and their clinical and endothelial outcomes in recipients. Methods: 419 corneas stored in organ culture were divided into group 1, donors under 85 years (330 corneas) and group 2, “very old” donors aged 85 years and over (89 corneas). Endothelial cell density (ECD) before and after organ culture, discard rate before and after storage, and clinical and endothelial outcomes of the 196 penetrating keratoplasties (PKP) (158 in group 1 and 38 in group 2) were compared in a prospective longitudinal study. Results: Initial ECD was lower in group 2 than in group 1 and elimination for low ECD was more frequent in group 2 (respectively 38% v 20.2%, p=0.001). At the end of storage, because very old corneas lost fewer ECs than younger ones (respectively 4.2% v 9.5%, p=0.022), ECD was comparable between the two groups. The corneas of very old donors had a poorer macroscopic appearance at procurement and during surgery. Despite this, in grafted patients, overall graft survival in groups 1 and 2 (respectively 87.4% v 80.6%, p=0.197), visual acuity, and ECD did not differ at completion of the study (mean follow up 25 months). Conclusion: This study suggests that endothelial cell count during banking ensures that functional and cellular results of PKPs are not dramatically influenced by very old donor age. Considering Europe's ageing population, the very elderly should not be deemed off limits for corneal procurement. PMID:11914209

  15. Hybrid H-mode scenario with nitrogen seeding and type III ELMs in JET

    NASA Astrophysics Data System (ADS)

    Corre, Y.; Joffrin, E.; Monier-Garbet, P.; Andrew, Y.; Arnoux, G.; Beurskens, M.; Brezinsek, S.; Brix, M.; Buttery, R.; Coffey, I.; Crombe, K.; de La Luna, E.; Felton, R.; Giroud, C.; Hacquin, S.; Hobirk, J.; Huber, A.; Imbeaux, F.; Jachmich, S.; Kempenaars, M.; Litaudon, X.; Leggate, H.; Loarer, T.; Maddison, G.; Rachlew, E.; Rapp, J.; Sauter, O.; Savchkov, A.; Telesca, G.; Widdowson, A.; Zastrow, K. D.; Zimmermann, O.; collaborators, JET-EFDA

    2008-11-01

    The performance of the 'hybrid' H-mode regime (long pulse operation with high neutron fluency) has been extensively investigated in JET during the 2005-2007 experimental campaign up to normalized pressure βN = 3, toroidal magnetic field Bt = 1.7 T, with type I ELMs plasma edge conditions. The optimized external current drive sources, self-generated non-inductive bootstrap current and plasma core stability properties provide a good prospect of achieving a high fusion gain at reduced plasma current for long durations in ITER. One of the remaining issues is the erosion of the divertor target plates associated with the type I ELM regime. A possible solution could be to operate with a plasma edge in the type III ELM regime (reduced transient and stationary heat loads) obtained with impurity seeding. An integrated hybrid type III ELM regime with a normalized pressure βN = 2.6 (PNBI ~ 20-22 MW) and a thermal confinement factor of H_{98}^\\ast (y,2)\\sim 0.83 has been recently successfully developed on JET with nitrogen seeding. This scenario shows good plasma edge condition (compatible with the future ITER-like wall on JET) and moderate MHD activity. In this paper, we report on the experimental development of the scenario (with plasma current Ip = 1.7 MA and magnetic field Bt = 1.7 T) and the trade-off between heat load reduction at the target plates and global confinement due to nitrogen seeding and type III ELM working conditions.

  16. Towards a better understanding of magnetic exchange mediated by hydrogen bonds in Mn(III)/Fe(III) salen-type supramolecular dimers.

    PubMed

    Nemec, Ivan; Herchel, Radovan; Šilha, Tomáš; Trávníček, Zdeněk

    2014-11-01

    A thorough study of structural and magnetic properties was performed on a series of trinuclear and dinuclear Mn(III)/Fe(III) complexes consisting of [M(L4)(Solv)](+) and [Fe(CN)5(NO)](2-) moieties (M = Fe(III) or Mn(III), Solv = H2O or CH3OH, L4 = tetradentate salen-type ligands), in which dominant magnetic exchange is mediated by O(S)-H···O(Ph) hydrogen bonds in [M(L4)(Solv)](+)···[M(L4)(Solv)](+) supramolecular dimers. As deduced from magnetic analysis involving the determination of zero-field splitting (ZFS) parameters for Mn(III) and Fe(III) ions, as well as from comprehensive DFT calculations and modelling, it may be concluded that the strength of the magnetic exchange is correlated with the number of hydrogen bonds and with the O(Ph)···O(S) distance between the phenolic oxygen atom of the salen-type ligand (O(Ph)) and the oxygen atom of the solvent molecule coordinated to the adjacent metal atom (O(S)). PMID:25208575

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

    PubMed

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

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells. PMID:26636765

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

    PubMed Central

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

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells. PMID:26636765

  19. Dynamic Sensing of Cornea Deformation during an Air Puff

    NASA Astrophysics Data System (ADS)

    Yamada, Kenji; Yamasaki, Naoyuki; Gosho, Takumi; Kiuchi, Yoshiaki; Takenaka, Jouji; Higashimori, Mitsuru; Kaneko, Makoto

    In early diagnosis of glancoma, intraocular pressure measurement is one of an important method. Non-contact method has measured eye pressure through the deformation of cornea during the increase of the force due to air puff. The deformation is influenced by the cornea stiffness as well as the eye internal pressure. Since the cornea stiffness is unknown in general, it is difficult to evaluate the ture eye pressure. The dynamic behavior of cornea under air puff may provide us with a good hint for evaluating the cornea stiffness appropriately. For this purpose, we develop the sensing system composed of a high speed camera, a mirror for producing a virtual camera, a non-contact tonometer and a slit light source. This system enables us to measure the cornea deformation under concave shape. We show the experimental data for human eyes as well as an artificial eye made by transparent material.

  20. Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea.

    PubMed

    Jiang, Hong; Zuo, Yi; Zhang, Li; Li, Jidong; Zhang, Aiming; Li, Yubao; Yang, Xiaochao

    2014-03-01

    Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt. PMID:24464723

  1. A neurodystrophic syndrome resembling carbohydrate-deficient glycoprotein syndrome type III.

    PubMed

    Stibler, H; Gylje, H; Uller, A

    1999-04-01

    A 10-month old girl is described with a serum transferrin isoform abnormality of the same kind as in two previously reported girls with carbohydrate-deficient glycoprotein syndrome type III. This patient presented with joint abnormalities and rapidly developing hypsarrhythmia, hypotonia, psychomotor delay and growth retardation. Fingers, toes, nails and local skin were dysmorphic. She had pale optic discs, thoracic syringomyelia and frontal lobe atrophy at three months. The CDT value in serum was greatly elevated. Several carbohydrate-deficient isoforms were found in transferrin (four), alpha1-antitrypsin (three), antithrombin (two) and thyroxine-binding globulin (four). Mutations in the CDGS 1-gene were excluded. The CDGS III glycoprotein abnormality most probably represents a distinct disorder of glycoprotein metabolism, and needs to be considered in unclear hypsarrhythmia with developmental delay. Dysmorphic features may be added to this syndrome. PMID:10401691

  2. Induction of Type I and Type III Interferons by Borrelia burgdorferi Correlates with Pathogenesis and Requires Linear Plasmid 36

    PubMed Central

    Krupna-Gaylord, Michelle A.; Liveris, Dionysios; Love, Andrea C.; Wormser, Gary P.; Schwartz, Ira; Petzke, Mary M.

    2014-01-01

    The capacity for Borrelia burgdorferi to cause disseminated infection in humans or mice is associated with the genotype of the infecting strain. The cytokine profiles elicited by B. burgdorferi clinical isolates of different genotype (ribosomal spacer type) groups were assessed in a human PBMC co-incubation model. RST1 isolates, which are more frequently associated with disseminated Lyme disease in humans and mice, induced significantly higher levels of IFN-α and IFN-λ1/IL29 relative to RST3 isolates, which are less frequently associated with disseminated infection. No differences in the protein concentrations of IFN-γ, IL-1β, IL-6, IL-8, IL-10 or TNF-α were observed between isolates of differing genotype. The ability of B. burgdorferi to induce type I and type III IFNs was completely dependent on the presence of linear plasmid (lp) 36. An lp36-deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and specific dendritic cell (DC) subsets less efficiently than its isogenic B31 parent strain. The association defect with mDC1s and pDCs could be restored by complementation of the mutant with the complete lp36. The RST1 clinical isolates studied were found to contain a 2.5-kB region, located in the distal one-third of lp36, which was not present in any of the RST3 isolates tested. This divergent region of lp36 may encode one or more factors required for optimal spirochetal recognition and the production of type I and type III IFNs by human DCs, thus suggesting a potential role for DCs in the pathogenesis of B. burgdorferi infection. PMID:24945497

  3. Type III interferon (IFN-lambda) antagonizes the antiviral activity of interferon-alpha in vitro.

    PubMed

    Bordi, L; Lalle, E; Lapa, D; Caglioti, C; Quartu, S; Capobianchi, M R; Castilletti, C

    2013-01-01

    Type III interferons (IFN-lambda) are the most recently discovered members of IFN family. Synergism between different IFN types is well established, but for type I and type III IFNs no conclusive evidence has been reported so far. Possible synergism/antagonism between IFN-alpha and IFN-lambda in the inhibition of virus replication (EMCV, WNV lineage 1 and 2, CHIKV and HSV-1), and in the activation of intracellular pathways of IFN response (MxA and 2'-5' OAS) was evaluated in different cell lines (Vero E6, A549 and Wish cells). The antiviral potency of IFN-lambda1 and -l2 was lower than that of IFN-alpha. When IFN-alpha and -lambda were used together, the Combination Index (CI) for virus inhibition was greater than 1 virtually for all virus/host cell systems, indicating antagonistic effect. Antagonism between IFN-alpha and -l was also observed for the induction of mRNA for both MxA and 2'-5'OAS. Elucidating the interplay between IFN-alpha and -lambda may help to better understand innate defence mechanisms against viral infections, including the molecular mechanisms underlying the influence of IL-28B polymorphisms in the response to HCV and other viral infections. PMID:24382181

  4. Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells▿ †

    PubMed Central

    Bras, Marlène; Yuste, Victor J.; Roué, Gaël; Barbier, Sandrine; Sancho, Patricia; Virely, Clémence; Rubio, Manuel; Baudet, Sylvie; Esquerda, Josep E.; Merle-Béral, Hélène; Sarfati, Marika; Susin, Santos A.

    2007-01-01

    Ligation of CD47 triggers caspase-independent programmed cell death (PCD) in normal and leukemic cells. Here, we characterize the morphological and biochemical features of this type of death and show that it displays the hallmarks of type III PCD. A molecular and biochemical approach has led us to identify a key mediator of this type of death, dynamin-related protein 1 (Drp1). CD47 ligation induces Drp1 translocation from cytosol to mitochondria, a process controlled by chymotrypsin-like serine proteases. Once in mitochondria, Drp1 provokes an impairment of the mitochondrial electron transport chain, which results in dissipation of mitochondrial transmembrane potential, reactive oxygen species generation, and a drop in ATP levels. Surprisingly, neither the activation of the most representative proapoptotic members of the Bcl-2 family, such as Bax or Bak, nor the release of apoptogenic proteins AIF (apoptosis-inducing factor), cytochrome c, endonuclease G (EndoG), Omi/HtrA2, or Smac/DIABLO from mitochondria to cytosol is observed. Responsiveness of cells to CD47 ligation increases following Drp1 overexpression, while Drp1 downregulation confers resistance to CD47-mediated death. Importantly, in B-cell chronic lymphocytic leukemia cells, mRNA levels of Drp1 strongly correlate with death sensitivity. Thus, this previously unknown mechanism controlling caspase-independent type III PCD may provide the basis for novel therapeutic approaches to overcome apoptotic avoidance in malignant cells. PMID:17682056

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Glucose and glycogen metabolism in erythrocytes from normal and glycogen storage disease type III subjects

    PubMed Central

    Moses, Shimon W.; Chayoth, Reuben; Levin, Stanley; Lazarovitz, Ela; Rubinstein, David

    1968-01-01

    Active glycogen metabolism has been demonstrated in both normal and glycogen-rich erythrocytes taken from patients with type III glycogen storage disease. Activity of all enzymes catalyzing the reactions required for the synthesis and degradation of glycogen have been demonstrated in the mature erythrocytes. Uniformly labeled glucose-14C is incorporated into glycogen in intact cells of both types during incubation. Replacement of the glucose-14C by unlabeled glucose in the medium resulted in a significant loss of radioactivity from cellular glycogen. In the absence of the substrate a progressive shortening of outer branches occurred during incubation of intact glucogen-rich cells. Using cells from patients with type III glycogen storage disease, which have sufficient glycogen content to be analyzed by β-amylolysis, we demonstrated that the glucosyl units are first incorporated in the outer tiers, then transferred to the core where they tend to accumulate due to the absence of amylo-1,6-glucosidase. The glycogen-rich cells have a more rapid rate of glucose utilization upon incubation which is not reflected by a higher lactate production. The increased rate of glucose utilization did not result from an increased rate of glucose incorporation into glycogen in affected cells. The rate of 14CO2 production from glucose-1-14C during incubation was not significantly different in the two types of cells unless methylene blue was added as an electron acceptor, in which case the glycogen-rich cells oxidized glucose to CO2 more rapidly. PMID:5240360

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

    SciTech Connect

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

    2006-10-06

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

  9. Supersymmetric type-III seesaw mechanism: Lepton flavor violating decays and dark matter

    SciTech Connect

    Esteves, J. N.; Romao, J. C.; Hirsch, M.

    2011-01-01

    We study a supersymmetric version of the seesaw mechanism type III. The model consists of the minimal supersymmetric extension of the standard model particle content plus three copies of 24 superfields. The fermionic part of the SU(2) triplet contained in the 24 is responsible for the type-III seesaw, which is used to explain the observed neutrino masses and mixings. Complete copies of 24 are introduced to maintain gauge coupling unification. These additional states change the beta functions of the gauge couplings above the seesaw scale. Using minimal Supergravity boundary conditions, we calculate the resulting supersymmetric mass spectra at the electroweak scale using full 2-loop renormalization group equations. We show that the resulting spectrum can be quite different compared to the usual minimal Supergravity spectrum. We discuss how this might be used to obtain information on the seesaw scale from mass measurements. Constraints on the model space due to limits on lepton flavour violating decays are discussed. The main constraints come from the bounds on {mu}{yields}e{gamma} but there are also regions where the decay {tau}{yields}{mu}{gamma} gives stronger constraints. We also calculate the regions allowed by the dark matter constraint. For the sake of completeness, we compare our results with those for the supersymmetric seesaw type II and, to some extent, with type I.

  10. Solution structure of monomeric BsaL, the type III secretion needle protein of Burkholderia pseudomallei.

    PubMed

    Zhang, Lingling; Wang, Yu; Picking, Wendy L; Picking, William D; De Guzman, Roberto N

    2006-06-01

    Many gram-negative bacteria that are important human pathogens possess type III secretion systems as part of their required virulence factor repertoire. During the establishment of infection, these pathogens coordinately assemble greater than 20 different proteins into a macromolecular structure that spans the bacterial inner and outer membranes and, in many respects, resembles and functions like a syringe. This type III secretion apparatus (TTSA) is used to inject proteins into a host cell's membrane and cytoplasm to subvert normal cellular processes. The external portion of the TTSA is a needle that is composed of a single type of protein that is polymerized in a helical fashion to form an elongated tube with a central channel of 2-3 nm in diameter. TTSA needle proteins from a variety of bacterial pathogens share sequence conservation; however, no atomic structure for any TTSA needle protein is yet available. Here, we report the structure of a TTSA needle protein called BsaL from Burkholderia pseudomallei determined by nuclear magnetic resonance (NMR) spectroscopy. The central part of the protein assumes a helix-turn-helix core domain with two well-defined alpha-helices that are joined by an ordered, four-residue linker. This forms a two-helix bundle that is stabilized by interhelix hydrophobic contacts. Residues that flank this presumably exposed core region are not completely disordered, but adopt a partial helical conformation. The atomic structure of BsaL and its sequence homology with other TTSA needle proteins suggest potentially unique structural dynamics that could be linked with a universal mechanism for control of type III secretion in diverse gram-negative bacterial pathogens. PMID:16631790

  11. Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation.

    PubMed

    Limpert, Allison S; Carter, Bruce D

    2010-05-28

    The formation of myelin requires a series of complex signaling events initiated by the axon to surrounding glial cells, which ultimately respond by tightly wrapping the axon with layers of specialized plasma membrane thereby allowing for saltatory conduction. Activation of the transcription factor NF-kappaB in Schwann cells has been suggested to be critical for these cells to differentiate into a myelinating phenotype; however, the mechanisms by which it is activated have yet to be elucidated. Here, we demonstrate that axonal membranes are sufficient to promote NF-kappaB activation in cultured Schwann cells and identify neuregulin 1 (NRG1), specifically the membrane-bound type III isoform, as the signal responsible for activating this transcription factor. Surprisingly, neither membrane-bound type I nor the soluble NRG1 EGF domain could activate NF-kappaB, indicating that type III induces a qualitatively unique signal. The transcriptional activity of NF-kappaB was significantly enhanced by treatment with forskolin, indicating these two signals converge for maximal activation. Both ErbB2 and -3 receptors were required for transducing the NRG1 signal, because gene deletion of ErbB3 in Schwann cells or treatment with the ErbB2 selective inhibitor, PKI-166, prevented the stimulation of NF-kappaB by axonal membranes. Finally, PKI-166 blocked the activation of the transcription factor in myelinating neuron/Schwann cell co-cultures and in vivo, in developing sciatic nerves. Taken together, these data establish NRG1 type III as the activator of NF-kappaB during myelin formation. PMID:20360002

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

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1992-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  14. The Type III Radio Burst Occurrence Rate as a New Solar Activity Index: Rieger-Type periodicity

    NASA Astrophysics Data System (ADS)

    Lobzin, V. V.; Cairns, I. H.

    2012-12-01

    The type III radio burst occurrence rate (T3BOR) strongly correlates with solar activity and was recently proposed as a new index of solar activity. This index can provide complementary information and may be useful in different studies including solar cycle predictions and searches for different periodicities in solar activity. The first observations of a Rieger-type periodicity with the period of 156 days in the daily T3BOR are presented. This periodicity was detected during the time interval from 22 June 2000 to 31 December 2003. This interval partially contains maximum and the declining phase of solar cycle 23. The radio spectra were provided by the Learmonth Solar Radio Observatory in Western Australia, part of the USAF Radio Solar Telescope Network (RSTN).

  15. Binding of heparin by type III domains and peptides from the carboxy terminal hep-2 region of fibronectin.

    PubMed

    Ingham, K C; Brew, S A; Migliorini, M M; Busby, T F

    1993-11-23

    The major sites of heparin binding by fibronectin are located in fragments of 30 or 40 kDa that contain type III modules 12 through 14 or 15. Various proteolytic or recombinant subfragments and several synthetic peptides derived from this region have been compared with respect to their binding to fluorescein-labeled heparin in solution. Binding was monitored by the change in fluorescence anisotropy at 25 degrees C and pH 7.4 in 0.02 M Tris buffer, alone (TB) or with 0.15M NaCl (TBS). A 23-kDa fragment containing III13 and III14 but lacking III12 had Kd values of 0.3 and 1.8 microM in TB, and TBS, respectively, indistinguishable from the 30-kDa parent. Fragments containing only module III13 bound 2-3-fold weaker than the parent while those containing only III14 bound 6-50-fold weaker depending on the ionic strength. Fragments containing only III12 or III15 failed to bind at all in TBS. A cationic peptide derived from the amino terminus of III13 and containing the Arg-Arg-Ala-Arg consensus sequence, whose integrity was shown by Barkalow and Schwarzbauer [Barkalow, F. J., & Schwarzbauer, J. E. (1991) J. Biol. Chem. 266, 7812-7818] to be critical, failed to bind in TBS but bound weakly in TB. Two additional cationic peptides derived from the middle and C-terminal regions of III14 showed similar behavior. Thus while the major determinant(s) of heparin binding are located in III13, those determinants are only active when part of a properly folded structure. Furthermore, module III13 when isolated had a slightly lower affinity than fragments containing both III13 and III14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8241146

  16. Complete Type III Secretion System of a Mesophilic Aeromonas hydrophila Strain

    PubMed Central

    Vilches, Silvia; Urgell, Cecilia; Merino, Susana; Chacón, Matilde R.; Soler, Lara; Castro-Escarpulli, Graciela; Figueras, Maria Jose; Tomás, Juan M.

    2004-01-01

    We have investigated the existence and genetic organization of a functional type III secretion system (TTSS) in a mesophilic Aeromonas strain by initially using the Aeromonas hydrophila strain AH-3. We report for the first time the complete TTSS DNA sequence of an Aeromonas strain that comprises 35 genes organized in a similar disposition as that in Pseudomonas aeruginosa. Using several gene probes, we also determined the presence of a TTSS in clinical or environmental strains of different Aeromonas species: A. hydrophila, A. veronii, and A. caviae. By using one of the TTSS genes (ascV), we were able to obtain a defined insertion mutant in strain AH-3 (AH-3AscV), which showed reduced toxicity and virulence in comparison with the wild-type strain. Complementation of the mutant strain with a plasmid vector carrying ascV was fully able to restore the wild-type toxicity and virulence. PMID:15528564

  17. Complexation behavior of Eu(III), Tb(III), Tm(III), and Am(III) with three 1,10-phenanthroline-type ligands: insights from density functional theory.

    PubMed

    Yang, Yanqiu; Fang, Yu; Liu, Jun; Hu, Shiyuan; Hu, Sheng; Yang, Liang; Wang, Dawei; Zhang, Huabei; Luo, Shunzhong

    2015-07-01

    Extraction complexes of Eu(III), Tb(III), Tm(III), and Am(III) with three 1,10-phenanthroline-type ligands have been studied, primarily using density functional theory (DFT). The same accuracies and optimized structural geometries were obtained whether optimization of the [ML2(NO3)](2+) complexes was performed at the B3LYP/6-31G(d)/RECP or the MP2/6-31G(d)/RECP level of theory. Calculations carried out at the B3LYP/6-311G(d, p)/RECP level of theory indicated that solvation does not favor the formation of these complexes. Moreover, the ΔGg and ΔGsolv values for the reactions leading to the formation of [LnL2(NO3)](2+) complexes were seen to decrease with increasing atomic number of the lanthanide (from Eu to Tb to Tm). In addition, when a strongly hydrophobic benzo[e][1,2,4]triazine group was created in each ligand, ligand selectivity for actinides/lanthanides in acidic media improved. Even greater ligand selectivity for actinides/lanthanides in acidic media was obtained when a 5,6-diphenyl-1,2,4-triazine group was created in each ligand instead of a benzo[e][1,2,4]triazine group. Vibrational analysis and NMR spectroscopic analysis were also performed on all of the studied ligands and the metal complexes that included them. Further in-depth investigations should be undertaken in this field. PMID:26141789

  18. The type III secretion system apparatus determines the intracellular niche of bacterial pathogens.

    PubMed

    Du, Juan; Reeves, Analise Z; Klein, Jessica A; Twedt, Donna J; Knodler, Leigh A; Lesser, Cammie F

    2016-04-26

    Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functional Shigella type III secretion system, but none of its effectors, into a laboratory strain of Escherichia coli is sufficient to promote the efficient vacuole lysis and escape of the modified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for the Shigella type III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain of Yersinia remains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA of Shigella, Salmonella, and Chromobacterium, we demonstrate that a single protein component of the T3SA translocon-Shigella IpaC, Salmonella SipC, or Chromobacterium CipC-determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established. PMID:27078095

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  20. InvB is a type III secretion chaperone specific for SspA.

    PubMed

    Bronstein, P A; Miao, E A; Miller, S I

    2000-12-01

    A wide variety of gram-negative bacteria utilize a specialized apparatus called the type III secretion system (TTSS) to translocate virulence factors directly into the cytoplasm of eukaryotic cells. These translocated effectors contribute to the pathogen's ability to infect and replicate within plant and animal hosts. The amino terminus of effector proteins contains sequences that are necessary and sufficient for both secretion and translocation by TTSS. Portions of these sequences contain binding sites for type III chaperones, which facilitate efficient secretion and translocation of specific effectors through TTSS. In this study, we have utilized the yeast two-hybrid assay to identify protein-protein interactions between effector and chaperone proteins encoded within Salmonella pathogenicity island 1 (SPI-1). Several interactions were identified including a novel interaction between the effector protein, SspA (SipA), and a putative chaperone, InvB. InvB was demonstrated to bind to the amino terminus of SspA in the bacterial cytoplasm. Furthermore, InvB acts as a type III chaperone for the efficient secretion and translocation of SspA by SPI-1. InvB also permitted translocation of SspA through the SPI-2 TTSS, indicating that it is an important regulator in the recognition of SspA as a target of TTSS. Finally, it was determined that InvB does not alter the transcription of sspA but that its absence results in reduced SspA protein levels in Salmonella enterica serovar Typhimurium. PMID:11073906

  1. A Pathogen Type III Effector with a Novel E3 Ubiquitin Ligase Architecture

    PubMed Central

    Skarina, Tatiana; Xu, Xiaohui; Cui, Hong; Eschen-Lippold, Lennart; Egler, Monique; Srikumar, Tharan; Raught, Brian; Lee, Justin; Scheel, Dierk; Savchenko, Alexei; Bonas, Ulla

    2013-01-01

    Type III effectors are virulence factors of Gram-negative bacterial pathogens delivered directly into host cells by the type III secretion nanomachine where they manipulate host cell processes such as the innate immunity and gene expression. Here, we show that the novel type III effector XopL from the model plant pathogen Xanthomonas campestris pv. vesicatoria exhibits E3 ubiquitin ligase activity in vitro and in planta, induces plant cell death and subverts plant immunity. E3 ligase activity is associated with the C-terminal region of XopL, which specifically interacts with plant E2 ubiquitin conjugating enzymes and mediates formation of predominantly K11-linked polyubiquitin chains. The crystal structure of the XopL C-terminal domain revealed a single domain with a novel fold, termed XL-box, not present in any previously characterized E3 ligase. Mutation of amino acids in the central cavity of the XL-box disrupts E3 ligase activity and prevents XopL-induced plant cell death. The lack of cysteine residues in the XL-box suggests the absence of thioester-linked ubiquitin-E3 ligase intermediates and a non-catalytic mechanism for XopL-mediated ubiquitination. The crystal structure of the N-terminal region of XopL confirmed the presence of a leucine-rich repeat (LRR) domain, which may serve as a protein-protein interaction module for ubiquitination target recognition. While the E3 ligase activity is required to provoke plant cell death, suppression of PAMP responses solely depends on the N-terminal LRR domain. Taken together, the unique structural fold of the E3 ubiquitin ligase domain within the Xanthomonas XopL is unprecedented and highlights the variation in bacterial pathogen effectors mimicking this eukaryote-specific activity. PMID:23359647

  2. Cornea Optical Topographical Scan System (COTSS)

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The Cornea Optical Topographical Scan System (COTSS) is an instrument designed for use by opthalmologist to aid in performing surgical procedures such as radial keratotomy and to provide quick accurate data to aid in prescribing contact lenses and eyeglasses. A breadboard of the system was built and demonstrated in June of 1984. Additional refinements to the breadboard are needed to meet systems requirements prior to proceeding with prototype development. The present status of the COTSS instrument is given and the areas in which system refinements are required, are defined.

  3. Glycogen storage disease type III: A novel Agl knockout mouse model.

    PubMed

    Pagliarani, Serena; Lucchiari, Sabrina; Ulzi, Gianna; Violano, Raffaella; Ripolone, Michela; Bordoni, Andreina; Nizzardo, Monica; Gatti, Stefano; Corti, Stefania; Moggio, Maurizio; Bresolin, Nereo; Comi, Giacomo P

    2014-11-01

    Glycogen storage disease type III is an autosomal recessive disease characterized by a deficiency in the glycogen debranching enzyme, encoded by AGL. Essential features of this disease are hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation. Progressive skeletal myopathy, neuropathy, and/or cardiomyopathy become prominent in adults. Currently, there is no available cure. We generated an Agl knockout mouse model by deletion of the carboxy terminus of the protein, including the carboxy end of the glucosidase domain and the glycogen-binding domain. Agl knockout mice presented serious hepatomegaly, but we did not observe signs of cirrhosis or adenomas. In affected tissues, glycogen storage was higher than in wild-type mice, even in the central nervous system which has never been tested in GSDIII patients. The biochemical findings were in accordance with histological data, which clearly documented tissue impairment due to glycogen accumulation. Indeed, electron microscopy revealed the disruption of contractile units due to glycogen infiltrations. Furthermore, adult Agl knockout animals appeared less prompt to move, and they exhibited kyphosis. Three-mo-old Agl knockout mice could not run, and adult mice showed exercise intolerance. In addition, older affected animals exhibited an accelerated respiratory rate even at basal conditions. This observation was correlated with severe glycogen accumulation in the diaphragm. Diffuse glycogen deposition was observed in the tongues of affected mice. Our results demonstrate that this Agl knockout mouse is a reliable model for human glycogenosis type III, as it recapitulates the essential phenotypic features of the disease. PMID:25092169

  4. Cornea-infiltrating and lymph node dendritic cells contribute to CD4+ T cell expansion after herpes simplex virus-1 ocular infection.

    PubMed

    Buela, Kristine-Ann G; Hendricks, Robert L

    2015-01-01

    After HSV type 1 corneal infection, CD4(+) T cells are expanded in the draining lymph nodes (DLNs) and restimulated in the infected cornea to regulate the destructive inflammatory disease herpes stromal keratitis (HSK). The contribution of cornea resident, cornea-infiltrating, and DLN resident dendritic cells (DC) to CD4(+) T cell expansion in DLNs and restimulation in corneas is unknown. Cornea resident and cornea-infiltrating DCs were selectively depleted by timed local (subconjunctival) injection of diphtheria toxin (DT) into mice that express high-affinity DT receptors from the CD11c promoter. Corneal and DLN DCs were depleted by systemic (i.p.) DT treatment. We found that: 1) DCs that were resident in the cornea and DLNs at the time of infection or that migrate into the tissues during the first 24 h postinfection were not required for CD4(+) T cell expansion; 2) DCs that infiltrated the cornea >24 h postinfection were responsible for most of the CD4(+) T cell expansion measured in the DLNs at 3 and 7 d postinfection (dpi); 3) non-cornea-derived DCs that infiltrate the DLNs >24 h postinfection made a modest contribution to CD4(+) T cell expansion at 3 dpi but did not contribute at 7 dpi; and 4) surprisingly, HSK development between 7 and 21 dpi did not require corneal DCs. DC-independent HSK development appears to reflect close interactions of CD4(+) T cells with MHC class II(+) corneal epithelial cells and macrophages in infected DC-depleted corneas. PMID:25422507

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

    SciTech Connect

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

    1997-03-01

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

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

    PubMed Central

    Bisceglia, L; Calonge, M J; Totaro, A; Feliubadaló, L; Melchionda, S; García, J; Testar, X; Gallucci, M; Ponzone, A; Zelante, L; Zorzano, A; Estivill, X; Gasparini, P; Nunes, V; Palacín, M

    1997-01-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (zeta max) of 13.11 at a maximum recombination fraction (theta max) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant zeta max = 3.11 at theta max of .00, with marker D19S225). PMID:9042921

  7. Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes.

    PubMed

    Teufel, Andreas; Malik, Nasir; Mukhopadhyay, Mahua; Westphal, Heiner

    2002-09-01

    The fibronectin type III (FNIII) repeat is one of three structural motifs originally identified in the fibronectin protein and has been well characterized in recent years. The consensus sequence has since been found in many different proteins including receptors and cell adhesion molecules. We report the cloning and expression analysis of Frcp1 and Frcp2, two members of a new FNIII repeat containing gene family. During embryonic development both genes are primarily expressed in the brain. In adult tissues, Frcp1 is strongly expressed in the liver and Frcp2 in the heart. PMID:12384288

  8. Dynamics of Anisotropic Bianchi Type-III Bulk Viscous String Model with Magnetic Field

    NASA Astrophysics Data System (ADS)

    Singh, M. K.; Ram, Shri

    2014-07-01

    In this paper, we discuss the dynamics of spatially homogeneous and anisotropic Bianchi type-III string cosmological model in presence of bulk viscous fluid and electromagnetic field. Exact solutions of Einstein's field equations are obtained by assuming (i) a special form of the deceleration parameter and (ii) the component of the shear scalar tensor is proportional to mean Hubble parameter. The source of magnetic field is due to an electric current produced along z-axis. The role of bulk viscosity and magnetic field in establishing string phase of universe is presented. The physical and kinematical features of solutions are also discussed in detail.

  9. Congenital Type III von Willebrand's disease unmasked by hypothyroidism in a Shetland sheepdog.

    PubMed

    Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

    2015-09-01

    A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand's disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog's sudden bleeding tendency as has been seen with hypothyroidism in humans. PMID:26347307

  10. Developmental Defects in a Caenorhabditis elegans Model for Type III Galactosemia

    PubMed Central

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

    2014-01-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosylation process. We also observed that gale-1 mutants are hypersensitive to galactose as well as to infections. Interestingly, we found interactions between gale-1 and the unfolded protein response. PMID:25298520

  11. Expression, purification and crystallization of a fungal type III polyketide synthase that produces the csypyrones

    PubMed Central

    Yang, Dengfeng; Mori, Takahiro; Matsui, Takashi; Hashimoto, Makoto; Morita, Hiroyuki; Fujii, Isao; Abe, Ikuro

    2014-01-01

    CsyB from Aspergillus oryzae is a novel type III polyketide synthase that catalyzes the formation of csypyrone B1 [4-(3-acetyl-4-hydroxy-2-oxo-2H-pyran-6-yl)butyric acid] from fatty acyl-CoA, malonyl-CoA and acetoacetyl-CoA. Recombinant CsyB expressed in Escherichia coli was crystallized by the sitting-drop vapour-diffusion method. The crystals belonged to space P21, with unit-cell parameters a = 70.0, b = 104.8, c = 73.5 Å, β = 114.4°. PMID:24915080

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

    PubMed

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

    2014-12-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosylation process. We also observed that gale-1 mutants are hypersensitive to galactose as well as to infections. Interestingly, we found interactions between gale-1 and the unfolded protein response. PMID:25298520

  13. Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

    PubMed Central

    Scuderi, Margaret; Bessey, Lauren; Snead, Elisabeth; Burgess, Hilary; Carr, Anthony

    2015-01-01

    A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans. PMID:26347307

  14. The effect of initial conditions on the electromagnetic radiation generation in type III solar radio bursts

    SciTech Connect

    Schmitz, H.; Tsiklauri, D.

    2013-06-15

    Extensive particle-in-cell simulations of fast electron beams injected in a background magnetised plasma with a decreasing density profile were carried out. These simulations were intended to further shed light on a newly proposed mechanism for the generation of electromagnetic waves in type III solar radio bursts [D. Tsiklauri, Phys. Plasmas, 18, 052903 (2011)]. The numerical simulations were carried out using different density profiles and fast electron distribution functions. It is shown that electromagnetic L and R modes are excited by the transverse current, initially imposed on the system. In the course of the simulations, no further interaction of the electron beam with the background plasma could be observed.

  15. Serum enzymes of collagen synthesis and type III procollagen amino-propeptide in Nigerian patients with sickle cell disease.

    PubMed

    Bolarin, M

    1986-07-01

    Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity and the aminoterminal propeptide of type III procollagen were measured in 20 patients with sickle cell disease and the values were compared with those in 20 apparently healthy Nigerians. The means for the two enzymes and serum aminoterminal propeptide of type III procollagen were significantly higher in the sickle cell disease patients. Significant correlations were found between the values for the two enzymes and the protein serum aminoterminal propeptide of type III procollagen within the sickle cell disease patients. The data confirm that collagen formation is found in the liver, bone and other organs of patients with this disease. The measurement of serum immunoreactive prolyl hydroxylase protein, serum galactosylhydroxylysyl glucosyltransferase activity and serum aminoterminal propeptide of type III procollagen in prospective studies might be helpful in predicting hepatic, bone or diffuse fibrogenesis in sickle cell disease. PMID:3016143

  16. Evidence for enhanced collagen type III deposition focally in the territorial matrix of osteoarthritic hip articular cartilage

    PubMed Central

    Hosseininia, S.; Weis, M.A.; Rai, J.; Kim, L.; Funk, S.; Dahlberg, L.E.; Eyre, D.R.

    2016-01-01

    SUMMARY Objective To determine if type III collagen is concentrated in the chymotrypsin-extractable collagen pool from osteoarthritic articular cartilage to assess its potential as a biomarker of Osteoarthritis (OA) pathogenic mechanisms. Methods Full thickness articular cartilage from grossly normal surfaces was analyzed from femoral heads, obtained at hip replacement surgery, from OA (n = 10) and fracture (n = 10) patients. Collagen, extracted by α-chymotrypsin, was characterized by SDS-PAGE/Western blot analysis, ELISA and immunohistochemistry using monoclonal antibodies specific to collagens types II and III. Results α-Chymotrypsin extracted more collagen from OA than control cartilage. The extractable pool included collagen types II and III from both OA and control hips. Importantly, OA cartilage contained 6-fold more collagen type III than control cartilage, based on ELISA. The estimated total tissue ratio of collagen III/II was in the 1–10% range for individual OA cartilage samples, based on pepsin-solubilized collagen using SDS-PAGE densitometry. Collagen type III N-propeptide trimers were the main molecular fragments seen on Western blot analysis of OA and control extracts. The chymotrypsin-extracted type II collagen gave primarily full-length α1(II) chains and chain fragments of α1(II) on Western blot analysis from both OA and control tissues. Immunohistochemistry showed that type III collagen was more concentrated in the upper half of OA cartilage and in the territorial matrix around individual chondrocytes and chondrocyte clusters. Conclusions The findings confirm that collagen type III deposition occurs in adult articular cartilage but significantly more pronounced in osteoarthritic joints, presenting a potential marker of matrix repair or pathobiology. PMID:26790721

  17. Collagen Type III and VI Turnover in Response to Long-Term Immobilization

    PubMed Central

    Sun, Shu; Henriksen, Kim; Karsdal, Morten A.; Byrjalsen, Inger; Rittweger, Jörn; Armbrecht, Gabriele; Belavy, Daniel L.; Felsenberg, Dieter; Nedergaard, Anders F.

    2015-01-01

    Background Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. Methods In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week’s strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. Results Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. Conclusion The Pro-C3 and–C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading. PMID:26641456

  18. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I

    SciTech Connect

    Zhang, Z.P.; Lindstedt, M.; Falk, G.; Blombaeck, M.; Egberg, N.; Anvret, M. )

    1992-10-01

    von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA[yields]TGA) were detected in exons 28, 32, and 45 by screening of all 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicted that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I found to be heterozygous for the mutation. 21 refs., 5 figs., 4 tabs.

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

    USGS Publications Warehouse

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

    2008-01-01

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

  20. SOLAR CYCLE VARIATIONS OF THE OCCURRENCE OF CORONAL TYPE III RADIO BURSTS AND A NEW SOLAR ACTIVITY INDEX

    SciTech Connect

    Lobzin, Vasili; Cairns, Iver H.; Robinson, Peter A.

    2011-07-20

    This Letter presents the results of studies of solar cycle variations of the occurrence rate of coronal type III radio bursts. The radio spectra are provided by the Learmonth Solar Radio Observatory (Western Australia), part of the USAF Radio Solar Telescope Network (RSTN). It is found that the occurrence rate of type III bursts strongly correlates with solar activity. However, the profiles for the smoothed type III burst occurrence rate differ considerably from those for the sunspot number, 10.7 cm solar radio flux, and solar flare index. The type III burst occurrence rate (T3BOR) is proposed as a new index of solar activity. T3BOR provides complementary information about solar activity and should be useful in different studies including solar cycle predictions and searches for different periodicities in solar activity. This index can be estimated from daily results of the Automated Radio Burst Identification System. Access to data from other RSTN sites will allow processing 24 hr radio spectra in near-real time and estimating true daily values of this index. It is also shown that coronal type III bursts can even occur when there are no visible sunspots on the Sun. However, no evidence is found that the bursts are not associated with active regions. It is also concluded that the type III burst productivity of active regions exhibits solar cycle variations.

  1. Biomechanics and Wound Healing in the Cornea

    PubMed Central

    Dupps, William J.; Wilson, Steven E.

    2009-01-01

    The biomechanical and wound healing properties of the cornea undermine the predictability and stability of refractive surgery and contribute to discrepancies between attempted and achieved visual outcomes after LASIK, surface ablation and other keratorefractive procedures. Furthermore, patients predisposed to biomechanical failure or abnormal wound healing can experience serious complications such as keratectasia or clinically significant corneal haze, and more effective means for the identification of such patients prior to surgery are needed. In this review, we describe the cornea as a complex structural composite material with pronounced anisotropy and heterogeneity, summarize current understanding of major biomechanical and reparative pathways that contribute to the corneal response to laser vision correction, and review the role of these processes in ectasia, intraocular pressure measurement artifact, diffuse lamellar keratitis (DLK) and corneal haze. The current understanding of differences in the corneal response after photorefractive keratectomy (PRK), LASIK and femtosecond-assisted LASIK are reviewed. Surgical and disease models that integrate corneal geometric data, substructural anatomy, elastic and viscoelastic material properties and wound healing behavior have the potential to improve clinical outcomes and minimize complications but depend on the identification of preoperative predictors of biomechanical and wound healing responses in individual patients. PMID:16720023

  2. Cornea, and the swelling of polyelectrolyte gels of biological interest

    NASA Astrophysics Data System (ADS)

    Elliott, Gerald F.; Hodson, Stuart A.

    1998-10-01

    Biological polyelectrolyte gels consist of insoluble aggregates of molecules which collectively form structural fibrils and these fibrils, or their chemically bound side chains, have a net electrical charge. These gels may be visualized as negatively charged fibrils immersed in aqueous solutions which include free diffusible ions (mainly sodium, potassium and chloride). All living cells and most of the extracellular spaces of the body are polyelectrolyte gels and they strive to swell by the absorption of additional fluid because of the Donnan potentials generated by their fixed charge. We review Donnan swelling using the cornea of the eye as prime material. Donnan swelling requires knowledge of only one parameter such as: (a) the electrical potential within the gel or (b) the distribution of any mobile ion inside and outside the gel or (c) measurement of the gel pressure or (d) the fixed charge density on the fibrils, in order to calculate all the other relevant factors. We describe the conditions (which usually exist in biological tissue) when the microscopic distribution of the fixed charge density within the gel is not important to the Donnan phenomena. Fixed charge density is generated by two sources: permanent negative charges in the structural fibrils and transient mobile ion binding to the fibrils. Ion binding to large molecules is reviewed. In the case of the cornea, transient mobile ion binding is the predominant factor in generating fixed charge density under physiological conditions. An irreversible thermodynamic treatment of gel swelling shows the intrinsic instability of polyelectrolyte gels and suggests new ways of approaching a microscopic model for osmosis. In order to stabilize the two forces (osmotic potential and chemical potential) which generate the polyelectrolyte gel instability we review the types of third forces which must be present in order to stabilize biological gels. These third forces include van der Waal's force, metabolically driven

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-10-01

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

  5. Spinal muscular atrophy type III: Molecular genetic characterization of Turkish patients.

    PubMed

    Bora-Tatar, Gamze; Yesbek-Kaymaz, Ayse; Bekircan-Kurt, Can Ebru; Erdem-Özdamar, Sevim; Erdem-Yurter, Hayat

    2015-12-01

    Spinal Muscular Atrophy (SMA) is a neurodegenerative disease with autosomal recessive inheritance. Homozygous loss of exon 7 of the Survival of motor neuron 1 (SMN1) gene is the main cause of SMA. Although progressive muscle weakness and atrophy are common symptoms, disease severity varies from severe to mild. Type III is one of the milder and less frequent forms of SMA. In this study, we report molecular genetic characteristics of 24 Turkish type III SMA patients. Homozygous loss of SMN1 exon 7 and 8 was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex ligation dependent probe amplification (MLPA). SMN2, homologue of SMN1, and Neuronal apoptosis inhibitory protein (NAIP) genes were also evaluated considering their influence on disease severity. We determined that male patients who were born in consanguineous families were predominant in our cohort and these patients mostly carry the homozygous loss of SMN1 exon 7 and 8 and four copies of SMN2 gene without NAIP deletions. PMID:26548498

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2006-07-01

    Chalcone synthase (CHS) related type III plant polyketide synthases (PKSs) are likely to be involved in the biosynthesis of diarylheptanoids (e.g. curcumin and polycyclic phenylphenalenones), but no such activity has been reported. Root cultures from Wachendorfia thyrsiflora (Haemodoraceae) are a suitable source to search for such enzymes because they synthesize large amounts of phenylphenalenones, but no other products that are known to require CHSs or related enzymes (e.g. flavonoids or stilbenes). A homology-based RT-PCR strategy led to the identification of cDNAs for a type III PKS sharing only approximately 60% identity with typical CHSs. It was named WtPKS1 (W. thyrsiflora polyketide synthase 1). The purified recombinant protein accepted a large variety of aromatic and aliphatic starter CoA esters, including phenylpropionyl- and side-chain unsaturated phenylpropanoid-CoAs. The simplest model for the initial reaction in diarylheptanoid biosynthesis predicts a phenylpropanoid-CoA as starter and a single condensation reaction to a diketide. Benzalacetones, the expected release products, were observed only with unsaturated phenylpropanoid-CoAs, and the best results were obtained with 4-coumaroyl-CoA (80% of the products). With all other substrates, WtPKS1 performed two condensation reactions and released pyrones. We propose that WtPKS1 catalyses the first step in diarylheptanoid biosynthesis and that the observed pyrones are derailment products in the absence of downstream processing proteins. PMID:16496097

  8. Visibility of Type III burst source location as inferred from stereoscopic space observations

    NASA Astrophysics Data System (ADS)

    Boudjada, M. Y.; Galopeau, P. H. M.; Maksimovic, M.; Rucker, H. O.

    2014-11-01

    We study solar Type III radio bursts simultaneously observed by RPWS/Cassini, URAP/Ulysses and WAVES/Wind experiments. The observations allows us to cover a large frequency bandwidth from 16MHz down to a few kHz. We consider the onset time of each burst, and estimate the corresponding intensity level. Also we measure the Langmuir frequency as observed on the dynamic spectra recorded by the Ulysses spacecraft. The distances of Wind, Ulysses and Cassini spacecraft, with regard to the Sun, were in the order of 1AU, 2.4AU and 4.5AU, respectively. The spacecraft trajectories were localized in the ecliptic plane in the case of Wind and Cassini, and for Ulysses in the southern hemisphere (i.e. heliocentric latitude higher than -50). Despite the different locations, the spectral patterns of the selected solar bursts are found to be similar between 10MHz and 2MHz but unalike at lower frequency. We discuss the variation of the intensity level as recorded by the three spacecraft. We show that the reception system of each experiment affected the way the Type III burst intensity is measured. Also we attempt to estimate the electron beam along the interplanetary magnetic field where the trajectory is an Archimedean spiral. This leads us to infer on the visibility of the source location with regard to the spacecraft position.

  9. Endofungal bacterium controls its host by an hrp type III secretion system.

    PubMed

    Lackner, Gerald; Moebius, Nadine; Hertweck, Christian

    2011-02-01

    Burkholderia rhizoxinica and Rhizopus microsporus form a unique symbiosis in which intracellular bacteria produce the virulence factor of the phytopathogenic fungus. Notably, the host strictly requires endobacteria to sporulate. In this study, we show that the endofungal bacteria possess a type III secretion system (T3SS), which has a crucial role in the maintenance of the alliance. Mutants defective in type III secretion show reduced intracellular survival and fail to elicit sporulation of the host. Furthermore, genes coding for T3SS components are upregulated during cocultivation of the bacterial symbiont with their host. This is the first report on a T3SS involved in bacterial-fungal symbiosis. Phylogenetic analysis revealed that the T3SS represents a prototype of a clade of yet uncharacterized T3SSs within the hrp superfamily of T3SSs from plant pathogenic microorganisms. In a control experiment, we demonstrate that under laboratory conditions, rhizoxin production was not required for establishment of the symbiotic interaction. PMID:20720578

  10. 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.

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

    PubMed Central

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

    2016-01-01

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

  12. Detergent Isolation Stabilizes and Activates the Shigella Type III Secretion System Translocator Protein IpaC.

    PubMed

    Bernard, Abram R; Duarte, Shari M; Kumar, Prashant; Dickenson, Nicholas E

    2016-07-01

    Shigella rely on a type III secretion system as the primary virulence factor for invasion and colonization of human hosts. Although there are an estimated 90 million Shigella infections, annually responsible for more than 100,000 deaths worldwide, challenges isolating and stabilizing many type III secretion system proteins have prevented a full understanding of the Shigella invasion mechanism and additionally slowed progress toward a much needed Shigella vaccine. Here, we show that the non-denaturing zwitterionic detergent N, N-dimethyldodecylamine N-oxide (LDAO) and non-ionic detergent n-octyl-oligo-oxyethylene efficiently isolated the hydrophobic Shigella translocator protein IpaC from the co-purified IpaC/IpgC chaperone-bound complex. Both detergents resulted in monomeric IpaC that exhibits strong membrane binding and lysis characteristics while the chaperone-bound complex does not, suggesting that the stabilizing detergents provide a means of following IpaC "activation" in vitro. Additionally, biophysical characterization found that LDAO provides significant thermal and temporal stability to IpaC, protecting it for several days at room temperature and brief exposure to temperatures reaching 90°C. In summary, this work identified and characterized conditions that provide stable, membrane active IpaC, providing insight into key interactions with membranes and laying a strong foundation for future vaccine formulation studies taking advantage of the native immunogenicity of IpaC and the stability provided by LDAO. PMID:27297397

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

    PubMed Central

    Hu, Soo-young; Choi, Jin-gyu

    2015-01-01

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

  14. Methicillin-resistant Staphylococcus aureus sequence type 239-III, Ohio, USA, 2007-2009.

    PubMed

    Wang, Shu-Hua; Khan, Yosef; Hines, Lisa; Mediavilla, José R; Zhang, Liangfen; Chen, Liang; Hoet, Armando; Bannerman, Tammy; Pancholi, Preeti; Robinson, D Ashley; Kreiswirth, Barry N; Stevenson, Kurt B

    2012-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen that has diverse molecular heterogeneity. Most MRSA strains in the United States are pulsed-field gel electrophoresis USA100 sequence type (ST) 5 and USA300 ST8. Infections with MRSA ST239-III are common and found during health care-associated outbreaks. However, this strain has been rarely reported in the United States. As part of a study supported by the Prevention Epicenter Program of the Centers for Disease Control and Prevention (Atlanta, GA, USA), which evaluated transmission of MRSA among hospitals in Ohio, molecular typing identified 78 (6%) of 1,286 patients with MRSA ST239-III infections. Ninety-five percent (74/78) of these infections were health care associated, and 65% (51/78) of patients had histories of invasive device use. The crude case-fatality rate was 22% (17/78). Identification of these strains, which belong to a virulent clonal group, emphasizes the need for molecular surveillance. PMID:23018025

  15. The Type III secretion system of Gram-negative bacteria: a potential therapeutic target?

    PubMed

    Müller, Simone; Feldman, Mario F; Cornelis, Guy R

    2001-06-01

    Several pathogenic Gram-negative bacteria, including Salmonella, Shigella, Yersinia, Pseudomonas aeruginosa and enteropathogenic Escherichia coli harbour a complex attack system called 'Type III secretion' which is, in every case, an essential virulence determinant. This system, activated by contact with an eukaryotic cell membrane, allows bacteria to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane, to reach the cell's cytosol and destroy or subvert the host cell. The Type III virulence mechanism consists of a secretion apparatus, made up of about 25 proteins, and a set of effector proteins released by this apparatus. The mechanism of protein secretion is highly conserved among the different bacteria, although they cause a variety of diseases with different symptoms and severities, from fatal septicaemia to mild diarrhoea or from fulgurant diarrhoea to chronic infection of the lung. This review focuses on the proteins that make up the secretion machinery and examine if it could be a potential target for novel antimicrobials. PMID:12540268

  16. Structure and Function of the Type III Secretion System of Pseudomonas aeruginosa

    PubMed Central

    Galle, Marlies; Carpentier, Isabelle; Beyaert, Rudi

    2012-01-01

    Pseudomonas aeruginosa is a dangerous pathogen particularly because it harbors multiple virulence factors. It causes several types of infection, including dermatitis, endocarditis, and infections of the urinary tract, eye, ear, bone, joints and, of particular interest, the respiratory tract. Patients with cystic fibrosis, who are extremely susceptible to Pseudomonas infections, have a bad prognosis and high mortality. An important virulence factor of P. aeruginosa, shared with many other gram-negative bacteria, is the type III secretion system, a hollow molecular needle that transfers effector toxins directly from the bacterium into the host cell cytosol. This complex macromolecular machine works in a highly regulated manner and can manipulate the host cell in many different ways. Here we review the current knowledge of the structure of the P. aeruginosa T3SS, as well as its function and recognition by the immune system. Furthermore, we describe recent progress in the development and use of therapeutic agents targeting the T3SS. PMID:23305368

  17. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review.

    PubMed

    Miranda, Amanda Rodrigues; Ue, Ana Paula Fusel de; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; Souza, Patrícia Karla de; Rotta, Osmar

    2013-01-01

    In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented. PMID:24068129

  18. Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.

    PubMed

    Graña, José Luis; Redondo, Natalia; Muñoz-Rivas, Marina J; Cantos, Arthur L

    2014-01-01

    This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%), moderate (27.8%) and high (7.1%). This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types. PMID:25329828

  19. Subtypes of Batterers in Treatment: Empirical Support for a Distinction between Type I, Type II and Type III

    PubMed Central

    Graña, José Luis; Redondo, Natalia; Muñoz-Rivas, Marina J.; Cantos, Arthur L.

    2014-01-01

    This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%), moderate (27.8%) and high (7.1%). This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types. PMID:25329828

  20. Bioengineered corneas for transplantation and in vitro toxicology.

    PubMed

    McLaughlin, Christopher R; Tsai, Ray J-F; Latorre, Malcolm A; Griffith, May

    2009-01-01

    Bioengineered corneas have been designed to replace partial or the full-thickness of defective corneas, as an alternative to using donor tissues. They range from prosthetic devices that solely address replacement of the cornea's function, to tissue engineered hydrogels that permit regeneration of host tissues. In cases where corneal stem cells have been depleted by injury or disease, most frequently involving the superficial epithelium, tissue engineered lamellar implants reconstructed with stem cells have been transplanted. In situ methods using ultraviolet A (UVA) crosslinking have also been developed to strengthen weakened corneas. In addition to the clinical need, bioengineered corneas are also rapidly gaining importance in the area of in vitro toxicology, as alternatives to animal testing. More complex, fully innervated, physiologically active, three-dimensional organotypic models are also being tested. PMID:19273277

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

    PubMed Central

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

    2015-01-01

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

  2. Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia

    PubMed Central

    Georgiadou, Dimitra; Chroni, Angeliki; Vezeridis, Alexander; Zannis, Vassilis I.; Stratikos, Efstratios

    2011-01-01

    Background Apolipoprotein E (apoE) is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136–150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. Methodology/Principal Findings In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD) spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS) binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. Conclusions/Significance Overall, our findings suggest that single amino acid changes in the functionally important region 136–150 of apoE3 can affect the molecule's stability and conformation in solution and may underlie

  3. UV Crosslinking of Donor Corneas Confers Resistance to Keratolysis

    PubMed Central

    Arafat, Samer N.; Robert, Marie-Claude; Shukla, Anita N.; Dohlman, Claes H.; Chodosh, James; Ciolino, Joseph B.

    2014-01-01

    Purpose To develop a modified ex vivo corneal crosslinking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. Methods Ex vivo crosslinking of human corneas was performed using Barron® artificial anterior chambers. The corneas were de-epithelialized, pre-treated with riboflavin solution (0.1% riboflavin/20% dextran) and irradiated with ultraviolet A (UVA) light (λ=370nm, irradiance=3mW/cm2) for various durations. The combined effect of UVA and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37 degrees Celsius with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. Results De-epithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Crosslinked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 +/− 2.6 hours (p < 0.0001). The corneal tissues’ resistance to collagenase increased with longer UVA exposure, reaching a plateau at 30 minutes. Crosslinking both the anterior and posterior corneas did not provide added resistance when compared to crosslinking the anterior corneas only (p>0.05). γ-irradiated corneas dissolved as readily as de-epithelialized controls regardless of whether they were further crosslinked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (p=0.43) Conclusions Collagen crosslinking of the de-epithelialized anterior cornea surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A. PMID:25014151

  4. Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas

    PubMed Central

    Kowalczuk, Laura; Latour, Gaël; Bourges, Jean-Louis; Savoldelli, Michèle; Jeanny, Jean-Claude; Plamann, Karsten; Schanne-Klein, Marie-Claire; Behar-Cohen, Francine

    2013-01-01

    Purpose This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas. Methods Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study. Results In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization. Conclusion Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients. Translational Relevance This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes. PMID:24049714

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

    PubMed Central

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

    2008-01-01

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

  6. Adenovirus type 2 VAI RNA transcription by polymerase III is blocked by sequence-specific methylation.

    PubMed Central

    Jüttermann, R; Hosokawa, K; Kochanek, S; Doerfler, W

    1991-01-01

    Sequence-specific methylation of the promoter and adjacent regions in mammalian genes transcribed by RNA polymerase II leads to the inhibition of these genes. So far, RNA polymerase III-transcribed genes have not been investigated in depth. We therefore studied methylation effects on the RNA polymerase III-transcribed VAI gene of adenovirus type 2 DNA. The VAI gene contains 20 5'-CG-3' dinucleotides, of which 4 (20%) can be methylated by HpaII (5'-CCGG-3') and HhaI (5'-GCGC-3'). Three of these 5'-CG-3' sequences are located close to the internal regulatory region of the VAI segment. An unmethylated, a 5'-CCGG-3'- and 5'-GCGC-3'-methylated, and a 5'-CG-3'-methylated pUC18 construct containing the VAI and VAII regions were transfected into mammalian cells. In many experiments, an inactivating effect of 5'-CCGG-3' and 5'-GCGC-3' DNA methylation on the VAI region was not observed. In contrast, methylation of all 20 5'-CG-3' sequences in the VAI region by a CpG-specific DNA methyltransferase from Spiroplasma species did interfere with VAI transcription. Transcription of the VAI- and VAII- and of the VAI-containing constructs was also shown to be inhibited in an in vitro cell-free transcription system after the constructs had been methylated at the 5'-CCGG-3' and 5'-GCGC-3' sequences or at all 5'-CG-3' sequences. When an oligodeoxyribonucleotide which carried the internal control block A of the VAI region was methylated at three 5'-CG-3' sequences, the formation of a complex with HeLa nuclear proteins was abrogated. The results presented support the notion that the VAI gene transcribed by the DNA-dependent RNA polymerase III is also inactivated by methylation of the decisive 5'-CG-3' sequences. Images PMID:2002541

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

    SciTech Connect

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

    1986-11-07

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

  8. Serum enzymes of collagen synthesis and type III procollagen aminopropeptide in Nigerian patients with sickle cell disease.

    PubMed

    Bolarin, D M

    1986-07-01

    Serum immunoreactive prolyl hydroxylase protein (S-IRPH), galactosylhydroxylysyl glucosyltransferase activity (S-GGT), and the aminoterminal propeptide of type III procollagen (S-Pro(III)-N-P) were measured in 20 patients with sickle cell disease and the values were compared with those in 20 apparently healthy Nigerians. The means for the two enzymes and S-Pro(III)-N-P were significantly elevated in the sickle cell disease patients. Significant correlations were found between the values of the two enzymes and the protein (S-Pro(III)-N-P) within the sickle cell disease patients. The data confirm that collagen formation is found in the bone, liver, or other organs of patients with this disease. The measurement of S-GGT and S-Pro(III)-N-P in prospective studies might be helpful in predicting general and hepatic fibrogenesis in sickle cell disease. PMID:3018272

  9. Serum Enzymes of Collagen Synthesis and Type III Procollagen Aminopropeptide in Nigerian Patients With Sickle Cell Disease

    PubMed Central

    Bolarin, Debayo M.

    1986-01-01

    Serum immunoreactive prolyl hydroxylase protein (S-IRPH), galactosylhydroxylysyl glucosyltransferase activity (S-GGT), and the aminoterminal propeptide of type III procollagen (S-Pro(III)-N-P) were measured in 20 patients with sickle cell disease and the values were compared with those in 20 apparently healthy Nigerians. The means for the two enzymes and S-Pro(III)-N-P were significantly elevated in the sickle cell disease patients. Significant correlations were found between the values of the two enzymes and the protein (S-Pro(III)-N-P) within the sickle cell disease patients. The data confirm that collagen formation is found in the bone, liver, or other organs of patients with this disease. The measurement of S-GGT and S-Pro(III)-N-P in prospective studies might be helpful in predicting general and hepatic fibrogenesis in sickle cell disease. PMID:3018272

  10. Cesarean delivery and colon resection in a patient with type III osteogenesis imperfecta.

    PubMed

    Fiegel, Matthew J

    2011-09-01

    OBJECTIVE. Osteogenesis imperfecta is a connective tissue disorder that results from the inability to produce normal collagen. Eight types are described; type II is considered the lethal variant. Because of abnormal collagen production, these patients possess many anatomic and functional abnormalities. In addition to the obvious brittle bones, osteogenesis imperfecta patients may also possess respiratory, cardiac, spinal, endocrine, and hematologic abnormalities. These numerous derangements can lead to a challenging perioperative course. CASE REPORT. This report describes a case of a 27-year-old woman, G1P0 with history of type III osteogenesis imperfecta presenting at 31+ weeks with preterm premature rupture of membranes, lower extremity edema, and constipation. Because of progressive labor and cephalopelvic disproportion, an urgent cesarean section was performed under general anesthesia. Intraoperative coagulopathy was noted. After hemostasis was achieved, a colonic mass below the splenic flexure that measured 20 × 10 cm was revealed. General surgery was consulted intraoperatively, and a rectosigmoid resection was performed for a presumed colonic pseudo-obstruction. Patient tolerated the procedure well and was extubated at the completion of the case. The patient was discharged home on postoperative day 5. CLINICAL CHALLENGES. (a) Preoperative assessment of an osteogenesis imperfecta patient, (b) determination of anesthetic type, (c) management of hemorrhage/cardiovascular instability, and (d) management of hyperthermia. CONCLUSIONS. This case report illustrates that, with proper knowledge of this disease state, osteogenesis imperfecta patients can undergo a safe anesthetic during a potentially challenging combined cesarean section/colonic resection. PMID:21813546

  11. T3_MM: A Markov Model Effectively Classifies Bacterial Type III Secretion Signals

    PubMed Central

    Wang, Yejun; Sun, Ming'an; Bao, Hongxia; White, Aaron P.

    2013-01-01

    Motivation Type III Secretion Systems (T3SSs) play important roles in the interaction between gram-negative bacteria and their hosts. T3SSs function by translocating a group of bacterial effector proteins into the host cytoplasm. The details of specific type III secretion process are yet to be clarified. This research focused on comparing the amino acid composition within the N-terminal 100 amino acids from type III secretion (T3S) signal sequences or non-T3S proteins, specifically whether each residue exerts a constraint on residues found in adjacent positions. We used these comparisons to set up a statistic model to quantitatively model and effectively distinguish T3S effectors. Results In this study, the amino acid composition (Aac) probability profiles conditional on its sequentially preceding position and corresponding amino acids were compared between N-terminal sequences of T3S and non-T3S proteins. The profiles are generally different. A Markov model, namely T3_MM, was consequently designed to calculate the total Aac conditional probability difference, i.e., the likelihood ratio of a sequence being a T3S or a non-T3S protein. With T3_MM, known T3S and non-T3S proteins were found to well approximate two distinct normal distributions. The model could distinguish validated T3S and non-T3S proteins with a 5-fold cross-validation sensitivity of 83.9% at a specificity of 90.3%. T3_MM was also shown to be more robust, accurate, simple, and statistically quantitative, when compared with other T3S protein prediction models. The high effectiveness of T3_MM also indicated the overall Aac difference between N-termini of T3S and non-T3S proteins, and the constraint of Aac exerted by its preceding position and corresponding Aac. Availability An R package for T3_MM is freely downloadable from: http://biocomputer.bio.cuhk.edu.hk/softwares/T3_MM. T3_MM web server: http://biocomputer.bio.cuhk.edu.hk/T3DB/T3_MM.php. PMID:23472154

  12. {nu}-gauge mediated supersymmetry breaking with type III seesaw mechanism and phenomenology

    SciTech Connect

    Mohapatra, R. N.; Okada, Nobuchika; Yu Haibo

    2008-10-01

    We show that when the supersymmetric SU(5) model is extended to explain small neutrino masses by the type III seesaw mechanism, the new 24-dimensional fields needed for the purpose can act as messengers for transmitting SUSY breaking from a hidden sector to the visible sector. For the three 24s case, the constraints of grand unification and suppressed lepton flavor violation restrict the seesaw scale in this case to be in the narrow range of 10{sup 12}-10{sup 13} GeV. The model predicts (i) a stable lightest superpartner gravitino with mass in the range of 1-10 MeV which can be a cold dark matter of the universe; (ii) a stau next to lightest superpartner, which is detectable at the LHC; (iii) a lower bound on the branching ratio BR({mu}{yields}e{gamma}) larger than 10{sup -14} testable by the ongoing Muegamma (MEG) experiment as well as a characteristic particle spectrum different from other SUSY breaking scenarios. We also discuss the case with two 24 fields, which is the minimal case that can explain neutrino oscillation data.

  13. Statistical study of the correlation of hard X-ray and type III radio bursts in solar flares

    NASA Technical Reports Server (NTRS)

    Hamilton, Russell J.; Petrosian, Vahe; Benz, A. O.

    1990-01-01

    A large number of hard X-ray events which occurred during the maximum of solar cycle 21 have been analyzed in order to study their correlation with type III bursts. It is found that the distribution of occurrences of hard X-ray bursts correlated with type III radio bursts is significantly different from the distribution of all hard X-ray bursts. This result is consistent with the assumption that the hard X-ray and type III intensities are somewhat correlated. A bivariate distribution function of the burst intensities is fitted to the data and is used to determine that the typical ratio of X-ray intensity to type II intensity is about 10 and that the ratio of the number of X-ray producing-electrons to type III-producing electrons is about 1000. Three models which have been proposed to explain the relation between the accelerated hard X-ray and type III-producing electrons are examined in the context of these observations.

  14. [Current regenerative therapy for the cornea].

    PubMed

    Nakamura, Takahiro; Kinoshita, Shigeru

    2008-05-01

    The cornea is the avascular, transparent, and main optical element of the eye consisting primarily of 3 layers: the corneal epithelium, stroma, and endothelium. It is believed that corneal epithelial stem cells exist in the basal cell layer of the limbal region. In cases of corneal epithelial stem cell deficiency, corneal epithelial replacement using a tissue engineering technique holds great promise for ocular surface reconstruction. Autologous cultivated corneal epithelial sheets are the safest and most reliable treatment, however, they are not useful for treating bilaterally affected ocular surface disorders. In order to treat these bilateral cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. PMID:18464516

  15. An Unusual Traumatic Lamellar Laceration of Cornea

    PubMed Central

    Karkhanis, Amar; Shitole, Satish C

    2015-01-01

    Lamellar laceration of the cornea may occur following ocular trauma. The management of lamellar laceration will depend on whether the lacerated corneal flaps are displaced or undisplaced. We hereby report an unusual case of large traumatic lamellar corneal laceration in right eye in a 14-year-old girl presenting with diminution of vision. Slit lamp biomicroscopic examination showed partial thickness corneal flap of 11.5mm X 7mm from 11o’clock to 6 o’clock position with 3 mm superonasal displacement associated with stromal folds and shifting of inferior limbus and conjunctiva. Surgery was the appropriate option which included visualization of inferior limbus by incising conjunctiva, repositioning of displaced corneal flap and securing it with sutures. Immediate examination and proper surgical management of lamellar corneal injuries results in good visual outcome and prevention of complications like fibrous ingrowth and infection. PMID:26266144

  16. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity.

    PubMed

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina; Staeheli, Peter; Hartmann, Rune; Jensen, Uffe B; Dagnaes-Hansen, Frederik; Thomsen, Allan R; Chen, Zhi; Haugen, Harald; Klucher, Kevin; Paludan, Søren R

    2008-02-15

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda was restricted to a narrow subset of cells, including plasmacytoid dendritic cells and epithelial cells. To examine the role of type III IFN in antiviral defense, we generated IL-28Ralpha-deficient mice. These mice were indistinguishable from wild-type mice with respect to clearance of a panel of different viruses, whereas mice lacking the type I IFN receptor (IFNAR(-/-)) were significantly impaired. However, the strong antiviral activity evoked by treatment of mice with TLR3 or TLR9 agonists was significantly reduced in both IL-28RA(-/-) and IFNAR(-/-) mice. The type I IFN receptor system has been shown to mediate positive feedback on IFN-alphabeta expression, and we found that the type I IFN receptor system also mediates positive feedback on IFN-lambda expression, whereas IL-28Ralpha signaling does not provide feedback on either type I or type III IFN expression in vivo. Finally, using bone-marrow chimeric mice we showed that TLR-activated antiviral defense requires expression of IL-28Ralpha only on nonhemopoietic cells. In this compartment, epithelial cells responded to IFN-lambda and directly restricted virus replication. Our data suggest type III IFN to target a specific subset of cells and to contribute to the antiviral response evoked by TLRs. PMID:18250457

  17. Hydration dependent viscoelastic tensile behavior of cornea.

    PubMed

    Hatami-Marbini, Hamed

    2014-08-01

    The cornea is a protective transparent connective tissue covering the front of the eye. The standard uniaxial tensile experiments are among the most popular techniques for investigating biomechanical properties of the cornea. This experimental method characterizes the stress-strain response of corneal strips immersed in a bathing solution. In the present study, the important roles of corneal hydration on tensile viscoelastic properties were investigated. The thickness was used as a surrogate for hydration and uniaxial tensile experiments were performed on bovine corneal samples with four different average thickness (hydration), i.e., 1100 μm (4.87 mg water/mg dry tissue), 900 μm (4.13 mg water/mg dry tissue), 700 μm (3.20 mg water/mg dry tissue), and 500 μm (1.95 mg water/mg dry tissue). The samples were immersed in mineral oil in order to prevent their swelling during the experiments. A quasilinear viscoelastic (QLV) model was used to analyze the experimental measurements and determine viscoelastic material constants. It was observed that both maximum and equilibrium (relaxed) stresses were exponentially increased with decreasing tissue thickness (hydration). Furthermore, the QLV model successfully captured the corneal viscoelastic response with an average R (2) value greater than 0.99. Additional experiments were conducted in OBSS in order to confirm that these significant changes in viscoelastic properties were because of corneal hydration and not the bathing solution. The findings of this study suggest that extra care must be taken in interpreting the results of earlier uniaxial tensile testings and their correspondence to the corneal biomechanical properties. PMID:24668183

  18. The SPI-1-like Type III secretion system: more roles than you think

    PubMed Central

    Egan, Frank; Barret, Matthieu; O’Gara, Fergal

    2014-01-01

    The type III secretion system (T3SS) is a protein delivery system which is involved in a wide spectrum of interactions, from mutualism to pathogenesis, between Gram negative bacteria and various eukaryotes, including plants, fungi, protozoa and mammals. Various phylogenetic families of the T3SS have been described, including the Salmonella Pathogenicity Island 1 family (SPI-1). The SPI-1 T3SS was initially associated with the virulence of enteric pathogens, but is actually found in a diverse array of bacterial species, where it can play roles in processes as different as symbiotic interactions with insects and colonization of plants. We review the multiple roles of the SPI-1 T3SS and discuss both how these discoveries are changing our perception of the SPI-1 family and what impacts this has on our understanding of the specialization of the T3SS in general. PMID:24575107

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

    SciTech Connect

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

    2007-11-01

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

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

    SciTech Connect

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

    2010-06-01

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

  1. Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein.

    PubMed

    Rayamajhi, Manira; Zak, Daniel E; Chavarria-Smith, Joseph; Vance, Russell E; Miao, Edward A

    2013-10-15

    The NAIP/NLRC4 inflammasomes activate caspase-1 in response to bacterial type III secretion systems (T3SSs). Inadvertent injection of the T3SS rod protein and flagellin into the cytosol is detected through murine NAIP2 and NAIP5/6, respectively. In this study, we identify the agonist for the orphan murine NAIP1 receptor as the T3SS needle protein. NAIP1 is poorly expressed in resting mouse bone marrow-derived macrophages; however, priming with polyinosinic-polycytidylic acid induces it and confers needle protein sensitivity. Further, overexpression of NAIP1 in immortalized bone marrow-derived macrophages by retroviral transduction enabled needle detection. In contrast, peritoneal cavity macrophages basally express NAIP1 and respond to needle protein robustly, independent of priming. Human macrophages are known to express only one NAIP gene, which detects the needle protein, but not rod or flagellin. Thus, murine NAIP1 is functionally analogous to human NAIP. PMID:24043898

  2. An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria

    PubMed Central

    Cha, Eun Jung; Hwang, Won Min; Yun, Sung-Ro; Park, Moon Hyang

    2016-01-01

    Bartter syndrome (BS) I–IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis. PMID:26755355

  3. Phase variable type III restriction-modification systems of host-adapted bacterial pathogens.

    PubMed

    Fox, Kate L; Srikhanta, Yogitha N; Jennings, Michael P

    2007-09-01

    Phase variation, the high-frequency on/off switching of gene expression, is a common feature of host-adapted bacterial pathogens. Restriction-modification (R-M) systems, which are ubiquitous among bacteria, are classically assigned the role of cellular defence against invasion of foreign DNA. These enzymes are not obvious candidates for phase variable expression, a characteristic usually associated with surface-expressed molecules subject to host immune selection. Despite this, numerous type III R-M systems in bacterial pathogens contain repetitive DNA motifs that suggest the potential for phase variation. Several roles have been proposed for phase variable R-M systems based on DNA restriction function. However, there is now evidence in several important human pathogens, including Haemophilus influenzae, Neisseria meningitidis and Neisseria gonorrhoeae, that these systems are 'phasevarions' (phase variable regulons) controlling expression of multiple genes via a novel epigenetic mechanism. PMID:17714447

  4. Pseudomonas syringae type III secretion system effectors: repertoires in search of functions.

    PubMed

    Cunnac, Sébastien; Lindeberg, Magdalen; Collmer, Alan

    2009-02-01

    The ability of Pseudomonas syringae to grow and cause diseases in plants is dependent on the injection of multiple effector proteins into plant cells via the type III secretion system (T3SS). Genome-enabled bioinformatic/experimental methods have comprehensively identified the repertoires of effectors and related T3SS substrates for P. syringae pv. tomato DC3000 and three other sequenced strains. The effector repertoires are diverse and internally redundant. Insights into effector functions are being gained through the construction of mutants lacking one or more effector genes, which may be reduced in growth in planta, and through gain-of-function assays for the ability of single effectors to suppress plant innate immune defenses, manipulate hormone signaling, elicit cell death, and/or display biochemical activities on plant protein targets. PMID:19168384

  5. Kilometer-wave type III burst - Harmonic emission revealed by direction and time of arrival

    NASA Technical Reports Server (NTRS)

    Alvarez, H.; Haddock, F. T.; Potter, W. H.

    1974-01-01

    A type III solar burst was observed at seven frequencies between 3.5 MHz and 80 kHz by the Michigan experiment aboard the IMP-6 satellite. From the data burst direction of arrival as well as time of arrival can be determined. These quantities are predicted, using simple models whose parameters are varied to obtain a good fit to the observations. It is found that between 3.5 MHz and 230 kHz the observed radiation was emitted at the fundamental of the local plasma frequency, while below 230 kHz it was emitted at the second harmonic. The exciter particles that produced the burst onset and burst peak have velocities of 0.27 and 0.12, respectively, in units of the velocity of light.

  6. A Type III restriction–modification system in Mycoplasma mycoides subsp. capri

    PubMed Central

    Algire, Mikkel A.; Montague, Michael G.; Vashee, Sanjay; Lartigue, Carole; Merryman, Chuck

    2012-01-01

    The sequenced genome of Mycoplasma mycoides subsp. capri revealed the presence of a Type III restriction–modification system (MmyCI). The methyltransferase (modification) subunit of MmyCI (M.MmyCI) was shown to recognize the sequence 5′-TGAG-3′ and methylate the adenine. The coding region of the methyltransferase gene contains 12 consecutive AG dinucleotide repeats that result in a translational termination at a TAA codon immediately beyond the repeat region. This strain does not have MmyCI activity. A clone was found with 10 AG repeats such that the gene is in frame, and this strain has MmyCI activity, suggesting that the expression of the MmyCI methyltransferase may be phase variable. PMID:23155485

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  9. Conserved type III secretion system exerts important roles in Chlamydia trachomatis

    PubMed Central

    Dai, Wenting; Li, Zhongyu

    2014-01-01

    Upon infection, Chlamydiae alter host cellular functions in a variety of ways. Chlamydial infection prevents host cell apoptosis, induces re-organization of the actin cytoskeleton and alters host cellular signaling mechanisms. Chlamydia is among the many pathogenic Gram-negative bacteria that employ the type III secretion system (T3SS) to overcome host defenses and exploit available resources. T3SS are used by many Gram-negative bacterial pathogens to manipulate eukaryotic host cells through the delivery of effector proteins into their cytosol and membranes. T3SS is an evolutionarily refined, virulence determinant of Gram-negative bacteria where more than 20 proteins form an apparatus, generally termed injectisome, to achieve the vectorial secretion and translocation of anti-host effector proteins. This review describes challenges and recent advances that have revealed how Chlamydia trachomatis utilizes diversification to produce a conserved T3SS that exerts an important role in Chlamydia trachomatis. PMID:25337183

  10. Progress and problems in the theory of type III solar radio emission

    NASA Technical Reports Server (NTRS)

    Goldman, M. V.

    1983-01-01

    The experimental and theoretical status of type III solar radio emission is considered in detail. Very recent developments which are relevant to the underlying plasma physics are emphasized. In particular, the identity of the submegahertz emissions as fundamental, or second harmonic, the degree of correlation between emissivities, electron streams, and plasma (Langmuir) waves, paradoxes concerned with the time-ordering of these phenomena, and the role of background density irregularities and ion-acoustic turbulence in the solar wind, are discussed. From the theoretical point of view, the current picture of the underlying Langmuir turbulence, including such effects as the interaction between Langmuir waves and stream electrons, induced scatter off ions, and strong turbulence effects such as modulational instability and soliton collapse, is discussed.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  12. Benzylidene Acylhydrazides Inhibit Chlamydial Growth in a Type III Secretion- and Iron Chelation-Independent Manner

    PubMed Central

    Bao, Xiaofeng; Gylfe, Åsa; Sturdevant, Gail L.; Gong, Zheng; Xu, Shuang; Caldwell, Harlan D.; Elofsson, Mikael

    2014-01-01

    Chlamydiae are widespread Gram-negative pathogens of humans and animals. Salicylidene acylhydrazides, developed as inhibitors of type III secretion system (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection. However, these inhibitors also have the capacity to chelate iron, and it is possible that their antichlamydial effects are caused by iron starvation. Therefore, we have explored the modification of salicylidene acylhydrazides with the goal to uncouple the antichlamydial effect from iron starvation. We discovered that benzylidene acylhydrazides, which cannot chelate iron, inhibit chlamydial growth. Biochemical and genetic analyses suggest that the derivative compounds inhibit chlamydiae through a T3SS-independent mechanism. Four single nucleotide polymorphisms were identified in a Chlamydia muridarum variant resistant to benzylidene acylhydrazides, but it may be necessary to segregate the mutations to differentiate their roles in the resistance phenotype. Benzylidene acylhydrazides are well tolerated by host cells and probiotic vaginal Lactobacillus species and are therefore of potential therapeutic value. PMID:24914180

  13. Architecture of the major component of the type III secretion system export apparatus

    PubMed Central

    Abrusci, Patrizia; Vergara–Irigaray, Marta; Johnson, Steven; Beeby, Morgan D; Hendrixson, David; Roversi, Pietro; Friede, Miriam E; Deane, Janet E; Jensen, Grant J; Tang, Christoph M; Lea, Susan M

    2012-01-01

    Type III secretion systems (T3SSs) are bacterial membrane-embedded secretion nanomachines designed to export specifically targeted sets of proteins from the bacterial cytoplasm. Secretion through T3SS is governed by a subset of inner membrane proteins termed the ‘export apparatus’. We show that a key member of the Shigella flexneri export apparatus, MxiA, assembles into a ring essential for secretion in vivo. The ring forming interfaces are well conserved in both non-flagellar and flagellar homologues, implying that the ring is an evolutionary conserved feature in these systems. Electron cryo-tomography reveals a T3SS-associated cytoplasmic torus of size and shape corresponding to the MxiA ring aligned to the secretion channel located between the secretion pore and the ATPase complex. This defines the molecular architecture of the dominant component of the export apparatus and allows us to propose a model for the molecular mechanisms controlling secretion. PMID:23222644

  14. Chemical shift assignments of the fibronectin III like domains 7-8 of type VII collagen.

    PubMed

    Hermsdorf, Ulrike; Seeger, Karsten

    2016-04-01

    Type VII collagen (Col7) is important for skin stability. This is underlined by the severe skin blistering phenotype in the Col7 related diseases dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita (EBA). Col7 has a large N-terminal non-collagenous domain (NC1) that is followed by the triple helical collagenous domain. The NC1 domain has subdomains with homology to adhesion molecules and mediates important interactions within the extracellular matrix. An 185 amino acid long part of the NC1-subdomain termed fibronectin III like domains 7 and 8 (FNIII7-8) was investigated. Antibodies against this region are pathogenic in a mouse model of EBA and one reported missense mutations of Col7 lies within these domains. The nearly complete NMR resonance assignment of recombinant FNIII7-8 of Col7 is reported. PMID:26364055

  15. Broadly protective Shigella vaccine based on type III secretion apparatus proteins.

    PubMed

    Martinez-Becerra, Francisco J; Kissmann, Julian M; Diaz-McNair, Jovita; Choudhari, Shyamal P; Quick, Amy M; Mellado-Sanchez, Gabriela; Clements, John D; Pasetti, Marcela F; Picking, Wendy L

    2012-03-01

    Shigella spp. are food- and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody- and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine. PMID:22202122

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

    SciTech Connect

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

    2014-07-11

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

  17. Observational Characteristics of Langmuir Turbulence Associated with Solar Type III Radio Bursts

    NASA Astrophysics Data System (ADS)

    Golla, T.; MacDowall, R. J.

    2015-12-01

    Solar flares present the most dramatic energy releases from the Sun. The solar flares accelerate electrons, which form bump-on-tail distributions, and excite electrostatic waves called Langmuir waves, which are subsequently converted into escaping radiation at the fundamental and second harmonic of the electron plasma frequency by some nonlinear processes. These radio emissions are called the type III radio bursts. The sources of these bursts represent natural laboratories of beam-plasma systems. The WAVES experiment on the STEREO spacecraft contains an improved Time Domain Sampler (TDS), improved over that of all similar high time resolution receivers flown in earlier spacecraft. It is primarily intended for the study of Langmuir waves. These in situ high time resolution wave measurements enable us to identify and understand the physical processes associated with beam-plasma systems, as well as for conversion of Langmuir waves into escaping radiation at the fundamental and second harmonic of the electron plasma frequency. The waveforms captured by the TDS usually contain a variety of distortions caused by various nonlinear processes. The normalized peak intensities, wave numbers and spectral widths of these wave packets determine the nonlinear processes, which control the evolution of these wave packets. We have analyzed the in situ high time resolution measurements of Langmuir wave packets and determined their three dimensional relative peak intensities, spectral components and spectral widths. Using the frequency drifts of the type III bursts, we have estimated the velocities of the electron beams which in turn yielded the corresponding wave numbers. We will present the distributions of these important physical quantities and their implications for the theoretical models.

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

    SciTech Connect

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

    2013-01-01

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

  19. Treatment of Rockwood type III acromioclavicular joint dislocation using autogenous semitendinosus tendon graft and endobutton technique

    PubMed Central

    Ye, Gang; Peng, Chao-An; Sun, Hua-Bin; Xiao, Jing; Zhu, Kang

    2016-01-01

    Background The aim of this study was to evaluate the therapeutic effect of autogenous semitendinosus graft and endobutton technique, and compare with hook plate in treatment of Rockwood type III acromioclavicular (AC) joint dislocation. Methods From April 2012 to April 2013, we treated 46 patients with Rockwood type III AC joint dislocation. Patients were randomly divided into two groups: Group A was treated using a hook plate and Group B with autogenous semitendinosus graft and endobutton technique. All participants were followed up for 12 months. Radiographic examinations were performed every 2 months postoperatively, and clinical evaluation was performed using the Constant–Murley score at the last follow-up. Results Results indicated that patients in Group B showed higher mean scores (90.3±5.4) than Group A (80.4±11.5) in terms of Constant–Murley score (P=0.001). Group B patients scored higher in terms of pain (P=0.002), activities (P=0.02), range of motion (P<0.001), and strength (P=0.004). In Group A, moderate pain was reported by 2 (8.7%) and mild pain by 8 (34.8%) patients. Mild pain was reported by 1 (4.3%) patient in Group B. All patients in Group B maintained complete reduction, while 2 (8.7%) patients in Group A experienced partial reduction loss. Two patients (8.7%) encountered acromial osteolysis on latest radiographs, with moderate shoulder pain and limited range of motion. Conclusion Autogenous semitendinosus graft and endobutton technique showed better results compared with the hook plate method and exhibited advantages of fewer complications such as permanent pain and acromial osteolysis. PMID:26811685

  20. Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach has had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN o...

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

    PubMed Central

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

    2016-01-01

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

  2. Customized Finite Element Modelling of the Human Cornea

    PubMed Central

    Simonini, Irene; Pandolfi, Anna

    2015-01-01

    Aim To construct patient-specific solid models of human cornea from ocular topographer data, to increase the accuracy of the biomechanical and optical estimate of the changes in refractive power and stress caused by photorefractive keratectomy (PRK). Method Corneal elevation maps of five human eyes were taken with a rotating Scheimpflug camera combined with a Placido disk before and after refractive surgery. Patient-specific solid models were created and discretized in finite elements to estimate the corneal strain and stress fields in preoperative and postoperative configurations and derive the refractive parameters of the cornea. Results Patient-specific geometrical models of the cornea allow for the creation of personalized refractive maps at different levels of IOP. Thinned postoperative corneas show a higher stress gradient across the thickness and higher sensitivity of all geometrical and refractive parameters to the fluctuation of the IOP. Conclusion Patient-specific numerical models of the cornea can provide accurate quantitative information on the refractive properties of the cornea under different levels of IOP and describe the change of the stress state of the cornea due to refractive surgery (PRK). Patient-specific models can be used as indicators of feasibility before performing the surgery. PMID:26098104

  3. Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation.

    PubMed

    Yang, Jieling; Zhao, Yue; Shi, Jianjin; Shao, Feng

    2013-08-27

    Inflammasome mediated by central nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) protein is critical for defense against bacterial infection. Here we show that type III secretion system (T3SS) needle proteins from several bacterial pathogens, including Salmonella typhimurium, enterohemorrhagic Escherichia coli, Shigella flexneri, and Burkholderia spp., can induce robust inflammasome activation in both human monocyte-derived and mouse bone marrow macrophages. Needle protein activation of human NRL family CARD domain containing 4 (NLRC4) inflammasome requires the sole human neuronal apoptosis inhibitory protein (hNAIP). Among the seven mouse NAIPs, NAIP1 functions as the mouse counterpart of hNAIP. We found that NAIP1 recognition of T3SS needle proteins was more robust in mouse dendritic cells than in bone marrow macrophages. Needle proteins, as well as flagellin and rod proteins from five different bacteria, exhibited differential and cell type-dependent inflammasome-stimulating activity. Comprehensive profiling of the three types of NAIP ligands revealed that NAIP1 sensing of the needle protein dominated S. flexneri-induced inflammasome activation, particularly in dendritic cells. hNAIP/NAIP1 and NAIP2/5 formed a large oligomeric complex with NLRC4 in the presence of corresponding bacterial ligands, and could support reconstitution of the NLRC4 inflammasome in a ligand-specific manner. PMID:23940371

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

    PubMed Central

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

    2015-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies—including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs block the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease. PMID:26633291

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

    PubMed

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

    2016-01-01

    Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease. PMID:26633291

  6. Expression of adenosine A2b receptor in rat type II and III taste cells.

    PubMed

    Nishida, Kentaro; Dohi, Yukari; Yamanaka, Yuri; Miyata, Ai; Tsukamoto, Katsunobu; Yabu, Miharu; Ohishi, Akihiro; Nagasawa, Kazuki

    2014-05-01

    We previously demonstrated that equilibrative nucleoside transporter 1 was expressed in taste cells, suggesting the existence of an adenosine signaling system, but whether or not the expression of an adenosine receptor occurs in rat taste buds remains unknown. Therefore, we examined the expression profiles of adenosine receptors and evaluated their functionality in rat circumvallate papillae. Among adenosine receptors, the mRNA for an adenosine A2b receptor (A2bR) was expressed by the rat circumvallate papillae, and its expression level was significantly greater in the circumvallate papillae than in the non-taste lingual epithelium. A2bR-immunoreactivity was detected primarily in type II taste cells, and partial, but significant expression was also observed in type III ones, but there was no immunoreactivity in type I ones. The cAMP generation in isolated epithelium containing taste buds treated with 500 μM adenosine or 10 μM BAY60-6583 was significantly increased compared to in the controls. These findings suggest that adenosine plays a role in signaling transmission via A2bR between taste cells in rats. PMID:24327108

  7. Diminished Type III Collagen Promotes Myofibroblast Differentiation and Increases Scar Deposition in Cutaneous Wound Healing

    PubMed Central

    Volk, Susan W.; Wang, Yanjian; Mauldin, Elizabeth A.; Liechty, Kenneth W.; Adams, Sherrill L.

    2011-01-01

    The repair of cutaneous wounds in the postnatal animal is associated with the development of scar tissue. Directing cell activities to efficiently heal wounds while minimizing the development of scar tissue is a major goal of wound management and the focus of intensive research efforts. Type III collagen (Col3), expressed in early granulation tissue, has been proposed to play a prominent role in cutaneous wound repair, although little is known about its role in this process. To establish the role of Col3 in cutaneous wound repair, we examined the healing of excisional wounds in a previously described murine model of Col3 deficiency. Col3 deficiency (Col3+/–) in aged mice resulted in accelerated wound closure with increased wound contraction. In addition, Col3-deficient mice had increased myofibroblast density in the wound granulation tissue as evidenced by an increased expression of the myofibroblast marker, α-smooth muscle actin. In vitro, dermal fibroblasts obtained from Col3-deficient embryos (Col3+/– and –/–) were more efficient at collagen gel contraction and also displayed increased myofibroblast differentiation compared to those harvested from wild-type (Col3+/+) embryos. Finally, wounds from Col3-deficient mice also had significantly more scar tissue area on day 21 postwounding compared to wild-type mice. The effect of Col3 expression on myofibroblast differentiation and scar formation in this model suggests a previously undefined role for this ECM protein in tissue regeneration and repair. PMID:21252470

  8. Serum type III procollagen peptide and laminin (Lam-P1) detect alcoholic hepatitis in chronic alcohol abusers.

    PubMed

    Annoni, G; Colombo, M; Cantaluppi, M C; Khlat, B; Lampertico, P; Rojkind, M

    1989-05-01

    The diagnosis of alcoholic hepatitis is difficult to establish by conventional clinical and laboratory methods, and a firm diagnosis relies on liver histology. Since there are severe limitations in following patients with repeated liver biopsies, noninvasive procedures are needed to assess the presence of alcoholic hepatitis in chronic alcohol abusers. It has been suggested that serum Type III procollagen peptide levels correlates with the degree of inflammation in chronic liver disease. Since inflammation is a major histological finding in alcoholic hepatitis, we therefore studied the usefulness of measuring serum Type III procollagen peptide and laminin values in 45 consecutive chronic alcohol abusers, with or without cirrhosis, in detecting those with alcoholic hepatitis. The results showed that both Type III procollagen peptide and laminin values were elevated in all of the patients with established liver damage. However, the values were highest in those with liver cirrhosis plus alcoholic hepatitis (Type III procollagen peptide 50.4 +/- 36.4 ng per ml vs. 8.1 +/- 2.6 in controls, p less than 0.01; laminin 4.50 +/- 1.49 units per liter vs. 1.24 +/- 0.26 units per liter in controls, p less than 0.01), followed by subjects with alcoholic hepatitis alone (Type III procollagen peptide 23.5 +/- 17.6 ng per ml, p less than 0.01; laminin 2.60 +/- 1.09 units per liter, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2707736

  9. Should Splenic Hilar Lymph Nodes be Dissected for Siewert Type II and III Esophagogastric Junction Carcinoma Based on Tumor Diameter?

    PubMed Central

    Lv, Chen-Bin; Huang, Chang-Ming; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Tu, Ru-Hong

    2016-01-01

    Abstract The aim of the study is to identify the value of a spleen-preserving No. 10 lymphadenectomy (SPL) for Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). From January 2007 to June 2014, 694 patients undergoing radical total gastrectomy for Siewert type II/III AEG were analyzed. Oncologic outcomes were compared between SPL and no SPL (No. 10D+ and No. 10D–) groups. The incidence of No. 10 lymph node metastasis (LNM) was 12.3%. No significant differences in the incidence of No. 10 LNM were found between Siewert type II AEG with tumor diameters of <4 cm and ≥4 cm (P = 0.071). However, Siewert type III AEG with a tumor diameter ≥4 cm showed a significantly higher frequency of No. 10 LNM compared with a tumor diameter <4 cm (P < 0.001). The No. 10D+ group had superior 3-year overall survival (OS) and disease-free survival (DFS) rates compared with the No. 10D− group (P = 0.030 and P = 0.005, respectively). For patients with Siewert type II and type III AEG with a tumor diameter <4 cm, the 3-year OS and DFS rates were similar between the 2 groups. However, the No. 10D+ group had better 3-year OS (66.6% vs 51.1%, P = 0.019) and DFS (63.2% vs 45.9%, P = 0.007) rates for Siewert type III AEG with a tumor diameter ≥4 cm. A multivariate Cox regression showed that SPL was an independent prognostic factor in Siewert type III AEG with a tumor diameter ≥4 cm. SPL may improve the prognosis of Siewert type III AEG with a tumor diameter ≥4 cm, whereas SPL may be omitted without decreasing survival in patients with Siewert type II or type III AEG with a tumor diameter <4 cm. PMID:27227913

  10. Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris.

    PubMed

    Keizer-Gunnink, I; Vuorela, A; Myllyharju, J; Pihlajaniemi, T; Kivirikko, K I; Veenhuis, M

    2000-02-01

    It was recently reported that co-expression of the proalpha1(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T., Kivirikko, K.I., 1997. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: formation of a stable enzyme tetramer requires coexpression with collagen and assembly of a stable collagen requires coexpression with prolyl 4-hydroxylase. EMBO J. 16, 6702-6712). These properly folded molecules accumulated inside the yeast cell, however, only approximately 10% were found in the culture medium. We report here that replacement of the authentic signal sequence of the human proalpha1(III) with the Saccharomyces cerevisiae alpha mating factor prepro sequence led only to a minor increase in the amount secreted. Immunoelectron microscopy studies indicated that the procollagen molecules accumulate in specific membranous vesicular compartments that are closely associated with the nuclear membrane. Prolyl 4-hydroxylase, an endoplasmic reticulum (ER) lumenal enzyme, was found to be located in the same compartments. Non-helical proalpha1(III) chains produced by expression without recombinant prolyl 4-hydroxylase likewise accumulated within these compartments. The data indicate that properly folded recombinant procollagen molecules accumulate within the ER and do not proceed further in the secretory pathway. This may be related to the large size of the procollagen molecule. PMID:10686423

  11. Abundances determined using Si ii and Si iii in B-type stars: evidence for stratification

    NASA Astrophysics Data System (ADS)

    Bailey, J. D.; Landstreet, J. D.

    2013-03-01

    Context. It is becoming clear that determination of the abundance of Si using lines of Si ii and Si iii can lead to quite discordant results in mid to late B-type stars. The difference between the Si abundances derived from the two ion states can exceed one dex in some cases. Aims: We have carried out a study intended to clarify which kinds of B stars exhibit this discrepancy, to try to identify regularities in the phenomenon, and to explore possible explanations such as abundance stratification by comparing models to observed spectra. Methods: We used spectra from the ESPaDOnS spectropolarimeter and FEROS spectrograph, supplemented with spectra from the ESO and ELODIE archives, of magnetic Bp, HgMn, and normal B-type stars ranging in effective temperature from about 10 500 to 15 000 K. Using these spectra, we derived abundances using the spectrum synthesis program zeeman, which can take the influence of magnetic fields into account. For each star, accurate abundances of Si ii, Si iii, Ti, Cr, and Fe were derived from two separate ~100 Å windows. Si ii abundances were deduced from multiple lines, and Si iii abundances were found using λλ 4552, 4567, and 4574. Results: All magnetic Bp stars in our sample show a discordance between the derived abundances of the first and second ions of silicon, with the latter being between 0.6-1.7 dex higher. The same behaviour is observed in the non-magnetic stars but to a much smaller extent: Si iii is enhanced by between 0.3-0.8 dex compared to Si ii. We do not detect the discrepancy in three stars, HD 22 136 (normal), HD 57 608 (HgMn) and HD 27 295 (HgMn); these are the only stars in our sample for which the microturbulence parameter is significantly different from zero, and which therefore probably have convection occurring in their atmospheres. Conclusions: We find that vertical stratification of silicon in the atmospheres of B-type stars may provide an explanation of this phenomenon, but our detailed stratification models

  12. The anisotropic material constitutive models for the human cornea.

    PubMed

    Li, Long-yuan; Tighe, Brian

    2006-03-01

    This paper presents an anisotropic analysis model for the human cornea. The model is based on the assumption that the fibrils in the cornea are organised into lamellae, which may have preferential orientation along the superior-inferior and nasal-temporal directions, while the alignment of lamellae with different orientations is assumed to be random. Hence, the cornea can be regarded as a laminated composite shell. The constitutive equation describing the relationships between membrane forces, bending moments, and membrane strains, bending curvatures are derived. The influences of lamella orientations and the random alignment of lamellae on the stiffness coefficients of the constitutive equation are discussed. PMID:16426861

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

    PubMed Central

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

    2012-01-01

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

  14. Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures-Apropos of Two Cases.

    PubMed

    Takai, Hirokazu; Konstantinidis, Lukas; Schmal, Hagen; Helwig, Peter; Knöller, Stefan; Südkamp, Norbert; Hauschild, Oliver

    2016-01-01

    Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced Anderson type III fractures with a characteristic fracture pattern that we refer to as "oblique type axis body fracture." Results. The female patients aged 90 and 72 years, respectively, were both diagnosed with minimally displaced Anderson type III fractures. Both fractures had a characteristic "oblique type" fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1-C3/4 posterior fusion and the course was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion for this injury and suggest early operative stabilization. PMID:27042372

  15. Type 1 AGN at low z - III. The optical narrow-line ratios

    NASA Astrophysics Data System (ADS)

    Stern, Jonathan; Laor, Ari

    2013-05-01

    We present the optical narrow-line ratios in a Sloan Digital Sky Survey (SDSS) based sample of 3175 broad Hα selected type 1 active galactic nuclei (AGN), and explore their positions in the BPT diagrams as a function of the AGN and the host properties. We find the following: (1) the luminosities of all measured narrow lines (Hα, Hβ, [O III], [N II], [S II], [O I]) show a Baldwin relation relative to the broad Hα luminosity LbHα, with slopes in the range of 0.53-0.72. (2) About 20 per cent of the type 1 AGN reside within the `Composite' and `star-forming' (SF) regions of the Baldwin, Phillips & Terlevich (BPT) diagrams. These objects also show excess narrow Hα and ultraviolet (UV) luminosities, for their LbHα, consistent with contribution from star formation which dominates the narrow-lines emission, as expected from their positions in the BPT diagrams. (3) The type 1 which reside within the AGN region in the BPT diagrams, are offset to lower [S II]/Hα and [N II]/Hα luminosity ratios, compared to type 2 AGN. This offset is a selection effect, related to the lower AGN/host luminosity selection of the type 2 AGN selected from the SDSS galaxy sample. (4) The [N II]/Hα and [N II]/[S II] ratios in type 1 AGN increase with the host mass, as expected if the mass-metallicity relation of quiescent galaxies holds for the AGN narrow-line region (NLR). (5) The broad lines optical Fe II is higher for a higher [N II]/Hα, at a fixed Lbol and Eddington ratio L/LEdd. This suggests that the broad line region metallicity is also related to the host mass. (6) The fraction of AGN which are low-ionization nuclear emission-line regions (LINERs) increases sharply with decreasing L/LEdd. This fraction is the same for type 1 and type 2 AGN. (7) The BPT position is unaffected by the amount of dust extinction of the optical-UV continuum, which suggests that the extincting dust resides on scales larger than the NLR.

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

    PubMed Central

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

    2011-01-01

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

  17. FLARE-ASSOCIATED TYPE III RADIO BURSTS AND DYNAMICS OF THE EUV JET FROM SDO/AIA AND RHESSI OBSERVATIONS

    SciTech Connect

    Chen Naihwa; Ip, Wing-Huen; Innes, Davina E-mail: wingip@astro.ncu.edu.tw

    2013-06-01

    We present a detailed description of the interrelation between the Type III radio bursts and energetic phenomena associated with the flare activities in active region AR11158 at 07:58 UT on 2011 February 15. The timing of the Type III radio burst measured by the radio wave experiment on Wind/WAVE and an array of ground-based radio telescopes coincided with an extreme-ultraviolet (EUV) jet and hard X-ray (HXR) emission observed by SDO/AIA and RHESSI, respectively. There is clear evidence that the EUV jet shares the same source region as the HXR emission. The temperature of the jet, as determined by multiwavelength measurements by Atmospheric Imaging Assembly, suggests that Type III emission is associated with hot, 7 MK, plasma at the jet's footpoint.

  18. The Bacterial Alarmone (p)ppGpp Activates the Type III Secretion System in Erwinia amylovora

    PubMed Central

    Ancona, Veronica; Lee, Jae Hoon; Chatnaparat, Tiyakhon; Oh, Jinrok; Hong, Jong-In

    2015-01-01

    ABSTRACT The hypersensitive response and pathogenicity (hrp) type III secretion system (T3SS) is a key pathogenicity factor in Erwinia amylovora. Previous studies have demonstrated that the T3SS in E. amylovora is transcriptionally regulated by a sigma factor cascade. In this study, the role of the bacterial alarmone ppGpp in activating the T3SS and virulence of E. amylovora was investigated using ppGpp mutants generated by Red recombinase cloning. The virulence of a ppGpp-deficient mutant (ppGpp0) as well as a dksA mutant of E. amylovora was completely impaired, and bacterial growth was significantly reduced, suggesting that ppGpp is required for full virulence of E. amylovora. Expression of T3SS genes was greatly downregulated in the ppGpp0 and dksA mutants. Western blotting showed that accumulations of the HrpA protein in the ppGpp0 and dksA mutants were about 10 and 4%, respectively, of that in the wild-type strain. Furthermore, higher levels of ppGpp resulted in a reduced cell size of E. amylovora. Moreover, serine hydroxamate and α-methylglucoside, which induce amino acid and carbon starvation, respectively, activated hrpA and hrpL promoter activities in hrp-inducing minimal medium. These results demonstrated that ppGpp and DksA play central roles in E. amylovora virulence and indicated that E. amylovora utilizes ppGpp as an internal messenger to sense environmental/nutritional stimuli for regulation of the T3SS and virulence. IMPORTANCE The type III secretion system (T3SS) is a key pathogenicity factor in Gram-negative bacteria. Fully elucidating how the T3SS is activated is crucial for comprehensively understanding the function of the T3SS, bacterial pathogenesis, and survival under stress conditions. In this study, we present the first evidence that the bacterial alarmone ppGpp-mediated stringent response activates the T3SS through a sigma factor cascade, indicating that ppGpp acts as an internal messenger to sense environmental/nutritional stimuli for

  19. Evidence for four- and three-wave interactions in solar type III radio emissions

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    The high time resolution observations obtained by the STEREO/WAVES experiment show that in the source regions of solar type III radio bursts, Langmuir waves often occur as intense localized wave packets with short durations of only few ms. One of these wave packets shows that it is a three-dimensional field structure with WLneTe ~ 10-3, where WL is the peak energy density, and ne and Te are the electron density and temperature, respectively. For this wave packet, the conditions of the oscillating two-stream instability (OTSI) and supersonic collapse are satisfied within the error range of determination of main parameters. The density cavity, observed during this wave packet indicates that its depth, width and temporal coincidence are consistent with those of a caviton, generated by the ponderomotive force of the collapsing wave packet. The spectrum of each of the parallel and perpendicular components of the wave packet contains a primary peak at fpe, two secondary peaks at fpe ± fS and a low-frequency enhancement below fS, which, as indicated by the frequency and wave number resonance conditions, and the fast Fourier transform (FFT)-based tricoherence spectral peak at (fpe, fpe, fpe + fS, fpe - fS), are coupled to each other by the OTSI type of four-wave interaction (fpe is the local electron plasma frequency and fS is the frequency of ion sound waves). In addition to the primary peak at fpe, each of these spectra also contains a peak at 2fpe, which as indicated by the frequency and wave number resonance conditions, and the wavelet-based bicoherence spectral peak at (fpe, fpe), appears to correspond to the second harmonic electromagnetic waves generated as a result of coalescence of oppositely propagating sidebands excited by the OTSI. Thus, these observations for

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

    PubMed

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

    2008-07-01

    We examined the distribution of immunofluorescence due to immunostaining of type III collagen, differential interference contrast (DIC) images and images obtained in the transmission mode after toluidine blue staining by laser-scanning microscopy of semi-ultrathin sections of epoxy resin-embedded samples, during morphogenesis of the filiform papillae, keratinization of the lingual epithelium, and myogenesis of the rat tongue. Immunoreactivity specific for type III collagen was distributed widely in the mesenchymal connective tissue in fetuses on day 15 after conception (E15), at which time the lingual epithelium was composed of one or two layers of cuboidal cells and the lingual muscle was barely recognizable. Immunoreactivity specific for type III collagen was clearly detected on the lamina propria in fetuses on E17 and E19, and it was relatively distinct just beneath the lingual epithelium. Immunoreactivity specific for type III collagen was sparsely distributed on the connective tissue around the developing lingual muscle. In fetuses on E19, the epithelium became clearly stratified and squamous. At postnatal stages from newborn (P0) to postnatal day 14 (P14), keratinization of the lingual epithelium advanced gradually with the development of filiform papillae. On P0, myogenesis of the tongue was almost completed. The intensity of the fluorescence immunoreactivity specific for type III collagen at postnatal stages was almost same as that on E19. The immunoreactivity around the fully mature muscle was relatively distinct between P0 and P14. Thus, type III collagen appeared in conjunction with the morphogenesis of filiform papillae and the keratinization of the lingual epithelium as well as in the connective tissue that surrounded the lingual muscle during myogenesis of the rat tongue. PMID:18661199

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

    SciTech Connect

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

    2010-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.

    PubMed

    Bierne, Hélène; Travier, Laetitia; Mahlakõiv, Tanel; Tailleux, Ludovic; Subtil, Agathe; Lebreton, Alice; Paliwal, Anupam; Gicquel, Brigitte; Staeheli, Peter; Lecuit, Marc; Cossart, Pascale

    2012-01-01

    Bacterial infections trigger the expression of type I and II interferon genes but little is known about their effect on type III interferon (IFN-λ) genes, whose products play important roles in epithelial innate immunity against viruses. Here, we studied the expression of IFN-λ genes in cultured human epithelial cells infected with different pathogenic bacteria and in the mouse placenta infected with Listeria monocytogenes. We first showed that in intestinal LoVo cells, induction of IFN-λ genes by L. monocytogenes required bacterial entry and increased further during the bacterial intracellular phase of infection. Other Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, also induced IFN-λ genes when internalized by LoVo cells. In contrast, Gram-negative bacteria Salmonella enterica serovar Typhimurium, Shigella flexneri and Chlamydia trachomatis did not substantially induce IFN-λ. We also found that IFN-λ genes were up-regulated in A549 lung epithelial cells infected with Mycobacterium tuberculosis and in HepG2 hepatocytes and BeWo trophoblastic cells infected with L. monocytogenes. In a humanized mouse line permissive to fetoplacental listeriosis, IFN-λ2/λ3 mRNA levels were enhanced in placentas infected with L. monocytogenes. In addition, the feto-placental tissue was responsive to IFN-λ2. Together, these results suggest that IFN-λ may be an important modulator of the immune response to Gram-positive intracellular bacteria in epithelial tissues. PMID:22720036

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2016-01-01

    Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3+/− mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3+/− mice compared to Col3+/+ littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma. PMID:25795282

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

    PubMed Central

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

    2015-01-01

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

  7. Procollagen-type III peptide serum concentrations in alcoholic and non-alcoholic liver disease.

    PubMed

    Monarca, A; Petrini, C; Perolini, S; Pozzi, F; Adelasco, L; Natangelo, R; Croce, G

    1985-01-01

    The type III procollagen aminopeptide (sPIIIP) serum levels were measured in 197 patients with liver disease and were correlated with morphological and serological alterations and with alcohol drinking habits. The sPIIIP levels resulted significantly increased in 51% of 43 patients with untreated chronic active hepatitis (CAH), in 61% of 36 patients with CAH plus cirrhosis, in 69% of 26 patients with inactive cirrhosis, in 4 out of 8 patients with alcoholic steatosis and fibrillogenesis, but remained unchanged in 38 cases of alcoholic steatosis plus siderosis and in 13 cases of chronic persistent hepatitis. A correlation between sPIIIP levels and the histological pattern of fibrosis could not be demonstrated in a single type of fibrotic liver disease and no differences were found between alcoholic and non-alcoholic patients. We agree upon the opinion that high sPIIIP levels may identify liver fibrogenic activity, but this test needs further technical improvements before it could be widely used in the clinical practice. PMID:4059796

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2008-03-01

    Fire blight is a disease affecting Maloideae caused by the necrogenic bacterium Erwinia amylovora, which requires the type III protein secretion system (TTSS) for pathogenicity. Profiles of methanol-extractable leaf phenolics of two apple (Malus x domestica) genotypes with contrasting susceptibility to this disease were analyzed by HPLC after infection. Some qualitative differences were recorded between the constitutive compositions of the two genotypes but in both of them dihydrochalcones accounted for more than 90% of total phenolics. Principal component analysis separated leaves inoculated with a virulent wild-type strain from those inoculated with a non-pathogenic TTSS-defective mutant or with water. The changes in levels of the various groups of phenolics in response to the virulent bacterium were similar between the two genotypes, with a significant decrease of dihydrochalcones and a significant increase of hydroxycinnamate derivatives. Differences between genotypes were, however, recorded in amplitude and kinetic of variation in these groups. Occurrence of oxidation and polymerization reactions is proposed, based on the browning process of infected tissues, but whether some by-products act in defense as toxic compounds remain to be tested. Among direct antibacterial constitutive compounds present in apple leaves, the dihydrochalcone phloretin only was found at levels close to lethal concentrations in both genotypes. However, E. amylovora exhibited the ability to stabilize this compound at sublethal levels even in the resistant apple, rejecting the hypothesis of its involvement in the resistance of this genotype. PMID:18275458

  10. Changes in serum type I and III procollagen levels in children with chronic renal failure.

    PubMed

    Cinaz, P; Buyan, N; Gökçora, N; Elbeg, S; Hasanoğlu, E

    1996-01-01

    Serum levels of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) can be used as markers of bone formation and the evaluation of children with growth disorders. We measured the serum levels of these collagens with radioimmunoassay in 24 children aged between 4 and 14 years with chronic renal failure (CRF; n = 12 dialysis, n = 12 nondialysis) and 12 age-matched healthy controls, to find out whether these parameters have a prognostic or therapeutic value in monitoring the growth retardation in CRF. Mean serum PIIINP levels in the dialysis patients were higher than in the control group; the difference between the groups was statistically significant (p < 0.05). It seemed that the pubertal stage of the patients did not affect the levels of PICP and PIIINP. There was no significant correlation between PICP and PIIINP in any patients. Neither PICP nor PIIINP correlated with the height z-score or bone age. It was concluded that the increased serum PIIINP levels in renal patients might be accepted as a poor prognostic factor leading to progressive renal failure and end-stage renal disease. Further investigations into the effects of these collagens on growth failure associated with CRF are needed. PMID:8684525

  11. Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa.

    PubMed

    Chen, Gukui; Zhao, Qiang; Zhu, Feng; Chen, Ronghao; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Jin, Shouguang; Wu, Weihui; Cheng, Zhihui

    2016-01-01

    Oligoribonuclease (Orn) is a 3' to 5' exonuclease that degrades nanoRNAs, which can serve as primers for transcription initiation at a significant fraction of promoters. One of Orn's substrates, pGpG inhibits the enzymatic activity of EAL-domain containing phosphodiesterases (PDEs), thereby increasing intracellular cyclic-di-GMP (c-di-GMP) level. Here, we found that an orn mutant of Pseudomonas aeruginosa displayed reduced cytotoxicity, which was mainly due to deficient type III secretion system (T3SS). Given the importance of T3SS in pathogenicity, we examined the bacterial virulence in a mouse acute pneumonia model and found that the Δorn mutant was highly attenuated compared to the wild type PA14 strain. Overexpression of an EAL domain-containing PDE reduced the c-di-GMP level as well as biofilm formation in the Δorn mutant. However, no effect was observed on the expression of T3SS genes, suggesting that increased c-di-GMP level is not the solely cause of defective T3SS in the Δorn mutant. Overall, our results demonstrated an essential role of Orn in the expression of T3SS as well as pathogenesis of P. aeruginosa. PMID:27296966

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

    PubMed

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

    2016-06-01

    Epithelial-Mesenchymal Transformation (EMT) and the subsequent invasion of epicardial and endocardial cells during cardiac development is critical to the development of the coronary vessels and heart valves. The transformed cells give rise to cardiac fibroblasts and vascular smooth muscle cells or valvular interstitial cells, respectively. The Type III Transforming Growth Factor β (TGFβR3) receptor regulates EMT and cell invasion in both cell types, but the signaling mechanisms downstream of TGFβR3 are not well understood. Here we use epicardial and endocardial cells in in vitro cell invasion assays to identify common mechanisms downstream of TGFβR3 that regulate cell invasion. Inhibition of NF-κB activity blocked cell invasion in epicardial and endocardial cells. NF-κB signaling was found to be dysregulated in Tgfbr3(-/-) epicardial cells which also show impaired cell invasion in response to ligand. TGFβR3-dependent cell invasion is also dependent upon Activin Receptor-Like Kinase (ALK) 2, ALK3, and ALK5 activity. A TGFβR3 mutant that contains a threonine to alanine substitution at residue 841 (TGFβR3-T841A) induces ligand-independent cell invasion in both epicardial and endocardial cells in vitro. These findings reveal a role for NF-κB signaling in the regulation of epicardial and endocardial cell invasion and identify a mutation in TGFβR3 which stimulates ligand-independent signaling. PMID:26970186

  13. Type III secretion: a bacterial device for close combat with cells of their eukaryotic host.

    PubMed

    Cornelis, G R

    2000-05-29

    Salmonella, Shigella, Yersinia, Pseudomonas aeruginosa, enteropathogenic Escherichia coli and several plant-pathogenic Gram-negative bacteria use a new type of systems called 'type III secretion' to attack their host. These systems are activated by contact with a eukaryotic cell membrane and they allow bacteria to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane to reach a given compartment and destroy or subvert the target cell. These systems consist of a secretion apparatus made up of about 25 individual proteins and a set of proteins released by this apparatus. Some of these released proteins are 'effectors' that are delivered by extracellular bacteria into the cytosol of the target cell while the others are 'translocators' that help the 'effectors' to cross the membrane of the eukaryotic cell. Most of the 'effectors' act on the cytoskeleton or on intracellular signalling cascades. One of the proteins injected by the enteropathogenic E. coli serves as a membrane receptor for the docking of the bacterium itself at the surface of the cell. PMID:10874740

  14. Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures—Apropos of Two Cases

    PubMed Central

    Konstantinidis, Lukas; Schmal, Hagen; Helwig, Peter; Knöller, Stefan; Südkamp, Norbert; Hauschild, Oliver

    2016-01-01

    Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced Anderson type III fractures with a characteristic fracture pattern that we refer to as “oblique type axis body fracture.” Results. The female patients aged 90 and 72 years, respectively, were both diagnosed with minimally displaced Anderson type III fractures. Both fractures had a characteristic “oblique type” fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1–C3/4 posterior fusion and the course was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion for this injury and suggest early operative stabilization. PMID:27042372

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Differential localization of type I and type III procollagen messenger ribonucleic acids in inflamed periodontal and periapical connective tissues by in situ hybridization.

    PubMed

    Larjava, H; Sandberg, M; Happonen, R P; Vuorio, E

    1990-01-01

    Inflammatory lesions of periodontal and periapical connective tissue were studied by in situ hybridization to detect cells responsible for type I and type III collagen production. Formalin-fixed and paraffin-embedded tissue specimens from patients with oral lesions of various stages of inflammation were hybridized with cDNA probes specific for human pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, and with bacteriophage lambda DNA as a control probe. This technique permitted us to localize fibroblasts active in type I collagen synthesis in the vicinity of inflammatory infiltrates in all the samples studied. Cells containing high levels of type III collagen mRNA were seen in early abscess formation and they were particularly abundant in pyogenic granuloma and irritation fibroma. Type I collagen mRNA was prominent in gingival fibrosis. In the infrabony lesions with active inflammatory infiltrations the production of collagen was confined mostly to the periphery of the lesions. These findings give indirect evidence that cytokines liberated during the early stages of the inflammatory process stimulate expression of the type III collagen gene by fibroblasts. In chronic lesions a gradual switch from type III to type I collagen gene expression occurs. The change in collagen types appears to underlie the observed isolation of the inflammation by a collagenous capsule. In all the samples studied fibroblasts exhibited marked variation in their levels of procollagen mRNAs, supporting previous views about their heterogeneity in connective tissues. The approach presented here offers new possibilities to study cellular interactions and metabolic activities in inflammatory lesions. PMID:2296161

  18. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    SciTech Connect

    Stevens, C.E.; Taylor, P.E.; Zang, E.A.; Morrison, J.M.; Harley, E.J.; de Cordoba, S.R.; Bacino, C.; Ting, R.C.; Bodner, A.J.; Sarngadharan, M.G.; Gallo, R.C.

    1986-04-25

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men.

  19. Confocal microscopic evaluation of cornea after AquaLase liquefaction cataract extraction

    PubMed Central

    Zhao, Jiang-Yue; Wang, Ming-Wu; Sun, Qi; Zhang, Jin-Song

    2011-01-01

    AIM The most recent and innovative AquaLase liquefaction technology has offered an alternative to lens extraction. Many studies have investigated its functions and advantages. This article focuses on evaluating the in vivo microscopic cornea changes after AquaLase liquefaction by using a laser confocal microscope. METHODS In this perspective, randomized case study, 37 eyes of 35 patients submitted to cataract surgery were chosen to undergo AquaLase liquefaction cataract extraction. Each patient was assessed before the operation, on the 1st, 7th, and 30th postoperative days, and 6 months after the cataract extraction. The morphologies and quantitative comparisons of corneal cells and corneal nerves layer by layer were evaluated in vivo with the Heidelberg Retina Tomograph III-Rostock Cornea Module (HRT-III RCM) confocal microscope. ANOVA and Post-Hoc Bonferroni test were carried out to compare the results pre- and post-operation. RESULTS ANOVA results indicated no post-operation changes for epithelium and anterior stroma cells. Irregular segments of sub-basal nerve fiber were most pronounced seven days post-operation. In the mid and posterior stroma, keratocytes were obvious compared with the preoperative condition. Corneal endothelium cells became obviously swollen in cytoplasm and nucleus. The mid and posterior stroma cell density decreased from the 1st to 7th postoperative days (P<0.05). The corneal endothelium cell density decreased (P<0.05) and did not revert to the preoperative level after six months (P<0.05). CONCLUSION Slight microstructural abnormalities were identified in the corneal recovery process after AquaLase liquefaction. AquaLase liquefaction cataract extraction is safe for cornea. PMID:22553665

  20. Association of bacterial carbohydrate-specific cold agglutinin antibody production with immunization by group C, group B type III, and Streptococcus pneumoniae type XIV streptococcal vaccines.

    PubMed Central

    Colling, R G; Pearson, T C; Brown, J C

    1983-01-01

    Rabbits immunized with group B type III, group C, and Streptococcus pneumoniae type XIV streptococcal vaccines developed autoantibodies reactive with autologous and isologous erythrocytes and human O-positive erythrocytes at reduced temperatures. The cold agglutinin antibodies were present in both the immunoglobulin M (IgM) and IgG fractions of group C streptococcal antiserum and in the IgM fraction of group B type III and S. pneumoniae type XIV antisera. BALB/c, CF1, and local strains of mice immunized with group B type III and S. pneumoniae type XIV streptococcal vaccines also produced a cold agglutinin antibody reactive with rabbit and human erythrocytes. The cold agglutinin antibodies were reactive with saccharide compounds representative of the determinants present on the individual bacterial carbohydrate structures, individual vaccine preparations, and isolated polysaccharides. The group C antibodies in rabbits were reactive with sugar ligands in the following order: N-acetylgalactosamine greater than melibiose greater than lactose greater than galactose greater than glucose. Group B type III and S. pneumoniae type XIV cold agglutinin antibodies in rabbit antisera, however, displayed reactivities different from group C antibodies and from each other. Group B type III antibodies reacted with galactose greater than lactose greater than N-acetylgalactosamine greater than glucose greater than rhamnose; S. pneumoniae type XIV antibodies reacted with lactose greater than melibiose greater than galactose greater than glucose greater than N-acetylgalactosamine. The same relative ligand specificity was observed for the cold agglutinin antibodies in S. pneumoniae type XIV mouse antisera. The cold agglutinin antibodies in group B type III and S. pneumoniae type XIV antiserum reacted with erythrocytes at higher temperatures (up to 31 degrees C) than did group C antibodies (up to 14 degrees C). In addition, S. pneumoniae type XIV antibodies did not discriminate between I

  1. Application Of The Excimer Laser To Area Recontouring Of The Cornea

    NASA Astrophysics Data System (ADS)

    Yoder, Paul R.; Telfair, William B.; Warner, John W.; Martin, Clifford A.; L'Esperance, Francis A.

    1989-04-01

    Excimer lasers operating at 193 nm are being used experimentally in a special type of materials processing wherein the central portion of the anterior surface of the human cornea is selectively ablated so as to change its refractive power and, hopefully, improve impaired vision. Research to date has demonstrated recontouring as a potential means for reducing myopia and hyperopia of cadaver eyes while studies of ablations on the corneas of living monkeys and of blind human volunteers show promise of prompt and successful healing. The procedure has also shown merit in removing superficial scars from the corneal surface. In this paper, we describe the electro-optical system used to deliver the UV laser beam in these experiments and report some preliminary results of the ablation studies.

  2. The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage.

    PubMed

    Cejkova, Jitka; Olmiere, Celine; Cejka, Cestmir; Trosan, Peter; Holan, Vladimir

    2014-04-01

    The efficacy of a chemically modified dextran - heparan sulfate mimicking regenerating agent (RGTA) on the healing of the rabbit cornea injured with alkali was examined. The eyes were injured with 0.15 N NaOH applied on the cornea or with 1.0 N NaOH using a 8 mm diameter filter paper disk. Then RGTA or placebo was applied on the cornea. In the last group of rabbits, corneas injured with the high alkali concentration were left without any treatment for four weeks; subsequently, the corneas were treated with RGTA or placebo. The central corneal thickness was measured using a pachymeter. The corneas were examined morphologically, immunohistochemically and for real time-PCR. Compared to control (unaffected) corneas, following the application of low alkali concentration the expression of urokinase-type plasminogen activator, metalloproteinase 9, nitric oxide synthase and xanthine oxidase was increased in the injured corneal epithelium of placebo-treated eyes, whereas the expression of antioxidant enzymes was reduced. Nitrotyrosine and malondialdehyde stainings appeared in the corneal epithelium. RGTA application suppressed the antioxidant/prooxidant imbalance and reduced the expression of the above-mentioned immunohistochemical markers. The corneal thickness increased after alkali injury, decreased during corneal healing after RGTA treatment faster than after placebo application. Following the injury with the high alkali concentration, corneal inflammation and neovascularization were highly pronounced in placebo-treated corneas, whereas in RGTA-treated corneas they were significantly supressed. When RGTA or placebo application was started later after alkali injury and corneas were ulcerated, subsequent RGTA treatment healed the majority of them. In conclusion, RGTA facilitates the healing of injured corneas via a reduction of proteolytic, oxidative and nitrosative damage. PMID:24105332

  3. Two Cases of Pulmonary Hypertension Associated with Type III Glycogen Storage Disease.

    PubMed

    Lee, Teresa M; Berman-Rosenzweig, Erika S; Slonim, Alfred E; Chung, Wendy K

    2011-01-01

    Glycogen storage diseases (GSDs) comprise a large, heterogeneous group of disorders characterized by abnormal glycogen deposition. Multiple cases in the literature have demonstrated an association between GSD type I and pulmonary arterial hypertension (PAH). We now also report on two patients with GSD type III and PAH, a novel association. The first patient was a 16-year-old girl of Nicaraguan descent with a history of hepatomegaly and growth retardation. Molecular testing identified a homozygous 17delAG mutation in AGL consistent with GSD type IIIb. At the age of 16, she was found to have PAH and was started on medical therapy. Two years later, she developed acute chest pain and died shortly thereafter. The second patient is a 13-year-old girl of Colombian descent homozygous for the c.3911dupA mutation consistent with GSD IIIa. An echocardiogram at age 2 showed left ventricular hypertrophy, which resolved following the institution of a high protein, moderate carbohydrate diet during the day and continuous gastric-tube feeding overnight. At the age of 12, she was found to have pulmonary hypertension. She was started on sildenafil, and her clinical status has shown marked improvement including normalization of her elevated transaminases. PAH may be a rare association in patients with GSD IIIa and IIIb and should be evaluated with screening echocardiograms for cardiac hypertrophy or if they present with symptoms of right-sided heart failure such as shortness of breath, chest pain, cyanosis, fatigue, dizziness, syncope, or edema. Early diagnosis of PAH is important as increasingly effective treatments are now available. PMID:23430832

  4. Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone.

    PubMed

    Volk, Susan W; Shah, Shalin R; Cohen, Arthur J; Wang, Yanjian; Brisson, Becky K; Vogel, Laurie K; Hankenson, Kurt D; Adams, Sherrill L

    2014-06-01

    Type III collagen (Col3), a fibril-forming collagen, is a major extracellular matrix component in a variety of internal organs and skin. It is also expressed at high levels during embryonic skeletal development and is expressed by osteoblasts in mature bone. Loss of function mutations in the gene encoding Col3 (Col3a1) are associated with vascular Ehlers-Danlos syndrome (EDS). Although the most significant clinical consequences of this syndrome are associated with catastrophic failure and impaired healing of soft tissues, several studies have documented skeletal abnormalities in vascular EDS patients. However, there are no reports of the role of Col3 deficiency on the murine skeleton. We compared craniofacial and skeletal phenotypes in young (6-8 weeks) and middle-aged (>1 year) control (Col3(+/+)) and haploinsufficient (Col3(+/-)) mice, as well as young null (Col3(-/-)) mice by microcomputed tomography (μCT). Although Col3(+/-) mice did not have significant craniofacial abnormalities based upon cranial morphometrics, μCT analysis of distal femur trabecular bone demonstrated significant reductions in bone volume (BV), bone volume fraction (BV/TV), connectivity density, structure model index and trabecular thickness in young adult female Col3(+/-) mice relative to wild-type littermates. The reduction in BV/TV persisted in female mice at 1 year of age. Next, we evaluated the role of Col3 in vitro. Osteogenesis assays revealed that cultures of mesenchymal progenitors collected from Col3(-/-) embryos display decreased alkaline phosphatase activity and reduced capacity to undergo mineralization. Consistent with this data, a reduction in expression of osteogenic markers (type I collagen, osteocalcin and bone sialoprotein) correlates with reduced bone Col3 expression in Col3(+/-) mice and with age in vivo. A small but significant reduction in osteoclast numbers was found in Col3(+/-) compared to Col3(+/+) bones. Taken together, these findings indicate that Col3 plays a

  5. Lysogeny with Shiga Toxin 2-Encoding Bacteriophages Represses Type III Secretion in Enterohemorrhagic Escherichia coli

    PubMed Central

    Xu, Xuefang; McAteer, Sean P.; Tree, Jai J.; Shaw, Darren J.; Wolfson, Eliza B. K.; Beatson, Scott A.; Roe, Andrew J.; Allison, Lesley J.; Chase-Topping, Margo E.; Mahajan, Arvind; Tozzoli, Rosangela; Woolhouse, Mark E. J.; Morabito, Stefano; Gally, David L.

    2012-01-01

    Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins. PMID:22615557

  6. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli.

    PubMed

    Xu, Xuefang; McAteer, Sean P; Tree, Jai J; Shaw, Darren J; Wolfson, Eliza B K; Beatson, Scott A; Roe, Andrew J; Allison, Lesley J; Chase-Topping, Margo E; Mahajan, Arvind; Tozzoli, Rosangela; Woolhouse, Mark E J; Morabito, Stefano; Gally, David L

    2012-01-01

    Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins. PMID:22615557

  7. [Fatigue properties of dental alloys. 12% Au-Pd-Ag alloy and type III gold alloy].

    PubMed

    Kato, H

    1989-12-01

    Usually the mechanical properties of dental alloys are determined from the values obtained through static tests of their tensile strength, hardness, etc. Generally, high tensile strength and ductility are preferred. However, when small stresses within proportional limits are applied repeatedly (even though not amounting to destructive forces in static tests), they may cause rupture in the alloy or, at least, cause it to lose its original mechanical properties. This phenomenon is called metal fatigue. It is estimated that the intraoral stress loads received by dental restorations during mastication or during insertion and removal of appliances are repeated more than 3 x 10(5) times/year. From this standpoint, it may be more appropriate to estimate the fracture strength of such dental alloys based on the fatigue properties of the restorative materials used for clasps, bars, and fixed bridges. For this reason, it is necessary to obtain data through fatigue tests on the fatigue strength and the fatigue endurance limits of dental alloys, and it is important to find a correlation between these data and the static data on tensile strengths and ductility obtained by tensile tests. Two alloys are used in these experiments. Both wrought specimens and cast specimens of 12% Au-Pd-Ag and Type III gold alloy were prepared for the fatigue tests. The size of the rectangular wrought specimens was 3 x 4 x 110 mm. The 12% Au-Pd-Ag alloy was heated to 800 degrees C for 15 minutes, quenched, and reheated to 400 degrees C for 20 minutes and quenched again according to the manufacturer's instructions for heat treatment. The Type III gold alloy was heated to 700 degrees C for 10 minutes, quenched, and reheated to 350 degrees C for 20 minutes and quenched again. The cylindrical cast specimens were 60 mm long and 2 mm in diameter. They were invested by conventional methods and cast in a centrifugal casting machine, Thermotrol Model 2500. The four point bending test for the wrought specimen

  8. Mechanics and spiral formation in the rat cornea.

    PubMed

    Mohammad Nejad, T; Iannaccone, S; Rutherford, W; Iannaccone, P M; Foster, C D

    2015-01-01

    During the maturation of some mammals such as mice and rats, corneal epithelial cells tend to develop into patterns such as spirals over time. A better understanding of these patterns can help to understand how the organ develops and may give insight into some of the diseases affecting corneal development. In this paper, a framework for explaining the development of the epithelial cells forming spiral patterns due to the effect of tensile and shear strains is proposed. Using chimeric animals, made by combining embryonic cells from genetically distinguishable strains, we can observe the development of patterns in the cornea. Aggregates of cell progeny from one strain or the other called patches form as organs and tissue develop. The boundaries of these patches are fitted with logarithmic spirals on confocal images of adult rat corneas. To compare with observed patterns, we develop a three-dimensional large strain finite element model for the rat cornea under intraocular pressure to examine the strain distribution on the cornea surface. The model includes the effects of oriented and dispersed fibrils families throughout the cornea and a nearly incompressible matrix. Tracing the directions of critical strain vectors on the cornea surface leads to spiral-like curves that are compared to the observed logarithmic spirals. Good agreement between the observed and numerical curves supports the proposed assumption that shear and tensile strains facilitate sliding of epithelial cells to develop spiral patterns. PMID:24897951

  9. Measurement of the anisotropic thermal conductivity of the porcine cornea.

    PubMed

    Barton, Michael D; Trembly, B Stuart

    2013-10-01

    Accurate thermal models for the cornea of the eye support the development of thermal techniques for reshaping the cornea and other scientific purposes. Heat transfer in the cornea must be quantified accurately so that a thermal treatment does not destroy the endothelial layer, which cannot regenerate, and yet is responsible for maintaining corneal transparency. We developed a custom apparatus to measure the thermal conductivity of ex vivo porcine corneas perpendicular to the surface and applied a commercial apparatus to measure thermal conductivity parallel to the surface. We found that corneal thermal conductivity is 14% anisotropic at the normal state of corneal hydration. Small numbers of ex vivo feline and human corneas had a thermal conductivity perpendicular to the surface that was indistinguishable from the porcine corneas. Aqueous humor from ex vivo porcine, feline, and human eyes had a thermal conductivity nearly equal to that of water. Including the anisotropy of corneal thermal conductivity will improve the predictive power of thermal models of the eye. PMID:23933570

  10. [Procedural guidelines. Good tissue practice for cornea banks].

    PubMed

    Schroeter, J; Maier, P; Bednarz, J; Blüthner, K; Quenzel, M; Pruss, A; Reinhard, T

    2009-03-01

    A cornea bank must have an organizational structure in which responsibility and authority to issue directives are clearly defined. It must also use a documented quality management system on the basis of good practice procedures which is maintained to the current standards. The personnel of a cornea bank must be present in sufficient numbers and be suitably qualified. A cornea bank must be in possession of appropriate facilities which are suitable for the main purpose of conservation of donor corneas. All equipment must be designed and maintained corresponding to the intended purpose. Deviations from the stipulated quality and safety standards must give rise to documented investigations which include decisions on options for correctional and preventive measures. Acquisition of donors and tissue sampling must be strictly controlled and documented. This also applies to entry of donor tissue in the cornea bank. During conservation a microscopic examination of the endothelial cell layer must be carried out at least once. Measures must be taken to keep the risk of contamination as low as possible. Donor corneal tissue can only be released if defined criteria are fulfilled. Any suspicion of severe undesired reactions and events for the recipient of a corneal transplant must be registered with the authorities. The activities of a cornea bank must maintain and adapt the state-of-the-art with respect to scientific progress. PMID:19263054

  11. Dielectric relaxation of normothermic and hypothermic rat corneas.

    PubMed

    Marzec, E; Sosnowski, P; Olszewski, J; Krauss, H; Bahloul, K; Samborski, W; Krawczyk-Wasielewska, A

    2015-02-01

    This paper aims at the presentation of the results of in vitro research on the dielectric properties of the cornea specimen collected from the rats subjected to in vivo hypothermia. The average values of the relative permittivity and dielectric loss are about 40% higher for the hypothermic cornea than those for the normothermic tissue at the same water content of 12% for both samples and at 25°C. Whereas, at 50°C this effect of increase in the dielectric properties of the hypothermic cornea when compared to the normothermic one is observed clearly only in the relative permittivity of about 19%. In the temperature range of 25-50°C, the activation energy of conductivity associated with the release of loosely bound water takes the average values of 45kJ/mol and 30kJ/mol for the normothermic and hypothermic corneas, respectively. The study provided information on dielectric polarization and conductance mechanisms in the cornea which may be helpful in interpreting clinical results of human cornea examination, currently obtained by means of such electrodiagnostic methods as conductive keratoplasty, electroretinography or electrooculography. PMID:25308935

  12. Cornea surgery with nanojoule femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Wang, Bagui; Riemann, Iris; Kobow, Jens

    2005-04-01

    We report on a novel optical method for (i) flap-generation in LASIK procedures as well as (ii) for flap-free intrastromal refractive surgery based on nanojoule femtosecond laser pulses. The near infrared 200 fs pulses for multiphoton ablation have been provided by ultracompact turn-key MHz laser resonators. LASIK flaps and intracorneal cavities have been realized with high precision within living New Zealand rabbits using the system FemtoCutO (JenLab GmbH, Jena, Germany) at 800 nm laser wavelength. Using low-energy sub-2 nJ laser pulses, collateral damage due to photodisruptive and self-focusing effects was avoided. The laser ablation system consists of fast galvoscanners, focusing optics of high numerical aperture as well as a sensitive imaging system and provides also the possibility of 3D multiphoton imaging of fluorescent cellular organelles and SHG signals from collagen. Multiphoton tomography of the cornea was used to determine the exact intratissue beam position and to visualize intraocular post-laser effects. The wound healing process has been investigated up to 90 days after instrastromal laser ablation by histological analysis. Regeneration of damaged collagen structures and the migration of inflammation cells have been detected.

  13. Femtosecond lasers for microsurgery of cornea

    NASA Astrophysics Data System (ADS)

    Vartapetov, Sergei K.; Khudyakov, D. V.; Lapshin, Konstantin E.; Obidin, Aleksei Z.; Shcherbakov, Ivan A.

    2012-03-01

    The review of femtosecond laser installations for medical applications is given and a new femtosecond ophthalmologic system for creation of a flap of corneal tissue during the LASIK operation is described. An all-fibre femtosecond laser emitting ~400-fs pulses at 1067 nm is used. The pulse repetition rate can vary from 200 kHz up to 1 MHz. The output energy of the femtosecond system does not exceed 1 μJ. A specially developed objective with small spherical and chromatic aberrations is applied to focus laser radiation to an area of an eye cornea. The size of the focusing spot does not exceed 3 μm. To process the required area, scanning by a laser beam is applied with a speed no less than 5 m s-1. At a stage of preliminary tests of the system, the Κ8 glass, organic PMMA glass and specially prepared agarose gels are used as a phantom of an eye. The femtosecond system is successfully clinically tested on a plenty of eyes of a pig and on several human eyes. The duration of the procedure of creation of a corneal flap does not exceed 20 s.

  14. Femtosecond lasers for microsurgery of cornea

    SciTech Connect

    Vartapetov, Sergei K; Khudyakov, D V; Lapshin, Konstantin E; Obidin, Aleksei Z; Shcherbakov, Ivan A

    2012-03-31

    The review of femtosecond laser installations for medical applications is given and a new femtosecond ophthalmologic system for creation of a flap of corneal tissue during the LASIK operation is described. An all-fibre femtosecond laser emitting {approx}400-fs pulses at 1067 nm is used. The pulse repetition rate can vary from 200 kHz up to 1 MHz. The output energy of the femtosecond system does not exceed 1 {mu}J. A specially developed objective with small spherical and chromatic aberrations is applied to focus laser radiation to an area of an eye cornea. The size of the focusing spot does not exceed 3 {mu}m. To process the required area, scanning by a laser beam is applied with a speed no less than 5 m s{sup -1}. At a stage of preliminary tests of the system, the {Kappa}8 glass, organic PMMA glass and specially prepared agarose gels are used as a phantom of an eye. The femtosecond system is successfully clinically tested on a plenty of eyes of a pig and on several human eyes. The duration of the procedure of creation of a corneal flap does not exceed 20 s.

  15. Correlating Type II and III Radio Bursts with Solar Energetic Particle Events

    NASA Astrophysics Data System (ADS)

    Ledbetter, K.; Winter, L. M.; Quinn, R. A.

    2013-12-01

    Solar energetic particles (SEPs) are high-energy particles, such as protons, which are accelerated at the Sun and speed outward into the solar system. If they reach Earth, they can be harmful to satellites, ionospheric communications, and humans in space or on polar airline routes. NOAA defines an SEP event as an occasion when the flux of protons with energies higher than 10 MeV exceeds 10 pfu (particle flux units) as measured by the GOES satellites in geosynchronous orbit. The most intense SEP events are associated with shocks, driven by coronal mass ejections (CMEs), which accelerate particles as they move through the corona. However, very few CMEs result in SEP events. To determine what factors are most important in distinguishing the shock waves that will result in SEP acceleration toward Earth, we take into account several variables and perform a principal component analysis (PCA) to examine their correlations. First, we examine Type II radio bursts, which are caused by electrons accelerating in the same CME-driven shocks that can accelerate SEPs. Using data from the WAVES instrument on the WIND satellite, these Type II radio bursts, as well as the Type III bursts that often accompany them, can be characterized by slope in 1/f space and by intensity. In addition, local Langmuir waves detected by WIND, which are caused by electrons speeding through the plasma surrounding the satellite, can be an indicator of the magnetic connectivity between the active region and Earth. Finally, X-ray flares directly preceding the Type II burst are also taken into consideration in the PCA analysis. The accompanying figure illustrates an example of the WAVES solar radio bursts along with the GOES solar proton flux >= 10 MeV during the SEP event on April 11, 2013. Using PCA to determine which of these factors are most relevant to the onset, intensity, and duration of SEP events will be valuable in future work to predict such events. In total, we present the analysis of all type

  16. Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic Compounds in Isolated Rabbit Cornea and Conjunctiva.

    PubMed

    Sekijima, Hidehisa; Ehara, Junya; Hanabata, Yusuke; Suzuki, Takumi; Kimura, Soichiro; Lee, Vincent H L; Morimoto, Yasunori; Ueda, Hideo

    2016-06-01

    Ocular iontophoresis (IP) in isolated rabbit cornea and conjunctiva was examined in terms of transport enhancement, tissue viability and integrity using electrophysiological parameters by the Ussing-type chamber technique. Lidocaine hydrochloride (LC, a cationic compound), sodium benzoate (BA, anionic compound), and fluorescein isothiocyanate labeled dextran (molecular weight 4400 Da, FD-4, hydrophilic large compound) were used as model permeants. Direct electric current was applied at 0.5-5.0 mA/cm(2) for the cornea and 0.5-20 mA/cm(2) for the conjunctiva for 30 min. LC and BA fluxes across the cornea and conjunctiva were significantly increased by the application of electric current up to 2.3- and 2.5-fold and 4.0- and 3.4-fold, respectively, and returned to their baseline level on stopping the current. Furthermore, a much higher increase by IP application was obtained for the FD-4 transport. The increased FD-4 flux in the conjunctiva returned to baseline on stopping the current, whereas the flux in the cornea was sustained at a higher level after stopping the current. The transepithelial electric resistance of the cornea and conjunctiva was lowered by electric current application but fully recovered after stopping the current up to 2.0 mA/cm(2) for the cornea and 10 mA/cm(2) for the conjunctiva, suggesting that the corneal and conjunctival viability and integrity are maintained even after application of these current densities. These results indicate that ocular IP may be a useful non-invasive technique to achieve drug delivery of hydrophilic large molecules into the eyes. PMID:27040754

  17. Bile salt receptor complex activates a pathogenic type III secretion system

    PubMed Central

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N; Salomon, Dor; Tomchick, Diana R; Grishin, Nick V; Orth, Kim

    2016-01-01

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment. DOI: http://dx.doi.org/10.7554/eLife.15718.001 PMID:27377244

  18. Bacteriophage-encoded type III effectors in Salmonella enterica subspecies 1 serovar Typhimurium.

    PubMed

    Ehrbar, Kristin; Hardt, Wolf-Dietrich

    2005-01-01

    Salmonella spp. are Gram-negative bacteria which cause infections ranging from mild, self-limiting enterocolitis to systemic (typhoid) disease. Recent work has established that the genetic makeup varies considerably between different Salmonella strains. Phages play an important role in this diversity. In fact, Salmonella has emerged as a prime example for the involvement of virulence factor encoding phages in the emergence of new epidemic strains. Among other virulence factors, Salmonella enterica utilizes two specialized protein secretion systems termed type III secretion systems (TTSS) to deliver effector proteins into host cells which manipulate host cell signaling cascades. These two TTSS and several effectors are encoded within Salmonella pathogenicity islands 1 and 2. Some effectors including SopE, SspH1, SseI and SopE2 are encoded by phages or phage remnants. These phage-encoded effectors seem to be transferred between different Salmonella strains. They have attracted much interest because they might contribute to the evolution of Salmonella spp. Here we will focus on SopEPhi which encodes the SPI-1 effector SopE. It provides an excellent example to illustrate how horizontally transferred effector proteins are integrated into the complex regulatory network of a TTSS in a recipient bacterium. Additional data supporting the hypothesis are presented. This is a prerequisite to allow optimization of the bacterium host cell interaction by reassortment of the phage-encoded effector protein repertoire. PMID:15567133

  19. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells

    PubMed Central

    Galán, Jorge E.; Lara-Tejero, Maria; Marlovits, Thomas C.; Wagner, Samuel

    2015-01-01

    One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilized complex nanomachines to deliver bacterially encoded effector proteins into target eukaryotic cells. These effector proteins modulate a variety of cellular functions for the pathogen’s benefit. One of these protein-delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants, but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great targets for novel antimicrobial strategies. PMID:25002086

  20. Hfq negatively regulates type III secretion in EHEC and several other pathogens

    PubMed Central

    Shakhnovich, Elizabeth A.; Davis, Brigid M.; Waldor, Matthew K.

    2009-01-01

    Summary Hfq is a conserved RNA-binding protein that regulates diverse cellular processes through post-transcriptional control of gene expression, often by functioning as a chaperone for regulatory sRNAs. Here, we explored the role of Hfq in enterohaemorrhagic E. coli (EHEC), a group of non-invasive intestinal pathogens. EHEC virulence is dependent on a Type III secretion system encoded in the LEE pathogenicity island. The abundance of transcripts for all 41 LEE genes and more than half of confirmed non-LEE-encoded T3 effectors were elevated in an EHEC hfq deletion mutant. Thus, Hfq promotes coordinated expression of the LEE-encoded T3S apparatus and both LEE- and non-LEE-encoded effectors. Increased transcript levels led to the formation of functional secretion complexes capable of secreting high quantities of effectors into the supernatant. The increase in LEE-derived transcripts and proteins was dependent on Ler, the LEE-encoded transcriptional activator, and the ler transcript appears to be a direct target of Hfq-mediated negative regulation. Finally, we found that Hfq contributes to the negative regulation of T3SSs in several other pathogens, suggesting that Hfq, potentially along with species-specific sRNAs, underlies a common means to prevent unfettered expression of T3SSs. PMID:19703108

  1. Serum type III procollagen N-terminal peptide in coal miners.

    PubMed

    Janssen, Y M; Engelen, J J; Giancola, M S; Low, R B; Vacek, P; Borm, P J

    1992-01-01

    Health surveillance of workers exposed to fibrogenic agents ideally should identify individuals at risk or detect pulmonary fibrosis in preclinical stages. We investigated serum procollagen type III N-terminal peptide (PIIIP) in several groups of active miners and in a nondust-exposed control group. The purpose of this study was to determine the applicability of PIIIP as an early noninvasive marker of pulmonary fibrosis in workers exposed to coal mine dust. PIIIP levels were significantly elevated in miners without radiological signs of coal workers pneumoconiosis (CWP) as compared with the nonexposed controls. However, in coal miners with CWP beyond ILO classification 1/0, PIIIP levels were not significantly different from nondust-exposed controls. Trend analysis within the miners group indicated a decrease in PIIIP levels with progression of the fibrosis. Our data suggest that detection of early lung fibrosis by measuring serum PIIIP values may be more sensitive than radiological diagnosis of CWP. However, follow-up of the control miners with respect to serum PIIIP and chest radiography is essential to validate PIIIP as a biological marker for CWP. PMID:1572317

  2. A bacterial type III secretion-based protein delivery tool for broad applications in cell biology

    PubMed Central

    Ittig, Simon J.; Schmutz, Christoph; Kasper, Christoph A.; Amstutz, Marlise; Schmidt, Alexander; Sauteur, Loïc; Vigano, M. Alessandra; Low, Shyan Huey; Affolter, Markus; Cornelis, Guy R.; Nigg, Erich A.

    2015-01-01

    Methods enabling the delivery of proteins into eukaryotic cells are essential to address protein functions. Here we propose broad applications to cell biology for a protein delivery tool based on bacterial type III secretion (T3S). We show that bacterial, viral, and human proteins, fused to the N-terminal fragment of the Yersinia enterocolitica T3S substrate YopE, are effectively delivered into target cells in a fast and controllable manner via the injectisome of extracellular bacteria. This method enables functional interaction studies by the simultaneous injection of multiple proteins and allows the targeting of proteins to different subcellular locations by use of nanobody-fusion proteins. After delivery, proteins can be freed from the YopE fragment by a T3S-translocated viral protease or fusion to ubiquitin and cleavage by endogenous ubiquitin proteases. Finally, we show that this delivery tool is suitable to inject proteins in living animals and combine it with phosphoproteomics to characterize the systems-level impact of proapoptotic human truncated BID on the cellular network. PMID:26598622

  3. PscI is a type III secretion needle anchoring protein with in vitro polymerization capacities.

    PubMed

    Monlezun, Laura; Liebl, David; Fenel, Daphna; Grandjean, Teddy; Berry, Alice; Schoehn, Guy; Dessein, Rodrigue; Faudry, Eric; Attree, Ina

    2015-04-01

    The export of bacterial toxins across the bacterial envelope requires the assembly of complex, membrane-embedded protein architectures. Pseudomonas aeruginosa employs type III secretion (T3S) injectisome to translocate exotoxins directly into the cytoplasm of a target eukaryotic cell. This multi-protein channel crosses two bacterial membranes and extends further as a needle through which the proteins travel. We show in this work that PscI, proposed to form the T3S system (T3SS) inner rod, possesses intrinsic properties to polymerize into flexible and regularly twisted fibrils and activates IL-1β production in mouse bone marrow macrophages in vitro. We also found that point mutations within C-terminal amphipathic helix of PscI alter needle assembly in vitro and T3SS function in cell infection assays, suggesting that this region is essential for an efficient needle assembly. The overexpression of PscF partially compensates for the absence of the inner rod in PscI-deficient mutant by forming a secretion-proficient injectisome. All together, we propose that the polymerized PscI in P. aeruginosa optimizes the injectisome function by anchoring the needle within the envelope-embedded complex of the T3S secretome and - contrary to its counterpart in Salmonella - is not involved in substrate switching. PMID:25614137

  4. Molecular insights into the biosynthesis of guadinomine: a type III secretion system inhibitor.

    PubMed

    Holmes, Tracy C; May, Aaron E; Zaleta-Rivera, Kathia; Ruby, J Graham; Skewes-Cox, Peter; Fischbach, Michael A; DeRisi, Joseph L; Iwatsuki, Masato; Ōmura, Satoshi; Khosla, Chaitan

    2012-10-24

    Guadinomines are a recently discovered family of anti-infective compounds produced by Streptomyces sp. K01-0509 with a novel mode of action. With an IC(50) of 14 nM, guadinomine B is the most potent known inhibitor of the type III secretion system (TTSS) of Gram-negative bacteria. TTSS activity is required for the virulence of many pathogenic Gram-negative bacteria including Escherichia coli , Salmonella spp., Yersinia spp., Chlamydia spp., Vibrio spp., and Pseudomonas spp. The guadinomine (gdn) biosynthetic gene cluster has been cloned and sequenced and includes 26 open reading frames spanning 51.2 kb. It encodes a chimeric multimodular polyketide synthase, a nonribosomal peptide synthetase, along with enzymes responsible for the biosynthesis of the unusual aminomalonyl-acyl carrier protein extender unit and the signature carbamoylated cyclic guanidine. Its identity was established by targeted disruption of the gene cluster as well as by heterologous expression and analysis of key enzymes in the biosynthetic pathway. Identifying the guadinomine gene cluster provides critical insight into the biosynthesis of these scarce but potentially important natural products. PMID:23030602

  5. T3DB: an integrated database for bacterial type III secretion system

    PubMed Central

    2012-01-01

    Background Type III Secretion System (T3SS), which plays important roles in pathogenesis or symbiosis, is widely expressed in a variety of gram negative bacteria. However, lack of unique nomenclature for T3SS genes has hindered T3SS related research. It is necessary to set up a knowledgebase integrating T3SS-related research data to facilitate the communication between different research groups interested in different bacteria. Description A T3SS-related Database (T3DB) was developed. T3DB serves as an integrated platform for sequence collection, function annotation, and ortholog classification for T3SS related apparatus, effector, chaperone and regulatory genes. The collection of T3SS-containing bacteria, T3SS-related genes, function annotation, and the ortholog information were all manually curated from literature. BPBAac, a highly efficient T3SS effector prediction tool, was also implemented. Conclusions T3DB is the first systematic platform integrating well-annotated T3SS-related gene and protein information to facilitate T3SS and bacterial pathogenecity related research. The newly constructed T3 ortholog clusters may faciliate effective communication between different research groups and will promote de novo discoveries. Besides, the manually-curated high-quality effector and chaperone data are useful for feature analysis and evolutionary studies of these important proteins. PMID:22545727

  6. Type III secretion needle proteins induce cell signaling and cytokine secretion via Toll-like receptors.

    PubMed

    Jessen, Danielle L; Osei-Owusu, Patrick; Toosky, Melody; Roughead, William; Bradley, David S; Nilles, Matthew L

    2014-06-01

    Pathogens are recognized by hosts by use of various receptors, including the Toll-like receptor (TLR) and Nod-like receptor (NLR) families. Ligands for these varied receptors, including bacterial products, are identified by the immune system, resulting in development of innate immune responses. Only a couple of components from type III secretion (T3S) systems are known to be recognized by TLR or NLR family members. Known T3S components that are detected by pattern recognition receptors (PRRs) are (i) flagellin, detected by TLR5 and NLRC4 (Ipaf); and (ii) T3S rod proteins (PrgJ and homologs) and needle proteins (PrgI and homologs), detected by NAIP and the NLRC4 inflammasome. In this report, we characterize the induction of proinflammatory responses through TLRs by the Yersinia pestis T3S needle protein, YscF, the Salmonella enterica needle proteins PrgI and SsaG, and the Shigella needle protein, MxiH. More specifically, we determine that the proinflammatory responses occur through TLR2 and -4. These data support the hypothesis that T3S needles have an unrecognized role in bacterial pathogenesis by modulating immune responses. PMID:24643544

  7. Compensatory mechanisms during walking in response to muscle weakness in spinal muscular atrophy, type III.

    PubMed

    Matjacić, Zlatko; Olensek, Andrej; Krajnik, Janez; Eymard, Bruno; Zupan, Anton; Praznikar, Ales

    2008-05-01

    Our knowledge on altered neurological control of walking due to weakness of various muscle groups of the lower extremities is limited. The aim of this study was to assess kinematic, kinetic and electromyographic (EMG) walking patterns in a functionally homogeneous group of seven subjects with spinal muscular atrophy, type III (SMA group) and compare them with normal data obtained from nine healthy subjects (CONTROL group) in order to identify characteristic compensatory changes. Muscle strength at the ankle and knee joints was assessed using isokinetic dynamometry to determine variability in muscle strength: this was found to be similar in the two groups. Kinematic, kinetic and EMG patterns were assessed during walking in the SMA and CONTROL groups. The results showed changes in the activity of ankle plantarflexors and associated control of the center of pressure during loading response and midstance, which facilitated minimization of the external flexion moment acting on the knee and hip in the SMA group. Additionally, we identified distinct and consistent changes in the control of hip rotators that act to rapidly extend the hip early in stance phase and in the control of contralateral hip abductors that act delay weight shift onto the leg entering the stance phase. From these results we can conclude that the most important muscle groups compensating for reduced strength in knee and hip muscles are the ankle plantarflexors, hip rotators and hip abductors. This finding would have direct application in rehabilitation treatment programs. PMID:17980600

  8. Pseudomonas syringae type III effector AvrRpt2 alters Arabidopsis thaliana auxin physiology

    PubMed Central

    Chen, Zhongying; Agnew, Jennifer L.; Cohen, Jerry D.; He, Ping; Shan, Libo; Sheen, Jen; Kunkel, Barbara N.

    2007-01-01

    The Pseudomonas syringae type III effector AvrRpt2 promotes bacterial virulence on Arabidopsis thaliana plants lacking a functional RPS2 gene (rps2 mutant plants). To investigate the mechanisms underlying the virulence activity of AvrRpt2, we examined the phenotypes of transgenic A. thaliana rps2 seedlings constitutively expressing AvrRpt2. These seedlings exhibited phenotypes reminiscent of A. thaliana mutants with altered auxin physiology, including longer primary roots, increased number of lateral roots, and increased sensitivity to exogenous auxin. They also had increased levels of free indole acetic acid (IAA). The presence of AvrRpt2 also was correlated with a further increase in free IAA levels during infection with P. syringae pv. tomato strain DC3000 (PstDC3000). These results indicate that AvrRpt2 alters A. thaliana auxin physiology. Application of the auxin analog 1-naphthaleneacetic acid promoted disease symptom development in PstDC3000-infected plants, suggesting that elevated auxin levels within host tissue promote PstDC3000 virulence. Thus, AvrRpt2 may be among the virulence factors of P. syringae that modulate host auxin physiology to promote disease. PMID:18056646

  9. Automated Recognition of Type III Solar Radio Bursts Using Mathematical Morphology

    NASA Astrophysics Data System (ADS)

    Jones, J.

    2014-09-01

    Modern technology, specifically radio communications, is particularly vulnerable to various aspects of space weather. The solar environment can disrupt satellite communications links which can have a variety of impacts from loss of data to loss of spacecraft control. Radio spectrograph instruments are used to monitor the suns coronal emissions of plasma that travel with the solar wind towards Earth. These radio bursts are detected by radio observatories around the world, analyzed manually and bulletins are created to notify satellite operators. This paper presents a real-time method to automatically detect and classify radio bursts measured by solar radio spectrographs using mathematical morphology, which is ideal for the identification of shapes or objects embedded in complex backgrounds. Since type III radio bursts typically last only about 1-3 seconds they have a distinctive shape, a vertical line that spans a wide frequency range in a short time period, the object can be detected with a single structuring element. Data from the current solar max were used to validate the method. Results were compared to the manual analysis from the observatories.

  10. Towards the Identification of Type III Effectors Associated with Ralstonia solanacearum Virulence on Tomato and Eggplant.

    PubMed

    Pensec, Flora; Lebeau, Aurore; Daunay, M C; Chiroleu, Frédéric; Guidot, Alice; Wicker, Emmanuel

    2015-12-01

    For the development of pathogen-informed breeding strategies, identifying the microbial genes involved in interactions with the plant is a critical step. To identify type III effector (T3E) repertoires associated with virulence of the bacterial wilt pathogen Ralstonia solanacearum on Solanaceous crops, we used an original association genetics approach combining DNA microarray data and pathogenicity data on resistant eggplant, pepper, and tomato accessions. From this first screen, 25 T3Es were further full-length polymerase chain reaction-amplified within a 35-strain field collection, to assess their distribution and allelic diversity. Six T3E repertoire groups were identified, within which 11 representative strains were chosen to challenge the bacterial wilt-resistant egg plants 'Dingras multiple Purple' and 'AG91-25', and tomato Hawaii 7996. The virulence or avirulence phenotypes could not be explained by specific T3E repertoires, but rather by individual T3E genes. We identified seven highly avirulence-associated genes, among which ripP2, primarily referenced as conferring avirulence to Arabidopsis thaliana. Interestingly, no T3E was associated with avirulence to both egg-plants. Highly virulence-associated genes were also identified: ripA5_2, ripU, and ripV2. This study should be regarded as a first step toward investigating both avirulence and virulence function of the highlighted genes, but also their evolutionary dynamics in natural R. solanacearum populations. PMID:26368514

  11. Distinct Structural Elements Dictate the Specificity of the Type III Pentaketide Synthase from Neurospora crassa

    SciTech Connect

    Rubin-Pitel, Sheryl B.; Zhang, Houjin; Vu, Trang; Brunzelle, Joseph S.; Zhao, Huimin; Nair, Satish K.

    2009-01-15

    The fungal type III polyketide synthase 2'-oxoalkylresorcyclic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C{sub 4}--C{sub 20}) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 {angstrom} resolution, the Phe-252{yields}Gly site-directed mutant to 2.1 {angstrom} resolution, and a binary conplex of ORAS with eicosanoic acid to 2.0 {angstrom} resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accomodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.

  12. Current understanding of the physics of type III solar radio bursts

    NASA Technical Reports Server (NTRS)

    Papadopoulos, K.

    1980-01-01

    One of the most exciting plasma physics investigations of recent years has been connected with the understanding of a new strong turbulent plasma state excited by propagating electron beams. This new state is initiated on the linear level by parametric instabilities (OTS, modulational, etc.) and results in a very dynamic state composed of collective clusters of modes called solitons, cavitons, spikons, etc. Introduction of these concepts into the classic beam-plasma interaction problem has rendered quasi-linear and weak turbulence theories inapplicable over most of the interesting parameter range, and helped explain many paradoxes connected with the propagation of beams in the laboratory and space. Following a brief review of these nonlinear notions, the means by which their application to type III solar radiobursts has revolutionized understanding of their propagation, radioemission and scaling properties and has guided the in situ observations towards a more complete understanding are demonstrated. A particular burst (May 16, 1971) is analyzed in detail and compared with numerical predictions.

  13. Dynamics of the Type III Secretion System Activity of Enteropathogenic Escherichia coli

    PubMed Central

    Mills, Erez; Baruch, Kobi; Aviv, Gili; Nitzan, Mor; Rosenshine, Ilan

    2013-01-01

    ABSTRACT Type III secretion systems (TTSSs) are employed by pathogens to translocate host cells with effector proteins, which are crucial for virulence. The dynamics of effector translocation, behavior of the translocating bacteria, translocation temporal order, and relative amounts of each of the translocated effectors are all poorly characterized. To address these issues, we developed a microscopy-based assay that tracks effector translocation. We used this assay alongside a previously described real-time population-based translocation assay, focusing mainly on enteropathogenic Escherichia coli (EPEC) and partly comparing it to Salmonella. We found that the two pathogens exhibit different translocation behaviors: in EPEC, a subpopulation that formed microcolonies carried out most of the translocation activity, while Salmonella executed protein translocation as planktonic bacteria. We also noted variability in host cell susceptibility, with some cells highly resistant to translocation. We next extended the study to determine the translocation dynamics of twenty EPEC effectors and found that all exhibited distinct levels of translocation efficiency. Further, we mapped the global effects of key TTSS-related components on TTSS activity. Our results provide a comprehensive description of the dynamics of the TTSS activity of EPEC and new insights into the mechanisms that control the dynamics. PMID:23900171

  14. Variation of Langmuir wave polarization with electron beam speed in type III radio bursts

    SciTech Connect

    Malaspina, David M.; Cairns, Iver H.; Ergun, Robert E.

    2013-06-13

    Observations by the twin STEREO spacecraft of in-situ electric field waveforms and radio signatures associated with type III radio bursts have demonstrated that the polarization of electron beam-driven waves near the local plasma frequency depends strongly on the speed of the driving electron beam. We expand upon a previous study by including all radio bursts with in-situ waveforms observed by STEREO in 2011. The expanded data set contains five times more radio bursts (35 up from 7) and three times as many Langmuir waves (663 up from 168). While this expanded study supports the results of the original study, that faster (slower) beam electrons drive waves with strong (weak) electric fields perpendicular to the local magnetic field, the larger data set emphasizes that the observation of strong perpendicular electric fields at high electron beam speeds is probabilistic rather than definite. This property supports the interpretation of wave polarization dependence on beam speed as Langmuir/z-mode waves shifted to small wave number through interaction with turbulent solar wind density fluctuations.

  15. a Computational Approach to Explore Protein Translocation Through Type III Secretion Apparatus

    NASA Astrophysics Data System (ADS)

    Rathinavelan, Thenmalarchelvi; Im, Wonpil

    2010-01-01

    Many Gram-negative bacteria initiate infections by injecting effector proteins into host cells through the type III secretion apparatus (TTSA) that is comprised of a basal body, a needle, and a tip. The needle channel is formed by the assembly of a single needle protein. To explore the export mechanisms of MxiH needle protein through the needle of Shigella flexneri, an essential step during needle assembly, we have performed steered molecular dynamics simulations in implicit solvent. Interestingly, the electronegative channel interior creates an energy barrier for MxiH to enter the channel, while the same may facilitate the ejection of the effectors into host cells. Structurally-known basal regions and ATPase underneath the basal region have also such electronegative interior, while effector proteins have considerable electronegative patches on their surfaces. Based on these observations, we propose a repulsive electrostatic mechanism for protein translocation through the TTSA. This mechanism is supported by the suggestion that an ATPase is required for protein translocation through these nanomachines, which may provide the energy to overcome the initial electrostatic energy barrier. A similar mechanism may be applicable to macromolecular channels in other secretion systems or viruses through which proteins or nucleic acids are transported.

  16. Structure of a bacterial type III secretion system in contact with a host membrane in situ

    NASA Astrophysics Data System (ADS)

    Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R.; Hayward, Richard D.

    2015-12-01

    Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking `pump-action' conformational changes that underpin effector injection.

  17. Structure of a bacterial type III secretion system in contact with a host membrane in situ

    PubMed Central

    Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R.; Hayward, Richard D.

    2015-01-01

    Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform–ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking ‘pump-action' conformational changes that underpin effector injection. PMID:26656452

  18. Using Transcriptional Control To Increase Titers of Secreted Heterologous Proteins by the Type III Secretion System

    PubMed Central

    Metcalf, Kevin J.; Finnerty, Casey; Azam, Anum; Valdivia, Elias

    2014-01-01

    The type III secretion system (T3SS) encoded at the Salmonella pathogenicity island 1 (SPI-1) locus secretes protein directly from the cytosol to the culture media in a concerted, one-step process, bypassing the periplasm. While this approach is attractive for heterologous protein production, product titers are too low for many applications. In addition, the expression of the SPI-1 gene cluster is subject to native regulation, which requires culturing conditions that are not ideal for high-density growth. We used transcriptional control to increase the amount of protein that is secreted into the extracellular space by the T3SS of Salmonella enterica. The controlled expression of the gene encoding SPI-1 transcription factor HilA circumvents the requirement of endogenous induction conditions and allows for synthetic induction of the secretion system. This strategy increases the number of cells that express SPI-1 genes, as measured by promoter activity. In addition, protein secretion titer is sensitive to the time of addition and the concentration of inducer for the protein to be secreted and SPI-1 gene cluster. Overexpression of hilA increases secreted protein titer by >10-fold and enables recovery of up to 28 ± 9 mg/liter of secreted protein from an 8-h culture. We also demonstrate that the protein beta-lactamase is able to adopt an active conformation after secretion, and the increase in secreted titer from hilA overexpression also correlates to increased enzyme activity in the culture supernatant. PMID:25038096

  19. Quorum Sensing Regulates Type III Secretion in Vibrio harveyi and Vibrio parahaemolyticus

    PubMed Central

    Henke, Jennifer M.; Bassler, Bonnie L.

    2004-01-01

    In a process known as quorum sensing, bacteria communicate with one another by producing, releasing, detecting, and responding to signal molecules called autoinducers. Vibrio harveyi, a marine pathogen, uses two parallel quorum-sensing circuits, each consisting of an autoinducer-sensor pair, to control the expression of genes required for bioluminescence and a number of other target genes. Genetic screens designed to discover autoinducer-regulated targets in V. harveyi have revealed genes encoding components of a putative type III secretion (TTS) system. Using transcriptional reporter fusions and TTS protein localization studies, we show that the TTS system is indeed functional in V. harveyi and that expression of the genes encoding the secretion machinery requires an intact quorum-sensing signal transduction cascade. The newly completed genome of the closely related marine bacterium Vibrio parahaemolyticus, which is a human pathogen, shows that it possesses the genes encoding both of the V. harveyi-like quorum-sensing signaling circuits and that it also has a TTS system similar to that of V. harveyi. We show that quorum sensing regulates TTS in V. parahaemolyticus. Previous reports connecting quorum sensing to TTS in enterohemorrhagic and enteropathogenic Escherichia coli show that quorum sensing activates TTS at high cell density. Surprisingly, we find that at high cell density (in the presence of autoinducers), quorum sensing represses TTS in V. harveyi and V. parahaemolyticus. PMID:15175293

  20. Crystal structure of Spa40, the specificity switch for the Shigella flexneri type III secretion system

    PubMed Central

    Deane, Janet E; Graham, Stephen C; Mitchell, Edward P; Flot, David; Johnson, Steven; Lea, Susan M

    2008-01-01

    The pathogenic bacterium Shigella flexneri uses a type III secretion system to inject virulence factors from the bacterial cytosol directly into host cells. The machinery that identifies secretion substrates and controls the export of extracellular components and effector proteins consists of several inner-membrane and cytoplasmic proteins. One of the inner membrane components, Spa40, belongs to a family of proteins proposed to regulate the switching of substrate specificity of the export apparatus. We show that Spa40 is cleaved within the strictly conserved amino acid sequence NPTH and substitution of the proposed autocatalytic residue abolishes cleavage. Here we also report the crystal structure of the cytoplasmic complex Spa40C and compare it with the recent structures of the homologues from Escherichia coli and Salmonella typhimurium. These structures reveal the tight association of the cleaved fragments and show that the conserved NPTH sequence lies on a loop which, when cleaved, swings away from the catalytic N257 residue, resulting in different surface features in this region. This structural rearrangement suggests a mechanism by which non-cleaving forms of these proteins interfere with correct substrate switching of the apparatus. PMID:18485071

  1. Phylogeny and Virulence of Naturally Occurring Type III Secretion System-Deficient Pectobacterium Strains▿

    PubMed Central

    Kim, Hye-Sook; Ma, Bing; Perna, Nicole T.; Charkowski, Amy O.

    2009-01-01

    Pectobacterium species are enterobacterial plant-pathogenic bacteria that cause soft rot disease in diverse plant species. Previous epidemiological studies of Pectobacterium species have suffered from an inability to identify most isolates to the species or subspecies level. We used three previously described DNA-based methods, 16S-23S intergenic transcribed spacer PCR-restriction fragment length polymorphism analysis, multilocus sequence analysis (MLSA), and pulsed-field gel electrophoresis, to examine isolates from diseased stems and tubers and found that MLSA provided the most reliable classification of isolates. We found that strains belonging to at least two Pectobacterium clades were present in each field examined, although representatives of only three of five Pectobacterium clades were isolated. Hypersensitive response and DNA hybridization assays revealed that strains of both Pectobacterium carotovorum and Pectobacterium wasabiae lack a type III secretion system (T3SS). Two of the T3SS-deficient strains assayed lack genes adjacent to the T3SS gene cluster, suggesting that multiple deletions occurred in Pectobacterium strains in this locus, and all strains appear to have only six rRNA operons instead of the seven operons typically found in Pectobacterium strains. The virulence of most of the T3SS-deficient strains was similar to that of T3SS-encoding strains in stems and tubers. PMID:19411432

  2. Magnetic Reconnection of Solar Flare Detected by Solar Radio Burst Type III

    NASA Astrophysics Data System (ADS)

    Hamidi, Z. S.; Shariff, N. N. M.; Ibrahim, Z. A.; Monstein, C.; Zulkifli, W. N. A. Wan; Ibrahim, M. B.; Arifin, N. S.; Amran, N. A.

    2014-10-01

    The Sun is an ideal object of a blackbody with a large and complex magnetic field. In solar activity specifically solar flare phenomenon, the magnetic reconnection is one of the most significant factors of the Sun that can simplify a better understanding of our nearest star. This factor is due to the motion of the plasma and other particles through the convection mechanism inside the Sun. In our work, we will highlight one of the solar burst events that associated with solar flares. This event occurred on 13th November 2012 from 2:00:03 UT till 2:00:06 UT. It peaked with M2.0 solar flare at 2.04 UT. Within short time intervals of about l02 ~ 103s, large quantities of energy of 1022 ~ 1026J are emancipated. The changing magnetic field converts magnetic potential energy into kinetic energy by accelerating plasmas in the solar corona. It is believed that the plasma is channelled by the magnetic field up and away from the Sun. It is also accelerated back down along the magnetic field into the chromosphere. In conclusion, we showed that the structure of the solar radio burst type III is an indicator of a starting point of magnetic reconnection.

  3. Evaluation of Salmonella enterica Type III Secretion System Effector Proteins as Carriers for Heterologous Vaccine Antigens

    PubMed Central

    Hegazy, Wael Abdel Halim; Xu, Xin; Metelitsa, Leonid

    2012-01-01

    Live attenuated strains of Salmonella enterica have a high potential as carriers of recombinant vaccines. The type III secretion system (T3SS)-dependent translocation of S. enterica can be deployed for delivery of heterologous antigens to antigen-presenting cells. Here we investigated the efficacy of various effector proteins of the Salmonella pathogenicity island (SPI2)-encoded T3SS for the translocation of model antigens and elicitation of immune responses. The SPI2 T3SS effector proteins SifA, SteC, SseL, SseJ, and SseF share an endosomal membrane-associated subcellular localization after translocation. We observed that all effector proteins could be used to translocate fusion proteins with the model antigens ovalbumin and listeriolysin into the cytosol of host cells. Under in vitro conditions, fusion proteins with SseJ and SteC stimulated T-cell responses that were superior to those triggered by fusion proteins with SseF. However, in mice vaccinated with Salmonella carrier strains, only fusion proteins based on SseJ or SifA elicited potent T-cell responses. These data demonstrate that the selection of an optimal SPI2 effector protein for T3SS-mediated translocation is a critical parameter for the rational design of effective Salmonella-based recombinant vaccines. PMID:22252866

  4. Phase Coupling Between Spectral Components of Collapsing Langmuir Solitons in Solar Type III Radio Bursts

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

    We present the high time resolution observations of one of the Langmuir wave packets obtained in the source region of a solar type III radio burst. This wave packet satisfies the threshold condition of the supersonic modulational instability, as well as the criterion of a collapsing Langmuir soliton, i.e., the spatial scale derived from its peak intensity is less than that derived from its short time scale. The spectrum of t his wave packet contains an intense spectral peak at local electron plasma frequency, f(sub pe) and relatively weaker peaks at 2f(sub pe) and 3f(sub pe). We apply the wavelet based bispectral analysis technique on this wave packet and compute the bicoherence between its spectral components. It is found that the bicoherence exhibits two peaks at (approximately f(sub pe), approximately f(sub pe)) and (approximately f(sub pe) approximately 2f(sub pe)), which strongly suggest that the spectral peak at 2f(sub pe) probably corresponds to the second harmonic radio emission, generated as a result of the merging of antiparallel propagating Langmuir waves trapped in the collapsing Langmuir soliton, and, the spectral peak at 3f(sub pe) probably corresponds to the third harmonic radio emission, generated as a result of merging of a trapped Langmuir wave and a second harmonic electromagnetic wave.

  5. Xenocin Export by the Flagellar Type III Pathway in Xenorhabdus nematophila

    PubMed Central

    Singh, Preeti; Park, Dongjin; Forst, Steven

    2013-01-01

    The xenocin operon of Xenorhabdus nematophila consists of xciA and ximB genes encoding a 64-kDa xenocin and 42-kDa immunity protein to kill competing microbes in the insect larva. The catalytic domain of xenocin has RNase activity and is responsible for its cytotoxicity. Under SOS conditions, xenocin is produced with immunity protein as a complex. Here, we show that xenocin and immunity protein complex are exported through the flagellar type III system of X. nematophila. Secretion of xenocin complex was abolished in an flhA strain but not in an fliC strain. The xenocin operon is not linked to the flagellar operon transcriptionally. The immunity protein is produced alone from a second, constitutive promoter and is targeted to the periplasm in a flagellum-independent manner. For stable expression of xenocin, coexpression of immunity protein was necessary. To examine the role of immunity protein in xenocin export, an enzymatically inactive protein was produced by site-directed mutagenesis in the active site of the catalytic domain. Toxicity was abolished in D535A and H538A variants of xenocin, which were expressed alone without an immunity domain and secreted in the culture supernatant through flagellar export. Secretion of xenocin through the flagellar pathway has important implications in the evolutionary success of X. nematophila. PMID:23335409

  6. Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma

    PubMed Central

    Knelson, Erik H.; Gaviglio, Angela L.; Tewari, Alok K.; Armstrong, Michael B.; Mythreye, Karthikeyan; Blobe, Gerard C.

    2013-01-01

    Growth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the pediatric tumor neuroblastoma remain unclear. Comparison of mRNA from benign neuroblastic tumors and neuroblastomas revealed that expression of the type III TGF-β receptor (TGFBR3) decreases with advancing stage of neuroblastoma and this loss correlates with a poorer prognosis. Patients with MYCN oncogene amplification and low TGFBR3 expression were more likely to have an adverse outcome. In vitro, TβRIII expression was epigenetically suppressed by MYCN-mediated recruitment of histone deacetylases to regions of the TGFBR3 promoter. TβRIII bound FGF2 and exogenous FGFR1, which promoted neuronal differentiation of neuroblastoma cells. TβRIII and FGF2 cooperated to induce expression of the transcription factor inhibitor of DNA binding 1 via Erk MAPK. TβRIII-mediated neuronal differentiation suppressed cell proliferation in vitro as well as tumor growth and metastasis in vivo. These studies characterize a coreceptor function for TβRIII in FGF2-mediated neuronal differentiation, while identifying potential therapeutic targets and clinical biomarkers for neuroblastoma. PMID:24216509

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

    PubMed Central

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

    2015-01-01

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

  8. Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

    PubMed

    Bayer, Avraham; Lennemann, Nicholas J; Ouyang, Yingshi; Bramley, John C; Morosky, Stefanie; Marques, Ernesto Torres De Azeved; Cherry, Sara; Sadovsky, Yoel; Coyne, Carolyn B

    2016-05-11

    During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. PMID:27066743

  9. Selective Purification of Recombinant Neuroactive Peptides Using the Flagellar Type III Secretion System

    PubMed Central

    Singer, Hanna M.; Erhardt, Marc; Steiner, Andrew M.; Zhang, Min-Min; Yoshikami, Doju; Bulaj, Grzegorz; Olivera, Baldomero M.; Hughes, Kelly T.

    2012-01-01

    ABSTRACT The structure, assembly, and function of the bacterial flagellum involves about 60 different proteins, many of which are selectively secreted via a specific type III secretion system (T3SS) (J. Frye et al., J. Bacteriol. 188:2233–2243, 2006). The T3SS is reported to secrete proteins at rates of up to 10,000 amino acid residues per second. In this work, we showed that the flagellar T3SS of Salmonella enterica serovar Typhimurium could be manipulated to export recombinant nonflagellar proteins through the flagellum and into the surrounding medium. We translationally fused various neuroactive peptides and proteins from snails, spiders, snakes, sea anemone, and bacteria to the flagellar secretion substrate FlgM. We found that all tested peptides of various sizes were secreted via the bacterial flagellar T3SS. We subsequently purified the recombinant μ-conotoxin SIIIA (rSIIIA) from Conus striatus by affinity chromatography and confirmed that T3SS-derived rSIIIA inhibited mammalian voltage-gated sodium channel NaV1.2 comparably to chemically synthesized SIIIA. PMID:22647788

  10. Type III Secretion-Dependent Sensitivity of Escherichia coli O157 to Specific Ketolides

    PubMed Central

    Fernandez-Brando, Romina J.; Yamaguchi, Nao; Tahoun, Amin; McAteer, Sean P.; Gillespie, Trudi; Wang, Dai; Argyle, Sally A.; Palermo, Marina S.

    2015-01-01

    A subset of Gram-negative bacterial pathogens uses a type III secretion system (T3SS) to open up a conduit into eukaryotic cells in order to inject effector proteins. These modulate pathways to enhance bacterial colonization. In this study, we screened established bioactive compounds for any that could repress T3SS expression in enterohemorrhagic Escherichia coli (EHEC) O157. The ketolides telithromycin and, subsequently, solithromycin both demonstrated repressive effects on expression of the bacterial T3SS at sub-MICs, leading to significant reductions in bacterial binding and actin-rich pedestal formation on epithelial cells. Preincubation of epithelial cells with solithromycin resulted in significantly less attachment of E. coli O157. Moreover, bacteria expressing the T3SS were more susceptible to solithromycin, and there was significant preferential killing of E. coli O157 bacteria when they were added to epithelial cells that had been preexposed to the ketolide. This killing was dependent on expression of the T3SS. Taken together, this research indicates that the ketolide that has accumulated in epithelial cells may traffic back into the bacteria via the T3SS. Considering that neither ketolide induces the SOS response, nontoxic members of this class of antibiotics, such as solithromycin, should be considered for future testing and trials evaluating their use for treatment of EHEC infections. These antibiotics may also have broader significance for treating infections caused by other pathogenic bacteria, including intracellular bacteria, that express a T3SS. PMID:26525795

  11. [Cloning, expression and functional identification of a type III polyketide synthase gene from Huperzia serrata].

    PubMed

    Ye, Jin-cui; Zhang, Ping; Sun, Jie-yin; Guo, Chao-tan; Chen, Guo-shen; Abe, Ikuro; Noguchi, Hiroshi

    2011-10-01

    A cDNA encoding novel type III polyketide synthase (PKS) was cloned and sequenced from young leaves of Chinese club moss Huperzia serrata (Thunb.) Trev. by RT-PCR using degenerated primers based on the conserved sequences of known CHSs, and named as H. serrata PKS2. The terminal sequences of cDNA were obtained by the 3'- and 5'-RACE method. The full-length cDNA of H. serrata PKS2 contained a 1212 bp open reading frame encoding a 46.4 kDa protein with 404 amino acids. The deduced amino acid sequence of H. serrata PKS2 showed 50%-66% identities to those of other chalcone synthase super family enzymes of plant origin. The recombinant H. serrata PKS2 was functionally expressed in Escherichia coli with an additional hexahistidine tag at the N-terminus and showed unusually versatile catalytic potency to produce various aromatic tetraketides, including chalcones, benzophenones, phloroglucinols, and acridones. In particular, the enzyme accepted bulky starter substrates N-methylanthraniloyl-CoA, and carried out three condensations with malonyl-CoA to produce 1, 3-dihydroxy-N-methylacridone. Interestingly, H. serrata PKS2 lacks most of the consensus active site sequences with acridone synthase from Ruta graveolens (Rutaceae). PMID:22242464

  12. A type III ACC synthase, ACS7, is involved in root gravitropism in Arabidopsis thaliana

    PubMed Central

    Chang, Ing-Feng

    2013-01-01

    Ethylene is an important plant hormone that regulates developmental processes in plants. The ethylene biosynthesis pathway is a highly regulated process at both the transcriptional and post-translational level. The transcriptional regulation of these ethylene biosynthesis genes is well known. However, post-translational modifications of the key ethylene biosynthesis enzyme 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS) are little understood. In vitro kinase assays were conducted on the type III ACS, AtACS7, fusion protein and peptides to determine whether the AtACS7 protein can be phosphorylated by calcium-dependent protein kinase (CDPK). AtACS7 was phosphorylated at Ser216, Thr296, and Ser299 by AtCDPK16 in vitro. To investigate further the function of the ACS7 gene in Arabidopsis, an acs7-1 loss-of-function mutant was isolated. The acs7-1 mutant exhibited less sensitivity to the inhibition of root gravitropism by treatment with the calcium chelator ethylene glycol tetraacetic acid (EGTA). Seedlings were treated with gradient concentrations of ACC. The results showed that a certain concentration of ethylene enhanced the gravity response. Moreover, the acs7-1 mutant was less sensitive to inhibition of the gravity response by treatment with the auxin polar transport inhibitor 1-naphthylphthalamic acid, but exogenous ACC application recovered root gravitropism. Altogether, the results indicate that AtACS7 is involved in root gravitropism in a calcium-dependent manner in Arabidopsis. PMID:23943848

  13. Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III.

    PubMed

    Welling, Lindsey; Marchal, Jan Pieter; van Hasselt, Peter; van der Ploeg, Ans T; Wijburg, Frits A; Boelens, Jaap Jan

    2015-01-01

    Mucopolysaccharidosis type III (MPS III), or Sanfilippo disease, is a neurodegenerative lysosomal storage disease (LSD) caused by defective lysosomal degradation of heparan sulfate (HS). No effective disease-modifying therapy is yet available. In contrast to some other neuronopathic LSDs, bone marrow-derived hematopoietic stem cell transplantation (HSCT) fails to prevent neurological deterioration in MPS III patients. We report on the 5-year outcome of early transplantation, i.e., before onset of clinical neurological disease, in combination with the use of umbilical cord blood-derived hematopoietic stem cells (UCBT), in two MPS III patients. Both patients had a normal developmental quotient at the time of UCBT. One patient had a combination of mutations predicting a classical severe phenotype (MPS IIIA), and one patient (MPS IIIB) had mutations predicting a very attenuated phenotype. Transplantation was uncomplicated with full engraftment of donor cells in both.Both patients showed progressive neurological deterioration with regression of cognitive skills and behavioral disturbances during 5 years after successful UCBT, comparable to the natural history of patients with the same combination of mutations. The concentration of HS in CSF in the patient with the attenuated phenotype of MPS IIIB 2 years after UCBT was very high and in the range of untreated MPS III patients.We conclude that the course of cognitive development, behavioral problems, and absence of biochemical correction in CSF demonstrate the absence of relevant effect of UCBT in MPS III patients, even when performed before clinical onset of CNS disease. PMID:25256447

  14. QCD corrections to pair production of Type III Seesaw leptons at hadron colliders

    NASA Astrophysics Data System (ADS)

    Ruiz, Richard

    2015-12-01

    If kinematically accessible, hadron collider experiments provide an ideal laboratory for the direct production of heavy lepton partners in Seesaw models. In the context of the Type III Seesaw Mechanism, the O({α}_s) rate and shape corrections are presented for the pair production of hypothetical, heavy SU(2) L triplet leptons in pp collisions at √{s} = 13, 14 and 100TeV. The next-to-leading order (NLO) K-factors span, approximately, K NLO = 1 .1 - 1 .4 for both charged current and neutral current processes over a triplet mass range m T = 100 GeV - 2 TeV. Total production cross sections exhibit a - 6 % + 5 % scale dependence at 14 TeV and ±1% at 100 TeV. The NLO differential K-factors for heavy lepton kinematics are largely flat, suggesting that na¨ıve scaling by the total K NLO is reasonably justified. The resummed transverse momentum distribution of the dilepton system is presented at leading logarithmic (LL) accuracy. The effects of resummation are large in TeV-scale dilepton systems. Discovery potential to heavy lepton pairs at 14 and 100 TeV is briefly explored: at the High-Luminosity LHC, we estimate a 4 .8 - 6 .3 σ discovery potential maximally for m T = 1 .5 - 1 .6 TeV after 3000 fb-1. With 300 (3000) fb-1, there is 2σ sensitivity up to m T = 1 .3 - 1 .4 TeV (1 .7 - 1 .8 TeV) in the individual channels. At 100 TeV and with 10 fb-1, a 5 σ discovery can be achieved for m T = 1 .4 - 1 .6 TeV. Due to the factorization properties of Drell-Yan-type systems, the fixed order and resummed calculations reduce to convolutions over tree-level quantities.

  15. Cross talk between type III secretion and flagellar assembly systems in Pseudomonas aeruginosa.

    PubMed

    Soscia, Chantal; Hachani, Abderrahman; Bernadac, Alain; Filloux, Alain; Bleves, Sophie

    2007-04-01

    Pseudomonas aeruginosa cytotoxicity is linked to a type III secretion system (T3SS) that delivers effectors into the host cell. We show here that a negative cross-control exists between T3SS and flagellar assembly. We observed that, in a strain lacking flagella, T3SS gene expression, effector secretion, and cytotoxicity were increased. Conversely, we revealed that flagellar-gene expression and motility were decreased in a strain overproducing ExsA, the T3SS master regulator. Interestingly, a nonmotile strain lacking the flagellar filament (DeltafliC) presented a hyperefficient T3SS and a nonmotile strain assembling flagella (DeltamotAB) did not. More intriguingly, a strain lacking motCD genes is a flagellated strain with a slight defect in swimming. However, in this strain, T3SS gene expression was up-regulated. These results suggest that flagellar assembly and/or mobility antagonizes the T3SS and that a negative cross talk exists between these two systems. An illustration of this is the visualization by electron microscopy of T3SS needles in a nonmotile P. aeruginosa strain, needles which otherwise are not detected. The molecular basis of the cross talk is complex and remains to be elucidated, but proteins like MotCD might have a crucial role in signaling between the two processes. In addition, we found that the GacA response regulator negatively affects the T3SS. In a gacA mutant, the T3SS effector ExoS is hypersecreted. Strikingly, GacA was previously reported as a positive regulator for motility. Globally, our data document the idea that some virulence factors are coordinately but inversely regulated, depending on the bacterial colonization phase and infection types. PMID:17307856

  16. Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1

    PubMed Central

    Mehershahi, Kurosh S.; Hsu, Li Yang; Koh, Tse Hsien

    2015-01-01

    Streptococcus agalactiae (group B Streptococcus) is a common commensal strain in the human gastrointestinal tract that can also cause invasive disease in humans and other animals. We report here the complete genome sequence of S. agalactiae SG-M1, a serotype III, multilocus sequence type 283 strain, isolated from a Singaporean patient suffering from meningitis. PMID:26494662

  17. Bi-Exact Groups, Strongly Ergodic Actions and Group Measure Space Type III Factors with No Central Sequence

    NASA Astrophysics Data System (ADS)

    Houdayer, Cyril; Isono, Yusuke

    2016-05-01

    We investigate the asymptotic structure of (possibly type III) crossed product von Neumann algebras {M = B rtimes Γ} arising from arbitrary actions {Γ &ucedil;rvearrowright B} of bi-exact discrete groups (e.g. free groups) on amenable von Neumann algebras. We prove a spectral gap rigidity result for the central sequence algebra {N' \\cap M^ω} of any nonamenable von Neumann subalgebra with normal expectation {N subset M} . We use this result to show that for any strongly ergodic essentially free nonsingular action {Γ &ucedil;rvearrowright (X, μ)} of any bi-exact countable discrete group on a standard probability space, the corresponding group measure space factor {L^∞(X) rtimes Γ} has no nontrivial central sequence. Using recent results of Boutonnet et al. (Local spectral gap in simple Lie groups and applications, 2015), we construct, for every {0 < λ ≤ 1} , a type {III_λ} strongly ergodic essentially free nonsingular action F_∞ &ucedil;rvearrowright (X_λ, μ_λ) of the free group F_∞ on a standard probability space so that the corresponding group measure space type {III_λ} factor {L^∞(X_λ, μ_λ) rtimes F_∞ has no nontrivial central sequence by our main result. In particular, we obtain the first examples of group measure space type {III} factors with no nontrivial central sequence.

  18. Functional and computational analysis of amino acid patterns predictive of type III secretion system substrates in Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial type III secretion systems (T3SSs) deliver proteins called effectors into eukaryotic cells. Although N-terminal amino acid sequences are required for translocation, the mechanism of substrate recognition by the T3SS is unknown. Almost all actively deployed T3SS substrates in the plant path...

  19. Die another day: molecular mechanisms of effector-triggered immunity elicited by type III secreted effector proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial pathogens inject type III secreted effector (T3SE) proteins into their hosts where they display dual roles depending on the host genotype. T3SEs promote bacterial virulence in susceptible hosts, and elicit immunity in resistant hosts. T3SEs are typically recognized when they modify a host ...

  20. Talents and Type Iiis: The Effects of the Talents Unlimited Model on Creative Productivity in Gifted Youngsters

    ERIC Educational Resources Information Center

    Newman, Jane L.

    2005-01-01

    This study examined a set of lessons that integrate the Talents Unlimited Model (TU; C. L. Schlichter, 1986) with the 10 steps of completing a Type III activity (J. S. Renzulli & S. M. Reis, 1985) to determine the effects of these lessons on the quality of students' creative products and on the number of students who completed their products.…

  1. Lack of immunogenicity of ice structuring protein type III HPLC12 preparation administered by the oral route to human volunteers.

    PubMed

    Crevel, R W R; Cooper, K J; Poulsen, L K; Hummelshoj, L; Bindslev-Jensen, C; Burks, A W; Sampson, H A

    2007-01-01

    Before a novel protein can be used in foods, its potential allergenicity must be assessed. In this study, healthy volunteers consumed ice structuring protein (ISP) Type III preparation or a control material 5 days a week for a total of 8 weeks. General measures of health were recorded during the study, and the immunogenicity of the protein was assessed by monitoring the levels of IgG and IgE antibodies specific for ISP Type III. The participants remained in good health throughout the study and during the 4 week follow-up period. No IgG or IgE antibodies specific for ISP Type III were detected in the blood of the participants. Investigations of immunogenicity in man have not been previously applied in the context of safety evaluation and they do not form part of the regimens proposed for the evaluation of protein allergenicity. Consequently no standardised protocols exist for such studies, nor any background against which to interpret the results. Nevertheless, the absence of an immune response using a protocol which could have been expected to result in a response with a strongly immunogenic protein, confirms the conclusions of earlier published work, and attests to the lack of allergenicity of ISP Type III preparation. PMID:17027137

  2. Identification of the epitope for a monoclonal antibody that blocks platelet aggregation induced by type III collagen.

    PubMed Central

    Glattauer, V; Werkmeister, J A; Kirkpatrick, A; Ramshaw, J A

    1997-01-01

    A library of eight conformation-dependent monoclonal antibodies that react with distinct epitopes on native human type III collagen has been examined for the ability of these antibodies to inhibit platelet aggregation induced by this collagen. Six of these antibodies had no effects; one, 1E7-D7/Col3, delayed the onset and slowed the rate of platelet aggregation, while another, 2G8-B1/Col3, completely inhibited aggregation. In order to identify the epitope recognized by this inhibitory antibody, a series of peptides that could fold to form triple-helical fragments was examined. Each peptide included six Gly-Xaa-Yaa triplets from the human type III collagen sequence, where Xaa and Yaa represent the particular amino acids in the sequence, and a C-terminal (Gly-Pro-Hyp)4 sequence to enhance triple-helical stability. Using these peptides we have identified the epitope as a nine-amino-acid sequence, GLAGAOGLR (where O is the one-letter code for 4-hydroxyproline), starting at position 520 in the human type III collagen helical domain. This sequence is proximal to the site proposed for the interaction of type III collagen with alpha2beta1-integrin of platelets. PMID:9173900

  3. Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1.

    PubMed

    Mehershahi, Kurosh S; Hsu, Li Yang; Koh, Tse Hsien; Chen, Swaine L

    2015-01-01

    Streptococcus agalactiae (group B Streptococcus) is a common commensal strain in the human gastrointestinal tract that can also cause invasive disease in humans and other animals. We report here the complete genome sequence of S. agalactiae SG-M1, a serotype III, multilocus sequence type 283 strain, isolated from a Singaporean patient suffering from meningitis. PMID:26494662

  4. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (L...

  5. Upregulation of heme oxygenase and collagen type III in the rat bladder after partial bladder outlet obstruction.

    PubMed

    Inaba, Mitsuhiko; Ukimura, Osamu; Yaoi, Takeshi; Kawauchi, Akihiro; Fushiki, Shinji; Miki, Tsuneharu

    2007-01-01

    The objective of the study was to evaluate possible changes of the gene expression and localization of the enzymes, heme oxygenase and nitric oxide synthase (NOS), with reference to increase of collagen type III in response to the partial obstruction of the bladder. Following initial obstruction, whole rat bladders were removed for real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Real-time RT-PCR demonstrated significantly enhanced expression of HO (p < 0.01) and collagen type III (p < 0.001) gene on postoperative day 14. Enhanced expression of NOS gene was seen only on postoperative day 4 (p < 0.01). Immunohistochemistry revealed that immunoreactivity to HO-1 had much in common in neural cells and fibers, although immunoreactivity to HO-2 and iNOS was relatively weak. This study suggested gene expression of HO, especially HO-1, was more dramatically changed than NOS, and was upregulated simultaneously with increase of collagen type III after obstruction. HO systems could be involved in the pathogenesis of bladder dysfunction related to increase of collagen type III after obstruction. PMID:17406140

  6. Localization of type III collagen in the lingual mucosa of rats during the morphogenesis of circumvallate papillae.

    PubMed

    Iwasaki, Shin-ichi; Yoshizawa, Hideki; Aoyagi, Hidekazu

    2012-01-01

    In an effort to identify a possible role for type III collagen in the morphogenesis of circumvallate papillae on the surface of the rat tongue, we examined its appearance by fluorescent immunostaining, in conjunction with differential interference contrast images and images obtained, after staining with toluidine blue, in the transmission mode by laser-scanning microscopy. We analyzed semi-ultrathin sections of epoxy resin-embedded samples of the lingual mucosa of embryonic and juvenile rats, 13 days after conception (E13) to day 21 after birth (P21). Immunoreactivity specific for type III collagen was recognized first in the mesenchymal connective tissue just beneath the circumvallate papilla placode in fetuses on E13. At this stage, most of the lingual epithelium with the exception of the circumvallate papilla placode was pseudostratified epithelium composed of one or two layers of cuboidal cells. However, the epithelium of the circumvallate papilla placode was composed of several layers of cuboidal cells. Immunoreactivity specific for type III collagen was detected mainly on the lamina propria just beneath the lingual epithelium of the rudiment of the circumvallate papilla and the developing circumvallate papilla in fetuses on E15 and E17, and slight immunostaining was detected on the lamina propria around the rudiment. In fetuses on E19, immunoreactivity specific for type III collagen was widely and densely distributed on the connective tissue around the developing circumvallate papillae and, also, on the connective tissue that surrounded the lingual muscle. However, the immunoreactivity specific for type III collagen was sparsely distributed on the lamina propria of each central papillar structure. After birth, from P0 to P14, morphogenesis of the circumvallate papillae advanced gradually with the increase in the total volume of the tongue. At these postnatal stages, the intensity of the fluorescence due to immunoreactivity specific for type III collagen was

  7. The low-high-low trend of type III radio burst starting frequencies and solar flare hard X-rays

    NASA Astrophysics Data System (ADS)

    Reid, Hamish A. S.; Vilmer, Nicole; Kontar, Eduard P.

    2014-07-01

    Aims: Using simultaneous X-ray and radio observations from solar flares, we investigate the link between the type III radio burst starting frequency and hard X-ray spectral index. For a proportion of events the relation derived between the starting height (frequency) of type III radio bursts and the electron beam velocity spectral index (deduced from X-rays) is used to infer the spatial properties (height and size) of the electron beam acceleration region. Both quantities can be related to the distance travelled before an electron beam becomes unstable to Langmuir waves. Methods: To obtain a list of suitable events we considered the RHESSI catalogue of X-ray flares and the Phoenix 2 catalogue of type III radio bursts. From the 200 events that showed both type III and X-ray signatures, we selected 30 events which had simultaneous emission in both wavelengths, good signal to noise in the X-ray domain and >20 s duration. Results: We find that >50% of the selected events show a good correlation between the starting frequencies of the groups of type III bursts and the hard X-ray spectral indices. A low-high-low trend for the starting frequency of type III bursts is frequently observed. Assuming a background electron density model and the thick target approximation for X-ray observations, this leads to a correlation between starting heights of the type III emission and the beam electron spectral index. Using this correlation we infer the altitude and vertical extents of the flare acceleration regions. We find heights from 183 Mm down to 25 Mm while the sizes range from 13 Mm to 2 Mm. These values agree with previous work that places an extended flare acceleration region high in the corona. We also analyse the assumptions that are required to obtain our estimates and explore possible extensions to our assumed model. We discuss these results with respect to the acceleration heights and sizes derived from X-ray observations alone. Appendices are available in electronic form

  8. A TRLFS study on the complexation of novel BTP type ligands with Cm(III).

    PubMed

    Beele, Björn B; Rüdiger, Elias; Schwörer, Felicitas; Müllich, Udo; Geist, Andreas; Panak, Petra J

    2013-09-14

    Two BTP-type N-donor ligands with different numbers of aromatic nitrogen atoms (2,6-bis(4-ethyl-pyridazin-1-yl)pyridine, Et-BDP and 2,6-bis(4-(n)propyl-2,3,5,6-tetrazine-1-yl)pyridine, (n)Pr-Tetrazine) have been synthesized and characterized by NMR and MS techniques. The complexation with Cm(III) in 2-propanol-water (1 : 1, vol.) is studied for both ligands using time resolved laser-induced fluorescence spectroscopy (TRLFS) and the complexation properties are compared to (n)Pr-BTP. With increasing the ligand concentration three different species, the 1 : 1-, 1 : 2- and 1 : 3-complex, were found. Log β3 values of 7.6 for the formation of Cm(Et-BDP)3 and 9.2 for the formation of Cm((n)Pr-Tetrazine)3 are determined. The complexation with (n)Pr-Tetrazine shows slow kinetics. Thermodynamic data of the complexation reactions are determined in a temperature range of 25 °C-60 °C. The complexation with Et-BDP is exothermic (ΔH = -16.3 ± 1.2 kJ mol(-1)) and exergonic (ΔG = -43.8 ± 2.6 kJ mol(-1)) whereas the complexation with (n)Pr-Tetrazine is endothermic (ΔH = 43.9 ± 3.1 kJ mol(-1)) and exergonic (ΔG = -51.7 ± 2.2 kJ mol(-1)). In the case of the latter the complexation is driven by a highly positive reaction entropy change (ΔS = 320.6 ± 15.4 J mol(-1) K(-1)). In comparison to (n)Pr-BTP, less negative ΔG values were found for the complexation of Cm(III) with both ligands. PMID:23552476

  9. Identification of prostamides, fatty acyl ethanolamines, and their biosynthetic precursors in rabbit cornea[S

    PubMed Central

    Urquhart, Paula; Wang, Jenny; Woodward, David F.; Nicolaou, Anna

    2015-01-01

    Arachidonoyl ethanolamine (anandamide) and pros­taglandin ethanolamines (prostamides) are biologically active derivatives of arachidonic acid. Although available through different precursor phospholipids, there is considerable overlap between the biosynthetic pathways of arachidonic acid-derived eicosanoids and anandamide-derived prostamides. Prostamides exhibit physiological actions and are involved in ocular hypotension, smooth muscle contraction, and inflammatory pain. Although topical application of bimatoprost, a structural analog of prostaglandin F2α ethanolamide (PGF2α-EA), is currently a first-line treatment for ocular hypertension, the endogenous production of prostamides and their biochemical precursors in corneal tissue has not yet been reported. In this study, we report the presence of anandamide, palmitoyl-, stearoyl-, α-linolenoyl docosahexaenoyl-, linoleoyl-, and oleoyl-ethanolamines in rabbit cornea, and following treatment with anandamide, the formation of PGF2α-EA, PGE2-EA, PGD2-EA by corneal extracts (all analyzed by LC/ESI-MS/MS). A number of N-acyl phosphatidylethanolamines, precursors of anandamide and other fatty acyl ethanolamines, were also identified in corneal lipid extracts using ESI-MS/MS. These findings suggest that the prostamide and fatty acid ethanolamine pathways are operational in the cornea and may provide valuable insight into corneal physiology and their potential influence on adjacent tissues and the aqueous humor. PMID:26031663

  10. Spatiotemporal Patterns of a Predator-Prey System with an Allee Effect and Holling Type III Functional Response

    NASA Astrophysics Data System (ADS)

    Li, Yuanyuan; Wang, Jinfeng

    A diffusive Gause type predator-prey system with Allee effect in prey growth and Holling type III response subject to Neumann boundary conditions is investigated. Existence of nonconstant positive steady state solutions is proved by Leray-Schauder degree theory and bifurcation theory. Global stability of the positive equilibrium of the system is also investigated. Moreover, bifurcations of spatially homogeneous and nonhomogeneous periodic solutions are analyzed. Our rigorous results justify some recent ecological observations.

  11. The Type III Secretion System of Bradyrhizobium japonicum USDA122 Mediates Symbiotic Incompatibility with Rj2 Soybean Plants

    PubMed Central

    Tsukui, Takahiro; Eda, Shima; Kaneko, Takakazu; Sato, Shusei; Okazaki, Shin; Kakizaki-Chiba, Kaori; Itakura, Manabu; Mitsui, Hisayuki; Yamashita, Akifumi; Terasawa, Kimihiro

    2013-01-01

    The rhcJ and ttsI mutants of Bradyrhizobium japonicum USDA122 for the type III protein secretion system (T3SS) failed to secrete typical effector proteins and gained the ability to nodulate Rj2 soybean plants (Hardee), which are symbiotically incompatible with wild-type USDA122. This suggests that effectors secreted via the T3SS trigger incompatibility between these two partners. PMID:23204412

  12. Tube shunt coverage with gamma-irradiated cornea allograft (VisionGraft)

    PubMed Central

    Ekici, Feyzahan; Moster, Marlene R; Cvintal, Victor; Hu, Wanda D; Waisbourd, Michael

    2015-01-01

    Purpose To investigate the clinical outcomes of tube shunt coverage using sterile gamma-irradiated cornea allograft. Patients and methods The Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the medical records of 165 patients who underwent glaucoma tube shunt procedures using sterile gamma-irradiated cornea allograft (VisionGraft) between December 2012 and November 2013. Demographic characteristics, type of tube shunt, and position were noted. Complications were recorded at 1 day; 1 week; 1, 3, 6, and 12 months; and on the final postoperative visit. Results One hundred and sixty-nine eyes of 165 patients were included. The mean follow-up time was 4.8±3.5 (ranging from 1 to 16) months. There was no evidence of immunological reaction, infection, or exposure in 166 eyes (98.2%). Three eyes (1.8%) experienced graft or tube exposure within the first 3 postoperative months. Two of the cases had underlying diseases: bullous pemphigoid and chronic allergic conjunctivitis. Conclusion Coverage of tube shunts using gamma-irradiated cornea allograft had a low exposure rate and was well tolerated. The graft can be stored long term at room temperature and has an excellent postoperative cosmetic appearance. PMID:25995612

  13. Study on the optical property and biocompatibility of a tissue engineering cornea

    PubMed Central

    Zhang, Xu; Nakahara, Yukiko; Xuan, Dwight; Wu, Di; Zhao, Fang-Kun; Li, Xiao-Yan; Zhang, Jin-Song

    2012-01-01

    AIM To study the optical property and biocompatibility of a tissue engineering cornea. METHODS : The cross-linker of N-(3-Dimethylaminoropyl)-N'ethylcarbodiimide hydrochloride (EDC)/N-Hydroxysuccinimide (NHS) was mixed with Type I collagen at 10% (weight/volume). The final solution was molded to the shape of a corneal contact lens. The collagen concentrations of 10%, 12.5%, 15%, 17.5% and 20% artificial corneas were tested by UV/vis-spectroscopy for their transparency compared with normal rat cornea. 10-0 sutures were knotted on the edges of substitute to measure the corneal buttons's mechanical properties. Normal rat corneal tissue primary culture on the collagen scaffold was observed in 4 weeks. Histopathologic examinations were performed after 4 weeks of in vitro culturing. RESULTS The collagen scaffold appearance was similar to that of soft contact lens. With the increase of collagen concentration, the transparency of artificial corneal buttons was diminished, but the toughness of the scaffold was enhanced. The scaffold transparency in the 10% concentration collagen group resembled normal rat cornea. To knot and embed the scaffold under the microscope, 20% concentration collagen group was more effective during implantation than lower concentrations of collagen group. In the first 3 weeks, corneal cell proliferation was highly active. The shapes of cells that grew on the substitute had no significant difference when compared with the cells before they were moved to the scaffold. However, on the fortieth day, most cells detached from the scaffold and died. Histopathologic examination of the primary culture scaffold revealed well grown corneal cells tightly attached to the scaffold in the former culturing. CONCLUSION Collagen scaffold can be molded to the shape of soft contact corneal lens with NHS/EDC. The biological stability and biocompatibility of collagen from animal species may be used as material in preparing to engineer artificial corneal scaffold. PMID

  14. The Type III Secretion System and Cytotoxic Enterotoxin Alter the Virulence of Aeromonas hydrophila

    PubMed Central

    Sha, Jian; Pillai, Lakshmi; Fadl, Amin A.; Galindo, Cristi L.; Erova, Tatiana E.; Chopra, Ashok K.

    2005-01-01

    Many gram-negative bacteria use a type III secretion system (TTSS) to deliver effector proteins into host cells. Here we report the characterization of a TTSS chromosomal operon from the diarrheal isolate SSU of Aeromonas hydrophila. We deleted the gene encoding Aeromonas outer membrane protein B (AopB), which is predicted to be involved in the formation of the TTSS translocon, from wild-type (WT) A. hydrophila as well as from a previously characterized cytotoxic enterotoxin gene (act)-minus strain of A. hydrophila, thus generating aopB and act/aopB isogenic mutants. The act gene encodes a type II-secreted cytotoxic enterotoxin (Act) that has hemolytic, cytotoxic, and enterotoxic activities and induces lethality in a mouse model. These isogenic mutants (aopB, act, and act/aopB) were highly attenuated in their ability to induce cytotoxicity in RAW 264.7 murine macrophages and HT-29 human colonic epithelial cells. The act/aopB mutant demonstrated the greatest reduction in cytotoxicity to cultured cells after 4 h of infection, as measured by the release of lactate dehydrogenase enzyme, and was avirulent in mice, with a 90% survival rate compared to that of animals infected with Act and AopB mutants, which caused 50 to 60% of the animals to die at a dose of three 50% lethal doses. In contrast, WT A. hydrophila killed 100% of the mice within 48 h. The effects of these mutations on cytotoxicity could be complemented with the native genes. Our studies further revealed that the production of lactones, which are involved in quorum sensing (QS), was decreased in the act (32%) and aopB (64%) mutants and was minimal (only 8%) in the act/aopB mutant, compared to that of WT A. hydrophila SSU. The effects of act and aopB gene deletions on lactone production could also be complemented with the native genes, indicating specific effects of Act and the TTSS on lactone production. Although recent studies with other bacteria have indicated TTSS regulation by QS, this is the first

  15. Yeast as a Heterologous Model System to Uncover Type III Effector Function

    PubMed Central

    Popa, Crina; Coll, Núria S.; Valls, Marc; Sessa, Guido

    2016-01-01

    Type III effectors (T3E) are key virulence proteins that are injected by bacterial pathogens inside the cells of their host to subvert cellular processes and contribute to disease. The budding yeast Saccharomyces cerevisiae represents an important heterologous system for the functional characterisation of T3E proteins in a eukaryotic environment. Importantly, yeast contains eukaryotic processes with low redundancy and are devoid of immunity mechanisms that counteract T3Es and mask their function. Expression in yeast of effectors from both plant and animal pathogens that perturb conserved cellular processes often resulted in robust phenotypes that were exploited to elucidate effector functions, biochemical properties, and host targets. The genetic tractability of yeast and its amenability for high-throughput functional studies contributed to the success of this system that, in recent years, has been used to study over 100 effectors. Here, we provide a critical view on this body of work and describe advantages and limitations inherent to the use of yeast in T3E research. “Favourite” targets of T3Es in yeast are cytoskeleton components and small GTPases of the Rho family. We describe how mitogen-activated protein kinase (MAPK) signalling, vesicle trafficking, membrane structures, and programmed cell death are also often altered by T3Es in yeast and how this reflects their function in the natural host. We describe how effector structure–function studies and analysis of candidate targeted processes or pathways can be carried out in yeast. We critically analyse technologies that have been used in yeast to assign biochemical functions to T3Es, including transcriptomics and proteomics, as well as suppressor, gain-of-function, or synthetic lethality screens. We also describe how yeast can be used to select for molecules that block T3E function in search of new antibacterial drugs with medical applications. Finally, we provide our opinion on the limitations of S

  16. Potassium transport of Salmonella is important for type III secretion and pathogenesis.

    PubMed

    Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C; Lu, Sangwei

    2013-08-01

    Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K(+)), sodium ion (Na(+)) and proton (H(+)) are involved in nearly all aspects of bacterial growth and survival. K(+) is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K(+) transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K(+) transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K(+) transport through deletion of K(+) transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K(+) transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K(+) transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria. PMID:23728623

  17. Intrinsic and Extrinsic Regulation of Type III Secretion Gene Expression in Pseudomonas Aeruginosa

    PubMed Central

    Diaz, Manisha R.; King, Jessica M.; Yahr, Timothy L.

    2011-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is particularly problematic in the healthcare setting where it is a frequent cause of pneumonia, bloodstream, and urinary tract infections. An important determinant of P. aeruginosa virulence is a type III secretion system (T3SS). T3SS-dependent intoxication is a complex process that minimally requires binding of P. aeruginosa to host cells, injection of the cytotoxic effector proteins through the host cell plasma membrane, and induction of T3SS gene expression. The latter process, referred to as contact-dependent expression, involves a well-characterized regulatory cascade that activates T3SS gene expression in response to host cell contact. Although host cell contact is a primary activating signal for T3SS gene expression, the involvement of multiple membrane-bound regulatory systems indicates that additional environmental signals also play a role in controlling expression of the T3SS. These regulatory systems coordinate T3SS gene expression with many other cellular activities including motility, mucoidy, polysaccharide production, and biofilm formation. The signals to which the organism responds are poorly understood but many seem to be coupled to the metabolic state of the cell and integrated within a master circuit that assimilates informational signals from endogenous and exogenous sources. Herein we review progress toward unraveling this complex circuitry, provide analysis of the current knowledge gaps, and highlight potential areas for future studies. Complete understanding of the regulatory networks that control T3SS gene expression will maximize opportunities for the development of strategies to treat P. aeruginosa infections. PMID:21833328

  18. The Type III Secretion System-Related CPn0809 from Chlamydia pneumoniae.

    PubMed

    Engel, Astrid C; Herbst, Frauke; Kerres, Anne; Galle, Jan N; Hegemann, Johannes H

    2016-01-01

    Chlamydia pneumoniae is an intracellular Gram-negative bacterium that possesses a type III secretion system (T3SS), which enables the pathogen to deliver, in a single step, effector proteins for modulation of host-cell functions into the human host cell cytosol to establish a unique intracellular niche for replication. The translocon proteins located at the top of the T3SS needle filament are essential for its function, as they form pores in the host-cell membrane. Interestingly, unlike other Gram-negative bacteria, C. pneumoniae has two putative translocon operons, named LcrH_1 and LcrH_2. However, little is known about chlamydial translocon proteins. In this study, we analyzed CPn0809, one of the putative hydrophobic translocators encoded by the LcrH_1 operon, and identified an 'SseC-like family' domain characteristic of T3S translocators. Using bright-field and confocal microscopy, we found that CPn0809 is associated with EBs during early and very late phases of a C. pneumoniae infection. Furthermore, CPn0809 forms oligomers, and interacts with the T3SS chaperone LcrH_1, via its N-terminal segment. Moreover, expression of full-length CPn0809 in the heterologous host Escherichia coli causes a grave cytotoxic effect that leads to cell death. Taken together, our data indicate that CPn0809 likely represents one of the translocon proteins of the C. pneumoniae T3SS, and possibly plays a role in the translocation of effector proteins in the early stages of infection. PMID:26895250

  19. Multiple Xanthomonas euvesicatoria Type III Effectors Inhibit flg22-Triggered Immunity.

    PubMed

    Popov, Georgy; Fraiture, Malou; Brunner, Frederic; Sessa, Guido

    2016-08-01

    Xanthomonas euvesicatoria is the causal agent of bacterial spot disease in pepper and tomato. X. euvesicatoria bacteria interfere with plant cellular processes by injecting effector proteins into host cells through the type III secretion (T3S) system. About 35 T3S effectors have been identified in X. euvesicatoria 85-10, and a few of them were implicated in suppression of pattern-triggered immunity (PTI). We used an Arabidopsis thaliana pathogen-free protoplast-based assay to identify X. euvesicatoria 85-10 effectors that interfere with PTI signaling induced by the bacterial peptide flg22. Of 33 tested effectors, 17 inhibited activation of a PTI-inducible promoter. Among them, nine effectors also interfered with activation of an abscisic acid-inducible promoter. However, effectors that inhibited flg22-induced signaling did not affect phosphorylation of mitogen-activated protein (MAP) kinases acting downstream of flg22 perception. Further investigation of selected effectors revealed that XopAJ, XopE2, and XopF2 inhibited activation of a PTI-inducible promoter by the bacterial peptide elf18 in Arabidopsis protoplasts and by flg22 in tomato protoplasts. The effectors XopF2, XopE2, XopAP, XopAE, XopH, and XopAJ inhibited flg22-induced callose deposition in planta and enhanced disease symptoms caused by attenuated Pseudomonas syringae bacteria. Finally, selected effectors were found to localize to various plant subcellular compartments. These results indicate that X. euvesicatoria bacteria utilize multiple T3S effectors to suppress flg22-induced signaling acting downstream or in parallel to MAP kinase cascades and suggest they act through different molecular mechanisms. PMID:27529660

  20. The Type III Secretion System-Related CPn0809 from Chlamydia pneumoniae

    PubMed Central

    Engel, Astrid C.; Herbst, Frauke; Kerres, Anne; Galle, Jan N.; Hegemann, Johannes H.

    2016-01-01

    Chlamydia pneumoniae is an intracellular Gram-negative bacterium that possesses a type III secretion system (T3SS), which enables the pathogen to deliver, in a single step, effector proteins for modulation of host-cell functions into the human host cell cytosol to establish a unique intracellular niche for replication. The translocon proteins located at the top of the T3SS needle filament are essential for its function, as they form pores in the host-cell membrane. Interestingly, unlike other Gram-negative bacteria, C. pneumoniae has two putative translocon operons, named LcrH_1 and LcrH_2. However, little is known about chlamydial translocon proteins. In this study, we analyzed CPn0809, one of the putative hydrophobic translocators encoded by the LcrH_1 operon, and identified an ‘SseC-like family’ domain characteristic of T3S translocators. Using bright-field and confocal microscopy, we found that CPn0809 is associated with EBs during early and very late phases of a C. pneumoniae infection. Furthermore, CPn0809 forms oligomers, and interacts with the T3SS chaperone LcrH_1, via its N-terminal segment. Moreover, expression of full-length CPn0809 in the heterologous host Escherichia coli causes a grave cytotoxic effect that leads to cell death. Taken together, our data indicate that CPn0809 likely represents one of the translocon proteins of the C. pneumoniae T3SS, and possibly plays a role in the translocation of effector proteins in the early stages of infection. PMID:26895250

  1. The Xanthomonas campestris Type III Effector XopJ Proteolytically Degrades Proteasome Subunit RPT61[OPEN

    PubMed Central

    2015-01-01

    Many animal and plant pathogenic bacteria inject type III effector (T3E) proteins into their eukaryotic host cells to suppress immunity. The Yersinia outer protein J (YopJ) family of T3Es is a widely distributed family of effector proteins found in both animal and plant pathogens, and its members are highly diversified in virulence functions. Some members have been shown to possess acetyltransferase activity; however, whether this is a general feature of YopJ family T3Es is currently unknown. The T3E Xanthomonas outer protein J (XopJ), a YopJ family effector from the plant pathogen Xanthomonas campestris pv vesicatoria, interacts with the proteasomal subunit Regulatory Particle AAA-ATPase6 (RPT6) in planta to suppress proteasome activity, resulting in the inhibition of salicylic acid-related immune responses. Here, we show that XopJ has protease activity to specifically degrade RPT6, leading to reduced proteasome activity in the cytoplasm as well as in the nucleus. Proteolytic degradation of RPT6 was dependent on the localization of XopJ to the plasma membrane as well as on its catalytic triad. Mutation of the Walker B motif of RPT6 prevented XopJ-mediated degradation of the protein but not XopJ interaction. This indicates that the interaction of RPT6 with XopJ is dependent on the ATP-binding activity of RPT6, but proteolytic cleavage additionally requires its ATPase activity. Inhibition of the proteasome impairs the proteasomal turnover of Nonexpressor of Pathogenesis-Related1 (NPR1), the master regulator of salicylic acid responses, leading to the accumulation of ubiquitinated NPR1, which likely interferes with the full induction of NPR1 target genes. Our results show that YopJ family T3Es are not only highly diversified in virulence function but also appear to possess different biochemical activities. PMID:25739698

  2. LOCALIZATION OF A TYPE III RADIO BURST OBSERVED BY THE STEREO SPACECRAFT

    SciTech Connect

    Thejappa, G.; MacDowall, R. J. E-mail: Robert.MacDowall@nasa.go

    2010-09-10

    Ray tracing calculations show that (1) emissions from a localized source escape as direct and reflected waves along different paths, (2) the reflected waves experience higher attenuation and group delay because they travel longer path lengths in regions of reduced refractive index, and (3) widely separated spacecraft 'A' and 'B' can detect the direct as well as reflected emissions escaping along different directions. It is proposed that the source of a radio burst observed by twin spacecraft 'A' and 'B' can be localized if at a given frequency the emission at one of them is identified as the direct emission and is identified at the other as the reflected emission by comparing the observed time delays {Delta}T, as well as intensity ratios I{sub B} /I{sub A} with the corresponding values of the direct and reflected emissions obtained for a given coronal model. A type III event observed by the STEREO spacecraft 'A' and 'B' shows that its characteristics are consistent with direct and reflected emissions by being less intense and delayed at 'A' in comparison to that at 'B'. By applying the proposed technique to this event, the location of its source is found to lie between the turning point of the ray and the harmonic layer corresponding to f {sub pe} = f/2, where f and f {sub pe} are the frequency of the emission and the electron plasma frequency, respectively. The comparisons of the widths of the fundamental and harmonic emission cones with the angular separation of spacecraft 'A' and 'B' indicate that the mode of the observed emission is probably the harmonic.

  3. Identification of a type III polyketide synthase involved in the biosynthesis of spirolaxine.

    PubMed

    Sun, Lei; Wang, Siyuan; Zhang, Shuwei; Yu, Dayu; Qin, Yuhui; Huang, Huiyong; Wang, Wei; Zhan, Jixun

    2016-08-01

    Spirolaxine is a natural product isolated from Sporotrichum laxum ATCC 15155, which has shown a variety of biological activities including promising anti-Helicobacter pylori property. To understand how this compound is biosynthesized, the genome of S. laxum was sequenced. Analysis of the genome sequence revealed two putative type III polyketide synthase (PKS) genes in this strain, Sl-pks1 and Sl-pks2, which are located adjacent to each other (~2.0 kb apart) in a tail-to-tail arrangement. Disruption of these two genes revealed that Sl-PKS2 is the dedicated PKS involved in the biosynthesis of spirolaxine. The intron-free Sl-pks2 gene was amplified from the cDNA of S. laxum and ligated into the expression vector pET28a for expression in Escherichia coli BL21-CodonPlus (DE3)-RIL. The major products of Sl-PKS2 in E. coli were characterized as alkylresorcinols that contain a C13-C17 saturated or unsaturated hydrocarbon side chain based on the spectral data. This enzyme was purified and reacted with malonyl-CoA and a series of fatty acyl-SNACs (C6-C10). Corresponding alkylresorcinols were formed from the decarboxylation of the synthesized tetraketide resorcylic acids, together with fatty acyl-primed triketide and tetraketide pyrones as byproducts. This work provides important information about the PKS involved in the biosynthesis of spirolaxine, which will facilitate further understanding and engineering of the biosynthetic pathway of this medicinally important molecule. PMID:27023915

  4. The Erwinia chrysanthemi Type III Secretion System Is Required for Multicellular Behavior

    PubMed Central

    Yap, Mee-Ngan; Yang, Ching-Hong; Barak, Jeri D.; Jahn, Courtney E.; Charkowski, Amy O.

    2005-01-01

    Enterobacterial animal pathogens exhibit aggregative multicellular behavior, which is manifested as pellicles on the culture surface and biofilms at the surface-liquid-air interface. Pellicle formation behavior requires production of extracellular polysaccharide, cellulose, and protein filaments, known as curli. Protein filaments analogous to curli are formed by many protein secretion systems, including the type III secretion system (TTSS). Here, we demonstrate that Erwinia chrysanthemi, which does not carry curli genes, requires the TTSS for pellicle formation. These data support a model where cellulose and generic protein filaments, which consist of either curli or TTSS-secreted proteins, are required for enterobacterial aggregative multicellular behavior. Using this assay, we found that hrpY, which encodes a two-component system response regulator homolog, is required for activity of hrpS, which encodes a σ54-dependent enhancer-binding protein homolog. In turn, hrpS is required for activity of the sigma factor homolog hrpL, which activates genes encoding TTSS structural and secreted proteins. Pellicle formation was temperature dependent and pellicles did not form at 36°C, even though TTSS genes were expressed at this temperature. We found that cellulose is a component of the E. chrysanthemi pellicle but that pellicle formation still occurs in a strain with an insertion in a cellulose synthase subunit homolog. Since the TTSS, but not the cellulose synthase subunit, is required for E. chrysanthemi pellicle formation, this inexpensive assay can be used as a high throughput screen for TTSS mutants or inhibitors. PMID:15629935

  5. A bacterial type III secretion assay for delivery of fungal effector proteins into wheat.

    PubMed

    Upadhyaya, Narayana M; Mago, Rohit; Staskawicz, Brian J; Ayliffe, Michael A; Ellis, Jeffrey G; Dodds, Peter N

    2014-03-01

    Large numbers of candidate effectors from fungal pathogens are being identified through whole-genome sequencing and in planta expression studies. Although Agrobacterium-mediated transient expression has enabled high-throughput functional analysis of effectors in dicot plants, this assay is not effective in cereal leaves. Here, we show that a nonpathogenic Pseudomonas fluorescens engineered to express the type III secretion system (T3SS) of P. syringae and the wheat pathogen Xanthomonas translucens can deliver fusion proteins containing T3SS signals from P. syringae (AvrRpm1) and X. campestris (AvrBs2) avirulence (Avr) proteins, respectively, into wheat leaf cells. A calmodulin-dependent adenylate cyclase reporter protein was delivered effectively into wheat and barley by both bacteria. Absence of any disease symptoms with P. fluorescens makes it more suitable than X. translucens for detecting a hypersensitive response (HR) induced by an effector protein with avirulence activity. We further modified the delivery system by removal of the myristoylation site from the AvrRpm1 fusion to prevent its localization to the plasma membrane which could inhibit recognition of an Avr protein. Delivery of the flax rust AvrM protein by the modified delivery system into transgenic tobacco leaves expressing the corresponding M resistance protein induced a strong HR, indicating that the system is capable of delivering a functional rust Avr protein. In a preliminary screen of effectors from the stem rust fungus Puccinia graminis f. sp. tritici, we identified one effector that induced a host genotype-specific HR in wheat. Thus, the modified AvrRpm1:effector-Pseudomonas fluorescens system is an effective tool for large-scale screening of pathogen effectors for recognition in wheat. PMID:24156769

  6. A genetic screen to isolate type III effectors translocated into pepper cells during Xanthomonas infection

    SciTech Connect

    Julie Anne Roden, Branids Belt, Jason Barzel Ross, Thomas Tachibana, Joe Vargas, Mary Beth Mudgett

    2004-11-23

    The bacterial pathogen Xanthomonas campestris pv. vesicatoria (Xcv) uses a type III secretion system (TTSS) to translocate effector proteins into host plant cells. The TTSS is required for Xcv colonization, yet the identity of many proteins translocated through this apparatus is not known. We used a genetic screen to functionally identify Xcv TTSS effectors. A transposon 5 (Tn5)-based transposon construct including the coding sequence for the Xcv AvrBs2 effector devoid of its TTSS signal was randomly inserted into the Xcv genome. Insertion of the avrBs2 reporter gene into Xcv genes coding for proteins containing a functional TTSS signal peptide resulted in the creation of chimeric TTSS effector::AvrBs2 fusion proteins. Xcv strains containing these fusions translocated the AvrBs2 reporter in a TTSS-dependent manner into resistant BS2 pepper cells during infection, activating the avrBs2-dependent hypersensitive response (HR). We isolated seven chimeric fusion proteins and designated the identified TTSS effectors as Xanthomonas outer proteins (Xops). Translocation of each Xop was confirmed by using the calmodulin-dependent adenylate cydase reporter assay. Three xop genes are Xanthomonas spp.-specific, whereas homologs for the rest are found in other phytopathogenic bacteria. XopF1 and XopF2 define an effector gene family in Xcv. XopN contains a eukaryotic protein fold repeat and is required for full Xcv pathogenicity in pepper and tomato. The translocated effectors identified in this work expand our knowledge of the diversity of proteins that Xcv uses to manipulate its hosts.

  7. Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases.

    PubMed

    Pandith, Shahzad A; Dhar, Niha; Rana, Satiander; Bhat, Wajid Waheed; Kushwaha, Manoj; Gupta, Ajai P; Shah, Manzoor A; Vishwakarma, Ram; Lattoo, Surrinder K

    2016-08-01

    Plants effectively defend themselves against biotic and abiotic stresses by synthesizing diverse secondary metabolites, including health-protective flavonoids. These display incredible chemical diversity and ubiquitous occurrence and confer impeccable biological and agricultural applications. Chalcone synthase (CHS), a type III plant polyketide synthase, is critical for flavonoid biosynthesis. It catalyzes acyl-coenzyme A thioesters to synthesize naringenin chalcone through a polyketidic intermediate. The functional divergence among the evolutionarily generated members of a gene family is pivotal in driving the chemical diversity. Against this backdrop, this study was aimed to functionally characterize members of the CHS gene family from Rheum emodi, an endangered and endemic high-altitude medicinal herb of northwestern Himalayas. Two full-length cDNAs (1,179 bp each), ReCHS1 and ReCHS2, encoding unique paralogs were isolated and characterized. Heterologous expression and purification in Escherichia coli, bottom-up proteomic characterization, high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis, and enzyme kinetic studies using five different substrates confirmed their catalytic potential. Phylogenetic analysis revealed the existence of higher synonymous mutations in the intronless divergents of ReCHS. ReCHS2 displayed significant enzymatic efficiency (Vmax/Km) with different substrates. There were significant spatial and altitudinal variations in messenger RNA transcript levels of ReCHSs correlating positively with metabolite accumulation. Furthermore, the elicitations in the form of methyl jasmonate, salicylic acid, ultraviolet B light, and wounding, chosen on the basis of identified cis-regulatory promoter elements, presented considerable differences in the transcript profiles of ReCHSs. Taken together, our results demonstrate differential propensities of CHS paralogs in terms of the accumulation of flavonoids and

  8. Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome

    PubMed Central

    Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres

    2013-01-01

    Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging. PMID:24324434

  9. Alterations in Fibronectin Type III Domain Containing 1 Protein Gene Are Associated with Hypertension

    PubMed Central

    Deng, Alan Y.; Chauvet, Cristina; Ménard, Annie

    2016-01-01

    Multiple quantitative trait loci (QTLs) for blood pressure (BP) have been detected in rat models of human polygenic hypertension. Great challenges confronting us include molecular identifications of individual QTLs. We first defined the chromosome region harboring C1QTL1 to a segment of 1.9 megabases that carries 9 genes. Among them, we identified the gene encoding the fibronectin type III domain containing 1 protein (Fndc1)/activator of G protein signaling 8 (Ags8) to be the strongest candidate for C1QTL1, since numerous non-synonymous mutations are found. Moreover, the 5’ Fndc1/Ags8 putative promoter contains numerous mutations that can account for its differential expression in kidneys and the heart, prominent organs in modulating BP, although the Fndc1/Ags8 protein was not detectable in these organs under our experimental conditions. This work has provided the premier evidence that Fndc1/Ags8 is a novel and strongest candidate gene for C1QTL1 without completely excluding other 8 genes in the C1QTL1-residing interval. If proven true by future in vivo function studies such as single-gene Fndc1/Ags8 congenics, transgenesis or targeted-gene modifications, it might represent a part of the BP genetic architecture that operates in the upstream position distant from the end-phase physiology of BP control, since it activates a Gbetagamma component in a signaling pathway. Its functional role could validate the concept that a QTL in itself can influence BP ‘indirectly’ by regulating other genes downstream in a pathway. The elucidation of the mechanisms initiated by Fndc/Ags8 variations will reveal novel insights into the BP modulation via a regulatory hierarchy. PMID:27064407

  10. Structure and unfolding of the third type III domain from human fibronectin.

    PubMed

    Stine, Jessica M; Sun, Yizhi; Armstrong, Geoffrey; Bowler, Bruce E; Briknarová, Klára

    2015-11-10

    Fibronectin is a modular extracellular matrix protein that is essential for vertebrate development. The third type III domain (3FN3) in fibronectin interacts with other parts of fibronectin and with anastellin, a protein fragment that causes fibronectin aggregation. 3FN3 opens readily both as an isolated domain in solution and when part of fibronectin in stretched fibrils, and it was proposed that this opening is important for anastellin binding. We determined the structure of 3FN3 using nuclear magnetic resonance spectroscopy, and we investigated its stability, folding, and unfolding. Similar to most other FN3 domains, 3FN3 contains two antiparallel β-sheets that are composed of three (A, B, and E) and four (C, D, F, and G) β-strands, respectively, and are held together by a conserved hydrophobic interface. cis-trans isomerization of P847 at the end of β-strand C leads to observable conformational heterogeneity in 3FN3, with a cis peptide bond present in almost one-quarter of the molecules. The chemical stability of 3FN3 is relatively low, but the folding rate constant in the absence of denaturant is in the same range as those of other, more stable FN3 domains. Interestingly, the unfolding rate constant in the absence of denaturant is several orders of magnitude higher than the unfolding rate constants of other FN3 domains investigated to date. This unusually fast rate is comparable to the rate of binding of 3FN3 to anastellin at saturating anastellin concentrations, consistent with the model in which 3FN3 has to unfold to interact with anastellin. PMID:26517579

  11. The SdiA-regulated gene srgE encodes a type III secreted effector.

    PubMed

    Habyarimana, Fabien; Sabag-Daigle, Anice; Ahmer, Brian M M

    2014-06-01

    Salmonella enterica serovar Typhimurium is a food-borne pathogen that causes severe gastroenteritis. The ability of Salmonella to cause disease depends on two type III secretion systems (T3SSs) encoded in two distinct Salmonella pathogenicity islands, 1 and 2 (SPI1 and SPI2, respectively). S. Typhimurium encodes a solo LuxR homolog, SdiA, which can detect the acyl-homoserine lactones (AHLs) produced by other bacteria and upregulate the rck operon and the srgE gene. SrgE is predicted to encode a protein of 488 residues with a coiled-coil domain between residues 345 and 382. In silico studies have provided conflicting predictions as to whether SrgE is a T3SS substrate. Therefore, in this work, we tested the hypothesis that SrgE is a T3SS effector by two methods, a β-lactamase activity assay and a split green fluorescent protein (GFP) complementation assay. SrgE with β-lactamase fused to residue 40, 100, 150, or 300 was indeed expressed and translocated into host cells, but SrgE with β-lactamase fused to residue 400 or 488 was not expressed, suggesting interference by the coiled-coil domain. Similarly, SrgE with GFP S11 fused to residue 300, but not to residue 488, was expressed and translocated into host cells. With both systems, translocation into host cells was dependent upon SPI2. A phylogenetic analysis indicated that srgE is found only within Salmonella enterica subspecies. It is found sporadically within both typhoidal and nontyphoidal serovars, although the SrgE protein sequences found within typhoidal serovars tend to cluster separately from those found in nontyphoidal serovars, suggesting functional diversification. PMID:24727228

  12. The SdiA-Regulated Gene srgE Encodes a Type III Secreted Effector

    PubMed Central

    Habyarimana, Fabien; Sabag-Daigle, Anice

    2014-01-01

    Salmonella enterica serovar Typhimurium is a food-borne pathogen that causes severe gastroenteritis. The ability of Salmonella to cause disease depends on two type III secretion systems (T3SSs) encoded in two distinct Salmonella pathogenicity islands, 1 and 2 (SPI1 and SPI2, respectively). S. Typhimurium encodes a solo LuxR homolog, SdiA, which can detect the acyl-homoserine lactones (AHLs) produced by other bacteria and upregulate the rck operon and the srgE gene. SrgE is predicted to encode a protein of 488 residues with a coiled-coil domain between residues 345 and 382. In silico studies have provided conflicting predictions as to whether SrgE is a T3SS substrate. Therefore, in this work, we tested the hypothesis that SrgE is a T3SS effector by two methods, a β-lactamase activity assay and a split green fluorescent protein (GFP) complementation assay. SrgE with β-lactamase fused to residue 40, 100, 150, or 300 was indeed expressed and translocated into host cells, but SrgE with β-lactamase fused to residue 400 or 488 was not expressed, suggesting interference by the coiled-coil domain. Similarly, SrgE with GFP S11 fused to residue 300, but not to residue 488, was expressed and translocated into host cells. With both systems, translocation into host cells was dependent upon SPI2. A phylogenetic analysis indicated that srgE is found only within Salmonella enterica subspecies. It is found sporadically within both typhoidal and nontyphoidal serovars, although the SrgE protein sequences found within typhoidal serovars tend to cluster separately from those found in nontyphoidal serovars, suggesting functional diversification. PMID:24727228

  13. Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn and preschool children. A systematic review.

    PubMed

    Sinikumpu, Juha-Jaakko; Ojaniemi, Marja; Lehenkari, Petri; Serlo, Willy

    2015-08-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders, of which Type III is the most severe among survivors. The disease is characterised in particular by bone fragility, decreased bone mass and increased incidence of fractures. Other usual findings are muscle hypotonia, joint hypermobility and short stature. Fractures and weak bones may consequently cause limb and spinal deformity and chronic physical disability. Bisphosphonates have revolutionised the treatment of newborn children with severe OI type III. Surgery is still needed in most patients due to high frequency of the fractures. In this systematic review we describe the present state-of-art in treating the most severe type of OI in newborn and preschool children with their bone fractures. PMID:25943292

  14. A simplified technique for in situ excision of cornea and evisceration of retinal tissue from human ocular globe.

    PubMed

    Parekh, Mohit; Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Camposampiero, Davide; Karali, Marianthi; Ponzin, Diego; Salvalaio, Gianni

    2012-01-01

    could lead to distracted, unclear vision. The cornea comprises of 5 layers; a) epithelium, b) Bowman's layer, c) stroma, d) Descemet's membrane and e) endothelium. All layers should function properly to ensure clear vision(4,5,6). The choroid is the intermediate tunic between the sclera and retina, bounded on the interior by the Bruch's membrane and is responsible for blood flow in the eye. The choroid also helps to regulate the temperature and supplies nourishment to the outer layers of the retina(5,6). The retina is a layer of nervous tissue that covers the back of the ocular globe (Suppl. Figure 1) and consists of two parts: a photoreceptive part and a non-receptive part. The retina helps to receive the light from the cornea and lens and converts it into the chemical energy eventually transmitted to the brain with help of the optic nerve(5,6). The aim of this paper is to provide a protocol for the dissection of corneal and retinal tissues from human ocular globes. Avoiding cross-contamination with adjacent tissues and preserving RNA integrity is of fundamental importance as such tissues are indispensable for research purposes aimed at (i) characterizing the transcriptome of the ocular tissues, (ii) isolating stem cells for regenerative medicine projects, and (iii) evaluating histological differences between tissues from normal/affected subjects. In this paper we describe the technique we currently use to remove the cornea, the choroid and retinal tissues from an ocular globe. Here we provide a detailed protocol for the dissection of the human ocular globe and the excision of corneal and retinal tissues. The accompanying video will help researchers to learn an appropriate technique for the retrieval of precious human tissues which are difficult to find regularly. PMID:22733120

  15. When is a type III functional response stabilizing? Theory and practice of predicting plankton dynamics under enrichment.

    PubMed

    Uszko, Wojciech; Diehl, Sebastian; Pitsch, Nadine; Lengfellner, Kathrin; Müller, Thomas

    2015-12-01

    The curvature of generalized Holling type functional response curves is controlled by a shape parameter b yielding hyperbolic type II (b = 1) to increasingly sigmoid type III (b > 1) responses. Empirical estimates of b vary considerably across taxa. Larger consumer-resource body mass ratios have been suggested to generate more pronounced type III responses and therefore to promote dynamic stability. The dependence of consumer- resource stability on b has, however, not been systematically explored, and the accurate empirical determination of b is challenging. Specifically, the shape of the functional response of the pelagic grazer Daphnia feeding on phytoplankton, and its consequences for stability, remain controversial. We derive a novel analytical condition relating b to local stability of consumer-resource interactions and use it to predict stability of empirically parameterized models of Daphnia and phytoplankton under enrichment. Functional response parameters were experimentally derived for two species of Daphnia feeding separately on single cultures of two different phytoplankton species. All experimentally studied Daphnia-algae systems exhibited type III responses. Parameterized type III responses are predicted to stabilize the modeled Daphnia-phytoplankton dynamics in some species pairs but not in others. Remarkably, stability predictions differ depending on whether functional response parameters are derived from clearance vs. ingestion rates. Accurate parameter estimation may therefore require fitting to both rates. In addition, our estimates of b for filter-feeding Daphnia are much smaller than predicted for actively hunting predators at similar consumer-resource body mass ratios. This suggests that the relationship between functional response shape and body mass ratios may vary with predation mode. PMID:26909430

  16. Differential expression of collagen types I and III in consequential and primary fibrosis in irradiated mouse colon

    SciTech Connect

    Followill, D.S.; Travis, E.L.

    1995-12-01

    These studies were undertaken to understand further the pathogenesis of consequential and primary fibrosis in mouse colon after irradiation. The distal 2.5 cm of colon of C3Hf/Kam mice was irradiated with either a single dose of 27 Gy or a split dose of 2 x 14.75 Gy separated by 10 days to induce a consequential or primary fibrotic lesion, respectively. The amount of total collagen in the two lesions was quantified by hydroxyproline, and tensile strength, an assay of tissue rigidity, was measured as a function of dose and time after irradiation. The relative distribution of collagen types I, III and IV in the colon was visualized by immunohistochemistry. Collagen types I, III and IV were quantified by immunoblot techniques, and in situ hybridization was used to identify and score the cells producing procollagen mRNA types I and III as a function of time after irradiation. The hydroxyproline and tensile strength measurements demonstrated that both lesions contained significantly increased amounts of collagen compared to controls. However, the ulcerated lesion of consequential fibrosis contained three times as much collagen and required a three- to fourfold increase in the peak force to rupture the colon as did the non-ulcerative lesion of primary fibrosis. The fibrosis accompanying the consequential lesion contained elevated levels of both collagen types I and III, but primary fibrosis contained only elevated levels of type I collagen compared to controls. The in situ hybridization studies showed cells producing increased amounts of procollagen mRNA 8 and 25 weeks before the elevated levels of collagen were detected for consequential and primary fibrosis, respectively. The cells producing the excess collagen mRNA were identified as fibroblasts. No distinction between the two lesions could be made based on the cell types producing the collagen. 48 refs., 7 figs.

  17. [Serum determination of N-terminal peptide of type III procollagen as a marker of fibrotic activity].

    PubMed

    García Montes, J M; De Bonilla Blánez, F; Herrerías Gutiérrez, J M

    1989-03-01

    Among the noninvasive methods proposed for the study of collagen metabolism as an of fibrosis and inflammation, the most widely accepted method is quantitation in serum of the N-terminal peptide of type III procollagen (P-III-Ps). We measured this variable in 87 subjects classified into five study groups: 19 controls (C), 18 alcoholics (E), 15 patients diagnosed as liver cirrhosis (CH), 11 chronic liver disease (HC) and 24 pregnant women (EMB). In our environment, the serum level of P-III-P in the healthy population was 9.12-12.8 ng/ml. In 27.77% of the alcoholics studied (5 cases) the mean value exceeded this level, 19.35 +/- 3.05 ng/ml. Forty percent of the cirrhotics (6 cases) presented the highest values, 26.54 +/- 11.45 ng/ml, while 83.33% of the patients with chronic active hepatitis presented a mean value of 18.53 +/- 3.8 ng/ml. Of the 24 pregnant women, 95.83% (23 cases) had higher than normal values, and concentrations roses in the last trimester of gestation with respect to the previous trimesters. Analysis of the correlations of all the biochemical parameters of liver function with P-III-Ps disclosed a relationship between P-III-Ps and alkaline phosphatase in the groups of cirrhotics and chronic persistent hepatitis (p less than 0.05). We conclude that the N-terminal peptide of type III procollagen is a useful marker of active fibrosis. PMID:2734469

  18. Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations.

    PubMed

    Lu, Chaoxia; Qiu, Zhengqing; Sun, Miao; Wang, Wei; Wei, Min; Zhang, Xue

    2016-07-01

    Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype-phenotype correlation in GSD III. PMID:26984562

  19. Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System.

    PubMed

    Dubytska, Lidiya P; Rogge, Matthew L; Thune, Ronald L

    2016-01-01

    Edwardsiella ictaluri, a major pathogen in channel catfish aquaculture, encodes a type III secretion system (T3SS) that is essential for intracellular replication and virulence. Previous work identified three putative T3SS effectors in E. ictaluri, and in silico analysis of the E. ictaluri genome identified six additional putative effectors, all located on the chromosome outside the T3SS pathogenicity island. To establish active translocation by the T3SS, we constructed translational fusions of each effector to the amino-terminal adenylate cyclase (AC) domain of the Bordetella pertussis adenylate cyclase toxin CyaA. When translocated through the membrane of the Edwardsiella-containing vacuole (ECV), the cyclic AMP produced by the AC domain in the presence of calmodulin in the host cell cytoplasm can be measured. Results showed that all nine effectors were translocated from E. ictaluri in the ECV to the cytoplasm of the host cells in the wild-type strain but not in a T3SS mutant, indicating that translocation is dependent on the T3SS machinery. This confirms that the E. ictaluri T3SS is similar to the Salmonella pathogenicity island 2 T3SS in that it translocates effectors through the membrane of the bacterial vacuole directly into the host cell cytoplasm. Additional work demonstrated that both initial acidification and subsequent neutralization of the ECV were necessary for effector translocation, except for two of them that did not require neutralization. Single-gene mutants constructed for seven of the individual effectors were all attenuated for replication in CCO cells, but only three were replication deficient in head kidney-derived macrophages (HKDM). IMPORTANCE The bacterial pathogen Edwardsiella ictaluri causes enteric septicemia of catfish (ESC), an economically significant disease of farm-raised channel catfish. Commercial catfish production accounts for the majority of the total fin fish aquaculture in the United States, with almost 300,000

  20. Identification and Characterization of Putative Translocated Effector Proteins of the Edwardsiella ictaluri Type III Secretion System

    PubMed Central

    Dubytska, Lidiya P.; Rogge, Matthew L.

    2016-01-01

    ABSTRACT Edwardsiella ictaluri, a major pathogen in channel catfish aquaculture, encodes a type III secretion system (T3SS) that is essential for intracellular replication and virulence. Previous work identified three putative T3SS effectors in E. ictaluri, and in silico analysis of the E. ictaluri genome identified six additional putative effectors, all located on the chromosome outside the T3SS pathogenicity island. To establish active translocation by the T3SS, we constructed translational fusions of each effector to the amino-terminal adenylate cyclase (AC) domain of the Bordetella pertussis adenylate cyclase toxin CyaA. When translocated through the membrane of the Edwardsiella-containing vacuole (ECV), the cyclic AMP produced by the AC domain in the presence of calmodulin in the host cell cytoplasm can be measured. Results showed that all nine effectors were translocated from E. ictaluri in the ECV to the cytoplasm of the host cells in the wild-type strain but not in a T3SS mutant, indicating that translocation is dependent on the T3SS machinery. This confirms that the E. ictaluri T3SS is similar to the Salmonella pathogenicity island 2 T3SS in that it translocates effectors through the membrane of the bacterial vacuole directly into the host cell cytoplasm. Additional work demonstrated that both initial acidification and subsequent neutralization of the ECV were necessary for effector translocation, except for two of them that did not require neutralization. Single-gene mutants constructed for seven of the individual effectors were all attenuated for replication in CCO cells, but only three were replication deficient in head kidney-derived macrophages (HKDM). IMPORTANCE The bacterial pathogen Edwardsiella ictaluri causes enteric septicemia of catfish (ESC), an economically significant disease of farm-raised channel catfish. Commercial catfish production accounts for the majority of the total fin fish aquaculture in the United States, with almost 300,000

  1. Matrix metalloproteinase expression in excimer laser wounded rabbit corneas

    NASA Astrophysics Data System (ADS)

    Hahn, Taewon; Chamon, Wallace; Akova, Yonja; Stark, Walter J.; Stetler-Stevenson, William G.; Azar, Dimitri T.

    1994-06-01

    This study was performed to obtain information about matrix metalloproteinase (MMP) expression in excimer-wounded corneas and to determine whether MMPs expression correlates with the depth of the ablation. 6-mm excimer keratectomy (60 or 180 micrometers ) was performed using the 193-mm ArF excimer laser on 12 NZW rabbits. Corneas treated with mechanical epithelial debridement and untreated corneas served as controls. Rabbits were killed at 20 and 30 hr after laser ablation. Zymography after SDS extraction was performed on regenerated central epithelium and the central stroma to determine MMPs expression. We observed enzymatic activity of a 92 KDa band in the epithelium of excimer-ablated corneas but not in that following debridement wounds and untreated controls. The expression of the 92 KDa MMP was most pronounced with the deeper excimer ablation. A 72 KDa band of enzymatic activity present in the stroma of all treated and control eyes was also seen in the epithelium of excimer-ablated