Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer

PubMed Central

Valladares-Ayerbes, Manuel; Blanco-Calvo, Moisés; Reboredo, Margarita; Lorenzo-Patiño, María J.; Iglesias-Díaz, Pilar; Haz, Mar; Díaz-Prado, Silvia; Medina, Vanessa; Santamarina, Isabel; Pértega, Sonia; Figueroa, Angélica; Antón-Aparicio, Luis M.

2012-01-01

We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3–pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes. PMID:22605983

Peter Agre and Aquaporin Water Channels

Science.gov Websites

as a postdoctoral fellow in cell biology. Dr. Agre joined the faculty in 1984 and has spent most of Hopkins Malaria Research Institute (JHMRI) in January, 2008. 'Agre will remain a professor of cell biology

Complete Genome Sequence of the MRSA Isolate HC1335 from ST239 Lineage Displaying a Truncated AgrC Histidine Kinase Receptor

PubMed Central

Botelho, Ana M. N.; Costa, Maiana O. C.; Beltrame, Cristiana O.; Ferreira, Fabienne A.; Lima, Nicholas C. B.; Costa, Bruno S. S.; de Morais, Guilherme L.; Souza, Rangel C.; Almeida, Luiz G. P.; Vasconcelos, Ana T. R.; Nicolás, Marisa F.; Figueiredo, Agnes M. S.

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is still one of the most important hospital pathogen globally. The multiresistant isolates of the ST239-SCCmecIII lineage are spread over large geographic regions, colonizing and infecting hospital patients in virtually all continents. The balance between fitness (adaptability) and virulence potential is likely to represent an important issue in the clonal shift dynamics leading the success of some specific MRSA clones over another. The accessory gene regulator (agr) is the master quorum sensing system of staphylococci playing a role in the global regulation of key virulence factors. Consequently, agr inactivation in S. aureus may represent a significant mechanism of genetic variability in the adaptation of this healthcare-associated pathogen. We report here the complete genome sequence of the methicillin-resistant S. aureus, isolate HC1335, a variant of the ST239 lineage, which presents a natural insertion of an IS256 transposase element in the agrC gene encoding AgrC histidine kinase receptor. PMID:27635055

Immunochemical cross-reactions between type III group B Streptococcus and type 14 Streptococcus pneumoniae.

PubMed Central

Crumrine, M H; Fischer, G W; Balk, M W

1979-01-01

Serological cross-reactions between certain streptococci and some serotypes of Streptococcus pneumoniae have been reported. These studies detail the serological cross-reactivity observed between hot HCl-extracted group b streptococcus type III (GBS III) antigens and S. pneumoniae type 14 (Pn 14) polysaccharide. Similar electrophoretic migration patterns of GBS III and Pn 14 were observed when either type-specific BGS III antisera or pneumococcal omniserum was utilized to precipitate these antigens. Both the GBS III antigen and the Pn 14 polysaccharide migrated toward the cathode, whereas all other pneumococcal polysaccharides migrated toward the anode. No cross-reactions were observed between GBS III antisera and the 11 other types of pneumococcal polysaccharides. Lines of identity were observed between type-specific GBS III antisera and monospecific Pn 14 antiserum with either GBS III antigens or purified Pn 14 polysaccharide. The cross-reacting antigens of GBS III and Pn 14 appear to be identical by immunodiffusion and immunoelectrophoresis. Images PMID:40876

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.

Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System

PubMed Central

Ma, Menglin; Li, Jihong

2015-01-01

ABSTRACT The accessory growth regulator (Agr)-like quorum sensing (QS) system of Clostridium perfringens controls the production of many toxins, including beta toxin (CPB). We previously showed (J. E. Vidal, M. Ma, J. Saputo, J. Garcia, F. A. Uzal, and B. A. McClane, Mol Microbiol 83:179–194, 2012, http://dx.doi.org/10.1111/j.1365-2958.2011.07925.x) that an 8-amino-acid, AgrD-derived peptide named 8-R upregulates CPB production by this QS system. The current study synthesized a series of small signaling peptides corresponding to sequences within the C. perfringens AgrD polypeptide to investigate the C. perfringens autoinducing peptide (AIP) structure-function relationship. When both linear and cyclic ring forms of these peptides were added to agrB null mutants of type B strain CN1795 or type C strain CN3685, the 5-amino-acid peptides, whether in a linear or ring (thiolactone or lactone) form, induced better signaling (more CPB production) than peptide 8-R for both C. perfringens strains. The 5-mer thiolactone ring peptide induced faster signaling than the 5-mer linear peptide. Strain-related variations in sensing these peptides were detected, with CN3685 sensing the synthetic peptides more strongly than CN1795. Consistent with those synthetic peptide results, Transwell coculture experiments showed that CN3685 exquisitely senses native AIP signals from other isolates (types A, B, C, and D), while CN1795 barely senses even its own AIP. Finally, a C. perfringens AgrD sequence-based peptide with a 6-amino-acid thiolactone ring interfered with CPB production by several C. perfringens strains, suggesting potential therapeutic applications. These results indicate that AIP signaling sensitivity and responsiveness vary among C. perfringens strains and suggest C. perfringens prefers a 5-mer AIP to initiate Agr signaling. IMPORTANCE Clostridium perfringens possesses an Agr-like quorum sensing (QS) system that regulates virulence, sporulation, and toxin production. The

Targeting agr- and agr-Like Quorum Sensing Systems for Development of Common Therapeutics to Treat Multiple Gram-Positive Bacterial Infections

PubMed Central

Gray, Brian; Hall, Pamela; Gresham, Hattie

2013-01-01

Invasive infection by the Gram-positive pathogen Staphylococcus aureus is controlled by a four gene operon, agr that encodes a quorum sensing system for the regulation of virulence. While agr has been well studied in S. aureus, the contribution of agr homologues and analogues in other Gram-positive pathogens is just beginning to be understood. Intriguingly, other significant human pathogens, including Clostridium perfringens, Listeria monocytogenes, and Enterococcus faecalis contain agr or analogues linked to virulence. Moreover, other significant human Gram-positive pathogens use peptide based quorum sensing systems to establish or maintain infection. The potential for commonality in aspects of these signaling systems across different species raises the prospect of identifying therapeutics that could target multiple pathogens. Here, we review the status of research into these agr homologues, analogues, and other peptide based quorum sensing systems in Gram-positive pathogens as well as the potential for identifying common pathways and signaling mechanisms for therapeutic discovery. PMID:23598501

Pentose sugars inhibit metabolism and increase expression of an AgrD-type cyclic pentapeptide in Clostridium thermocellum

DOE PAGES

Verbeke, Tobin J.; Giannone, Richard J.; Klingeman, Dawn M.; ...

2017-02-23

Significant hurdles exist in efforts to domesticate and industrialize a microbial species for biotechnological application as specific metabolic functions found in natural communities disappear in axenic cultures. For the lignocellulose-deconstructing specialist Clostridium thermocellum, the catabolism of hemicellulose-derived pentoses, which the bacterium cannot ferment, is one such function. Here, we report that various xylo-oligomers significantly inhibit C. thermocellum metabolism and growth and that microbe-sugar interactions occur across multiple dimensions. First, stable isotope metabolomics confirmed C. thermocellum s ability to transport and metabolize pentose sugars. This transport occurs, at least in part, through the ATP-dependent transporter, CbpD. Secondly, xylose is an electronmore » sink for C. thermocellum metabolism leading to the production of xylitol. Deletion of Clo1313_0076, annotated as a xylitol dehydrogenase, reduced the total production and molar xylitol yields by 41% and 46%, respectively. However, it also altered the relative end-product distribution patterns confirming that external electron acceptors may influence the bacterium s redox metabolism to a greater extent than previously considered. Finally, xylose-induced inhibition corresponds with the up-regulation and biogenesis of an AgrD-type, lactone cyclized pentapeptide signaling molecule; which is the first report of an AgrD-type signaling peptide in any thermophile. Addition of synthetic versions of the cyclic peptide inhibited cultures grown in the absence of xylose, but had no effect on cultures already inhibited by the pentose sugar. Together, our findings identify that C. thermocellum has evolved previously unrecognized strategies to cope with C5-sugars, but the absence of a native catabolic sink negatively affects strain metabolism and growth.« less

Pentose sugars inhibit metabolism and increase expression of an AgrD-type cyclic pentapeptide in Clostridium thermocellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verbeke, Tobin J.; Giannone, Richard J.; Klingeman, Dawn M.

Significant hurdles exist in efforts to domesticate and industrialize a microbial species for biotechnological application as specific metabolic functions found in natural communities disappear in axenic cultures. For the lignocellulose-deconstructing specialist Clostridium thermocellum, the catabolism of hemicellulose-derived pentoses, which the bacterium cannot ferment, is one such function. Here, we report that various xylo-oligomers significantly inhibit C. thermocellum metabolism and growth and that microbe-sugar interactions occur across multiple dimensions. First, stable isotope metabolomics confirmed C. thermocellum s ability to transport and metabolize pentose sugars. This transport occurs, at least in part, through the ATP-dependent transporter, CbpD. Secondly, xylose is an electronmore » sink for C. thermocellum metabolism leading to the production of xylitol. Deletion of Clo1313_0076, annotated as a xylitol dehydrogenase, reduced the total production and molar xylitol yields by 41% and 46%, respectively. However, it also altered the relative end-product distribution patterns confirming that external electron acceptors may influence the bacterium s redox metabolism to a greater extent than previously considered. Finally, xylose-induced inhibition corresponds with the up-regulation and biogenesis of an AgrD-type, lactone cyclized pentapeptide signaling molecule; which is the first report of an AgrD-type signaling peptide in any thermophile. Addition of synthetic versions of the cyclic peptide inhibited cultures grown in the absence of xylose, but had no effect on cultures already inhibited by the pentose sugar. Together, our findings identify that C. thermocellum has evolved previously unrecognized strategies to cope with C5-sugars, but the absence of a native catabolic sink negatively affects strain metabolism and growth.« less

Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration

PubMed Central

Wodziak, Dariusz; Dong, Aiwen; Basin, Michael F.; Lowe, Anson W.

2016-01-01

A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2-/- null mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2-/- null mouse. AG1478-treated and AGR2-/- null mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis. PMID:27764193

Oral findings in patients with mucolipidosis type III.

PubMed

Cavalcante, Weber Céo; Santos, Luciano Cincurá Silva; Dos Santos, Josiane Nascimento; de Vasconcellos, Sara Juliana de Abreu; de Azevedo, Roberto Almeida; Dos Santos, Jean Nunes

2012-01-01

Mucolipidosis type III is a rare, autosomal recessive disorder, which is part of a group of storage diseases as a result of inborn error of lysosomal enzyme metabolism. It is characterized by the gradual onset of signs and symptoms affecting the physical and mental development as well as visual changes, heart, skeletal and joint. Although oral findings associated with mucolipidosis type II have been extensively reported, there is a shortage of information on mucolipidosis type III. This paper presents radiological and histological findings of multiple radiolucent lesions associated with impacted teeth in the jaw of a 16 year-old youngster with mucolipidosis type III.

Analysis of type II and type III solar radio bursts

NASA Astrophysics Data System (ADS)

Wijesekera, J. V.; Jayaratne, K. P. S. C.; Adassuriya, J.

2018-04-01

Solar radio burst is an arrangement of a frequency space that variation with time. Most of radio burst can be identified in low frequency range such as below 200 MHz and depending on frequencies. Solar radio bursts were the first phenomenon identified in the field of radio astronomy field. Solar radio frequency range is from 70 MHz to 2.2 GHz. Most of the radio burst can be identified in a low frequency range such as below 200 MHz. Properties of low-frequency radio were analyzed this research. There are two types of solar radio bursts were analyzed, named as type II and type III radio bursts. Exponential decay type could be seen in type II, and a linear could be indicated in type III solar radio bursts. The results of the drift rate graphs show the values of each chosen solar radio burst. High drift rate values can be seen in type III solar flares whereas low to medium drift rate values can be seen in type II solar flares. In the second part of the research the Newkirk model electron density model was used to estimate the drift velocities of the solar radio bursts. Although the special origin of the solar radio burst is not known clearly we assumed. The chosen solar radio bursts were originated within the solar radius of 0.9 - 1.3 range from the photosphere. We used power low in the form of (x) = A × 10‑bx were that the electron density related to the height of the solar atmosphere. The calculation of the plasma velocity of each solar radio burst was done using the electron density model and drift rates. Therefore velocity of chosen type II solar radio bursts indicates low velocities. The values are 233.2499 Km s‑1, 815.9522 Km s‑1 and 369.5425 Km s‑1. Velocity of chosen type III solar radio bursts were 1443.058 Km s‑1and 1205.05Km s ‑1.

[Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer].

PubMed

Akazawa, S; Fujiki, T; Kanda, Y; Kumai, R; Yoshida, S

1985-04-01

Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.

Blood groups and acute aortic dissection type III.

PubMed

Fatic, Nikola; Nikolic, Aleksandar; Vukmirovic, Mihailo; Radojevic, Nemanja; Zornic, Nenad; Banzic, Igor; Ilic, Nikola; Kostic, Dusan; Pajovic, Bogdan

2017-04-01

Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood groups among patients with acute aortic type III dissection and to identify any kind of relationship between blood type and patient's survival. From January 2005 to December 2014, 115 patients with acute aortic type III dissection were enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia and retrospectively analyzed. Patients were separated into two groups. The examination group consisted of patients with a lethal outcome, and the control group consisted of patients who survived. The analysis of the blood groups and RhD typing between groups did not reveal a statistically significant difference ( p = 0.220). Our results indicated no difference between different blood groups and RhD typing with respect to in-hospital mortality of patients with acute aortic dissection type III.

AGR-1 Irradiation Test Final As-Run Report, Rev. 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collin, Blaise P.

2015-01-01

This document presents the as-run analysis of the AGR-1 irradiation experiment. AGR-1 is the first of eight planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the US Department of Energy (DOE) as part of the Next-Generation Nuclear Plant (NGNP) project. The objectives of the AGR-1 experiment are: 1. To gain experience with multi-capsule test train design, fabrication, and operation with the intent to reduce the probability of capsule or test train failure in subsequent irradiation tests. 2. To irradiate fuel produced in conjunction with the AGR fuel processmore » development effort. 3. To provide data that will support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. In order to achieve the test objectives, the AGR-1 experiment was irradiated in the B-10 position of the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL) for a total duration of 620 effective full power days of irradiation. Irradiation began on December 24, 2006 and ended on November 6, 2009 spanning 13 ATR cycles and approximately three calendar years. The test contained six independently controlled and monitored capsules. Each capsule contained 12 compacts of a single type, or variant, of the AGR coated fuel. No fuel particles failed during the AGR-1 irradiation. Final burnup values on a per compact basis ranged from 11.5 to 19.6 %FIMA, while fast fluence values ranged from 2.21 to 4.39 x 10 25 n/m 2 (E >0.18 MeV). We’ll say something here about temperatures once thermal recalc is done. Thermocouples performed well, failing at a lower rate than expected. At the end of the irradiation, nine of the originally-planned 19 TCs were considered functional. Fission product release-to-birth (R/B) ratios were quite low. In most capsules, R/B values at the end of the irradiation were at or below 10 -7 with

Molecular architectures of benzoic acid-specific type III polyketide synthases

PubMed Central

Stewart, Charles; Woods, Kate; Macias, Greg; Allan, Andrew C.; Noel, Joseph P.

2017-01-01

Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants. PMID:29199980

Cranial mononeuropathy III - diabetic type

MedlinePlus

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

[Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

PubMed

Akazawa, S; Harada, A; Futatsuki, K

1984-07-01

It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

AGR2, an Endoplasmic Reticulum Protein, Is Secreted into the Gastrointestinal Mucus

PubMed Central

Bergström, Joakim H.; Berg, Katarina A.; Rodríguez-Piñeiro, Ana M.; Stecher, Bärbel; Johansson, Malin E. V.; Hansson, Gunnar C.

2014-01-01

The MUC2 mucin is the major constituent of the two mucus layers in colon. Mice lacking the disulfide isomerase-like protein Agr2 have been shown to be more susceptible to colon inflammation. The Agr2−/− mice have less filled goblet cells and were now shown to have a poorly developed inner colon mucus layer. We could not show AGR2 covalently bound to recombinant MUC2 N- and C-termini as have previously been suggested. We found relatively high concentrations of Agr2 in secreted mucus throughout the murine gastrointestinal tract, suggesting that Agr2 may play extracellular roles. In tissue culture (CHO-K1) cells, AGR2 is normally not secreted. Replacement of the single Cys in AGR2 with Ser (C81S) allowed secretion, suggesting that modification of this Cys might provide a mechanism for circumventing the KTEL endoplasmic reticulum retention signal. In conclusion, these results suggest that AGR2 has both intracellular and extracellular effects in the intestine. PMID:25111734

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus

PubMed Central

2011-01-01

Background The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. Methods 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 106 and 108 cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. Results 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 106 cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 108 cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log10 CFU/ml for agr functional vs. 2.41 log10 CFU/ml for agr dysfunctional MRSA (p = 0.0007). Conclusions Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections. PMID:21599878

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus.

PubMed

Tsuji, Brian T; MacLean, Robert D; Dresser, Linda D; McGavin, Martin J; Simor, Andrew E

2011-05-20

The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10(6) and 10(8) cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10(6) cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 10(8) cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log(10) CFU/ml for agr functional vs. 2.41 log(10) CFU/ml for agr dysfunctional MRSA (p = 0.0007). Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.

Type III restriction-modification enzymes: a historical perspective.

PubMed

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.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

PubMed

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio

2017-08-17

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

Comparative analysis of agr groups and virulence genes among subclinical and clinical mastitis Staphylococcus aureus isolates from sheep flocks of the Northeast of Brazil.

PubMed

de Almeida, Lara M; de Almeida, Mayra Zilta P R B; de Mendonça, Carla L; Mamizuka, Elsa M

2013-01-01

Staphylococcus aureus is one of the most frequent mastitis causative agents in small ruminants. The expression of most virulence genes of S. aureus is controlled by an accessory gene regulator (agr) locus. This study aimed to ascertain the prevalence of the different agr groups and to evaluate the occurrence of encoding genes for cytotoxin, adhesins and toxins with superantigen activity in S. aureus isolates from milk of ewes with clinical and subclinical mastitis in sheep flocks raised for meat production The agr groups I and II were identified in both cases of clinical and subclinical mastitis. Neither the arg groups III and IV nor negative agr were found. The presence of cflA gene was identified in 100% of the isolates. The frequency of hla and lukE-D genes was high - 77.3 and 82.8%, respectively and all isolates from clinical mastitis presented these genes. The sec gene, either associated to tst gene or not, was identified only in isolates from subclinical mastitis. None of the following genes were identified: bbp, ebpS, cna, fnbB, icaA, icaD, bap, hlg, lukM-lukF-PV and se-a-b-d-e.

Usher syndrome type III can mimic other types of Usher syndrome.

PubMed

Pennings, Ronald J E; Fields, Randall R; Huygen, Patrick L M; Deutman, August F; Kimberling, William J; Cremers, Cor W R J

2003-06-01

Clinical and genetic characteristics are presented of 2 patients from a Dutch Usher syndrome type III family who have a new homozygous USH3 gene mutation: 149-152delCAGG + insTGTCCAAT. One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata albescens (RPA). The other individual is also profoundly hearing impaired, but has well-developed speech, vestibular areflexia, and retinitis pigmentosa sine pigmento (RPSP). These findings suggest that Usher syndrome type III can be clinically misdiagnosed as either Usher type I or II; that Usher syndrome patients who are profoundly hearing impaired and have normal vestibular function should be tested for USH3 mutations; and that RPA and RPSP can occur as fundoscopic manifestations of pigmentary retinopathy in Usher syndrome.

AGR-2 Irradiated Test Train Preliminary Inspection and Disassembly First Look

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ploger, Scott; Demkowciz, Paul; Harp, Jason

2015-05-01

The AGR 2 irradiation experiment began in June 2010 and was completed in October 2013. The test train was shipped to the Materials and Fuels Complex in July 2014 for post-irradiation examination (PIE). The first PIE activities included nondestructive examination of the test train, followed by disassembly of the test train and individual capsules and detailed inspection of the capsule contents, including the fuel compacts and their graphite fuel holders. Dimensional metrology was then performed on the compacts, graphite holders, and steel capsule shells. AGR 2 disassembly and metrology were performed with the same equipment used successfully on AGR 1more » test train components. Gamma spectrometry of the intact test train gave a preliminary look at the condition of the interior components. No evidence of damage to compacts or graphite components was evident from the isotopic and gross gamma scans. Disassembly of the AGR 2 test train and its capsules was conducted rapidly and efficiently by employing techniques refined during the AGR 1 disassembly campaign. Only one major difficulty was encountered while separating the test train into capsules when thermocouples (of larger diameter than used in AGR 1) and gas lines jammed inside the through tubes of the upper capsules, which required new tooling for extraction. Disassembly of individual capsules was straightforward with only a few minor complications. On the whole, AGR 2 capsule structural components appeared less embrittled than their AGR 1 counterparts. Compacts from AGR 2 Capsules 2, 3, 5, and 6 were in very good condition upon removal. Only relatively minor damage or markings were visible using high resolution photographic inspection. Compact dimensional measurements indicated radial shrinkage between 0.8 to 1.7%, with the greatest shrinkage observed on Capsule 2 compacts that were irradiated at higher temperature. Length shrinkage ranged from 0.1 to 0.9%, with by far the lowest axial shrinkage on Capsule 3

Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties

PubMed Central

Fessart, Delphine; Domblides, Charlotte; Avril, Tony; Eriksson, Leif A; Begueret, Hugues; Pineau, Raphael; Malrieux, Camille; Dugot-Senant, Nathalie; Lucchesi, Carlo; Chevet, Eric; Delom, Frederic

2016-01-01

The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.13887.001 PMID:27240165

Microscopic analysis of irradiated AGR-1 coated particle fuel compacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott A. Ploger; Paul A. Demkowicz; John D. Hunn

The AGR-1 experiment involved irradiation of 72 TRISO-coated particle fuel compacts to a peak compact-average burnup of 19.5% FIMA with no in-pile failures observed out of 3 x 105 total particles. Irradiated AGR-1 fuel compacts have been cross-sectioned and analyzed with optical microscopy to characterize kernel, buffer, and coating behavior. Six compacts have been examined, spanning a range of irradiation conditions (burnup, fast fluence, and irradiation temperature) and including all four TRISO coating variations irradiated in the AGR-1 experiment. The cylindrical specimens were sectioned both transversely and longitudinally, then polished to expose from 36 to 79 individual particles near midplanemore » on each mount. The analysis focused primarily on kernel swelling and porosity, buffer densification and fracturing, buffer–IPyC debonding, and fractures in the IPyC and SiC layers. Characteristic morphologies have been identified, 981 particles have been classified, and spatial distributions of particle types have been mapped. No significant spatial patterns were discovered in these cross sections. However, some trends were found between morphological types and certain behavioral aspects. Buffer fractures were found in 23% of the particles, and these fractures often resulted in unconstrained kernel protrusion into the open cavities. Fractured buffers and buffers that stayed bonded to IPyC layers appear related to larger pore size in kernels. Buffer–IPyC interface integrity evidently factored into initiation of rare IPyC fractures. Fractures through part of the SiC layer were found in only four classified particles, all in conjunction with IPyC–SiC debonding. Compiled results suggest that the deliberate coating fabrication variations influenced the frequencies of IPyC fractures and IPyC–SiC debonds.« less

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems

PubMed Central

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C

2017-01-01

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an ‘arms race’ in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems. PMID:28826484

Safety Testing of AGR-2 UCO Compacts 6-4-2 and 2-3-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunn, John D.; Morris, Robert N.; Baldwin, Charles A.

2017-08-01

Post-irradiation examination (PIE) and elevated-temperature safety testing are being performed on tristructural-isotropic (TRISO) coated-particle fuel compacts from the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program second irradiation experiment (AGR-2). Details on this irradiation experiment have been previously reported [Collin 2014]. The AGR-2 PIE effort builds upon the understanding acquired throughout the AGR-1 PIE campaign [Demkowicz et al. 2015] and is establishing a database for the different AGR-2 fuel designs.

AGR-3/4 Irradiation Test Predictions using PARFUME

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skerjanc, William Frances; Collin, Blaise Paul

2016-03-01

PARFUME, a fuel performance modeling code used for high temperature gas reactors, was used to model the AGR-3/4 irradiation test using as-run physics and thermal hydraulics data. The AGR-3/4 test is the combined third and fourth planned irradiations of the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. The AGR-3/4 test train consists of twelve separate and independently controlled and monitored capsules. Each capsule contains four compacts filled with both uranium oxycarbide (UCO) unaltered “driver” fuel particles and UCO designed-to-fail (DTF) fuel particles. The DTF fraction was specified to be 1×10-2. This report documents the calculations performed to predictmore » failure probability of TRISO-coated fuel particles during the AGR-3/4 experiment. In addition, this report documents the calculated source term from both the driver fuel and DTF particles. The calculations include the modeling of the AGR-3/4 irradiation that occurred from December 2011 to April 2014 in the Advanced Test Reactor (ATR) over a total of ten ATR cycles including seven normal cycles, one low power cycle, one unplanned outage cycle, and one Power Axial Locator Mechanism cycle. Results show that failure probabilities are predicted to be low, resulting in zero fuel particle failures per capsule. The primary fuel particle failure mechanism occurred as a result of localized stresses induced by the calculated IPyC cracking. Assuming 1,872 driver fuel particles per compact, failure probability calculated by PARFUME leads to no predicted particle failure in the AGR-3/4 driver fuel. In addition, the release fraction of fission products Ag, Cs, and Sr were calculated to vary depending on capsule location and irradiation temperature. The maximum release fraction of Ag occurs in Capsule 7 reaching up to 56% for the driver fuel and 100% for the DTF fuel. The release fraction of the other two fission products, Cs and Sr, are much smaller and in most cases less than 1% for

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

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

Plant-bacterial pathogen interactions mediated by type III effectors.

PubMed

Feng, Feng; Zhou, Jian-Min

2012-08-01

Effectors secreted by the bacterial type III system play a central role in the interaction between Gram-negative bacterial pathogens and their host plants. Recent advances in the effector studies have helped cementing several key concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co-evolution. Type III effectors use a variety of biochemical mechanisms to target specific host proteins or DNA for pathogenesis. The identifications of their host targets led to the identification of novel components of plant innate immune system. Key modules of plant immune signaling pathways such as immune receptor complexes and MAPK cascades have emerged as a major battle ground for host-pathogen adaptation. These modules are attacked by multiple type III effectors, and some components of these modules have evolved to actively sense the effectors and trigger immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Type-III and IV interacting Weyl points

NASA Astrophysics Data System (ADS)

Nissinen, J.; Volovik, G. E.

2017-04-01

3+1-dimensional Weyl fermions in interacting systems are described by effective quasi-relativistic Green's functions parametrized by a 16-element matrix e α μ in an expansion around the Weyl point. The matrix e α μ can be naturally identified as an effective tetrad field for the fermions. The correspondence between the tetrad field and an effective quasi-relativistic metric gμν governing the Weyl fermions allows for the possibility to simulate different classes of metric fields emerging in general relativity in interacting Weyl semimetals. According to this correspondence, there can be four types of Weyl fermions, depending on the signs of the components g 00 and g 00 of the effective metric. In addition to the conventional type-I fermions with a tilted Weyl cone and type-II fermions with an overtilted Weyl cone for g 00 > 0 and, respectively, g 00 > 0 or g 00 < 0, we find additional "type-III" and "type-IV" Weyl fermions with instabilities (complex frequencies) for g 00 < 0 and g 00 > 0 or g 00 < 0, respectively. While the type-I and type-II Weyl points allow us to simulate the black hole event horizon at an interface where g 00 changes sign, the type-III Weyl point leads to effective spacetimes with closed timelike curves.

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.

Crystal Structure of AGR_C_4470p from Agrobacterium tumefaciens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorobiev,S.; Neely, H.; Seetharaman, J.

2007-01-01

We report here the crystal structure at 2.0 {angstrom} resolution of the AGR{_}C{_}4470p protein from the Gram-negative bacterium Agrobacterium tumefaciens. The protein is a tightly associated dimer, each subunit of which bears strong structural homology with the two domains of the heme utilization protein ChuS from Escherichia coli and HemS from Yersinia enterocolitica. Remarkably, the organization of the AGR{_}C{_}4470p dimer is the same as that of the two domains in ChuS and HemS, providing structural evidence that these two proteins evolved by gene duplication. However, the binding site for heme, while conserved in HemS and ChuS, is not conserved inmore » AGR{_}C{_}4470p, suggesting that it probably has a different function. This is supported by the presence of two homologs of AGR{_}C{_}4470p in E. coli, in addition to the ChuS protein.« less

Functional Reconstitution of Staphylococcus aureus Truncated AgrC Histidine Kinase in a Model Membrane System

PubMed Central

Liu, Baoquan; Wang, Jianfeng; Xiong, Wen; Zhao, Pengchao; Fan, Shengdi

2013-01-01

The integral membrane protein AgrC is a histidine kinase whose sensor domains interact with an autoinducing peptide, resulting in a series of downstream responses. In this study, truncated AgrCTM5-6C and AgrCTM5-6C-GFP with GFP as a reporter gene were produced using a bacterial system. Purified AgrCTM5-6C and AgrCTM5-6C-GFP were reconstituted into liposomes by a detergent-mediated method. To achieve high-yield protein incorporation, we investigated the effect of different detergents on protein reconstitution efficiency. The highest incorporation was found with N,N-dimethyldode-cylamine N-oxide during complete liposome solubilization, which resulted in a yield of 85±5%. The COOH-terminus of the protein AgrCTM5-6C was almost exclusively oriented towards the inside of the vesicles. AgrCTM5-6C in proteoliposomes exhibited approximately a 6-fold increase in constitutive activity compared with AgrCTM5-6C in detergent micelles. The reconstitution of AgrCTM5-6C or AgrCTM5-6C-GFP was characterized using dynamic light scattering, fluorescence microscopy, and transmission electron microscopy. Based on the results, the optimal conditions for protein incorporation were defined. These findings contribute to the study of membrane protein structure and function in vitro using a reconstitution system. PMID:24303011

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

NASA Astrophysics Data System (ADS)

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

2015-09-01

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

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

PubMed

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

2016-09-28

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

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…

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

PubMed Central

Büttner, Daniela

2016-01-01

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

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

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

PubMed Central

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

2016-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

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.

PIE on Safety-Tested AGR-1 Compact 5-1-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunn, John D.; Morris, Robert Noel; Baldwin, Charles A.

Post-irradiation examination (PIE) is being performed in support of tristructural isotropic (TRISO) coated particle fuel development and qualification for High-Temperature Gas-cooled Reactors (HTGRs). AGR-1 was the first in a series of TRISO fuel irradiation experiments initiated in 2006 under the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program; this work continues to be funded by the Department of Energy's Office of Nuclear Energy as part of the Advanced Reactor Technologies (ART) initiative. AGR-1 fuel compacts were fabricated at Oak Ridge National Laboratory (ORNL) in 2006 and irradiated for three years in the Idaho National Laboratory (INL) Advanced Test Reactormore » (ATR) to demonstrate and evaluate fuel performance under HTGR irradiation conditions. PIE is being performed at INL and ORNL to study how the fuel behaved during irradiation, and to examine fuel performance during exposure to elevated temperatures at or above temperatures that could occur during a depressurized conduction cooldown event. This report summarizes safety testing of irradiated AGR-1 Compact 5-1-1 in the ORNL Core Conduction Cooldown Test Facility (CCCTF) and post-safety testing PIE.« less

Aircraft evacuations through type-III exits II : effects of individual subject differences.

DOT National Transportation Integrated Search

1995-08-01

Simulated emergency egress from Type III over-wing exits was studied to support regulatory action by the FAA. Passageway width from the aircraft center aisle to the Type-III exit was the major variable of interest; effects of individual subject attri...

Ceramography of Irradiated tristructural isotropic (TRISO) Fuel from the AGR-2 Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rice, Francine Joyce; Stempien, John Dennis

2016-09-01

Ceramography was performed on cross sections from four tristructural isotropic (TRISO) coated particle fuel compacts taken from the AGR-2 experiment, which was irradiated between June 2010 and October 2013 in the Advanced Test Reactor (ATR). The fuel compacts examined in this study contained TRISO-coated particles with either uranium oxide (UO2) kernels or uranium oxide/uranium carbide (UCO) kernels that were irradiated to final burnup values between 9.0 and 11.1% FIMA. These examinations are intended to explore kernel and coating morphology evolution during irradiation. This includes kernel porosity, swelling, and migration, and irradiation-induced coating fracture and separation. Variations in behavior within amore » specific cross section, which could be related to temperature or burnup gradients within the fuel compact, are also explored. The criteria for categorizing post-irradiation particle morphologies developed for AGR-1 ceramographic exams, was applied to the particles in the AGR-2 compacts particles examined. Results are compared with similar investigations performed as part of the earlier AGR-1 irradiation experiment. This paper presents the results of the AGR-2 examinations and discusses the key implications for fuel irradiation performance.« less

Unusual case of failure to thrive: Type III Bartter syndrome.

PubMed

Agrawal, S; Subedi, K; Ray, P; Rayamajhi, A

2016-09-01

Bartter syndrome Type III is a rare autosomal recessive disorder resulting from an inherited defect in the thick ascending limb of the loop of henle of the nephrons in kidney. The typical clinical manifestations in childhood are failure to thrive and recurrent episodes of vomiting. Typical laboratory findings which help in the diagnosis are hypokalemic metabolic alkalosis, hypomagnesemia and hypercalciuria. We report a case of Type III Bartter syndrome not responding to repeated conventional treatment of failure to thrive.

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

PubMed Central

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

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

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

PubMed

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

2011-04-01

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

Safety Testing of AGR-2 UCO Compacts 5-2-2, 2-2-2, and 5-4-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunn, John D.; Morris, Robert Noel; Baldwin, Charles A.

2016-08-01

Post-irradiation examination (PIE) is being performed on tristructural-isotropic (TRISO) coated-particle fuel compacts from the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program second irradiation experiment (AGR-2). This effort builds upon the understanding acquired throughout the AGR-1 PIE campaign, and is establishing a database for the different AGR-2 fuel designs. The AGR-2 irradiation experiment included TRISO fuel particles coated at BWX Technologies (BWXT) with a 150-mm-diameter engineering-scale coater. Two coating batches were tested in the AGR-2 irradiation experiment. Batch 93085 had 508-μm-diameter uranium dioxide (UO 2) kernels. Batch 93073 had 427-μm-diameter UCO kernels, which is a kernel design where somemore » of the uranium oxide is converted to uranium carbide during fabrication to provide a getter for oxygen liberated during fission and limit CO production. Fabrication and property data for the AGR-2 coating batches have been compiled and compared to those for AGR-1. The AGR-2 TRISO coatings were most like the AGR-1 Variant 3 TRISO deposited in the 50-mm-diameter ORNL lab-scale coater. In both cases argon-dilution of the hydrogen and methyltrichlorosilane coating gas mixture employed to deposit the SiC was used to produce a finer-grain, more equiaxed SiC microstructure. In addition to the fact that AGR-1 fuel had smaller, 350-μm-diameter UCO kernels, notable differences in the TRISO particle properties included the pyrocarbon anisotropy, which was slightly higher in the particles coated in the engineering-scale coater, and the exposed kernel defect fraction, which was higher for AGR-2 fuel due to the detected presence of particles with impact damage introduced during TRISO particle handling.« less

Staphylococcus intermedius produces a functional agr autoinducing peptide containing a cyclic lactone.

PubMed

Ji, Guangyong; Pei, Wuhong; Zhang, Linsheng; Qiu, Rongde; Lin, Jianqun; Benito, Yvonne; Lina, Gerard; Novick, Richard P

2005-05-01

The agr system is a global regulator of accessory functions in staphylococci, including genes encoding exoproteins involved in virulence. The agr locus contains a two-component signal transduction module that is activated by an autoinducing peptide (AIP) encoded within the agr locus and is conserved throughout the genus. The AIP has an unusual partially cyclic structure that is essential for function and that, in all but one case, involves an internal thiolactone bond between a conserved cysteine and the C-terminal carboxyl group. The exceptional case is a strain of Staphylococcus intermedius that has a serine in place of the conserved cysteine. We demonstrate here that the S. intermedius AIP is processed by the S. intermedius AgrB protein to generate a cyclic lactone, that it is an autoinducer as well as a cross-inhibitor, and that all of five other S. intermedius strains examined also produce serine-containing AIPs.

AGR-5/6/7 Irradiation Test Predictions using PARFUME

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skerjanc, William F.

PARFUME, (PARticle FUel ModEl) a fuel performance modeling code used for high temperature gas-cooled reactors (HTGRs), was used to model the Advanced Gas Reactor (AGR)-5/6/7 irradiation test using predicted physics and thermal hydraulics data. The AGR-5/6/7 test consists of the combined fifth, sixth, and seventh planned irradiations of the AGR Fuel Development and Qualification Program. The AGR-5/6/7 test train is a multi-capsule, instrumented experiment that is designed for irradiation in the 133.4-mm diameter north east flux trap (NEFT) position of Advanced Test Reactor (ATR). Each capsule contains compacts filled with uranium oxycarbide (UCO) unaltered fuel particles. This report documents themore » calculations performed to predict the failure probability of tristructural isotropic (TRISO)-coated fuel particles during the AGR-5/6/7 experiment. In addition, this report documents the calculated source term from the driver fuel. The calculations include modeling of the AGR-5/6/7 irradiation that is scheduled to occur from October 2017 to April 2021 over a total of 13 ATR cycles, including nine normal cycles and four Power Axial Locator Mechanism (PALM) cycle for a total between 500 – 550 effective full power days (EFPD). The irradiation conditions and material properties of the AGR-5/6/7 test predicted zero fuel particle failures in Capsules 1, 2, and 4. Fuel particle failures were predicted in Capsule 3 due to internal particle pressure. These failures were predicted in the highest temperature compacts. Capsule 5 fuel particle failures were due to inner pyrolytic carbon (IPyC) cracking causing localized stresses concentrations in the SiC layer. This capsule predicted the highest particle failures due to the lower irradiation temperature. In addition, shrinkage of the buffer and IPyC layer during irradiation resulted in formation of a buffer-IPyC gap. The two capsules at the two ends of the test train, Capsules 1 and 5 experienced the smallest buffer-IPyC gap

Immunochemical characterization of the "native" type III polysaccharide of group B Streptococcus

PubMed Central

1976-01-01

The type III polysaccharide of -roup B Streptococcus has been isolated and purified by a method that employs washing of intact cells at neutral pH. That the polysaccharide prepared by this procedure is the "native" type III antigen is suggested by its molecular size in excess of 10(6) daltons, its degradation by acid and heat treatment to a fragment with immunologic characteristics of the classical HCl antigen, and its type-specific serologic activity. The type III polysaccharide in native form contains sialic acid, galactose, glucose, glucosamine, heptose, and mannose. It is acidic in nature, is resistant to neuramindiase degradation, contains no O-acetyl groups, and does not share antigenic determinants with capsular type K1 antigen of Escherichia coli or Group B polysaccharide antigen of Neiserria meningitidis. PMID:55450

Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut.

PubMed

Pervolaraki, Kalliopi; Stanifer, Megan L; Münchau, Stephanie; Renn, Lynnsey A; Albrecht, Dorothee; Kurzhals, Stefan; Senís, Elena; Grimm, Dirk; Schröder-Braunstein, Jutta; Rabin, Ronald L; Boulant, Steeve

2017-01-01

Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined. Here, we used mini-gut organoids to define the functions of types I and III IFNs to protect the human gut against viral infection. We show that primary non-transformed human IECs, upon viral challenge, upregulate the expression of both type I and type III IFNs at the transcriptional level but only secrete type III IFN in the supernatant. However, human IECs respond to both type I and type III IFNs by producing IFN-stimulated genes that in turn induce an antiviral state. Using genetic ablation of either type I or type III IFN receptors, we show that either IFN can independently restrict virus infection in human IECs. Importantly, we report, for the first time, differences in the mechanisms by which each IFN establishes the antiviral state. Contrary to type I IFN, the antiviral activity induced by type III IFN is strongly dependent on the mitogen-activated protein kinases signaling pathway, suggesting a pathway used by type III IFNs that non-redundantly contributes to the antiviral state. In conclusion, we demonstrate that human intestinal epithelial cells specifically regulate their innate immune response favoring type III IFN-mediated signaling, which allows for efficient protection against pathogens without producing excessive inflammation. Our results strongly suggest that type III IFN constitutes the frontline of antiviral response in the human gut. We propose that

Type III bursts in interplanetary space - Fundamental or harmonic?

NASA Technical Reports Server (NTRS)

Dulk, G. A.; Steinberg, J. L.; Hoang, S.

1984-01-01

ISEE-3 spacecraft observation of 120 relatively simple, isolated bursts in the 30-1980 kHz range are the basis of the present study of Type III bursts in the solar wind. Several characteristics are identified for many of these bursts which imply that the mode of emission changes from predominantly fundamental plasma radiation during the rise phase to predominantly second harmonic during decay. The fundamental emission begins in time coincidence with the start of Langmuir waves, confirming the conventional belief in these waves' causation of Type III bursts. Attention is given to the characteristics of fundamental components, by comparison to harmonics, at km-wavelengths.

Distinct Pseudomonas type-III effectors use a cleavable transit peptide to target chloroplasts.

PubMed

Li, Guangyong; Froehlich, John E; Elowsky, Christian; Msanne, Joseph; Ostosh, Andrew C; Zhang, Chi; Awada, Tala; Alfano, James R

2014-01-01

The pathogen Pseudomonas syringae requires a type-III protein secretion system and the effector proteins it injects into plant cells for pathogenesis. The primary role for P. syringae type-III effectors is the suppression of plant immunity. The P. syringae pv. tomato DC3000 HopK1 type-III effector was known to suppress the hypersensitive response (HR), a programmed cell death response associated with effector-triggered immunity. Here we show that DC3000 hopK1 mutants are reduced in their ability to grow in Arabidopsis, and produce reduced disease symptoms. Arabidopsis transgenically expressing HopK1 are reduced in PAMP-triggered immune responses compared with wild-type plants. An N-terminal region of HopK1 shares similarity with the corresponding region in the well-studied type-III effector AvrRps4; however, their C-terminal regions are dissimilar, indicating that they have different effector activities. HopK1 is processed in planta at the same processing site found in AvrRps4. The processed forms of HopK1 and AvrRps4 are chloroplast localized, indicating that the shared N-terminal regions of these type-III effectors represent a chloroplast transit peptide. The HopK1 contribution to virulence and the ability of HopK1 and AvrRps4 to suppress immunity required their respective transit peptides, but the AvrRps4-induced HR did not. Our results suggest that a primary virulence target of these type-III effectors resides in chloroplasts, and that the recognition of AvrRps4 by the plant immune system occurs elsewhere. Moreover, our results reveal that distinct type-III effectors use a cleavable transit peptide to localize to chloroplasts, and that targets within this organelle are important for immunity. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

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

Antiviral type I and type III interferon responses in the central nervous system.

PubMed

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

2013-03-15

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.

Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

PubMed Central

Canovas, Jaime; Baldry, Mara; Bojer, Martin S.; Andersen, Paal S.; Gless, Bengt H.; Grzeskowiak, Piotr K.; Stegger, Marc; Damborg, Peter; Olsen, Christian A.; Ingmer, Hanne

2016-01-01

Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for Staphylococcus epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to better understand the interaction between staphylococci and S. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus agr. The dog pathogen, Staphylococcus schleiferi, expressed the most potent inhibitory activity and was active against all four agr classes found in S. aureus. By employing a S. aureus strain encoding a constitutively active AIP receptor we show that the activity is mediated via agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in S. aureus demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic S. schleiferi AIP was able to completely abolish agr induction of an S. aureus reporter strain. To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species suggesting that agr is an inter-species communication system. Based on these results we speculate that interactions between S. aureus and other colonizing staphylococci will significantly

Type III interferon is a critical regulator of innate antifungal immunity.

PubMed

Espinosa, Vanessa; Dutta, Orchi; McElrath, Constance; Du, Peicheng; Chang, Yun-Juan; Cicciarelli, Bryan; Pitler, Amy; Whitehead, Ian; Obar, Joshua J; Durbin, Joan E; Kotenko, Sergei V; Rivera, Amariliz

2017-10-06

Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus ( Af ) as a model to study antifungal immune responses, we found that depletion of CCR2 + monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2 + monocytes are an important early source of type I IFNs that prime optimal expression of IFN-λ. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2 + monocytes or by exogenous administration of IFN-α and IFN-λ. Thus, CCR2 + monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-λ expression. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness of Endometrial Cancer Cells.

PubMed

Hrstka, Roman; Podhorec, Jan; Nenutil, Rudolf; Sommerova, Lucia; Obacz, Joanna; Durech, Michal; Faktor, Jakub; Bouchal, Pavel; Skoupilova, Hana; Vojtesek, Borivoj

2017-05-28

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.

An EGFR wild type-EGFRvIII-HB-EGF feed forward loop regulates the activation of EGFRvIII

PubMed Central

Li, Li; Chakraborty, Sharmistha; Yang, Chin-Rang; Hatanpaa, Kimmo J.; Cipher, Daisha J.; Puliyappadamba, Vineshkumar Thidil; Rehman, Alizeh; Jiwani, Ameena J.; Mickey, Bruce; Madden, Christopher; Raisanen, Jack; Burma, Sandeep; Saha, Debabrata; Wang, Zhixiang; Pingle, Sandeep C.; Kesari, Santosh; Boothman, David A.; Habib, Amyn A.

2014-01-01

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in frame deletion in the extracellular domain of EGFR, does not bind ligand, and is thought to be constitutively active. While EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study we show that HB-EGF, is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HBEGF loop, potentially an attractive target for therapeutic intervention. PMID:24077285

Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance

PubMed Central

Sully, Erin K.; Malachowa, Natalia; Elmore, Bradley O.; Alexander, Susan M.; Femling, Jon K.; Gray, Brian M.; DeLeo, Frank R.; Otto, Michael; Cheung, Ambrose L.; Edwards, Bruce S.; Sklar, Larry A.; Horswill, Alexander R.; Hall, Pamela R.; Gresham, Hattie D.

2014-01-01

Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Δagr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Δagr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in

The type III secretion system is involved in Escherichia coli K1 interactions with Acanthamoeba.

PubMed

Siddiqui, Ruqaiyyah; Malik, Huma; Sagheer, Mehwish; Jung, Suk-Yul; Khan, Naveed Ahmed

2011-08-01

The type III secretion system among Gram-negative bacteria is known to deliver effectors into host cell to interfere with host cellular processes. The type III secretion system in Yersina, Pseudomonas and Enterohemorrhagic Escherichia coli have been well documented to be involved in the bacterial pathogenicity. The existence of type III secretion system has been demonstrated in neuropathogenic E. coli K1 strains. Here, it is observed that the deletion mutant of type III secretion system in E. coli strain EC10 exhibited defects in the invasion and intracellular survival in Acanthamoeba castellanii (a keratitis isolate) compared to its parent strain. Next, it was determined whether type III secretion system plays a role in E. coli K1 survival inside Acanthamoeba during the encystment process. Using encystment assays, our findings revealed that the type III secretion system-deletion mutant exhibited significantly reduced survival inside Acanthamoeba cysts compared with its parent strain, EC10 (P<0.01). This is the first demonstration that the type III secretion system plays an important role in E. coli interactions with Acanthamoeba. A complete understanding of how amoebae harbor bacterial pathogens will help design strategies against E. coli transmission to the susceptible hosts. Copyright © 2011 Elsevier Inc. All rights reserved.

Fuel of the Bacterial Flagellar Type III Protein Export Apparatus.

PubMed

Minamino, Tohru; Kinoshita, Miki; Namba, Keiichi

2017-01-01

The flagellar type III export apparatus utilizes ATP and proton motive force (PMF) across the cytoplasmic membrane as the energy sources and transports flagellar component proteins from the cytoplasm to the distal growing end of the growing structure to construct the bacterial flagellum beyond the cellular membranes. The flagellar type III export apparatus coordinates flagellar protein export with assembly by ordered export of substrates to parallel with their order of the assembly. The export apparatus is composed of a PMF-driven transmembrane export gate complex and a cytoplasmic ATPase complex. Since the ATPase complex is dispensable for flagellar protein export, PMF is the primary fuel for protein unfolding and translocation. Interestingly, the export gate complex can also use sodium motive force across the cytoplasmic membrane in addition to PMF when the ATPase complex does not work properly. Here, we describe experimental protocols, which have allowed us to identify the export substrate class and the primary fuel of the flagellar type III protein export apparatus in Salmonella enterica serovar Typhimurium.

The Agr communication system provides a benefit to the populations of Listeria monocytogenes in soil.

PubMed

Vivant, Anne-Laure; Garmyn, Dominique; Gal, Laurent; Piveteau, Pascal

2014-01-01

In this study, we investigated whether the Agr communication system of the pathogenic bacterium Listeria monocytogenes was involved in adaptation and competitiveness in soil. Alteration of the ability to communicate, either by deletion of the gene coding the response regulator AgrA (response-negative mutant) or the signal pro-peptide AgrD (signal-negative mutant), did not affect population dynamics in soil that had been sterilized but survival was altered in biotic soil suggesting that the Agr system of L. monocytogenes was involved to face the complex soil biotic environment. This was confirmed by a set of co-incubation experiments. The fitness of the response-negative mutant was lower either in the presence or absence of the parental strain but the fitness of the signal-negative mutant depended on the strain with which it was co-incubated. The survival of the signal-negative mutant was higher when co-cultured with the parental strain than when co-cultured with the response-negative mutant. These results showed that the ability to respond to Agr communication provided a benefit to listerial cells to compete. These results might also indicate that in soil, the Agr system controls private goods rather than public goods.

Trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus causing invasive infections in Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST) study, 2006-2010.

PubMed

Tsao, Shin-Ming; Wang, Wei-Yao; Ko, Wen-Chien; Huang, Cheng-Hua; Lu, Chin-Te; Chuang, Yin-Ching; Liu, Chia-Ying; Liao, Chun-Hsing; Chen, Yao-Shen; Liu, Yung-Ching; Chen, Wei-Yu; Jang, Tsrang-Neng; Lin, Hsiu-Chen; Chen, Chih-Ming; Shi, Zhi-Yuan; Pan, Sung-Ching; Yang, Jia-Ling; Kung, Hsiang-Chi; Liu, Chun-Eng; Cheng, Yu-Jen; Liu, Jien-Wei; Sun, Wu; Wang, Lih-Shinn; Yu, Kwok-Woon; Chiang, Ping-Cherng; Lee, Ming-Hsun; Lee, Chun-Ming; Hsu, Gwo-Jong; Chen, Yen-Hsu; Lu, Po-Liang; Thomas, Chang-Yao Tsao; Hsueh, Po-Ren

2014-10-01

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time. Copyright © 2014 Elsevier Inc. All rights reserved.

Receptosecretory nature of type III cells in the taste bud.

PubMed

Yoshie, Sumio

2009-01-01

Type III cells in taste buds form chemical synapses with intragemmal afferent nerve fibers and are characterized by the presence of membrane-bound vesicles in the cytoplasm. Although the vesicles differ in shape and size among species, they are primarily categorized into small clear (40 nm in diameter) and large dense-cored (90-200 nm) types. As such vesicles tend to be closely juxtaposed to the synaptic membrane of the cells, it is reasonable to consider that the vesicles include transmitter(s) towards the gustatory nerve. In the guinea-pig taste bud, stimulation with various taste substances (sucrose, sodium chloride, quinine hydrochloride, or monosodium L-glutamate) causes ultrastructural alterations of the type III cells. At the synapse, the presynaptic plasma membrane often displays invaginations of 90 nm in a mean diameter towards the cytoplasm, which indicates the dense-cored vesicles opening into the synaptic cleft by means of exocytosis. The vesicles are also exocytosed at the non-synaptic region into the intercellular space. These findings strongly suggest that the transmitters presumably contained in the vesicles are released to conduct the excitement of the type III cells to the nerves and also to exert their paracrine effects upon the surroundings, such as the Ebner's salivary gland, acting as local hormones.

LcrV Mutants That Abolish Yersinia Type III Injectisome Function

PubMed Central

Ligtenberg, Katherine Given; Miller, Nathan C.; Mitchell, Anthony; Plano, Gregory V.

2013-01-01

LcrV, the type III needle cap protein of pathogenic Yersinia, has been proposed to function as a tether between YscF, the needle protein, and YopB-YopD to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. Further, insertion of LcrV-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. Here, we used a genetic approach to test the hypothesis that the needle cap responds to the low-calcium signal by promoting injectisome assembly. Growth restriction of Yersinia pestis in the absence of calcium (low-calcium response [LCR+] phenotype) was exploited to isolate dominant negative lcrV alleles with missense mutations in its amber stop codon (lcrV*327). The addition of at least four amino acids or the eight-residue Strep tag to the C terminus was sufficient to generate an LCR− phenotype, with variant LcrV capping type III needles that cannot assemble the YopD injectisome component. The C-terminal Strep tag appears buried within the cap structure, blocking effector transport even in Y. pestis yscF variants that are otherwise calcium blind, a constitutive type III secretion phenotype. Thus, LcrV*327 mutants arrest the needle cap in a state in which it cannot respond to the low-calcium signal with either injectisome assembly or the activation of type III secretion. Insertion of the Strep tag at other positions of LcrV produced variants with wild-type LCR+, LCR−, or dominant negative LCR− phenotypes, thereby allowing us to identify discrete sites within LcrV as essential for its attributes as a secretion substrate, needle cap, and injectisome assembly factor. PMID:23222719

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sweeny, Larissa, E-mail: larissasweeny@gmail.com; Liu, Zhiyong; Bush, Benjamin D.

2012-08-15

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: Black-Right-Pointing-Pointer We investigated AGR2more » in head and neck squamous cell carcinoma for the first time. Black-Right-Pointing-Pointer We explored the relationship between AGR2 and CD147 for the first time. Black-Right-Pointing-Pointer AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 decreased metastasis in vivo.« less

Conservation and Evolutionary Dynamics of the agr Cell-to-Cell Communication System across Firmicutes▿ †

PubMed Central

Wuster, Arthur; Babu, M. Madan

2008-01-01

We present evidence that the agr cell-to-cell communication system is present across firmicutes, including the human pathogen Clostridium perfringens. Although we find that the agr system is evolutionarily conserved and that the general functions which it regulates are similar in different species, the individual regulated genes are not the same. This suggests that the regulatory network controlled by agr is dynamic and evolves rapidly. PMID:17933897

The Agr communication system provides a benefit to the populations of Listeria monocytogenes in soil

PubMed Central

Vivant, Anne-Laure; Garmyn, Dominique; Gal, Laurent; Piveteau, Pascal

2014-01-01

In this study, we investigated whether the Agr communication system of the pathogenic bacterium Listeria monocytogenes was involved in adaptation and competitiveness in soil. Alteration of the ability to communicate, either by deletion of the gene coding the response regulator AgrA (response-negative mutant) or the signal pro-peptide AgrD (signal-negative mutant), did not affect population dynamics in soil that had been sterilized but survival was altered in biotic soil suggesting that the Agr system of L. monocytogenes was involved to face the complex soil biotic environment. This was confirmed by a set of co-incubation experiments. The fitness of the response-negative mutant was lower either in the presence or absence of the parental strain but the fitness of the signal-negative mutant depended on the strain with which it was co-incubated. The survival of the signal-negative mutant was higher when co-cultured with the parental strain than when co-cultured with the response-negative mutant. These results showed that the ability to respond to Agr communication provided a benefit to listerial cells to compete. These results might also indicate that in soil, the Agr system controls private goods rather than public goods. PMID:25414837

SiC layer microstructure in AGR-1 and AGR-2 TRISO fuel particles and the influence of its variation on the effective diffusion of key fission products

DOE PAGES

Gerczak, Tyler J.; Hunn, John D.; Lowden, Richard A.; ...

2016-08-15

Tristructural isotropic (TRISO) coated particle fuel is a promising fuel form for advanced reactor concepts such as high temperature gas-cooled reactors (HTGR) and is being developed domestically under the US Department of Energy’s Nuclear Reactor Technologies Initiative in support of Advanced Reactor Technologies. The fuel development and qualification plan includes a series of fuel irradiations to demonstrate fuel performance from the laboratory to commercial scale. The first irradiation campaign, AGR-1, included four separate TRISO fuel variants composed of multiple, laboratory-scale coater batches. The second irradiation campaign, AGR-2, included TRISO fuel particles fabricated by BWX Technologies with a larger coater representativemore » of an industrial-scale system. The SiC layers of as-fabricated particles from the AGR-1 and AGR-2 irradiation campaigns have been investigated by electron backscatter diffraction (EBSD) to provide key information about the microstructural features relevant to fuel performance. The results of a comprehensive study of multiple particles from all constituent batches are reported. The observations indicate that there were microstructural differences between variants and among constituent batches in a single variant. Finally, insights on the influence of microstructure on the effective diffusivity of key fission products in the SiC layer are also discussed.« less

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

USDA-ARS?s Scientific Manuscript database

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...

Crystal structure of the Yersinia type III secretion protein YscE

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry.

PubMed

Yu, Qiang; Lepp, Dion; Mehdizadeh Gohari, Iman; Wu, Tao; Zhou, Hongzhuan; Yin, Xianhua; Yu, Hai; Prescott, John F; Nie, Shao-Ping; Xie, Ming-Yong; Gong, Joshua

2017-06-01

Clostridium perfringens encodes at least two different quorum sensing (QS) systems, the Agr-like and LuxS, and recent studies have highlighted their importance in the regulation of toxin production and virulence. The role of QS in the pathogenesis of necrotic enteritis (NE) in poultry and the regulation of NetB, the key toxin involved, has not yet been investigated. We have generated isogenic agrB -null and complemented strains from parent strain CP1 and demonstrated that the virulence of the agrB -null mutant was strongly attenuated in a chicken NE model system and restored by complementation. The production of NetB, a key NE-associated toxin, was dramatically reduced in the agrB mutant at both the transcriptional and protein levels, though not in a luxS mutant. Transwell assays confirmed that the Agr-like QS system controls NetB production through a diffusible signal. Global gene expression analysis of the agrB mutant identified additional genes modulated by Agr-like QS, including operons related to phospholipid metabolism and adherence, which may also play a role in NE pathogenesis. This study provides the first evidence that the Agr-like QS system is critical for NE pathogenesis and identifies a number of Agr-regulated genes, most notably netB , that are potentially involved in mediating its effects. The Agr-like QS system thus may serve as a target for developing novel interventions to prevent NE in chickens. © Crown copyright 2017.

High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene in a semi-extensive red deer (Cervus elaphus hispanicus) farm in Southern Spain.

PubMed

Gómez, Paula; Lozano, Carmen; González-Barrio, David; Zarazaga, Myriam; Ruiz-Fons, Francisco; Torres, Carmen

2015-06-12

The objective was to determine the prevalence of Staphylococcus aureus nasal carriage in red deer of a semi-extensive farm and in humans in contact with the estate animals, and to characterize obtained isolates. Nasal swabs of 65 deer and 15 humans were seeded on mannitol-salt-agar and oxacillin-resistance-screening-agar-base. Isolates were identified by microbiological and molecular methods. Antimicrobial susceptibility profile was determined for 16 antibiotics by disk-diffusion and the presence of eight antibiotic resistance genes, seven virulence genes and genes of immune-evasion-cluster (IEC) was analyzed by PCR. S. aureus was typed by PFGE-SmaI, spa, agr, SCCmec and MLST. Isolates were detected in 16 deer (24.6%). Eleven S. aureus isolates were methicillin-resistant (MRSA), and five were methicillin-susceptible (MSSA). All MRSA harbored mecC gene and were agr-III/SCCmecXI/ST1945 (four spa-t843 and seven spa-t1535). All mecC-MRSA carried blaZ-SCCmecXI and etd2, were IEC-type-E, and belonged to the same PFGE pattern. The five MSSA were typed as spa-t2420/agr-I/ST133. Regarding humans, S. aureus was recovered from six samples (40%). The isolates were MSSA and were typed as spa-t002/agr-II, spa-t012/agr-III or spa-t822/agr-III and showed different IEC types (A, B, D and F). blaZ and erm(A) genes were detected, as well as cna and tst genes. As conclusion, red deer analyzed in this study are frequent carriers of mecC-MRSA CC130 (16.9%), they are characterized by few resistance and virulence determinants, and by the presence of IEC type-E. Deer could be a source of mecC-MRSA which could potentially be transmitted to other animals, or even to humans. Copyright © 2015 Elsevier B.V. All rights reserved.

[Sublethal microcephalic chondrodysplasia. Taybi-Linder syndrome, primordial microcephalic nanism types I and III].

PubMed

Maroteaux, P; Badoual, J

1990-02-01

The authors describe a case of microcephalic dwarfism observed in a newborn until 10 months of age and discuss the diagnostic challenge. They show that the Taybi-Linder syndrome and the primordial dwarfism type I and type III of Majewski are an identical recessive autosomal entity. The radiological evolution explains the initial separation of type I and type III. Because of the skeletal lesions, lacking in the Seckel syndrome, the name of sublethal microcephalic chondrodysplasia is proposed for this disease.

AGR-2 Irradiation Test Final As-Run Report, Rev 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collin, Blaise P.

2014-08-01

This document presents the as-run analysis of the AGR-2 irradiation experiment. AGR-2 is the second of the planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the U.S. Department of Energy as part of the Very High Temperature Reactor (VHTR) Technical Development Office (TDO) program. The objectives of the AGR-2 experiment are to: (a) Irradiate UCO (uranium oxycarbide) and UO 2 (uranium dioxide) fuel produced in a large coater. Fuel attributes are based on results obtained from the AGR-1 test and other project activities. (b) Provide irradiated fuel samplesmore » for post-irradiation experiment (PIE) and safety testing. (c) Support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. The primary objective of the test was to irradiate both UCO and UO 2 TRISO (tri-structural isotropic) fuel produced from prototypic scale equipment to obtain normal operation and accident condition fuel performance data. The UCO compacts were subjected to a range of burnups and temperatures typical of anticipated prismatic reactor service conditions in three capsules. The test train also includes compacts containing UO 2 particles produced independently by the United States, South Africa, and France in three separate capsules. The range of burnups and temperatures in these capsules were typical of anticipated pebble bed reactor service conditions. The results discussed in this report pertain only to U.S. produced fuel. In order to achieve the test objectives, the AGR-2 experiment was irradiated in the B-12 position of the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for a total irradiation duration of 559.2 effective full power days (EFPD). Irradiation began on June 22, 2010, and ended on October 16, 2013, spanning 12 ATR power cycles and approximately three and a half calendar years. The

Estándar para la Protección del Trabajador Agrícola Revisado

EPA Pesticide Factsheets

Estas revisiones al Estándar de Protección a los Trabajadores Agrícolas, promulgado en 1992, proporcionarán protecciones de salud a los trabajadores agrícolas similares a las que ya disponen trabajadores en otras industrias.

The C. elegans PRMT-3 possesses a type III protein arginine methyltransferase activity.

PubMed

Takahashi, Yuta; Daitoku, Hiroaki; Yokoyama, Atsuko; Nakayama, Kimihiro; Kim, Jun-Dal; Fukamizu, Akiyoshi

2011-04-01

Protein arginine methylation is a common post-translational modification in eukaryotes that is catalyzed by a family of the protein arginine methyltransferases (PRMTs). PRMTs are classified into three types: type I and type II add asymmetrically and symmetrically dimethyl groups to arginine, respectively, while type III adds solely monomethyl group to arginine. However, although the enzymatic activity of type I and type II PRMTs have been reported, the substrate specificity and the methylation activity of type III PRMTs still remains unknown. Here, we report the characterization of Caenorhabditis elegans PRMT-2 and PRMT-3, both of which are highly homologous to human PRMT7. We find that these two PRMTs can bind to S-adenosyl methionine (SAM), but only PRMT-3 has methyltransferase activity for histone H2A depending on its SAM-binding domain. Importantly, thin-layer chromatographic analysis demonstrates that PRMT-3 catalyzes the formation of monomethylated, but not dimethylated arginine. Our study thus identifies the first type III PRMT in C. elegans and provides a means to elucidate the physiological significance of arginine monomethylation in multicellular organisms.

Quantity of 135I released from the AGR-1, AGR-2, and AGR-3/4 experiments and discovery of 131I at the FPMS traps during the AGR-3/4 experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scates, Dawn M.

2014-09-01

A series of three Advanced Gas Reactor (AGR) experiments have been conducted in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL). From 2006 through 2014, these experiments supported the development and qualification of the new U.S. tristructural isotropic (TRISO) particle fuel for Very High Temperature Reactors (VHTR). Each AGR experiment consisted of multiple fueled capsules, each plumbed for independent temperature control using a mix of helium and neon gases. The gas leaving a capsule was routed to individual Fission Product Monitor (FPM) detectors. For intact fuel particles, the TRISO particle coatings provide a substantial barrier to fission productmore » release. However, particles with failed coatings, whether because of a minute percentage of initially defective particles, those which fail during irradiation, or those designed to fail (DTF) particles, can release fission products to the flowing gas stream. Because reactive fission product elements like iodine and cesium quickly deposit on cooler capsule components and piping structures as the effluent gas leaves the reactor core, only the noble fission gas isotopes of Kr and Xe tend to reach FPM detectors. The FPM system utilizes High Purity Germanium (HPGe) detectors coupled with a thallium activated sodium iodide NaI(Tl) scintillator. The HPGe detector provides individual isotopic information, while the NaI(Tl) scintillator is used as a gross count rate meter. During irradiation, the 135mXe concentration reaching the FPM detectors is from both direct fission and by decay of the accumulated 135I. About 2.5 hours after irradiation (ten 15.3 minute 135mXe half lives) the directly produced 135mXe has decayed and only the longer lived 135I remains as a source. Decay systematics dictate that 135mXe will be in secular equilibrium with its 135I parent, such that its production rate very nearly equals the decay rate of the parent, and its concentration in the flowing gas stream will appear to

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

ERIC Educational Resources Information Center

Mendes, Mehmet

2007-01-01

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

Aircraft evacuations through type-III exits I : effects of seat placement at the exit.

DOT National Transportation Integrated Search

1995-07-01

Simulated emergency egress from Type III over-wing exits was studied to support regulatory action by the FAA. Passageway width and seat encroachment distance adjacent to the Type-III exit were the major variables of interest. : Methods. Two subject g...

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

PubMed Central

Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

2008-01-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

PubMed

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-05-05

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

PubMed

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-06-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

[Cannulated lag screw combined with lateral supporting plate for treatment of Hoffa fracture of Letenneur type I and type III].

PubMed

Lin, Tao; Yang, Shuhua; Xiao, Baojun; Fu, Dehao

2013-09-01

To investigate the effectiveness of cannulated lag screws combined with lateral supporting plates in the treatment of Hoffa fracture of Letenneur type I and type III. Between May 2004 and April 2011, 11 patients with Hoffa fracture of Letenneur type I and type III were treated, including 6 males and 5 females with an average age of 36 years (range, 25-47 years). Factures were caused by traffic accident in 8 cases, by falling in 2 cases, and by the other in 1 case. Fracture involved the left knee in 7 patients and the right knee in 4 patients. According Letenneur's classification criteria, there were 7 type I fractures (6 lateral condyle fractures and 1 medial condyle fracture) and 4 type III fractures (3 lateral condyle fractures and 1 medial condyle fracture). Of 11 fractures, 9 were fresh fractures and 2 were old fractures. Two 6.5 mm cannulated lag screws combined with lateral supporting plates were used to fix fractures by anterolateral or anteromedial incision. All incisions achieved primary healing with no early complication. All patients were followed up 12-26 months (mean, 15 months). X-ray films showed bone healing with an average healing time of 15 weeks (range, 10-18 weeks). No loosening or breaking of internal fixator was observed; the removal time of internal fixation was 9-15 months (mean, 12 months). Accoding to Letenneur's functional assessment system, the results were excellent in 7 cases, good in 3 cases, and poor in 1 case at last follow-up. Cannulated lag screws combined with lateral supporting plates fixation is effective in treatment of Hoffa fracture of Letenneur type I and type III with a high union rate; anterolateral or anteromedial approach is the first choice for Hoffa fracture of type I and type III, especially for complicating by tibial plateau fracture or patella fracture.

Transposon mutagenesis of type III group B Streptococcus: correlation of capsule expression with virulence.

PubMed

Rubens, C E; Wessels, M R; Heggen, L M; Kasper, D L

1987-10-01

The capsular polysaccharide of type III group B Streptococcus (GBS) is thought to be a major factor in the virulence of this organism. Transposon mutagenesis was used to obtain isogenic strains of a GBS serotype III clinical isolate (COH 31r/s) with site-specific mutations in the gene(s) responsible for capsule production. The self-conjugative transposon Tn916 was transferred to strain COH 31r/s during incubation with Streptococcus faecalis strain CG110 on membrane filters. Eleven transconjugant clones did not bind type III GBS antiserum by immunoblot. Immunofluorescence, competitive ELISA, and electron microscopy confirmed the absence of detectable GBS type III capsular polysaccharide in one of the transconjugants, COH 31-15. Southern hybridization analysis with a Tn916 probe confirmed the presence of the transposon sequence within each mutant. A 3.0-kilobase EcoRI fragment that flanked the Tn916 sequence was subcloned from mutant COH 31-15. This fragment shared homology with DNA from the other GBS serotypes, suggesting a common sequence for capsulation shared by organisms of different capsular types. Loss of capsule expression resulted in loss of virulence in a neonatal rat model. We conclude that a gene common to all capsular types of GBS is required for surface expression of the type III capsule and that inactivation of this gene by Tn916 results in the loss of virulence.

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

PubMed

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

2017-04-01

Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively. © 2016 British Society for Immunology.

Methods for enhancing P-type doping in III-V semiconductor films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Feng; Stringfellow, Gerald; Zhu, Junyi

2017-08-01

Methods of doping a semiconductor film are provided. The methods comprise epitaxially growing the III-V semiconductor film in the presence of a dopant, a surfactant capable of acting as an electron reservoir, and hydrogen, under conditions that promote the formation of a III-V semiconductor film doped with the p-type dopant. In some embodiments of the methods, the epitaxial growth of the doped III-V semiconductor film is initiated at a first hydrogen partial pressure which is increased to a second hydrogen partial pressure during the epitaxial growth process.

AGR-1 Post Irradiation Examination Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demkowicz, Paul Andrew

The post-irradiation examination (PIE) of the Advanced Gas Reactor (AGR)-1 experiment was a multi-year, collaborative effort between Idaho National Laboratory (INL) and Oak Ridge National Laboratory (ORNL) to study the performance of UCO (uranium carbide, uranium oxide) tristructural isotropic (TRISO) coated particle fuel fabricated in the U.S. and irradiated at the Advanced Test Reactor at INL to a peak burnup of 19.6% fissions per initial metal atom. This work involved a broad array of experiments and analyses to evaluate the level of fission product retention by the fuel particles and compacts (both during irradiation and during post-irradiation heating tests tomore » simulate reactor accident conditions), investigate the kernel and coating layer morphology evolution and the causes of coating failure, and explore the migration of fission products through the coating layers. The results have generally confirmed the excellent performance of the AGR-1 fuel, first indicated during the irradiation by the observation of zero TRISO coated particle failures out of 298,000 particles in the experiment. Overall release of fission products was determined by PIE to have been relatively low during the irradiation. A significant finding was the extremely low levels of cesium released through intact coatings. This was true both during the irradiation and during post-irradiation heating tests to temperatures as high as 1800°C. Post-irradiation safety test fuel performance was generally excellent. Silver release from the particles and compacts during irradiation was often very high. Extensive microanalysis of fuel particles was performed after irradiation and after high-temperature safety testing. The results of particle microanalysis indicate that the UCO fuel is effective at controlling the oxygen partial pressure within the particle and limiting kernel migration. Post-irradiation examination has provided the final body of data that speaks to the quality of the AGR-1 fuel

Interplanetary Type III Bursts and Electron Density Fluctuations in the Solar Wind

NASA Astrophysics Data System (ADS)

Krupar, V.; Maksimovic, M.; Kontar, E. P.; Zaslavsky, A.; Santolik, O.; Soucek, J.; Kruparova, O.; Eastwood, J. P.; Szabo, A.

2018-04-01

Type III bursts are generated by fast electron beams originated from magnetic reconnection sites of solar flares. As propagation of radio waves in the interplanetary medium is strongly affected by random electron density fluctuations, type III bursts provide us with a unique diagnostic tool for solar wind remote plasma measurements. Here, we performed a statistical survey of 152 simple and isolated type III bursts observed by the twin-spacecraft Solar TErrestrial RElations Observatory mission. We investigated their time–frequency profiles in order to retrieve decay times as a function of frequency. Next, we performed Monte Carlo simulations to study the role of scattering due to random electron density fluctuations on time–frequency profiles of radio emissions generated in the interplanetary medium. For simplification, we assumed the presence of isotropic electron density fluctuations described by a power law with the Kolmogorov spectral index. Decay times obtained from observations and simulations were compared. We found that the characteristic exponential decay profile of type III bursts can be explained by the scattering of the fundamental component between the source and the observer despite restrictive assumptions included in the Monte Carlo simulation algorithm. Our results suggest that relative electron density fluctuations < δ {n}{{e}}> /{n}{{e}} in the solar wind are 0.06–0.07 over wide range of heliospheric distances.

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

PubMed

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

2013-01-18

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.

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

PubMed Central

2013-01-01

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

Hierarchical protein export mechanism of the bacterial flagellar type III protein export apparatus.

PubMed

Minamino, Tohru

2018-06-01

The bacterial flagellum is supramolecular motility machinery consisting of the basal body, the hook and the filament. Flagellar proteins are translocated across the cytoplasmic membrane via a type III protein export apparatus, diffuse down the central channel of the growing structure and assemble at the distal end. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. The completion of hook assembly is the most important morphological checkpoint of the sequential flagellar assembly process. When the hook reaches its mature length of about 55 nm in Salmonella enterica, the type III protein export apparatus switches export specificity from proteins required for the structure and assembly of the hook to those responsible for filament assembly, thereby terminating hook assembly and initiating filament assembly. Three flagellar proteins, namely FliK, FlhB and FlhA, are responsible for this substrate specificity switching. Upon completion of the switching event, interactions among FlhA, the cytoplasmic ATPase complex and flagellar type III export chaperones establish the assembly order of the filament at the hook tip. Here, we describe our current understanding of a hierarchical protein export mechanism used in flagellar type III protein export.

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.

Listeria monocytogenes differential transcriptome analysis reveals temperature-dependent Agr regulation and suggests overlaps with other regulons.

PubMed

Garmyn, Dominique; Augagneur, Yoann; Gal, Laurent; Vivant, Anne-Laure; Piveteau, Pascal

2012-01-01

Listeria monocytogenes is a ubiquitous, opportunistic pathogenic organism. Environmental adaptation requires constant regulation of gene expression. Among transcriptional regulators, AgrA is part of an auto-induction system. Temperature is an environmental cue critical for in vivo adaptation. In order to investigate how temperature may affect AgrA-dependent transcription, we compared the transcriptomes of the parental strain L. monocytogenes EGD-e and its ΔagrA mutant at the saprophytic temperature of 25°C and in vivo temperature of 37°C. Variations of transcriptome were higher at 37°C than at 25°C. Results suggested that AgrA may be involved in the regulation of nitrogen transport, amino acids, purine and pyrimidine biosynthetic pathways and phage-related functions. Deregulations resulted in a growth advantage at 37°C, but affected salt tolerance. Finally, our results suggest overlaps with PrfA, σB, σH and CodY regulons. These overlaps may suggest that through AgrA, Listeria monocytogenes integrates information on its biotic environment.

Listeria monocytogenes Differential Transcriptome Analysis Reveals Temperature-Dependent Agr Regulation and Suggests Overlaps with Other Regulons

PubMed Central

Garmyn, Dominique; Augagneur, Yoann; Gal, Laurent; Vivant, Anne-Laure; Piveteau, Pascal

2012-01-01

Listeria monocytogenes is a ubiquitous, opportunistic pathogenic organism. Environmental adaptation requires constant regulation of gene expression. Among transcriptional regulators, AgrA is part of an auto-induction system. Temperature is an environmental cue critical for in vivo adaptation. In order to investigate how temperature may affect AgrA-dependent transcription, we compared the transcriptomes of the parental strain L. monocytogenes EGD-e and its ΔagrA mutant at the saprophytic temperature of 25°C and in vivo temperature of 37°C. Variations of transcriptome were higher at 37°C than at 25°C. Results suggested that AgrA may be involved in the regulation of nitrogen transport, amino acids, purine and pyrimidine biosynthetic pathways and phage-related functions. Deregulations resulted in a growth advantage at 37°C, but affected salt tolerance. Finally, our results suggest overlaps with PrfA, σB, σH and CodY regulons. These overlaps may suggest that through AgrA, Listeria monocytogenes integrates information on its biotic environment. PMID:23024744

Selective thoracic surgery in the Lenke type 1A: King III and King IV type curves.

PubMed

Parisini, P; Di Silvestre, M; Lolli, F; Bakaloudis, G

2009-06-01

Pedicle screw fixation enables enhanced three-dimensional correction of spinal deformities and effectively shortens the distal fusion level. However, the choice of distal fusion level is still controversial in single thoracic idiopathic scoliosis with the lumbar compensatory curve not crossing the middle line (Lenke type 1 with modifier A or King type III and IV curves).The authors retrospectively analyzed 31 patients treated by segmental pedicular instrumentation alone, affected by a single thoracic adolescent idiopathic scoliosis with a compensatory lumbar curve not crossing the midline (Lenke 1A), with an average age of 16.3 years (range 10-22 years). The patients with regard to the King classification were also assessed. A statistical analysis was performed to determine whether the two groups (King III, King IV) presented differences concerning the level of the stable vertebra (SV), end vertebra (EV), and neutral vertebra (NV) and were also analyzed the results at follow-up regarding the relationships between the SV, EV, and lowest instrumented vertebra (LIV). The statistical analysis showed a significant difference between the two curve types. In the King III type curve the SV, EV, and NV appeared to be more proximal than those of the King IV type curve and the segments between the SV, EV, and NV appeared to be reduced in King III curves compared with King IV curves. At a follow-up of 3.2 years (range 2.2-5) the thoracic curve showed a correction of 58.4% (from 62.3 degrees to 26.6 degrees ) and compensatory lumbar curve an average spontaneous correction of 52.4% (from 38.1 degrees to 18.1 degrees ).The position of the LIV was shorter than the position of the SV in 30 patients (97%) with an average "salvage" of 2.1 (from 1 to 4) distal fusion levels. Four cases (13%), all affected by a King IV type curve, presented at follow-up an unsatisfactory results due to an "adding on" phenomenon. The statistical analysis confirmed that this phenomenon was correlated

AGR-3/4 Final Data Qualification Report for ATR Cycles 151A through 155B-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, Binh T.

2015-03-01

This report provides the qualification status of experimental data for the entire Advanced Gas Reactor 3/4 (AGR 3/4) fuel irradiation. AGR-3/4 is the third in a series of planned irradiation experiments conducted in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for the AGR Fuel Development and Qualification Program, which supports development of the advanced reactor technology under the INL ART Technology Development Office (TDO). The main objective of AGR-3/4 irradiation is to provide a known source of fission products for subsequent transport through compact matrix and structural graphite materials due to the presence of designed-to-fail fuel particles.more » Full power irradiation of the AGR 3/4 test began on December 14, 2011 (ATR Cycle 151A), and was completed on April 12, 2014 (end of ATR Cycle 155B) after 369.1 effective full power days of irradiation. The AGR-3/4 test was in the reactor core for eight of the ten ATR cycles between 151A and 155B. During the unplanned outage cycle, 153A, the experiment was removed from the ATR northeast flux trap (NEFT) location and stored in the ATR canal. This was to prevent overheating of fuel compacts due to higher than normal ATR power during the subsequent Powered Axial Locator Mechanism cycle, 153B. The AGR 3/4 test was inserted back into the ATR NEFT location during the outage of ATR Cycle 154A on April 26, 2013. Therefore, the AGR-3/4 irradiation data received during these 2 cycles (153A and 153B) are irrelevant and their qualification status isnot included in this report. Additionally, during ATR Cycle 152A the ATR core ran at low power for a short enough duration that the irradiation data are not used for physics and thermal calculations. However, the qualification status of irradiation data for this cycle is still covered in this report. As a result, this report includes data from 8 ATR Cycles: 151A, 151B, 152A, 152B, 154A, 154B, 155A, and 155B, as recorded in the Nuclear Data Management and

Infection Reduces Return-to-duty Rates for Soldiers with Type III Open Tibia Fractures

DTIC Science & Technology

2014-09-01

Infection reduces return-to-duty rates for soldiers with Type III open tibia fractures Matthew A. Napierala, MD, Jessica C. Rivera, MD, Travis C... Type III open tibia fracture and tabulated the prevalence of infectious complications.We searched the Physical Evaluation Board database to determine...were not infected ( p 0.1407). Soldiers who experienced any type of infectious complication ( p 0.0470) and having osteomyelitis ( p 0.0335) had a lower

Ultrastructural sinusoidal changes in extrahepatic cholestasis. Light and electron microscopic immunohistochemical localization of collagen type III and type IV.

PubMed

Gulubova, M V

1996-07-01

Extrahepatic cholestasis causes excessive extracellular matrix formation perisinusoidally. Ito cells, transitional and endothelial cells are considered to be a source of extracellular matrix proteins in experimental cholestasis. The localization of collagens type III and type IV in human liver in extrahepatic cholestasis was investigated immunohistochemically in the present study. Immersion fixation was used after modification to be applied to surgical biopsies with commercially available kits. Sinusoidal changes were observed that indicated excessive collagen and matrix formation. Light microscopically, increased immunostaining with the two collagen antibodies was found perisinusoidally and portally. Ultrastructurally, collagen type III positive fibres were found beneath basement membranes of vessels, in collagen bundles and as a fibrillar network in the space of Disse. Collagen type IV immunostaining was located in portal tracts and near hepatocyte microvilli. Intracellular staining with collagen type IV was detected in the rough endoplasmic reticulum of some transitional cells. Immunostaining was located around transitional cells, Ito cells or endothelial cells mainly. Our study indicates that Ito cells, transitional and endothelial cells are the main source of collagens type III and IV in the space of Disse in extrahepatic cholestasis in humans.

Emission Patterns of Solar Type III Radio Bursts: Stereoscopic Observations

NASA Technical Reports Server (NTRS)

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

2012-01-01

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 Rj = Ij /[Sigma]Ij (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 approximately 2 deg and (2) bursts emitting into a wider cone with angular width spanning from [approx] -100 deg to approximately 100 deg. 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.

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

PubMed Central

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

2017-01-01

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

Kernel based machine learning algorithm for the efficient prediction of type III polyketide synthase family of proteins.

PubMed

Mallika, V; Sivakumar, K C; Jaichand, S; Soniya, E V

2010-07-13

Type III Polyketide synthases (PKS) are family of proteins considered to have significant roles in the biosynthesis of various polyketides in plants, fungi and bacteria. As these proteins shows positive effects to human health, more researches are going on regarding this particular protein. Developing a tool to identify the probability of sequence being a type III polyketide synthase will minimize the time consumption and manpower efforts. In this approach, we have designed and implemented PKSIIIpred, a high performance prediction server for type III PKS where the classifier is Support Vector Machines (SVMs). Based on the limited training dataset, the tool efficiently predicts the type III PKS superfamily of proteins with high sensitivity and specificity. The PKSIIIpred is available at http://type3pks.in/prediction/. We expect that this tool may serve as a useful resource for type III PKS researchers. Currently work is being progressed for further betterment of prediction accuracy by including more sequence features in the training dataset.

Type III Neuregulin-1 is required for normal sensorimotor gating, memory related behaviors and cortico-striatal circuit components

PubMed Central

Chen, Ying-Jiun J.; Johnson, Madeleine A.; Lieberman, Michael D.; Goodchild, Rose E.; Schobel, Scott; Lewandowski, Nicole; Rosoklija, Gorazd; Liu, Ruei-Che; Gingrich, Jay A.; Small, Scott; Moore, Holly; Dwork, Andrew J.; Talmage, David A.; Role, Lorna W.

2008-01-01

Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of Nrg1 signaling to adult brain structure and behaviors, we have studied the regulation of Type III Nrg1 expression and evaluated the effect of decreased expression of the Type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus and ventral subiculum, regions involved in the regulation of sensorimotor gating and short term memory. Adult heterozygous mutant mice with a targeted disruption for Type III Nrg1 (Nrg1tm1.1Lwr+/-) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. MRI imaging of Type III Nrg1 heterozygous mice revealed hypo-function in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between Type III Nrg1 heterozygous mice and their wild type littermates. Our findings demonstrate a role of Type III Nrg1-signaling in the maintenance of cortico-striatal components, and in the neural circuits involved in sensorimotor gating and short term memory. PMID:18596162

Hepatitis E virus persists in the presence of a type III interferon response.

PubMed

Yin, Xin; Li, Xinlei; Ambardekar, Charuta; Hu, Zhimin; Lhomme, Sébastien; Feng, Zongdi

2017-05-01

The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes. HEV infection resulted in persistent virus replication despite poor spread. This was companied by a type III IFN response that upregulated multiple IFN-stimulated genes (ISGs), but type I IFNs were barely detected. Blocking type III IFN production or signaling resulted in reduced ISG expression and enhanced HEV replication. Unlike HAV and HCV, HEV did not cleave MAVS; MAVS protein size, mitochondrial localization, and function remained unaltered in HEV-replicating cells. Depletion of MAVS or MDA5, and to a less extent RIG-I, also diminished IFN production and increased HEV replication. Furthermore, persistent activation of the JAK/STAT signaling rendered infected cells refractory to exogenous IFN treatment, and depletion of MAVS or the receptor for type III IFNs restored the IFN responsiveness. Collectively, these results indicate that unlike other hepatotropic RNA viruses, HEV does not target MAVS and its persistence is associated with continuous production of type III IFNs.

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.

Closed reduction of a rare type III dislocation of the first metatarsophalangeal joint.

PubMed

Tondera, E K; Baker, C C

1996-09-01

To discuss a rare Type III dislocation of the first metatarsophalangeal (MP) joint, without fracture, that used a closed reduction technique for correction. A 43-yr-old man suffered from an acute severe dislocation of his great toe as the result of acute forceful motion applied to the toe as his foot was depressed onto a brake pedal to avoid a motor vehicle accident. Physical examination and X-rays revealed the dislocation, muscle spasm, edema and severely restricted range of motion. The dislocation was corrected using a closed reduction technique, in this case a chiropractic manipulation. Fourteen months after reduction, the joint was intact, muscle strength was graded +5 normal, ranges of motion were within normal limits and no crepitation was noted. X-rays revealed normal intact joint congruency. The patient experienced full weight bearing, range of motion and function of the joint. Although a Type III dislocation of the great toe has only once been cited briefly in the literature, this classification carries a recommended surgical treatment protocol for correction. No literature describes a closed reduction of a Type III dislocation as described in this case report. It is apparent that a closed reduction technique using a chiropractic manipulation may be considered a valid alternative correction technique for Type III dislocations of the great toe.

Readiness Review of BWXT for Fabrication of AGR 5/6/7 Compacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Douglas William; Sharp, Michelle Tracy

In support of preparations for fabricating compacts for the Advanced Gas Reactor (AGR) fuel qualification irradiation experiments (AGR-5/6/7), Idaho National Laboratory (INL) conducted a readiness review of the BWX Technology (BWXT) procedures, processes, and equipment associated with compact fabrication activities at the BWXT Nuclear Operations Group (BWXT-NOG) facility outside Lynchburg, VirginiaVA. The readiness review used quality assurance requirements taken from the American Society of Mechanical Engineers (ASME) Nuclear Quality Assurance Standard (NQA-1-2008/1a-2009) as a basis to assess readiness to start compact fabrication.

A Novel Type III Endosome Transmembrane Protein, TEMP

PubMed Central

Aturaliya, Rajith N.; Kerr, Markus C.; Teasdale, Rohan D.

2012-01-01

As part of a high-throughput subcellular localisation project, the protein encoded by the RIKEN mouse cDNA 2610528J11 was expressed and identified to be associated with both endosomes and the plasma membrane. Based on this, we have assigned the name TEMP for Type III Endosome Membrane Protein. TEMP encodes a short protein of 111 amino acids with a single, alpha-helical transmembrane domain. Experimental analysis of its membrane topology demonstrated it is a Type III membrane protein with the amino-terminus in the lumenal, or extracellular region, and the carboxy-terminus in the cytoplasm. In addition to the plasma membrane TEMP was localized to Rab5 positive early endosomes, Rab5/Rab11 positive recycling endosomes but not Rab7 positive late endosomes. Video microscopy in living cells confirmed TEMP’s plasma membrane localization and identified the intracellular endosome compartments to be tubulovesicular. Overexpression of TEMP resulted in the early/recycling endosomes clustering at the cell periphery that was dependent on the presence of intact microtubules. The cellular function of TEMP cannot be inferred based on bioinformatics comparison, but its cellular distribution between early/recycling endosomes and the plasma membrane suggests a role in membrane transport. PMID:24710541

Inhibiting PSMα-induced neutrophil necroptosis protects mice with MRSA pneumonia by blocking the agr system.

PubMed

Zhou, Ying; Niu, Chao; Ma, Bo; Xue, Xiaoyan; Li, Zhi; Chen, Zhou; Li, Fen; Zhou, Shan; Luo, Xiaoxing; Hou, Zheng

2018-03-02

Given its high resistance, enhanced virulence, and high transmissibility, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia is highly associated with high morbidity and mortality. Anti-virulence therapy is a promising strategy that bypasses the evolutionary pressure on the bacterium to develop resistance. RNAIII-inhibiting peptide (RIP), as an accessory gene regulator (agr)-specific inhibitor, significantly restricts the virulence of S. aureus and protects infected mice from death by blocking the agr quorum sensing system. The protective effects of RIP on the neutropenic mice completely disappeared in a neutrophil-deleted mouse infection model, but not in the macrophage-deleted mice. This result confirmed that the in vivo antibacterial activity of RIP is highly associated with neutrophil function. Phenol-soluble modulins (PSMs), as major leukocyte lysis toxins of CA-MRSA, are directly regulated by the agr system. In this experiment, PSMα1, 2, and 3 significantly induced neutrophil necroptosis by activating mixed lineage kinase-like protein (MLKL) phosphorylation and increasing lactate dehydrogenase release. The S. aureus supernatants harvested from the agr or psmα mutant strains both decreased the phosphorylation level of MLKL and cell lysis. PSMα1-mediated neutrophil lysis was significantly inhibited by necrosulfonamide, necrostatin-1, TNFα antibody, and WRW4. These results showed PSMα1 induced necroptosis depends on formylpeptide receptor 2 (FPR2)-mediated autocrine TNFα. Moreover, the neutrophil necroptosis induced by S. aureus was significantly suppressed and pneumonia was effectively prevented by the blockage of agrA and psmα expression levels. These findings indicate that PSMα-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest that interfering with the agr quorum sensing signaling pathway is a potential therapeutic strategy.

Design and synthesis of type-III mimetics of ShK toxin

NASA Astrophysics Data System (ADS)

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

2002-04-01

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

The Sequence-specific Peptide-binding Activity of the Protein Sulfide Isomerase AGR2 Directs Its Stable Binding to the Oncogenic Receptor EpCAM.

PubMed

Mohtar, M Aiman; Hernychova, Lenka; O'Neill, J Robert; Lawrence, Melanie L; Murray, Euan; Vojtesek, Borek; Hupp, Ted R

2018-04-01

AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a specific peptide motif (TTIYY). A synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for AGR2 by measuring its activity against a mutant peptide library. Screening the human proteome for proteins harboring this motif revealed an enrichment in transmembrane proteins and we focused on validating EpCAM as a potential AGR2-interacting protein. AGR2 and EpCAM proteins formed a dose-dependent protein-protein interaction in vitro Proximity ligation assays demonstrated that endogenous AGR2 and EpCAM protein associate in cells. Introducing a single alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a stable binding site for AGR2 on EpCAM, adjacent to the TLIYY motif and surrounding EpCAM's detergent binding site. These data define a dominant site on AGR2 that mediates its specific peptide-binding function. EpCAM forms a model client protein for AGR2 to study how an ER-resident chaperone can dock specifically to a peptide motif and regulate the trafficking a protein destined for the secretory pathway. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Prediction of type III secretion signals in genomes of gram-negative bacteria.

PubMed

Löwer, Martin; Schneider, Gisbert

2009-06-15

Pathogenic bacteria infecting both animals as well as plants use various mechanisms to transport virulence factors across their cell membranes and channel these proteins into the infected host cell. The type III secretion system represents such a mechanism. Proteins transported via this pathway ("effector proteins") have to be distinguished from all other proteins that are not exported from the bacterial cell. Although a special targeting signal at the N-terminal end of effector proteins has been proposed in literature its exact characteristics remain unknown. In this study, we demonstrate that the signals encoded in the sequences of type III secretion system effectors can be consistently recognized and predicted by machine learning techniques. Known protein effectors were compiled from the literature and sequence databases, and served as training data for artificial neural networks and support vector machine classifiers. Common sequence features were most pronounced in the first 30 amino acids of the effector sequences. Classification accuracy yielded a cross-validated Matthews correlation of 0.63 and allowed for genome-wide prediction of potential type III secretion system effectors in 705 proteobacterial genomes (12% predicted candidates protein), their chromosomes (11%) and plasmids (13%), as well as 213 Firmicute genomes (7%). We present a signal prediction method together with comprehensive survey of potential type III secretion system effectors extracted from 918 published bacterial genomes. Our study demonstrates that the analyzed signal features are common across a wide range of species, and provides a substantial basis for the identification of exported pathogenic proteins as targets for future therapeutic intervention. The prediction software is publicly accessible from our web server (www.modlab.org).

Expression of adenylyl cyclase types III and VI in human hyperfunctioning thyroid nodules.

PubMed

Celano, M; Arturi, F; Presta, I; Bruno, R; Scarpelli, D; Calvagno, M G; Cristofaro, C; Bulotta, S; Giannasio, P; Sacco, R; Filetti, S; Russo, D

2003-05-30

Hyperfunctioning thyroid nodules are characterized by the presence of spontaneous somatic mutations responsible for constitutive activation of the cAMP pathway. However, alterations affecting other elements of the cAMP signaling system may counteract the effects of the mutations. In this study, the expression of the adenylyl cyclase (AC) types III and VI was investigated by Western blot in 18 hyperfunctioning thyroid nodules; in 12 samples, we also assessed the presence of TSH receptor (TSHR) or gsp mutations and levels of AC VI and III mRNA. We found that the expression of nodular AC VI (but not AC III) was significantly lower (85.1% of normal, P=0.014) than the expression of both adenylyl cycles types of perinodular tissue from the same patients. Slightly, but not significant differences were detected in nodules with or without mutations and AC protein levels generally showed correlation with the levels of the transcripts detected by RT-PCR. In addition, AC III and AC VI expression levels within a given nodule were characterized by a significant positive correlation. These findings indicate that a diminished expression of AC type VI may be part of the mechanisms occurring in the hyperfunctioning nodules, independently of the presence of TSHR or gsp mutations, which influence the resulting phenotype.

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.

Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions.

PubMed

Cairns, I H; Lobzin, V V; Donea, A; Tingay, S J; McCauley, P I; Oberoi, D; Duffin, R T; Reiner, M J; Hurley-Walker, N; Kudryavtseva, N A; Melrose, D B; Harding, J C; Bernardi, G; Bowman, J D; Cappallo, R J; Corey, B E; Deshpande, A; Emrich, D; Goeke, R; Hazelton, B J; Johnston-Hollitt, M; Kaplan, D L; Kasper, J C; Kratzenberg, E; Lonsdale, C J; Lynch, M J; McWhirter, S R; Mitchell, D A; Morales, M F; Morgan, E; Ord, S M; Prabu, T; Roshi, A; Shankar, N Udaya; Srivani, K S; Subrahmanyan, R; Wayth, R B; Waterson, M; Webster, R L; Whitney, A R; Williams, A; Williams, C L

2018-01-26

Type III solar radio bursts are the Sun's most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5-10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.

Escherichia coli type III secretion system 2: a new kind of T3SS?

PubMed

Zhou, Mingxu; Guo, Zhiyan; Duan, Qiangde; Hardwidge, Philip R; Zhu, Guoqiang

2014-03-19

Type III secretion systems (T3SSs) are employed by Gram-negative bacteria to deliver effector proteins into the cytoplasm of infected host cells. Enteropathogenic Escherichia coli use a T3SS to deliver effector proteins that result in the creation of the attaching and effacing lesions. The genome sequence of the Escherichia coli pathotype O157:H7 revealed the existence of a gene cluster encoding components of a second type III secretion system, the E. coli type III secretion system 2 (ETT2). Researchers have revealed that, although ETT2 may not be a functional secretion system in most (or all) strains, it still plays an important role in bacterial virulence. This article summarizes current knowledge regarding the E. coli ETT2, including its genetic characteristics, prevalence, function, association with virulence, and prospects for future work.

ELECTRON PROBE MICROANALYSIS OF IRRADIATED AND 1600°C SAFETY-TESTED AGR-1 TRISO FUEL PARTICLES WITH LOW AND HIGH RETAINED 110MAG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Karen E.; van Rooyen, Isabella J.

2016-11-01

AGR-1 fuel Compact 4-3-3 achieved 18.63% FIMA and was exposed subsequently to a safety test at 1600°C. Two particles, AGR1-433-003 and AGR1-433-007, with measured-to-calculated 110mAg inventories of <22% and 100%, respectively, were selected for comparative electron microprobe analysis to determine whether the distribution or abundance of fission products differed proximally and distally from the deformed kernel in AGR1-433-003, and how this compared to fission product distribution in AGR1-433-007. On the deformed side of AGR1-433-003, Xe, Cs, I, Eu, Sr, and Te concentrations in the kernel buffer interface near the protruded kernel were up to six times higher than on themore » opposite, non-deformed side. At the SiC-inner pyrolytic carbon (IPyC) interface proximal to the deformed kernel, Pd and Ag concentrations were 1.2 wt% and 0.04 wt% respectively, whereas on the SiC-IPyC interface distal from the kernel deformation those elements measured 0.4 and 0.01 wt%, respectively. Palladium and Ag concentrations at the SiC-IPyC interface of AGR1-433-007 were 2.05 and 0.05 wt.%, respectively. Rare earth element concentrations at the SiC-IPyC interface of AGR1-433-007 were a factor of ten higher than at the SiC-IPyC interfaces measured in particle AGR1-433-003. Palladium permeated the SiC layer of AGR1-433-007 and the non-deformed SiC layer of AGR1-433-003.« less

Surgical versus conservative management of Type III acromioclavicular dislocation: a systematic review.

PubMed

Longo, Umile Giuseppe; Ciuffreda, Mauro; Rizzello, Giacomo; Mannering, Nicholas; Maffulli, Nicola; Denaro, Vincenzo

2017-06-01

The management of Type III acromioclavicular (AC) dislocations is still controversial. We wished to compare the rate of recurrence and outcome scores of operative versus non-operative treatment of patients with Type III AC dislocations. A systematic review of the literature was performed by applying the PRISMA guidelines according to the PRISMA checklist and algorithm. A search in Medline, PubMed, Cochrane and CINAHL was performed using combinations of the following keywords: 'dislocation', 'Rockwood', 'type three', 'treatment', 'acromioclavicular' and 'joint'. Fourteen studies were included, evaluating 646 shoulders. The rate of recurrence in the surgical group was 14%. No statistical significant differences were found between conservative and surgical approaches in terms of postoperative osteoarthritis and persistence of pain, although persistence of pain seemed to occur less frequently in patients undergoing a surgical treatment. Persistence of pain seemed to occur less frequently in patients undergoing surgery. Persistence of pain seems to occur less frequently in patients treated surgically for a Type III AC dislocation. There is insufficient evidence to establish the effects of surgical versus conservative treatment on functional outcome of patients with AC dislocation. High-quality randomized controlled clinical trials are needed to establish whether there is a difference in functional outcome. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Late Presentation of a Type III Axis Fracture with Spondyloptosis

PubMed Central

Jayakumar, Prakash; Choi, David; Casey, Adrian

2008-01-01

A 58-year-old man presented with an undiagnosed Effendi type III classification fracture and spondyloptosis of the axis with remarkably normal neurology. We discuss his surgery 4 years since the initial injury, and the presentation, features and management of fractures of the axis. PMID:18430325

Pro-metastatic activity of AGR2 interrupts angiogenesis target bevacizumab efficiency via direct interaction with VEGFA and activation of NF-κB pathway.

PubMed

Jia, Mengqi; Guo, Yanxia; Zhu, Deyu; Zhang, Nianzhao; Li, Lin; Jiang, Jin; Dong, Yiwen; Xu, Qingqing; Zhang, Xiulei; Wang, Meijuan; Yu, Haina; Wang, Fang; Tian, Keli; Zhang, Jinsan; Young, Charles Y F; Lou, Hongxiang; Yuan, Huiqing

2018-05-01

Anterior gradient 2 (AGR2), an endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI), is associated with cancer development and malignant progression. Here, we show that high level of AGR2 promotes the aggressive phenotype of prostate cancer (PCa) mouse models developed by either patient-derived xenografts or surgical intra-prostate implantation of PCa cells, associated with enrichment of the blood vessel network in tumor tissues. Angiogenesis markers VEGFR2 and CD34, accompanied with the invasive marker Vimentin, were predominantly stained in metastatic liver tissues. Secreted AGR2 was defined to enhance VEGFR2 activity as evidenced by physical interaction of purified recombinant human AGR2 (rhAGR2) with rhVEGFA through the formation of a disulfide bond. Mutant or deleted thioredoxin motif in rhAGR2 was also unable to bind to rhVEGFA that led to the significant abolishment in the vessel formation, but partially affecting the aggressive process, implicating alternative mechanisms are required for AGR2-conferring metastasis. Cytosolic AGR2 contributed to cell metastasis ascribed to its stabilizing effect on p65 protein, which subsequently activated the NF-κB and facilitated epithelial to mesenchymal transition (EMT). Importantly, GSH and cabozantinib, but not bevacizumab, effectively blocked the pro-angiogenic effect of rhAGR2 in vitro and in vivo, providing evidence that secreted AGR2 acts as a predictive biomarker for selection of angiogenesis-targeting therapeutic drugs based on its levels in the circular system. Copyright © 2018 Elsevier B.V. All rights reserved.

Glycogen storage disease type III in Israel: presentation and long-term outcome.

PubMed

Hershkovitz, Eli; Forschner, Itay; Mandel, Hanna; Spiegel, Ronen; Lerman-Sagie, Tally; Anikster, Yair; Zeharia, A; Moses, Shimon

2014-03-01

Glycogen storage disease type III (GSD III) was found in the past with an unusual frequency among North African Jews in Israel. The aim of this study was to review the long-term clinical course of GSD III's patients in Israel. Relevant pediatric and adult clinical units of all Israeli hospitals were approached to report on their GSD III patients. 21 (14 M/7F) live patients were located. The average age of the patients was nearly twenty years. Eleven patients were older than 18 years of age. 76% of the patients were of Jewish North African origin, 14% of Jewish European origin, and 10% were Arab Muslims. The symptoms at presentation were fasting, hypoglycemia, hepatomegaly slight hypotonia in infancy and delayed growth. Although in most of the patients their signs and symptoms ameliorated after childhood, significant complications were observed in some 20% of the patients. Consequently, a life long follow up of GSD-III patients is required.

Solar type III radio burst time characteristics at LOFAR frequencies and the implications for electron beam transport

NASA Astrophysics Data System (ADS)

Reid, Hamish A. S.; Kontar, Eduard P.

2018-06-01

Context. Solar type III radio bursts contain a wealth of information about the dynamics of electron beams in the solar corona and the inner heliosphere; this information is currently unobtainable through other means. However, the motion of different regions of an electron beam (front, middle, and back) have never been systematically analysed before. Aims: We characterise the type III burst frequency-time evolution using the enhanced resolution of LOFAR (LOw Frequency ARray) in the frequency range 30-70 MHz and use this to probe electron beam dynamics. Methods: The rise, peak, and decay times with a 0.2 MHz spectral resolution were defined for a collection of 31 type III bursts. The frequency evolution was used to ascertain the apparent velocities of the front, middle, and back of the type III sources, and the trends were interpreted using theoretical and numerical treatments. Results: The type III time profile was better approximated by an asymmetric Gaussian profile and not an exponential, as was used previously. Rise and decay times increased with decreasing frequency and showed a strong correlation. Durations were shorter than previously observed. Drift rates from the rise times were faster than from the decay times, corresponding to inferred mean electron beam speeds for the front, middle, and back of 0.2, 0.17, 0.15 c, respectively. Faster beam speeds correlate with shorter type III durations. We also find that the type III frequency bandwidth decreases as frequency decreases. Conclusions: The different speeds naturally explain the elongation of an electron beam in space as it propagates through the heliosphere. The expansion rate is proportional to the mean speed of the exciter; faster beams expand faster. Beam speeds are attributed to varying ensembles of electron energies at the front, middle, and back of the beam.

Early prophylactic autogenous bone grafting in type III open tibial fractures.

PubMed

Kesemenli, Cumhur C; Kapukaya, Ahmet; Subaşi, Mehmet; Arslan, Huseyin; Necmioğlu, Serdar; Kayikçi, Cuma

2004-08-01

The authors report the results achieved in patients with type III open tibial fractures who underwent primary autogenous bone grafting at the time of debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8 years (range, 24-55) were treated between 1996 and 1999. Eight fractures were type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound debridement, external fixation and autogenous bone grafting with bone coverage were achieved. The mean follow-up period was 46 months (range, 34-55). The mean time to fixator removal was 21 weeks (range, 14-35), and the mean time to union was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in 2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of the patients experienced delayed union, and 1 (5%) developed infection. In tibial type III open fractures, skin coverage may be delayed, using the surrounding soft tissue to cover any exposed bone after thorough débridement and wound cleansing. Primary prophylactic bone grafting performed at the same time reduces the rate of delayed union, shortens the time to union, and does not increase the infection rate.

Fine Structures of Solar Radio Type III Bursts and Their Possible Relationship with Coronal Density Turbulence

NASA Astrophysics Data System (ADS)

Chen, Xingyao; Kontar, Eduard P.; Yu, Sijie; Yan, Yihua; Huang, Jing; Tan, Baolin

2018-03-01

Solar radio type III bursts are believed to be the most sensitive signatures of near-relativistic electron beam propagation in the corona. A solar radio type IIIb-III pair burst with fine frequency structures, observed by the Low Frequency Array (LOFAR) with high temporal (∼10 ms) and spectral (12.5 kHz) resolutions at 30–80 MHz, is presented. The observations show that the type III burst consists of many striae, which have a frequency scale of about 0.1 MHz in both the fundamental (plasma) and the harmonic (double plasma) emission. We investigate the effects of background density fluctuations based on the observation of striae structure to estimate the density perturbation in the solar corona. It is found that the spectral index of the density fluctuation spectrum is about ‑1.7, and the characteristic spatial scale of the density perturbation is around 700 km. This spectral index is very close to a Kolmogorov turbulence spectral index of ‑5/3, consistent with a turbulent cascade. This fact indicates that the coronal turbulence may play the important role of modulating the time structures of solar radio type III bursts, and the fine structure of radio type III bursts could provide a useful and unique tool to diagnose the turbulence in the solar corona.

Cambios al Estándar de Protección a los Trabajadores Agrícolas de la EPA

EPA Pesticide Factsheets

Estos cambios proporcionarán protecciones de salud a los trabajadores agrícolas similares a las que ya disponen trabajadores en otras industrias, teniendo en cuenta el entorno laboral único de muchos trabajos agrícolas.

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

Impact of Type III Secretion Effectors and of Phenoxyacetamide Inhibitors of Type III Secretion on Abscess Formation in a Mouse Model of Pseudomonas aeruginosa Infection

PubMed Central

Berube, Bryan J.; Murphy, Katherine R.; Torhan, Matthew C.; Bowlin, Nicholas O.; Williams, John D.; Bowlin, Terry L.; Moir, Donald T.

2017-01-01

ABSTRACT Pseudomonas aeruginosa is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or microabscess formation. The rising incidence of multidrug resistance among P. aeruginosa isolates has increased both the economic burden and the morbidity and mortality associated with P. aeruginosa disease and necessitates a search for novel therapeutics. Previous work from our group detailed novel phenoxyacetamide inhibitors that block type III secretion and injection into host cells in vitro. In this study, we used a mouse model of P. aeruginosa abscess formation to test the in vivo efficacy of these compounds against the P. aeruginosa type III secretion system (T3SS). Bacteria used the T3SS to intoxicate infiltrating neutrophils to establish abscesses. Despite this antagonism, sufficient numbers of functioning neutrophils remained for proper containment of the abscesses, as neutrophil depletion resulted in an increased abscess size, the formation of dermonecrotic lesions on the skin, and the dissemination of P. aeruginosa to internal organs. Consistent with the specificity of the T3SS-neutrophil interaction, P. aeruginosa bacteria lacking a functional T3SS were fully capable of causing abscesses in a neutropenic host. Phenoxyacetamide inhibitors attenuated abscess formation and aided in the immune clearance of the bacteria. Finally, a P. aeruginosa strain resistant to the phenoxyacetamide compound was fully capable of causing abscess formation even in the presence of the T3SS inhibitors. Together, our results further define the role of type III secretion in murine abscess formation and demonstrate the in vivo efficacy of phenoxyacetamide inhibitors in P. aeruginosa infection. PMID:28807906

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.

Studying the evolution of a type III radio from the Sun up to 1 AU

NASA Astrophysics Data System (ADS)

Mann, Gottfried; Breitling, Frank; Vocks, Christian; Fallows, Richard; Melnik, Valentin; Konovalenko, Alexander

2017-04-01

On March 16, 2016, a type III burst was observed with the ground-based radio telescopes LOFAR and URAN-2 as well as with the radiospectrometer aboard the spacecraft WIND.It started at 80 MHz at 06:37 UT and reached 50 kHz after 23 minutes. A type III burst are considered as the radio signature of an electron beam travelling from the corona into the interplanetary space. The energetic electrons carrying the beam excites Langmuir waves, which convert into radio waves by wave-particle interaction. The relationship between the drift rate and the frequency as derived from the dynamic radio spectra reveals that the velocity of the electrons generating the radio waves of the type III burst is increasing with increasing distance from the center of the Sun.

Loss of Anterior Gradient 2 (Agr2) Expression Results in Hyperplasia and Defective Lineage Maturation in the Murine Stomach*

PubMed Central

Gupta, Aparna; Wodziak, Dariusz; Tun, May; Bouley, Donna M.; Lowe, Anson W.

2013-01-01

Recent studies of epithelial tissues have revealed the presence of tissue-specific stem cells that are able to establish multiple cell lineages within an organ. The stem cells give rise to progenitors that replicate before differentiating into specific cell lineages. The mechanism by which homeostasis is established between proliferating stem or progenitor cells and terminally differentiated cells is unclear. This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while also inhibiting the proliferation of stem or progenitor cells. When Agr2 expression is absent, gastric mucous neck cells increased in number as does the number of proliferating cells. Agr2 expression loss also resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling. Sox9 expression has been associated with progenitor and stem cells. Similar effects of the Agr2 null on cell proliferation in the intestine were also observed. Agr2 consequently serves to maintain the balance between proliferating and differentiated epithelial cells. PMID:23209296

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

PubMed Central

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

2013-01-01

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

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.

Advanced Electron Microscopy and Micro analytical technique development and application for Irradiated TRISO Coated Particles from the AGR-1 Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Rooyen, Isabella Johanna; Lillo, Thomas Martin; Wen, Haiming

2017-01-01

A series of up to seven irradiation experiments are planned for the Advanced Gas Reactor (AGR) Fuel Development and Quantification Program, with irradiation completed at the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) for the first experiment (i.e., AGR-1) in November 2009 for an effective 620 full power days. The objective of the AGR-1 experiment was primarily to provide lessons learned on the multi-capsule test train design and to provide early data on fuel performance for use in fuel fabrication process development and post-irradiation safety testing data at high temperatures. This report describes the advanced microscopy and micro-analysismore » results on selected AGR-1 coated particles.« less

Crystal structure of tandem type III fibronectin domains from Drosophila neuroglian at 2.0 A.

PubMed

Huber, A H; Wang, Y M; Bieber, A J; Bjorkman, P J

1994-04-01

We report the crystal structure of two adjacent fibronectin type III repeats from the Drosophila neural cell adhesion molecule neuroglian. Each domain consists of two antiparallel beta sheets and is folded topologically identically to single fibronectin type III domains from the extracellular matrix proteins tenascin and fibronectin. beta bulges and left-handed polyproline II helices disrupt the regular beta sheet structure of both neuroglian domains. The hydrophobic interdomain interface includes a metal-binding site, presumably involved in stabilizing the relative orientation between domains and predicted by sequence comparision to be present in the vertebrate homolog molecule L1. The neuroglian domains are related by a near perfect 2-fold screw axis along the longest molecular dimension. Using this relationship, a model for arrays of tandem fibronectin type III repeats in neuroglian and other molecules is proposed.

The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine intracranial abscesses model.

PubMed

Gong, Jian; Li, Dongzhi; Yan, Jun; Liu, Yu; Li, Di; Dong, Jie; Gao, Yaping; Sun, Tao; Yang, Guang

2014-01-01

Intracranial abscesses are associated with high mortality. Staphylococcus aureus is one of the main pathogens that cause intracranial infection. Until now, there is no report to identify the key effectors of S. aureus during the intracranial infection. The murine intracranial abscesses model induced by S. aureus was constructed. The vital sign and survival rate of mice were observed to evaluate the infection. Histological examination was used to diagnose the pathological alterations of mouse tissues. The sensitivity of S. aureus to whole blood was evaluated by whole-blood killing assay. In murine intracranial abscesses model, it was shown that the mortality caused by the accessory gene regulator (agr) locus deficient strain was significant decreased compared with its parent strain. Moreover, we found that RNAIII, the effector of agr system, was essential for the intracranial infection caused by S. aureus. In the further investigation, it was shown that restoration the expression of α-toxin in agr deficient strain could partially recover the mortality in the murine intracranial abscesses model. Our data suggested that the agr system of S. aureus is an important virulence determinant in the induction and mortality of intracranial abscesses in mice. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Distinct Effects of Type I and III Interferons on Enteric Viruses

PubMed Central

Peterson, Stefan T.

2018-01-01

Interferons (IFNs) are key host cytokines in the innate immune response to viral infection, and recent work has identified unique roles for IFN subtypes in regulating different aspects of infection. Currently emerging is a common theme that type III IFNs are critical in localized control of infection at mucosal barrier sites, while type I IFNs are important for broad systemic control of infections. The intestine is a particular site of interest for exploring these effects, as in addition to being the port of entry for a multitude of pathogens, it is a complex tissue with a variety of cell types as well as the presence of the intestinal microbiota. Here we focus on the roles of type I and III IFNs in control of enteric viruses, discussing what is known about signaling downstream from these cytokines, including induction of specific IFN-stimulated genes. We review viral strategies to evade IFN responses, effects of IFNs on the intestine, interactions between IFNs and the microbiota, and briefly discuss the role of IFNs in controlling viral infections at other barrier sites. Enhanced understanding of the coordinate roles of IFNs in control of viral infections may facilitate development of antiviral therapeutic strategies; here we highlight potential avenues for future exploration. PMID:29361691

Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.

PubMed Central

Mancuso, G; Tomasello, F; von Hunolstein, C; Orefici, G; Teti, G

1994-01-01

Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data

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.

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

On the theory of the type III burst exciter

NASA Technical Reports Server (NTRS)

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

1976-01-01

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

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.

Corrosion behavior of as-received and previously cast type III gold alloy.

PubMed

Ayad, Mohamed F; Ayad, Ghada M

2010-04-01

The rationale for using gold alloys is based largely upon their alleged ability to resist corrosion, but little information is available to determine the corrosion behavior of recast alloys. This study characterized the elemental composition of as-received and recast type III gold alloy and examined the in vitro corrosion behavior in two media using a potentiodynamic polarization technique. Seventy-eight disk-shaped specimens were prepared from a type III gold alloy under three casting protocols according to the proportion of as-received and recast gold alloy (n = 26). (1) Group as received (100% as-received metal), (2) group 50% to 50% (50% wt. new metal, 50% wt. once recast metal), and (3) group recast (100% once recast metal). The surface structures of 20 specimens from each group were examined under scanning electron microscopy, and their elemental compositions were determined using X-ray energy-dispersive spectroscopy. Further, the potentiodynamic cyclic polarization between -1000 and +1000 mV (SCE) were performed for six specimens from each casting protocol in 0.09% NaCl solution (n = 3) and Fusayama artificial saliva (n = 3) at 37 degrees C. Zero-current potential and corrosion current density were determined. The data were analyzed with 1-way ANOVA and the Ryan-Einot-Gabriel-Welsch multiple-range test t (alpha= 0.05). Elemental composition was significantly different among the casting groups (p < 0.001). The mean weight percentage values were 72.4 to 75.7% Au, 4.5 to 7.0% Pd, 10.7 to 11.1% Ag, 7.8 to 8.4% Cu, and 1.0 to 1.4% Zn. The mean values for Zero-current potential and corrosion current density for all casting protocols were not significant (p > 0.05); however, the difference between the electrolytes was significant (p < 0.001). Fusayama artificial saliva seemed to offer the most corrosive environment. Type III gold alloy in any casting protocol retained passivity under electrochemical conditions similar to the oral environment. Moreover, high

AGR-1 Compact 1-3-1 Post-Irradiation Examination Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demkowicz, Paul Andrew

The Advanced Gas Reactor (AGR) Fuel Development and Qualification Program was established to perform the requisite research and development on tristructural isotropic (TRISO) coated particle fuel to support deployment of a high-temperature gas-cooled reactor (HTGR). The work continues as part of the Advanced Reactor Technologies (ART) TRISO Fuel program. The overarching program goal is to provide a baseline fuel qualification data set to support licensing and operation of an HTGR. To achieve these goals, the program includes the elements of fuel fabrication, irradiation, post-irradiation examination (PIE) and safety testing, fuel performance modeling, and fission product transport (INL 2015). A seriesmore » of fuel irradiation experiments is being planned and conducted in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL). These experiments will provide data on fuel performance under irradiation, support fuel process development, qualify the fuel for normal operating conditions, provide irradiated fuel for safety testing, and support the development of fuel performance and fission product transport models. The first of these irradiation tests, designated AGR-1, began in the ATR in December 2006 and ended in November 2009. This experiment was conducted primarily to act as a shakedown test of the multicapsule test train design and provide early data on fuel performance for use in fuel fabrication process development. It also provided samples for post-irradiation safety testing, where fission product retention of the fuel at high temperatures will be experimentally measured. The capsule design and details of the AGR-1 experiment have been presented previously (Grover, Petti, and Maki 2010, Maki 2009).« less

AGR-1 Compact 5-3-1 Post-Irradiation Examination Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demkowicz, Paul; Harp, Jason; Winston, Phil

The Advanced Gas Reactor (AGR) Fuel Development and Qualification Program was established to perform the requisite research and development on tristructural isotropic (TRISO) coated particle fuel to support deployment of a high-temperature gas-cooled reactor (HTGR). The work continues as part of the Advanced Reactor Technologies (ART) TRISO Fuel program. The overarching program goal is to provide a baseline fuel qualification data set to support licensing and operation of an HTGR. To achieve these goals, the program includes the elements of fuel fabrication, irradiation, post-irradiation examination (PIE) and safety testing, fuel performance, and fission product transport (INL 2015). A series ofmore » fuel irradiation experiments is being planned and conducted in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL). These experiments will provide data on fuel performance under irradiation, support fuel process development, qualify the fuel for normal operating conditions, provide irradiated fuel for safety testing, and support the development of fuel performance and fission product transport models. The first of these irradiation tests, designated AGR-1, began in the ATR in December 2006 and ended in November 2009. This experiment was conducted primarily to act as a shakedown test of the multicapsule test train design and provide early data on fuel performance for use in fuel fabrication process development. It also provided samples for post-irradiation safety testing, where fission product retention of the fuel at high temperatures will be experimentally measured. The capsule design and details of the AGR-1 experiment have been presented previously.« less

Satellite observations of type III solar radio bursts at low frequencies

NASA Technical Reports Server (NTRS)

Fainberg, J.; Stone, R. G.

1974-01-01

Type III solar radio bursts have been observed from 10 MHz to 10 kHz by satellite experiments above the terrestrial plasmasphere. Solar radio emission in this frequency range results from excitation of the interplanetary plasma by energetic particles propagating outward along open field lines over distances from 5 earth radii to at least 1 AU from the sun. This review summarizes the morphology, characteristics, and analysis of individual as well as storms of bursts. Substantial evidence is available to show that the radio emission is observed at the second harmonic instead of the fundamental of the plasma frequency. This brings the density scale derived by radio observations into better agreement with direct solar wind density measurements at 1 AU and relaxes the requirement for type III propagation along large density-enhanced regions. This density scale with the measured direction of arrival of the radio burst allows the trajectory of the exciter path to be determined from 10 earth radii to 1 AU.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

PubMed Central

Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

2017-01-01

AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

PubMed

Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

2017-08-15

Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

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.

Bartter syndrome type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation.

PubMed

Westland, Rik; Hack, Wilfried W; van der Horst, Henricus J R; Uittenbogaard, Lukas B; van Hagen, Johanna M; van der Valk, Paul; Kamsteeg, Erik J; van den Heuvel, Lambert P; van Wijk, Joanna A E

2012-12-01

Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type III has an antenatal presentation with polyhydramnios, premature delivery and severe dehydration in the first weeks of life. Associations between congenital anomalies of the kidney and urinary tract and Bartter syndrome are extremely rare. This case report presents a girl with Bartter syndrome Type III due to a homozygous CLCNKB mutation and bilateral congenital anomalies of the kidney and urinary tract. In addition, we describe the antenatal presentation as well as its perinatal management.

Analysis of Fission Products on the AGR-1 Capsule Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul A. Demkowicz; Jason M. Harp; Philip L. Winston

2013-03-01

The components of the AGR-1 irradiation capsules were analyzed to determine the retained inventory of fission products in order to determine the extent of in-pile fission product release from the fuel compacts. This includes analysis of (i) the metal capsule components, (ii) the graphite fuel holders, (iii) the graphite spacers, and (iv) the gas exit lines. The fission products most prevalent in the components were Ag-110m, Cs 134, Cs 137, Eu-154, and Sr 90, and the most common location was the metal capsule components and the graphite fuel holders. Gamma scanning of the graphite fuel holders was also performed tomore » determine spatial distribution of Ag-110m and radiocesium. Silver was released from the fuel components in significant fractions. The total Ag-110m inventory found in the capsules ranged from 1.2×10 2 (Capsule 3) to 3.8×10 1 (Capsule 6). Ag-110m was not distributed evenly in the graphite fuel holders, but tended to concentrate at the axial ends of the graphite holders in Capsules 1 and 6 (located at the top and bottom of the test train) and near the axial center in Capsules 2, 3, and 5 (in the center of the test train). The Ag-110m further tended to be concentrated around fuel stacks 1 and 3, the two stacks facing the ATR reactor core and location of higher burnup, neutron fluence, and temperatures compared with Stack 2. Detailed correlation of silver release with fuel type and irradiation temperatures is problematic at the capsule level due to the large range of temperatures experienced by individual fuel compacts in each capsule. A comprehensive Ag 110m mass balance for the capsules was performed using measured inventories of individual compacts and the inventory on the capsule components. For most capsules, the mass balance was within 11% of the predicted inventory. The Ag-110m release from individual compacts often exhibited a very large range within a particular capsule.« less

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Certification of certain Type III devices. 159.12a Section 159.12a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Certification Procedures § 159.12a Certification...

MODELING AND ANALYSIS OF FISSION PRODUCT TRANSPORT IN THE AGR-3/4 EXPERIMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humrickhouse, Paul W.; Collin, Blaise P.; Hawkes, Grant L.

In this work we describe the ongoing modeling and analysis efforts in support of the AGR-3/4 experiment. AGR-3/4 is intended to provide data to assess fission product retention and transport (e.g., diffusion coefficients) in fuel matrix and graphite materials. We describe a set of pre-test predictions that incorporate the results of detailed thermal and fission product release models into a coupled 1D radial diffusion model of the experiment, using diffusion coefficients reported in the literature for Ag, Cs, and Sr. We make some comparisons of the predicted Cs profiles to preliminary measured data for Cs and find these to bemore » reasonable, in most cases within an order of magnitude. Our ultimate objective is to refine the diffusion coefficients using AGR-3/4 data, so we identify an analytical method for doing so and demonstrate its efficacy via a series of numerical experiments using the model predictions. Finally, we discuss development of a post-irradiation examination plan informed by the modeling effort and simulate some of the heating tests that are tentatively planned.« less

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

PubMed

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

2008-06-15

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

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.

Identification of a high-virulence clone of type III Streptococcus agalactiae (group B Streptococcus) causing invasive neonatal disease.

PubMed

Musser, J M; Mattingly, S J; Quentin, R; Goudeau, A; Selander, R K

1989-06-01

Chromosomal genotypes of 128 isolates of six serotypes (Ia, Ib, Ic, II, Ic/II, and III) of Streptococcus agalactiae (group B Streptococcus) recovered predominantly from human infants in the United States were characterized by an analysis of electrophoretically demonstrable allelic profiles at 11 metabolic enzyme loci. Nineteen distinctive electrophoretic types (ETs), representing multilocus clonal genotypes, were identified. Mean genetic diversity per locus among ETs of isolates of the same serotype was, on average, nearly equal to that in all 19 ETs. Cluster analysis of the ETs revealed two primary phylogenetic divisions at a genetic distance of 0.65. A single clone (ET 1) represented by 40 isolates expressing type III antigen formed division I. Division II was composed of 18 ETs in three major lineages diverging from one another at distances greater than 0.35 and included strains of all six antigenic classes. The type III organisms in division I produce more extracellular neuraminidase and apparently are more virulent than the type III strains in division II, which are related to strains of other serotypes that cause disease much less frequently. The existence of this unusually virulent clone accounts, in major part, for the high morbidity and mortality associated with infection by type III organisms.

Concomitant glenohumeral pathologies in high-grade acromioclavicular separation (type III - V).

PubMed

Markel, Jochen; Schwarting, Tim; Malcherczyk, Dominik; Peterlein, Christian-Dominik; Ruchholtz, Steffen; El-Zayat, Bilal Farouk

2017-11-10

Acromioclavicular joint (ACJ) dislocations are common injuries of the shoulder associated with physical activity. The diagnosis of concomitant injuries proves complicated due to the prominent clinical symptoms of acute ACJ dislocation. Because of increasing use of minimally invasive surgery techniques concomitant pathologies are diagnosed more often than with previous procedures. The aim of this study was to identify the incidence of concomitant intraarticular injuries in patients with high-grade acromioclavicular separation (Rockwood type III - V) as well as to reveal potential risk constellations. The concomitant pathologies were compiled during routine arthroscopically assisted treatment in altogether 163 patients (147 male; 16 female; mean age 36.8 years) with high-grade acromioclavicular separation (Rockwood type III: n = 60; Rockwood type IV: n = 6; Rockwood type V: n = 97). Acromioclavicular separation occurred less often in women than men (1:9). In patients under 35, the most common cause for ACJ dislocation was sporting activity (37.4%). Rockwood type V was observed significantly more often than the other types with 57.5% (Rockwood type III = 36.8%, Rockwood type IV 3.7%). Concomitant pathologies were diagnosed in 39.3% of the patients with that number rising to as much as 57.3% in patients above 35 years. Most common associated injuries were rotator cuff injuries (32.3%), chondral defects (30.6%) and SLAP-lesions (22.6%). Of all patients, 8.6% needed additional reconstructive surgery. Glenohumeral injuries are a much more common epiphenomenon during acromioclavicular separation than previously ascertained. High risk group for accompanying injuries are patients above 35 years with preexisting degenerative disease. The increasing use of minimally invasive techniques allows for an easier diagnosis and simultaneous treatment of the additional pathologies.

Selective expression of muscarinic acetylcholine receptor subtype M3 by mouse type III taste bud cells.

PubMed

Mori, Yusuke; Eguchi, Kohgaku; Yoshii, Kiyonori; Ohtubo, Yoshitaka

2016-11-01

Each taste bud cell (TBC) type responds to a different taste. Previously, we showed that an unidentified cell type(s) functionally expresses a muscarinic acetylcholine (ACh) receptor subtype, M3, and we suggested the ACh-dependent modification of its taste responsiveness. In this study, we found that M3 is expressed by type III TBCs, which is the only cell type that possesses synaptic contacts with taste nerve fibers in taste buds. The application of ACh to the basolateral membrane of mouse fungiform TBCs in situ increased the intracellular Ca 2+ concentration in 2.4 ± 1.4 cells per taste bud (mean ± SD, n = 14). After Ca 2+ imaging, we supravitally labeled type II cells (phospholipase C β2 [PLCβ2]-immunoreactive cells) with Lucifer yellow CH (LY), a fluorescent dye and investigated the positional relationship between ACh-responding cells and LY-labeled cells. After fixation, the TBCs were immunohistostained to investigate the positional relationships between immunohistochemically classified cells and LY-labeled cells. The overlay of the two positional relationships obtained by superimposing the LY-labeled cells showed that all of the ACh-responding cells were type III cells (synaptosomal-associated protein 25 [SNAP-25]-immunoreactive cells). The ACh responses required no added Ca 2+ in the bathing solution. The addition of 1 μM U73122, a phospholipase C inhibitor, decreased the magnitude of the ACh response, whereas that of 1 μM U73343, a negative control, had no effect. These results suggest that type III cells respond to ACh and release Ca 2+ from intracellular stores. We also discuss the underlying mechanism of the Ca 2+ response and the role of M3 in type III cells.

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review

ERIC Educational Resources Information Center

Wolfenden, C.; Wittkowski, A.; Hare, D. J.

2017-01-01

The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD…

Processing and microstructural characterisation of a UO2-based ceramic for disposal studies on spent AGR fuel

NASA Astrophysics Data System (ADS)

Hiezl, Z.; Hambley, D. I.; Padovani, C.; Lee, W. E.

2015-01-01

Preparation and characterisation of a Simulated Spent Nuclear Fuel (SIMFuel), which replicates the chemical state and microstructure of Spent Nuclear Fuel (SNF) discharged from a UK Advanced Gas-cooled Reactor (AGR) after a cooling time of 100 years is described. Given the relatively small differences in radionuclide inventory expected over longer time periods, the SIMFuel studied in this work is expected to be also representative of spent fuel after significantly longer periods (e.g. 1000 years). Thirteen stable elements were added to depleted UO2 and sintered to simulate the composition of fuel pellets after burn-ups of 25 and 43 GWd/tU and, as a reference, pure UO2 pellets were also investigated. The fission product distribution was calculated using the FISPIN code provided by the UK National Nuclear Laboratory. SIMFuel pellets were up to 92% dense and during the sintering process in H2 atmosphere Mo-Ru-Rh-Pd metallic precipitates and grey-phase ((Ba, Sr)(Zr, RE) O3 oxide precipitates) formed within the UO2 matrix. These secondary phases are present in real PWR and AGR SNF. Metallic precipitates are generally spherical and have submicron particle size (0.8 ± 0.7 μm). Spherical oxide precipitates in SIMFuel measured up to 30 μm in diameter, but no data were available in the public domain to compare this to AGR SNF. The grain size of actual AGR SNF (∼ 3-30 μm) is larger than that measured in AGR SIMFuel (∼ 2-5 μm).

AGR-2 Final Data Qualification Report for U.S. Capsules - ATR Cycles 147A Through 154B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, Binh T.; Einerson, Jeffrey J.

2014-07-01

This report provides the data qualification status of AGR-2 fuel irradiation experimental data in four U.S. capsules from all 15 Advanced Test Reactor (ATR) Cycles 147A, 148A, 148B, 149A, 149B, 150A, 150B, 151A, 151B, 152A, 152B, 153A, 153B, 154A, and 154B, as recorded in the Nuclear Data Management and Analysis System (NDMAS). Thus, this report covers data qualification status for the entire AGR-2 irradiation and will replace four previously issued AGR-2 data qualification reports (e.g., INL/EXT-11-22798, INL/EXT-12-26184, INL/EXT-13-29701, and INL/EXT-13-30750). During AGR-2 irradiation, two cycles, 152A and 153A, occurred when the ATR core was briefly at low power, so AGR-2more » irradiation data are not used for physics and thermal calculations. Also, two cycles, 150A and 153B, are Power Axial Locator Mechanism (PALM) cycles when the ATR power is higher than during normal cycles. During the first PALM cycle, 150A, the experiment was temporarily moved from the B-12 location to the ATR water canal and during the second PALM cycle, 153B, the experiment was temporarily moved from the B-12 location to the I-24 location to avoid being overheated. During the “Outage” cycle, 153A, seven flow meters were installed downstream from seven Fission Product Monitoring System (FPMS) monitors to measure flows from the monitors and these data are included in the NDMAS database.« less

Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation.

PubMed

Canetta, Sarah E; Luca, Edlira; Pertot, Elyse; Role, Lorna W; Talmage, David A

2011-01-01

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs). Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chang Lan; Shim, Myoung Sup; Chung, Jiyeol

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 ofmore » 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.« less

Arabidopsis CYP86A2 represses Pseudomonas syringae type III genes and is required for cuticle development

PubMed Central

Xiao, Fangming; Mark Goodwin, S; Xiao, Yanmei; Sun, Zhaoyu; Baker, Douglas; Tang, Xiaoyan; Jenks, Matthew A; Zhou, Jian-Min

2004-01-01

Pseudomonas syringae relies on type III secretion system to deliver effector proteins into the host cell for parasitism. Type III genes are induced in planta, but host factors affecting the induction are poorly understood. Here we report on the identification of an Arabidopsis mutant, att1 (for aberrant induction of type three genes), that greatly enhances the expression of bacterial type III genes avrPto and hrpL. att1 plants display enhanced disease severity to a virulent strain of P. syringae, suggesting a role of ATT1 in disease resistance. ATT1 encodes CYP86A2, a cytochrome P450 monooxygenase catalyzing fatty acid oxidation. The cutin content is reduced to 30% in att1, indicating that CYP86A2 plays a major role in the biosynthesis of extracellular lipids. att1 has a loose cuticle membrane ultrastructure and shows increased permeability to water vapor, demonstrating the importance of the cuticle membrane in controlling water loss. The enhanced avrPto-luc expression is specific to att1, but not another cuticle mutant, wax2. The results suggest that certain cutin-related fatty acids synthesized by CYP86A2 may repress bacterial type III gene expression in the intercellular spaces. PMID:15241470

The type III inositol 1,4,5-trisphosphate receptor preferentially transmits apoptotic Ca2+ signals into mitochondria.

PubMed

Mendes, Carolina C P; Gomes, Dawidson A; Thompson, Mayerson; Souto, Natalia C; Goes, Tercio S; Goes, Alfredo M; Rodrigues, Michele A; Gomez, Marcus V; Nathanson, Michael H; Leite, M Fatima

2005-12-09

There are three isoforms of the inositol 1,4,5- trisphosphate receptor (InsP(3)R), each of which has a distinct effect on Ca(2+) signaling. However, it is not known whether each isoform similarly plays a distinct role in the activation of Ca(2+)-mediated events. To investigate this question, we examined the effects of each InsP(3)R isoform on transmission of Ca(2+) signals to mitochondria and induction of apoptosis. Each isoform was selectively silenced using isoform-specific small interfering RNA in Chinese hamster ovary cells, which express all three InsP(3)R isoforms. ATP-induced cytosolic Ca(2+) signaling patterns were altered, regardless of which isoform was silenced, but in a different fashion depending on the isoform. ATP also induced Ca(2+) signals in mitochondria, which were inhibited more effectively by silencing the type III InsP(3)R than by silencing either the type I or type II isoform. The type III isoform also co-localized most strongly with mitochondria. When apoptosis was induced by activation of either the extrinsic or intrinsic apoptotic pathway, induction was reduced most effectively by silencing the type III InsP(3)R. These findings provide evidence that the type III isoform of the InsP(3)R plays a special role in induction of apoptosis by preferentially transmitting Ca(2+) signals into mitochondria.

Quantitative comparisons of type III radio burst intensity and fast electron flux at 1 AU

NASA Technical Reports Server (NTRS)

Fitzenreiter, R. J.; Evans, L. G.; Lin, R. P.

1976-01-01

We compare the flux of fast solar electrons and the intensity of the type III radio emission generated by these particles at 1 AU. We find that there are two regimes in the generation of type III radiation: one where the radio intensity is linearly proportional to the electron flux, and the second regime, which occurs above a threshold electron flux, where the radio intensity is proportional to the approximately 2.4 power of the electron flux. This threshold appears to reflect a transition to a different emission mechanism.

[Efficacy and safety of Longjintonglin Capsule for the treatment of type III prostatitis].

PubMed

Shang, Xue-Jun; Geng, Qiang; Duan, Jian-Min; Zheng, De-Quan; Xie, Lei; Guo, Jun

2014-12-01

To study the therapeutic effect and safety of Longjintonglin Capsule in the treatment of type III prostatitis (chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS). We selected 240 patients with type III prostatitis according to the diagnostic standards of the American National Institute of Health (NIH) and treated them with Longjintonglin Capsule orally 3 capsules once tid for 12 weeks. Based on the NIH chronic prostatitis symptom index (NIH-CPSI), traditional Chinese medicine (TCM) syndrome score, and leukocyte count in the expressed prostatic secretion (EPS), we evaluated the results of treatment. Totally 238 patients completed the treatment, including 108 IIIA and 120 III B prostatitis cases. Before and after 4, 8, and 12 weeks of treatment, the total NIH-CPSI scores were 23.12 ± 6.99, 18.22 ± 6.39, 14.12 ± 5.88, and 12.36 ± 6.04 (P < 0.01) in the IIIA prostatitis patients and 22.01 ± 6.28, 17.56 ± 5.89, 13.67 ± 5.18, and 11.45 ± 5.22 in the III prostatitis patients (P < 0.01), the TCM syndrome scores were 52.12 ± 13.08, 48.13 ± 12.11, 43.05 ± 11.19, and 40.78 ± 10. 59 in the former (P < 0.01) and 53.02 ± 12.12, 49.32 ± 12.78, 44.01 ± 11.79, and 39.67 ± 10.26 in the latter (P < 0.01), and the leukocyte counts were 26.09 ± 21.55, 23.02 ± 18.61, 18.25 ± 17.79, and 15.36 ± 16.38 in the IIIA cases (P < 0.01). Neither abnormalities in liver and renal function nor obvious adverse events were observed during the experiment. Longjintonglin Capsule, with its advantages of safety, effectiveness, and no obvious adverse reactions in the treatment of type III prostatitis, deserves to be recommended for clinical application.

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

PubMed Central

2009-01-01

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

Usher syndrome type III (USH3) linked to chromosome 3q in an Italian family.

PubMed

Gasparini, P; De Fazio, A; Croce, A I; Stanziale, P; Zelante, L

1998-08-01

We report an Italian family affected by Usher type III syndrome. Linkage study, performed using markers corresponding to the Usher loci already mapped, clearly showed linkage with markers on chromosome 3q24-25. Our data further support the presence of an Usher III locus on chromosome 3, as recently reported in a Finnish population.

Genetic diversity of methicillin resistant Staphylococcus aureus strains isolated from burn patients in Iran: ST239-SCCmec III/t037 emerges as the major clone.

PubMed

Goudarzi, Mehdi; Bahramian, Mahnaz; Satarzadeh Tabrizi, Mahboobeh; Udo, Edet E; Figueiredo, Agnes Marie Sá; Fazeli, Maryam; Goudarzi, Hossein

2017-04-01

Methicillin-resistant Staphylococcus aureus (MRSA) as a major cause of infection in health care, hospital and community settings is a global health concern. The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of circulating molecular types of MRSA in a burn hospital in Tehran, the capital of Iran. During a 10-month study period, 106 Staphylococcus aureus isolates were assessed. Isolates were subjected to susceptibility testing using the disk diffusion method and Polymerase Chain Reaction (PCR) for detection of mecA, fem and nuc genes. The presence of PVL and tst encoding genes were determined by PCR method. All the MRSA isolates were genotyped by multilocus sequence typing (MLST), spa typing, SCCmec typing and agr typing. The presence of mecA gene was confirmed in all the Staphylococcus aureus isolates. Antimicrobial susceptibility testing revealed a high resistance rate (90.6%) to ampicillin, tetracycline, and erythromycin. The rates of resistance to remaining antibiotics tested varied between 18.9% and 84.9%. The high- level of resistance to mupirocin was confirmed in 19.8% of MRSA strains isolated from burn patients. Multi-drug resistance was observed in 90.6% of isolates. Sixteen of the 106 MRSA isolates (15.1%) harbored PVL-encoding genes. The majority of our MRSA strains carried SCCmec III (71.7%). ST239-SCCmec III/t037 (34%) was the most common genotype followed by ST239-SCCmec III/t030 (24.5%), ST15-SCCmec IV/t084 (15.1%), ST22-SCCmec IV/t790 (13.2%), and ST239-SCCmec III/t631 (13.2%). Mupirocin resistant MRSA isolates belonged to ST15-SCCmec IV/t084 (40%), ST22-SCCmec IV/t790 (23.3%), ST239-SCCmec III/t631 (20%), and ST239-SCCmec III/t030 (16.7%) clones. The results showed that genetically diverse strains of MRSA are circulating in our burn hospitals with relatively high prevalence of ST239-SCCmec III/t037 clone. The findings support the need for regular surveillance of MRSA to determine the distribution of

The YopJ superfamily of type III efforts in plant-associated bacteria

USDA-ARS?s Scientific Manuscript database

Bacterial pathogens employ the type III secretion system to secrete and translocate effector proteins into their hosts. The primary function of these effector proteins is believed to be the suppression of host defense responses or innate immunity. However, some effector proteins may be recognized by...

Treatment of type II and type III open tibia fractures in children.

PubMed

Bartlett, C S; Weiner, L S; Yang, E C

1997-07-01

To determine whether severe open tibial fractures in children behave like similar fractures in adults. A combined retrospective and prospective review evaluated treatment protocol for type II and type III open tibial fractures in children over a ten-year period from 1984 to 1993. Twenty-three fractures were studied in children aged 3.5 to 14.5 (18 boys and 5 girls). There were six type II, eight type IIIA, and nine type IIIB fractures. Type I fractures were not included. Seven fractures were comminuted with significant butterfly fragments or segmental patterns. Treatment consisted of adequate debridement of soft tissues, closure of dead space, and stabilization with external fixation. Bone debridement only included contaminated devitalized bone or devitalized bone without soft tissue coverage. Bone that could be covered despite periosteal stripping was preserved. Clinical and roentgenographic examinations were used to determine time to union. All fractures in this series healed between eight and twenty-six weeks. Wound coverage included two flaps, three skin grafts, and two delayed primary closures. No bone grafts were required. There were no deep infections, growth arrests, or malunions. Follow-up has ranged from six months to four years. Open tibia fractures in children differ from similar fractures in adults in the following ways: soft tissues have excellent healing capacity, devitalized bone that is not contaminated or exposed can be saved and will become incorporated, and external fixation can be maintained until the fracture has healed. Periosteum in young children can form bone even in the face of bone loss.

Type III Nrg1 Back Signaling Enhances Functional TRPV1 along Sensory Axons Contributing to Basal and Inflammatory Thermal Pain Sensation

PubMed Central

Canetta, Sarah E.; Luca, Edlira; Pertot, Elyse; Role, Lorna W.; Talmage, David A.

2011-01-01

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs) [1]. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons [2]. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions [3]. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K [4], [5], [6], making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function. PMID:21949864

Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

PubMed Central

Douam, Florian; Soto Albrecht, Yentli E.; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V.

2017-01-01

ABSTRACT Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR−/−) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/−) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. PMID:28811340

Evidence of scattering effects on the sizes of interplanetary Type III radio bursts

NASA Technical Reports Server (NTRS)

Steinberg, J. L.; Hoang, S.; Dulk, G. A.

1985-01-01

An analysis is conducted of 162 interplanetary Type III radio bursts; some of these bursts have been observed in association with fast electrons and Langmuir wave events at 1 AU and, in addition, have been subjected to in situ plasma parameter measurements. It is noted that the sizes of burst sources are anomalously large, compared to what one would anticipate on the basis of the interplanetary plasma density distribution, and that the variation of source size with frequency, when compared with the plasma frequency variation measured in situ, implies that the source sizes expand with decreasing frequency to fill a cone whose apex is at the sun. It is also found that some local phenomenon near the earth controls the apparent size of low frequency Type III sources.

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

PubMed Central

Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

2015-01-01

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

Data Compilation for AGR-3/4 Designed-to-Fail (DTF) Fuel Particle Batch LEU04-02DTF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunn, John D; Miller, James Henry

2008-10-01

This document is a compilation of coating and characterization data for the AGR-3/4 designed-to-fail (DTF) particles. The DTF coating is a high density, high anisotropy pyrocarbon coating of nominal 20 {micro}m thickness that is deposited directly on the kernel. The purpose of this coating is to fail early in the irradiation, resulting in a controlled release of fission products which can be analyzed to provide data on fission product transport. A small number of DTF particles will be included with standard TRISO driver fuel particles in the AGR-3 and AGR-4 compacts. The ORNL Coated Particle Fuel Development Laboratory 50-mm diametermore » fluidized bed coater was used to coat the DTF particles. The coatings were produced using procedures and process parameters that were developed in an earlier phase of the project as documented in 'Summary Report on the Development of Procedures for the Fabrication of AGR-3/4 Design-to-Fail Particles', ORNL/TM-2008/161. Two coating runs were conducted using the approved coating parameters. NUCO425-06DTF was a final process qualification batch using natural enrichment uranium carbide/uranium oxide (UCO) kernels. After the qualification run, LEU04-02DTF was produced using low enriched UCO kernels. Both runs were inspected and determined to meet the specifications for DTF particles in section 5 of the AGR-3 & 4 Fuel Product Specification (EDF-6638, Rev.1). Table 1 provides a summary of key properties of the DTF layer. For comparison purposes, an archive sample of DTF particles produced by General Atomics was characterized using identical methods. This data is also summarized in Table 1.« less

Complex regulation of Arabidopsis AGR1/PIN2-mediated root gravitropic response and basipetal auxin transport by cantharidin-sensitive protein phosphatases

NASA Technical Reports Server (NTRS)

Shin, Heungsop; Shin, Hwa-Soo; Guo, Zibiao; Blancaflor, Elison B.; Masson, Patrick H.; Chen, Rujin

2005-01-01

Polar auxin transport, mediated by two distinct plasma membrane-localized auxin influx and efflux carrier proteins/complexes, plays an important role in many plant growth and developmental processes including tropic responses to gravity and light, development of lateral roots and patterning in embryogenesis. We have previously shown that the Arabidopsis AGRAVITROPIC 1/PIN2 gene encodes an auxin efflux component regulating root gravitropism and basipetal auxin transport. However, the regulatory mechanism underlying the function of AGR1/PIN2 is largely unknown. Recently, protein phosphorylation and dephosphorylation mediated by protein kinases and phosphatases, respectively, have been implicated in regulating polar auxin transport and root gravitropism. Here, we examined the effects of chemical inhibitors of protein phosphatases on root gravitropism and basipetal auxin transport, as well as the expression pattern of AGR1/PIN2 gene and the localization of AGR1/PIN2 protein. We also examined the effects of inhibitors of vesicle trafficking and protein kinases. Our data suggest that protein phosphatases, sensitive to cantharidin and okadaic acid, are likely involved in regulating AGR1/PIN2-mediated root basipetal auxin transport and gravitropism, as well as auxin response in the root central elongation zone (CEZ). BFA-sensitive vesicle trafficking may be required for the cycling of AGR1/PIN2 between plasma membrane and the BFA compartment, but not for the AGR1/PIN2-mediated root basipetal auxin transport and auxin response in CEZ cells.

What's the point of the type III secretion system needle?

PubMed Central

Blocker, Ariel J.; Deane, Janet E.; Veenendaal, Andreas K. J.; Roversi, Pietro; Hodgkinson, Julie L.; Johnson, Steven; Lea, Susan M.

2008-01-01

Recent work by several groups has significantly expanded our knowledge of the structure, regulation of assembly, and function of components of the extracellular portion of the type III secretion system (T3SS) of Gram-negative bacteria. This perspective presents a structure-informed analysis of functional data and discusses three nonmutually exclusive models of how a key aspect of T3SS biology, the sensing of host cells, may be performed. PMID:18458349

Counselling for deinfibulation among women with type III female genital mutilation: A systematic review.

PubMed

Bello, Segun; Ogugbue, Miriam; Chibuzor, Moriam; Okomo, Uduak; Meremikwu, Martin M

2017-02-01

Counselling is a routine practice done before deinfibulation in women with type III female genital mutilation (FGM). However, cultural and social pressures, in addition to maladaptation to the changes in the body post deinfibulation, cause some women to choose to be reinfibulated after being deinfibulated. To conduct a systematic review of the impact of counselling prior to deinfibulation on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation among women living with type III FGM. The secondary aim was to assess the impact of male partner involvement in counselling on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation. Major databases including Cochrane Central Register of Controlled Trials, Medline, SCOPUS, and ClinicalTrials.gov were searched until August 2015. Studies comparing women with type III FGM who received counselling before deinfibulation versus no counselling were included. Two team members independently screened and collected data. No eligible studies were identified. There is no evidence to conclude that counselling before deinfibulation influences patients' satisfaction with overall quality of care or rates of request for reinfibulation. CRD42015024675. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Parent-of-origin effects on schizophrenia-relevant behaviours of type III neuregulin 1 mutant mice.

PubMed

Shang, Kani; Talmage, David A; Karl, Tim

2017-08-14

A robust, disease-relevant phenotype is paramount to the validity of genetic mouse models, which are an important tool in understanding complex diseases. Recent evidence from genome-wide association studies suggests the genetic contribution of parents to offspring is not equivalent. Despite this, few studies to date have examined the potential impact of parent genotype (i.e. origin of mutation) on the offspring of disease-relevant genetic mouse models. To elucidate the potential impact of the sex of the mutant parent on offspring phenotype, we characterized male and female offspring of an established schizophrenia mouse model, which had been generated using two different breeding schemes, in a range of disease-relevant behaviours. We compared heterozygous type III neuregulin 1 mutant (type III Nrg1 +/- ) and wild type-like control (WT) offspring from mutant father x WT mother pairings with offspring from mutant mother x WT father pairings. Offspring were tested in schizophrenia-relevant paradigms including the elevated plus maze (EPM), fear conditioning (FC), prepulse inhibition (PPI), social interaction (SI), and open field (OF). We found type III Nrg1 +/- males from mutant fathers, but not mutant mothers, showed deficits in contextual fear-associated memory and exhibited increased social interaction, compared to their WT littermates. Type III Nrg1 +/- females across breeding colonies only exhibited a subtle change to their acoustic startle response and sensorimotor gating. These results suggest a paternal-dependent transmission of genetically induced behavioural characteristics. Though the mechanisms governing this phenomenon are unclear, our results show that parental origin of mutation can alter the behavioural phenotype of genetic mouse models. Thus, researchers should carefully consider their breeding scheme when dealing with genetic mouse models of diseases such as schizophrenia. Copyright © 2017. Published by Elsevier B.V.

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

2016-12-01

We investigate the asymptotic structure of (possibly type III) crossed product von Neumann algebras {M = B rtimes Γ} arising from arbitrary actions {Γ \\curvearrowright 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 \\curvearrowright (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_∞ \\curvearrowright (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.

Identification of a Hydrophobic Cleft in the LytTR Domain of AgrA as a Locus for Small Molecule Interactions that Inhibit DNA Binding

PubMed Central

Leonard, Paul G.; Bezar, Ian F.; Sidote, David J.; Stock, Ann M.

2012-01-01

The AgrA transcription factor regulates the quorum-sensing response in Staphylococcus aureus, controlling the production of hemolysins and other virulence factors. AgrA binds to DNA via its C-terminal LytTR domain, a domain not found in humans but common in many pathogenic bacteria, making it a potential target for antimicrobial development. We have determined the crystal structure of the apo AgrA LytTR domain and screened a library of 500 fragment compounds to find inhibitors of AgrA DNA-binding activity. Using NMR, the binding site for five compounds has been mapped to a common locus at the C-terminal end of the LytTR domain, a site known to be important for DNA-binding activity. Three of these compounds inhibit AgrA DNA binding. These results provide the first evidence that LytTR domains can be targeted by small organic compounds. PMID:23181972

A Type III Protein Arginine Methyltransferase from the Protozoan Parasite Trypanosoma brucei*

PubMed Central

Fisk, John C.; Sayegh, Joyce; Zurita-Lopez, Cecilia; Menon, Sarita; Presnyak, Vladimir; Clarke, Steven G.; Read, Laurie K.

2009-01-01

Arginine methylation is a widespread post-translational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). The ancient protozoan parasite, Trypanosoma brucei, possesses five putative PRMTs, a relatively large number for a single-celled eukaryote. Trypanosomatids lack gene regulation at the level of transcription, instead relying on post-transcriptional control mechanisms that act at the levels of RNA turnover, translation, and editing, all processes that likely involve multiple RNA-binding proteins, which are common targets of arginine methylation. Here, we report the characterization of a trypanosome PRMT, TbPRMT7, which is homologous to human PRMT7. Interestingly, trypanosomatids are the only single-celled eukaryotes known to harbor a PRMT7 homologue. TbPRMT7 differs dramatically from all known metazoan PRMT7 homologues in lacking the second AdoMet binding-like domain that is required for activity of the human enzyme. Nevertheless, bacterially expressed TbPRMT7 exhibits robust methyltransferase activity toward multiple targets in vitro. High resolution ion exchange chromatography analysis of methylated substrates reveals that TbPRMT7 is a type III PRMT, catalyzing the formation of only monomethylarginine, thereby representing the only exclusively type III PRMT identified to date. TbPRMT7 is expressed in both mammalian and insect stage T. brucei and is apparently dispensable for growth in both life cycle stages. The enzyme is cytoplasmically localized and is a component of several higher order complexes in vivo. Together, our studies indicate that TbPRMT7 is a Type III PRMT, and its robust activity and presence in numerous complexes suggest it plays multiple roles during the complex T. brucei life cycle. PMID:19254949

A type III protein arginine methyltransferase from the protozoan parasite Trypanosoma brucei.

PubMed

Fisk, John C; Sayegh, Joyce; Zurita-Lopez, Cecilia; Menon, Sarita; Presnyak, Vladimir; Clarke, Steven G; Read, Laurie K

2009-04-24

Arginine methylation is a widespread post-translational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). The ancient protozoan parasite, Trypanosoma brucei, possesses five putative PRMTs, a relatively large number for a single-celled eukaryote. Trypanosomatids lack gene regulation at the level of transcription, instead relying on post-transcriptional control mechanisms that act at the levels of RNA turnover, translation, and editing, all processes that likely involve multiple RNA-binding proteins, which are common targets of arginine methylation. Here, we report the characterization of a trypanosome PRMT, TbPRMT7, which is homologous to human PRMT7. Interestingly, trypanosomatids are the only single-celled eukaryotes known to harbor a PRMT7 homologue. TbPRMT7 differs dramatically from all known metazoan PRMT7 homologues in lacking the second AdoMet binding-like domain that is required for activity of the human enzyme. Nevertheless, bacterially expressed TbPRMT7 exhibits robust methyltransferase activity toward multiple targets in vitro. High resolution ion exchange chromatography analysis of methylated substrates reveals that TbPRMT7 is a type III PRMT, catalyzing the formation of only monomethylarginine, thereby representing the only exclusively type III PRMT identified to date. TbPRMT7 is expressed in both mammalian and insect stage T. brucei and is apparently dispensable for growth in both life cycle stages. The enzyme is cytoplasmically localized and is a component of several higher order complexes in vivo. Together, our studies indicate that TbPRMT7 is a Type III PRMT, and its robust activity and presence in numerous complexes suggest it plays multiple roles during the complex T. brucei life cycle.

A model of high-affinity antibody binding to type III group B Streptococcus capsular polysaccharide.

PubMed

Wessels, M R; Muñoz, A; Kasper, D L

1987-12-01

We recently reported that the single repeating-unit pentasaccharide of type III group B Streptococcus (GBS) capsular polysaccharide is only weakly reactive with type III GBS antiserum. To further elucidate the relationship between antigen-chain length and antigenicity, tritiated oligosaccharides derived from type III capsular polysaccharide were used to generate detailed saturation binding curves with a fixed concentration of rabbit antiserum in a radioactive antigen-binding assay. A graded increase in affinity of antigen-antibody binding was seen as oligosaccharide size increased from 2.6 repeating units to 92 repeating units. These differences in affinity of antibody binding to oligosaccharides of different molecular size were confirmed by immunoprecipitation and competitive ELISA, two independent assays of antigen-antibody binding. Analysis of the saturation binding experiment indicated a difference of 300-fold in antibody-binding affinity for the largest versus the smallest tested oligosaccharides. Unexpectedly, the saturation binding values approached by the individual curves were inversely related to oligosaccharide chain length on a molar basis but equivalent on a weight basis. This observation is compatible with a model in which binding of an immunoglobulin molecule to an antigenic site on the polysaccharide facilitates subsequent binding of antibody to that antigen.

Relative quantitative comparisons of the extracellular protein profiles of Staphylococcus aureus UAMS-1 and its sarA, agr, and sarA agr regulatory mutants using one-dimensional polyacrylamide gel electrophoresis and nanocapillary liquid chromatography coupled with tandem mass spectrometry.

PubMed

Jones, Richard C; Deck, Joanna; Edmondson, Ricky D; Hart, Mark E

2008-08-01

One-dimensional polyacrylamide gel electrophoresis followed by nanocapillary liquid chromatography coupled with mass spectrometry was used to analyze proteins isolated from Staphylococcus aureus UAMS-1 after 3, 6, 12, and 24 h of in vitro growth. Protein abundance was determined using a quantitative value termed normalized peptide number, and overall, proteins known to be associated with the cell wall were more abundant early on in growth, while proteins known to be secreted into the surrounding milieu were more abundant late in growth. In addition, proteins from spent media and cell lysates of strain UAMS-1 and its isogenic sarA, agr, and sarA agr regulatory mutant strains during exponential growth were identified, and their relative abundances were compared. Extracellular proteins known to be regulated by the global regulators sarA and agr displayed protein levels in accordance with what is known regarding the effects of these regulators. For example, cysteine protease (SspB), endopeptidase (SspA), staphopain (ScpA), and aureolysin (Aur) were higher in abundance in the sarA and sarA agr mutants than in strain UAMS-1. The immunoglobulin G (IgG)-binding protein (Sbi), immunodominant staphylococcal antigen A (IsaA), IgG-binding protein A (Spa), and the heme-iron-binding protein (IsdA) were most abundant in the agr mutant background. Proteins whose abundance was decreased in the sarA mutant included fibrinogen-binding protein (Fib [Efb]), IsaA, lipase 1 and 2, and two proteins identified as putative leukocidin F and S subunits of the two-component leukotoxin family. Collectively, this approach identified 1,263 proteins (matches of two peptides or more) and provided a convenient and reliable way of identifying proteins and comparing their relative abundances.

Anti-freezing-protein type III strongly influences the expression of relevant genes in cryopreserved potato shoot tips.

PubMed

Seo, Ji Hyang; Naing, Aung Htay; Jeon, Su Min; Kim, Chang Kil

2018-06-04

AFP improved cryopreservation efficiency of potato (Solanum tuberosum cv. Superior) by regulating transcript levels of CBF1 and DHN1. However, the optimal AFP concentration required for strong induction of the genes was dependent on the type of vitrification solution to which the AFP was added: This finding suggests that AFP increased cryopreservation efficiency by transcriptional regulation of these genes, which might protect plant cell membranes from cold stress during cryopreservation. Despite the availability of many studies reporting the benefits of anti-freeze protein III (AFP III) as a cryoprotectant, the role of AFP III in this process has not been well demonstrated using molecular analysis. In addition, AFP III has not been exploited in the cryopreservation of potato thus far. Therefore, we studied the effects of AFP III on the cryopreservation of potato (Solanum tuberosum cv. Superior). We found that CBF1 and DHN1 genes are low temperature-inducible in potato leaves (S. tuberosum cv. Superior). Transcript levels of these genes expressed in shoot tips cryopreserved with AFP III were higher than those of the controls. However, the optimal AFP III concentration required for strong induction of the genes was dependent on the type of cryoprotection solution to which the AFP III was added: 500 ng/mL worked best for PVS2, while 1500 ng/mL was optimal for LS. Interestingly, the involvement of AFP III in the cryoprotection solutions improved cryopreservation efficiency as compared to the control, and expression levels of the detected genes were associated with cryopreservation efficiency. This finding suggests that AFP III increased cryopreservation efficiency by transcriptional regulation of these genes, which might protect plant cell membranes from cold stress during cryopreservation. Therefore, we expect that our findings will lead to the successful application of AFP III as a potent cryoprotectant in the cryopreservation of rare and commercially important

Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression.

PubMed

Bolen, Christopher R; Ding, Siyuan; Robek, Michael D; Kleinstein, Steven H

2014-04-01

Despite activating similar signaling cascades, the type I and type III interferons (IFNs) differ in their ability to antagonize virus replication. However, it is not clear whether these cytokines induce unique antiviral states, particularly in the liver, where the clinically important hepatitis B and C viruses cause persistent infection. Here, clustering and promoter analyses of microarray-based gene expression profiling were combined with mechanistic studies of signaling pathways to dynamically characterize the transcriptional responses induced by these cytokines in Huh7 hepatoma cells and primary human hepatocytes. Type I and III IFNs differed greatly in their level of interferon-stimulated gene (ISG) induction with a clearly detectable hierarchy (IFN-β > IFN-α > IFN-λ3 > IFN-λ1 > IFN-λ2). Notably, although the hierarchy identified varying numbers of differentially expressed genes when quantified using common statistical thresholds, further analysis of gene expression over multiple timepoints indicated that the individual IFNs do not in fact regulate unique sets of genes. The kinetic profiles of IFN-induced gene expression were also qualitatively similar with the important exception of IFN-α. While stimulation with either IFN-β or IFN-λs resulted in a similar long-lasting ISG induction, IFN-α signaling peaked early after stimulation then declined due to a negative feedback mechanism. The quantitative expression hierarchy and unique kinetics of IFN-α reveal potential specific roles for individual IFNs in the immune response, and elucidate the mechanism behind previously observed differences in IFN antiviral activity. While current clinical trials are focused on IFN-λ1 as a potential antiviral therapy, the finding that IFN-λ3 invariably possesses the highest activity among type III IFNs suggests that this cytokine may have superior clinical activity. © 2014 by the American Association for the Study of Liver Diseases.

ON THE BRIGHTNESS AND WAITING-TIME DISTRIBUTIONS OF A TYPE III RADIO STORM OBSERVED BY STEREO/WAVES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eastwood, J. P.; Hudson, H. S.; Krucker, S.

2010-01-10

Type III solar radio storms, observed at frequencies below {approx}16 MHz by space-borne radio experiments, correspond to the quasi-continuous, bursty emission of electron beams onto open field lines above active regions. The mechanisms by which a storm can persist in some cases for more than a solar rotation whilst exhibiting considerable radio activity are poorly understood. To address this issue, the statistical properties of a type III storm observed by the STEREO/WAVES radio experiment are presented, examining both the brightness distribution and (for the first time) the waiting-time distribution (WTD). Single power-law behavior is observed in the number distribution asmore » a function of brightness; the power-law index is {approx}2.1 and is largely independent of frequency. The WTD is found to be consistent with a piecewise-constant Poisson process. This indicates that during the storm individual type III bursts occur independently and suggests that the storm dynamics are consistent with avalanche-type behavior in the underlying active region.« less

Increased severity of type III supracondylar humerus fractures in the preteen population.

PubMed

Fletcher, Nicholas D; Schiller, Jonathan R; Garg, Sumeet; Weller, Amanda; Larson, A Noelle; Kwon, Michael; Browne, Richard; Copley, Lawson; Ho, Christine

2012-09-01

Supracondylar humerus fractures are the most common operative fractures in children; however, no studies describe the older child with this injury. The purpose of this study was to compare Gartland type III supracondylar humerus fractures in children older than 8 years of age with those in younger children than age 8. We hypothesized that there would be more complications in older children, reflecting a higher-energy injury mechanism. A retrospective chart review of supracondylar humerus fractures managed at a single level I pediatric trauma institution from 2004 to 2007 was performed. Patients with type III fractures were divided into groups based on age at presentation greater or less than 8. Baseline demographics, fracture characteristics, mechanism of injury, operative technique, and complications were analyzed. A consecutive series of 1297 pediatric patients with surgically treated supracondylar humerus fractures was retrospectively reviewed including 873 (67.3%) type III fractures. Of those, 160 (18.3%) patients were older than age 8 at time of injury. Older children were more likely to have fractures from high-energy mechanisms (45.1% vs. 28.7%, P<0.001) and more open fracture (3.8% vs. 1.3%, P=0.0097). There was no difference in preoperative or iatrogenic neuropraxias between groups. There was a shorter delay between presentation and surgery in older children (mean, 217 vs. 451 min, P<0.0001). Three or more pins were used more often in older patients (61.8% in older children vs. 43.6% in younger children, P<0.0001). Major complications including reoperation, loss of fixation, or compartment syndrome were rare in both groups (1.1% in younger group vs. 0.6% in older group, P=1.000). There was a trend toward more pin site infections in older children (3.75% vs. 1.56%, P=0.071). Physical therapy was required nearly 4 times more frequently in older children for management of residual stiffness (20.0% vs. 5.7%, P<0.0001). Children older than 8 years of age have a

Properties of Decameter IIIb-III Pairs

NASA Astrophysics Data System (ADS)

Melnik, V. N.; Brazhenko, A. I.; Frantsuzenko, A. V.; Dorovskyy, V. V.; Rucker, H. O.

2018-02-01

A large number of Type IIIb-III pairs, in which the first component is a Type IIIb burst and the second one is a Type III burst, are often recorded during decameter Type III burst storms. From the beginning of their observation, the question of whether the components of these pairs are the first and the second harmonics of radio emission or not has remained open. We discuss properties of decameter IIIb-III pairs in detail to answer this question. The components of these pairs, Type IIIb bursts and Type III bursts, have essentially different durations and polarizations. At the same time their frequency drift rates are rather close, provided that the drift rates of Type IIIb bursts are a little larger those of Type III bursts at the same frequency. Frequency ratios of the bursts at the same moment are close to two. This points at a harmonic connection of the components in IIIb-III pairs. At the same time there was a serious difficulty, namely why the first harmonic had fine frequency structure in the form of striae and the second harmonic did not have it. Recently Loi, Cairns, and Li ( Astrophys. J. 790, 67, 2014) succeeded in solving this problem. The physical aspects of observational properties of decameter IIIb-III pairs are discussed and pros and cons of harmonic character of Type IIIb bursts and Type III bursts in IIIb-III pairs are presented. We conclude that practically all properties of the IIIb-III pair components can be understood in the framework of the harmonic relation of the components of the IIIb-III pairs.

Tetracycline treatment of type III prostatitis nanobacteria infection of 100 cases report

NASA Astrophysics Data System (ADS)

Guo, Junyi; Li, Chongxian; Wu, Baisuo; Hao, Shaojun; Ming, Aimin; Zhang, Xinji; Li, Wenjun; Zhang, Zhengchen

2018-04-01

To investigate the efficacy of tetracycline treatment of nanobacterial infection in 100 cases of type III prostatitis. randomly divided into treatment group and control group with double blind method, the treatment group was given Tetracycline Tablets 250mg, oral, 2 times a day; the control group were treated with Levofloxacin Tablets 0.lg, oral, 2 times a day; observation of curative effect of two groups of patients after 1 months of treatment. after the treatment group patients NIH-CPSI score and pain, urinary symptoms and quality of life scores were significantly lower than that of control group (P<0.01); after treatment, observation group lecithin corpuscle scale score was significantly higher than the control group (P<0.05). The treatment group and the control group patients after prostate fluid and cultured positive cases of nanobacterial numbers were 21 (21%) and 100 cases (100%), the positive rate of nanobacteria in observation group was significantly lower than the control group (P<0.05). There is a good effect Tetracycline Tablets treatment of nanobacterial infection of type III prostatitis.

The ophthalmological course of Usher syndrome type III.

PubMed

Pakarinen, L; Tuppurainen, K; Laippala, P; Mäntyjärvi, M; Puhakka, H

Usher syndrome is a recessive hereditary disease group with clinical and genetical heterogeneity leading to handicapped hearing and visual loss until middle age. It is the most common cause for deaf-blindness. Three distinct phenotypes and five distinct genotypes are already known. In Finland the distribution of known Usher types is different than elsewhere. Usher syndrome type III (USH3) is common in Finland and it is thought to include 40% of patients. Progressive hearing loss is characteristic of USH3. Elsewhere USH3 has been regarded as a rarity covering only several percent of the whole Usher population. The aim of this paper is to describe, for the first time, the course of visual handicap and typical refractive errors in USH3 and compare it with other USH types. From a total patient sample consisting of 229 Finnish USH patients, 200 patients' visual findings were analyzed in a multicenter retrospective follow-up study. The average progress rate during a 10-year follow-up period in different USH types was similar. The essential progress occurred below the age of 40 and was continuous up to that age. Visual acuity dropped below 0.05 (severely impaired) at the age of 37 and the visual fields were of tubular shape without any peripheric islands at the average age of 30. Clinically significant hypermetropia with astigmatism seems to be a pathognomonic clinical sign of USH3.

Cochlear implantation using a custom guide catheter in fourteen patients with incomplete partition type III.

PubMed

Tian, Hao; Wang, Line; Gao, Fenqi; Liang, Wenqi; Peng, Kevin A

2018-05-22

Incomplete partition type III (IP-III), also termed X-linked deafness with stapes gusher, is a heterogeneous condition that predominantly affects males; however, females demonstrating the phenotype also exist. The absence of a bony partition between the fundus of the internal auditory canal (IAC) and cochlea predisposes these patients to cerebrospinal fluid leak or electrode passage into the IAC when performing cochlear implantation. We describe a surgeon-fabricated guide catheter, made intraoperatively from a 16-gauge intravenous catheter, that helps avoid electrode passage into the IAC during CI for patients with IP-III. Acceptable cochlear implant outcomes were attainable in IP-III patients, but these patients scored worse than matched CI patients with normal inner ear structures. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Purification of preparative quantities of group B Streptococcus type III oligosaccharides.

PubMed

Paoletti, L C; Johnson, K D

1995-06-30

Many bacterial capsular polysaccharides are regularly repeating units of oligosaccharides. Bacterial oligosaccharides have been used in neoglycoconjugate vaccines and as reagents in the study of specific antibody binding. Unfortunately, separation methods have not been adequate for the purification of preparative quantities of bacterial oligosaccharides. Here we describe a size-exclusion procedure that resulted in the resolution of group B Streptococcus type III oligosaccharides composed of 4-25 sugars.

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review.

PubMed

Wolfenden, C; Wittkowski, A; Hare, D J

2017-11-01

The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.

Modified closed-loop double-endobutton technique for repair of rockwood type III acromioclavicular dislocation

PubMed Central

Zhang, Lei; Zhou, Xin; Qi, Ji; Zeng, Yan; Zhang, Shaoqun; Liu, Gang; Ping, Ruiyue; Li, Yikai; Fu, Shijie

2018-01-01

Acromioclavicular dislocation (ACD) is a common injury. According to the Rockwood classification, ACD is classified into six types (type I–VI); however, for type III injuries, it remains controversial whether or not operative treatment should be applied. Numerous studies have advocated early surgical treatment to ensure early rehabilitation activities. Thus, the present study aimed to investigate a modified closed-loop double-endobutton technique (MCDT), that may be used to repair Rockwood type III ACD. In the current study, 61 patients with Rockwood type III ACD were enrolled during a period of 5 years at the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. Patients were divided into three groups according to the surgical method used, the MCDT group (n=20), the common closed-loop double-endobutton technique (CCDT) group (n=21), and the clavicular hook plate fixation (CHPF) group (n=20). Preoperative and intraoperative information were recorded. Furthermore, the functional scores of injured shoulder were evaluated prior to surgery and following surgery with a 1-year follow-up. Among the three groups, postoperative functional scores were significantly more improved compared with those prior to surgery (P<0.05), and no significant difference was observed regarding the coracoclavicular interval with the 1-year follow-up (P>0.05). Postoperative functional scores in the MCDT and CCDT groups were significantly more improved compared those in the CHPF group (P<0.05). In addition, the duration of surgery in the MCDT group was significantly shorter compared with that in the CCDT group (P<0.05). Furthermore, compared with the CHPF group, the incision length was significantly shorter with reduced hemorrhage in the MCDT group (P<0.05). In conclusion, the results of the current study suggest that MCDT is more simple, convenient and efficient compared with CCDT, and is worth popularizing. PMID:29399102

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

Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

PubMed

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

2015-08-01

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 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 triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma

Decimetric type III radio bursts and associated hard X-ray spikes

NASA Technical Reports Server (NTRS)

Dennis, B. R.; Benz, A. O.; Ranieri, M.; Simnett, G. M.

1984-01-01

For a relatively weak solar flare on August 6, 1981, at 10:32 UT, a detailed comparison is made between hard X-ray spikes and decimetric type III radio bursts. The hard X-ray observations are made at energies above 30 keV, and the radio data are obtained in the frequency range from 100 to 1000 MHz. The time resolution for all the data sets is approximately 0.1 s or better. The dynamic radio spectrum exhibits many fast drift type III radio bursts with both normal and reverse slope, whereas the X-ray time profile contains many well resolved short spikes with durations less than or equal to 1 s. Some of the X-ray spikes are seen to be associated in time with reverse-slope bursts, indicating either that the electron beams producing the radio burst contain two or three orders of magnitude more fast electrons than has previously been assumed or that the electron beams can induce the acceleration of additional electrons or occur in coincidence with this acceleration. A case is presented in which a normal slope radio burst at approximately 600 MHz occurs in coincidence with the peak of an X-ray spike to within 0.1 s.

Visualization and characterization of individual type III protein secretion machines in live bacteria

PubMed Central

Lara-Tejero, María; Bewersdorf, Jörg; Galán, Jorge E.

2017-01-01

Type III protein secretion machines have evolved to deliver bacterially encoded effector proteins into eukaryotic cells. Although electron microscopy has provided a detailed view of these machines in isolation or fixed samples, little is known about their organization in live bacteria. Here we report the visualization and characterization of the Salmonella type III secretion machine in live bacteria by 2D and 3D single-molecule switching superresolution microscopy. This approach provided access to transient components of this machine, which previously could not be analyzed. We determined the subcellular distribution of individual machines, the stoichiometry of the different components of this machine in situ, and the spatial distribution of the substrates of this machine before secretion. Furthermore, by visualizing this machine in Salmonella mutants we obtained major insights into the machine’s assembly. This study bridges a major resolution gap in the visualization of this nanomachine and may serve as a paradigm for the examination of other bacterially encoded molecular machines. PMID:28533372

[Elective visceral hybrid repair of type III thoracoabdominal aortic aneurysm].

PubMed

Marjanović, Ivan; Jevtić, Miodrag; Misović, Sidor; Zoranović, Uros; Tomić, Aleksandar; Rusović, Sinisa; Sarac, Momir

2012-03-01

According to the classification given by Crawford et al. type III thoracoabdominal aortic aneurysm (TAAA) is dilatation of the aorta from the level of the rib 6 to the separation of the aorta below the renal arteries, capturing all the visceral branch of aorta. Visceral hybrid reconstruction of TAAA is a procedure developed in recent years in the world, which involves a combination of conventional, open and endovascular aortic reconstruction surgery at the level of separation of the left subclavian artery to the level of visceral branches of aorta. We presented a 75-years-old man, with elective visceral hybrid reconstruc tion of type III TAAA. Computerized scanning (CT) angiography of the patient showed type III TAAA with the maximum transverse diameter of aneurysm of 92 mm. Aneurysm started at the level of the sixth rib, and the end of the aneurysm was 1 cm distal to the level of renal arteries. Aneurysm compressed the esophagus, causing the patient difficulty in swallowing act, especially solid food, and frequent back pain. From the other comorbidity, the patient had been treated for a long time, due to chronic obstructive pulmonary disease and hypertension. In general endotracheal anesthesia with epidural analgesia, the patient underwent visceral hybrid reconstruction of TAAA, which combines classic, open vascular surgery and endovascular procedures. Classic vascular surgery is visceral reconstruction using by-pass procedure from the distal, normal aorta to all visceral branches: celiac trunk, superior mesenteric artery and both renal arteries, with ligature of all arteries very close to the aorta. After that, by synchronous endovascular technique a complete aneurysmal exclusion of thoracoabdominal aneurysm with thoracic stent-graft was performed. The postoperative course was conducted properly and the patient left the Clinic for Vascular Surgery on postoperative day 21. Control CT, performed 3 months after the surgery showed that the patient's vascular status

Type III Cells in Anterior Taste Fields Are More Immunohistochemically Diverse Than Those of Posterior Taste Fields in Mice.

PubMed

Wilson, Courtney E; Finger, Thomas E; Kinnamon, Sue C

2017-10-31

Activation of Type III cells in mammalian taste buds is implicated in the transduction of acids (sour) and salty stimuli. Several lines of evidence suggest that function of Type III cells in the anterior taste fields may differ from that of Type III cells in posterior taste fields. Underlying anatomy to support this observation is, however, scant. Most existing immunohistochemical data characterizing this cell type focus on circumvallate taste buds in the posterior tongue. Equivalent data from anterior taste fields-fungiform papillae and soft palate-are lacking. Here, we compare Type III cells in four taste fields: fungiform, soft palate, circumvallate, and foliate in terms of reactivity to four canonical markers of Type III cells: polycystic kidney disease 2-like 1 (PKD2L1), synaptosomal associated protein 25 (SNAP25), serotonin (5-HT), and glutamate decarboxylase 67 (GAD67). Our findings indicate that while PKD2L1, 5-HT, and SNAP25 are highly coincident in posterior taste fields, they diverge in anterior taste fields. In particular, a subset of taste cells expresses PKD2L1 without the synaptic markers, and a subset of SNAP25 cells lacks expression of PKD2L1. In posterior taste fields, GAD67-positive cells are a subset of PKD2L1 expressing taste cells, but anterior taste fields also contain a significant population of GAD67-only expressing cells. These differences in expression patterns may underlie the observed functional differences between anterior and posterior taste fields. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ultrasonographic prenatal diagnosis of microcephalic osteodysplastic primordial dwarfism types I/III.

PubMed

Nadjari, M; Fasouliotis, S J; Ariel, I; Raas-Rothschild, A; Bar-Ziv, J; Elchalal, U

2000-08-01

Microcephalic osteodysplastic primordial dwarfism is a rare disease characterized by unique clinical appearance and specific radiographic findings, and distinctive brain abnormalities. We describe the prenatal diagnosis of two siblings with microcephalic osteodysplastic primordial dwarfism types I/III at 23 and 26 weeks of gestation, respectively. Early detection by sequential antenatal sonographic evaluation is important for counselling families known to be at risk of this rare disease. Copyright 2000 John Wiley & Sons, Ltd.

Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

PubMed Central

Cázares-Domínguez, Vicenta; Ochoa, Sara A.; Cruz-Córdova, Ariadnna; Rodea, Gerardo E.; Escalona, Gerardo; Olivares, Alma L.; Olivares-Trejo, José de Jesús; Velázquez-Guadarrama, Norma; Xicohtencatl-Cortes, Juan

2015-01-01

Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus. Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of

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

PubMed

Macho, Alberto P

2016-04-01

Most bacterial plant pathogens employ a type-III secretion system to inject type-III effector (T3E) proteins directly inside plant cells. These T3Es manipulate host cellular processes in order to create a permissive niche for bacterial proliferation, allowing development of the disease. An important role of T3Es in plant pathogenic bacteria is the suppression of plant immune responses. However, in recent years, research has uncovered T3E functions different from direct immune suppression, including the modulation of plant hormone signaling, metabolism or organelle function. This insight article discusses T3E functions other than suppression of immunity, which may contribute to the modulation of plant cells in order to promote bacterial survival, nutrient release, and bacterial replication and dissemination. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

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.

The influence of adjacent seating configurations on egress through a type III emergency exit.

DOT National Transportation Integrated Search

1989-12-01

When the United Kingdom Civil Aviation Authority (CAA) established a mandatory action intended to improve access to, and opening of, Type III emergency exits, the Northwest Mountain Region identified a need for a study to evaluate the proposed change...

X-ray Analysis of Defects and Anomalies in AGR-5/6/7 TRISO Particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmreich, Grant W.; Hunn, John D.; Skitt, Darren J.

2017-06-01

Coated particle fuel batches J52O-16-93164, 93165, 93166, 93168, 93169, 93170, and 93172 were produced by Babcock and Wilcox Technologies (BWXT) for possible selection as fuel for the Advanced Gas Reactor Fuel Development and Qualification (AGR) Program’s AGR-5/6/7 irradiation test in the Idaho National Laboratory (INL) Advanced Test Reactor (ATR), or may be used for other tests. Each batch was coated in a 150-mm-diameter production-scale fluidized-bed chemical vapor deposition (CVD) furnace. Tristructural isotropic (TRISO) coatings were deposited on 425-μm-nominal-diameter spherical kernels from BWXT lot J52R-16-69317 containing a mixture of 15.4%-enriched uranium carbide and uranium oxide (UCO), with the exception of Batchmore » 93164, which used similar kernels from BWXT lot J52L-16-69316. The TRISO-coatings consisted of a ~50% dense carbon buffer layer with 100-μmnominal thickness, a dense inner pyrolytic carbon (IPyC) layer with 40-μm-nominal thickness, a silicon carbide (SiC) layer with 35-μm-nominal thickness, and a dense outer pyrolytic carbon (OPyC) layer with 40-μm-nominal thickness. Each coated particle batch was sieved to upgrade the particles by removing over-sized and under-sized material, and the upgraded batch was designated by appending the letter A to the end of the batch number (e.g., 93164A). Secondary upgrading by sieving was performed on the upgraded batches to remove specific anomalies identified during analysis for Defective IPyC, and the upgraded batches were designated by appending the letter B to the end of the batch number (e.g., 93165B). Following this secondary upgrading, coated particle composite J52R-16-98005 was produced by BWXT as fuel for the AGR Program’s AGR-5/6/7 irradiation test in the INL ATR. This composite was comprised of coated particle fuel batches J52O-16-93165B, 93168B, 93169B, and 93170B.« less

Comparison of silver release predictions using PARFUME with results from the AGR-2 irradiation experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collin, Blaise P.; Demkowicz, Paul A.; Baldwin, Charles A.

2016-11-01

The PARFUME (PARticle FUel ModEl) code was used to predict silver release from tristructural isotropic (TRISO) coated fuel particles and compacts during the second irradiation experiment (AGR-2) of the Advanced Gas Reactor Fuel Development and Qualification program. The PARFUME model for the AGR-2 experiment used the fuel compact volume average temperature for each of the 559 days of irradiation to calculate the release of fission product silver from a representative particle for a select number of AGR-2 compacts and individual fuel particles containing either mixed uranium carbide/oxide (UCO) or 100% uranium dioxide (UO2) kernels. Post-irradiation examination (PIE) measurements were performedmore » to provide data on release of silver from these compacts and individual fuel particles. The available experimental fractional releases of silver were compared to their corresponding PARFUME predictions. Preliminary comparisons show that PARFUME under-predicts the PIE results in UCO compacts and is in reasonable agreement with experimental data for UO2 compacts. The accuracy of PARFUME predictions is impacted by the code limitations in the modeling of the temporal and spatial distributions of the temperature across the compacts. Nevertheless, the comparisons on silver release lie within the same order of magnitude.« less

Epigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth

PubMed Central

Ding, Siyuan; Khoury-Hanold, William; Iwasaki, Akiko; Robek, Michael D.

2014-01-01

Type III interferon (IFN-λ) exhibits potent antiviral activity similar to IFN-α/β, but in contrast to the ubiquitous expression of the IFN-α/β receptor, the IFN-λ receptor is restricted to cells of epithelial origin. Despite the importance of IFN-λ in tissue-specific antiviral immunity, the molecular mechanisms responsible for this confined receptor expression remain elusive. Here, we demonstrate that the histone deacetylase (HDAC) repression machinery mediates transcriptional silencing of the unique IFN-λ receptor subunit (IFNLR1) in a cell-type-specific manner. Importantly, HDAC inhibitors elevate receptor expression and restore sensitivity to IFN-λ in previously nonresponsive cells, thereby enhancing protection against viral pathogens. In addition, blocking HDAC activity renders nonresponsive cell types susceptible to the pro-apoptotic activity of IFN-λ, revealing the combination of HDAC inhibitors and IFN-λ to be a potential antitumor strategy. These results demonstrate that the type III IFN response may be therapeutically harnessed by epigenetic rewiring of the IFN-λ receptor expression program. PMID:24409098

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

[Clavicular hook plate combined with suture anchor for the treatment of type Tossy III chronic acromioclavicular dislocation].

PubMed

Xu, Zhi-Bin; Wang, Jin

2014-05-01

To observe the clinical effects of clavicular hook plate combined with suture anchor in treating type Tossy III chronic acromioclavicular dislocation. From January 2008 to December 2012,18 patients with type Tossy III chronic acromioclavicular dislocation were treated with clavicular hook plate and suture anchor. There were 12 males and 6 females, aged from 20 to 56 years old with an average of 31.5 years. Ten cases were left dislocation and 8 cases were right dislocation. Operation time was 3 weeks to 4 months after injury with a mean of 1.8 months. Functional exercise was adopted 2 weeks after operation. And Karlsson standard was used to evaluate curative effect. All patients were followed up for 6 to 24 months with an average of 16 months. According to Karlsson standard, 17 cases were excellent and 1 was poor. Clavicular hook plate combined with suture anchor can repair conoid ligament and trapezoid ligament in treating type Tossy III chronic acromioclavicular dislocation, and had advantages of simple operation, less trauma, stable fixation, it can obtain satisfactory effects.

Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed

Meinecke, P; Passarge, E

1991-11-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus.

PubMed

García-Betancur, Juan-Carlos; Goñi-Moreno, Angel; Horger, Thomas; Schott, Melanie; Sharan, Malvika; Eikmeier, Julian; Wohlmuth, Barbara; Zernecke, Alma; Ohlsen, Knut; Kuttler, Christina; Lopez, Daniel

2017-09-12

A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus , which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureus teichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.

Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus

PubMed Central

García-Betancur, Juan-Carlos; Goñi-Moreno, Angel; Horger, Thomas; Schott, Melanie; Sharan, Malvika; Eikmeier, Julian; Wohlmuth, Barbara; Zernecke, Alma; Ohlsen, Knut; Kuttler, Christina

2017-01-01

A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types. PMID:28893374

Small-molecule type III secretion system inhibitors block assembly of the Shigella type III secreton.

PubMed

Veenendaal, Andreas K J; Sundin, Charlotta; Blocker, Ariel J

2009-01-01

Type III secretion systems (T3SSs) are essential virulence devices for many gram-negative bacteria that are pathogenic for plants, animals, and humans. They serve to translocate virulence effector proteins directly into eukaryotic host cells. T3SSs are composed of a large cytoplasmic bulb and a transmembrane region into which a needle is embedded, protruding above the bacterial surface. The emerging antibiotic resistance of bacterial pathogens urges the development of novel strategies to fight bacterial infections. Therapeutics that rather than kill bacteria only attenuate their virulence may reduce the frequency or progress of resistance emergence. Recently, a group of salicylidene acylhydrazides were identified as inhibitors of T3SSs in Yersinia, Chlamydia, and Salmonella species. Here we show that these are also effective on the T3SS of Shigella flexneri, where they block all related forms of protein secretion so far known, as well as the epithelial cell invasion and induction of macrophage apoptosis usually demonstrated by this bacterium. Furthermore, we show the first evidence for the detrimental effect of these compounds on T3SS needle assembly, as demonstrated by increased numbers of T3S apparatuses without needles or with shorter needles. Therefore, the compounds generate a phenocopy of T3SS export apparatus mutants but with incomplete penetrance. We discuss why this would be sufficient to almost completely block the later secretion of effector proteins and how this begins to narrow the search for the molecular target of these compounds.

Secretion of Pseudomonas aeruginosa type III cytotoxins is dependent on pseudomonas quinolone signal concentration.

PubMed

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

2010-10-01

Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent post-translational control, specifically governing type III cytotoxin secretion, exists in this species. Copyright 2010 Elsevier Ltd. All rights reserved.

The Effect of Birthrate Granularity on the Release- to- Birth Ratio for the AGR-1 In-core Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawn Scates; John Walter

The AGR-1 Advanced Gas Reactor (AGR) tristructural-isotropic-particle fuel experiment underwent 13 irradiation intervals from December 2006 until November 2009 within the Idaho National Laboratory Advanced Test Reactor in support of the Next Generation Nuclear Power Plant program. During this multi-year experiment, release-to-birth rate ratios were computed at the end of each operating interval to provide information about fuel performance. Fission products released during irradiation were tracked daily by the Fission Product Monitoring System using 8-hour measurements. Birth rates calculated by MCNP with ORIGEN for as-run conditions were computed at the end of each irradiation interval. Each time step in MCNPmore » provided neutron flux, reaction rates and AGR-1 compact composition, which were used to determine birth rates using ORIGEN. The initial birth-rate data, consisting of four values for each irradiation interval at the beginning, end, and two intermediate times, were interpolated to obtain values for each 8-hour activity. The problem with this method is that any daily changes in heat rates or perturbations, such as shim control movement or core/lobe power fluctuations, would not be reflected in the interpolated data and a true picture of the system would not be presented. At the conclusion of the AGR-1 experiment, great efforts were put forth to compute daily birthrates, which were reprocessed with the 8-hour release activity. The results of this study are presented in this paper.« less

The effect of birthrate granularity on the release-to-birth ratio for the AGR-1 in-core experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

D. M. Scates; J. B. Walter; J. T. Maki

The AGR-1 Advanced Gas Reactor (AGR) tristructural-isotropic-particle fuel experiment underwent 13 irradiation intervals from December 2006 until November 2009 within the Idaho National Laboratory Advanced Test Reactor in support of the Next Generation Nuclear Power Plant program. During this multi-year experiment, release-to-birth rate ratios were computed at the end of each operating interval to provide information about fuel performance. Fission products released during irradiation were tracked daily by the Fission Product Monitoring System using 8-h measurements. Birth rate calculated by MCNP with ORIGEN for as-run conditions were computed at the end of each irradiation interval. Each time step in MCNPmore » provided neutron flux, reaction rates and AGR-1 compact composition, which were used to determine birth rate using ORIGEN. The initial birth-rate data, consisting of four values for each irradiation interval at the beginning, end, and two intermediate times, were interpolated to obtain values for each 8-h activity. The problem with this method is that any daily changes in heat rates or perturbations, such as shim control movement or core/lobe power fluctuations, would not be reflected in the interpolated data and a true picture of the system would not be presented. At the conclusion of the AGR-1 experiment, great efforts were put forth to compute daily birthrates, which were reprocessed with the 8-h release activity. The results of this study are presented in this paper.« less

The effects of wearing Passenger Protective Breathing Equipment on evacuation times through type III and type IV emergency aircraft exits in clear air and smoke.

DOT National Transportation Integrated Search

1989-11-01

The effects of Passenger Protective Breathing Equipment (PPBE) on the time required for simulated emergency evacuations through Type III and Type IV overwing aircraft exits were studied in two quasi-independent experiments, one in clear air and anoth...

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Comparison of fission product release predictions using PARFUME with results from the AGR-1 safety tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collin, Blaise P.; Petti, David A.; Demkowicz, Paul A.

Safety tests were conducted on fuel compacts from AGR-1, the first irradiation experiment of the Advanced Gas Reactor (AGR) Fuel Development and Qualification program, at temperatures ranging from 1600 to 1800 °C to determine fission product release at temperatures that bound reactor accident conditions. The PARFUME (PARticle FUel ModEl) code was used to predict the release of fission products silver, cesium, strontium, and krypton from fuel compacts containing tristructural isotropic (TRISO) coated particles during 15 of these safety tests. Comparisons between PARFUME predictions and post-irradiation examination results of the safety tests were conducted on two types of AGR-1 compacts: compactsmore » containing only intact particles and compacts containing one or more particles whose SiC layers failed during safety testing. In both cases, PARFUME globally over-predicted the experimental release fractions by several orders of magnitude: more than three (intact) and two (failed SiC) orders of magnitude for silver, more than three and up to two orders of magnitude for strontium, and up to two and more than one orders of magnitude for krypton. The release of cesium from intact particles was also largely over-predicted (by up to five orders of magnitude) but its release from particles with failed SiC was only over-predicted by a factor of about 3. These over-predictions can be largely attributed to an over-estimation of the diffusivities used in the modeling of fission product transport in TRISO-coated particles. The integral release nature of the data makes it difficult to estimate the individual over-estimations in the kernel or each coating layer. Nevertheless, a tentative assessment of correction factors to these diffusivities was performed to enable a better match between the modeling predictions and the safety testing results. The method could only be successfully applied to silver and cesium. In the case of strontium, correction factors could not be assessed

Comparison of fission product release predictions using PARFUME with results from the AGR-1 safety tests

DOE PAGES

Collin, Blaise P.; Petti, David A.; Demkowicz, Paul A.; ...

2016-04-07

Safety tests were conducted on fuel compacts from AGR-1, the first irradiation experiment of the Advanced Gas Reactor (AGR) Fuel Development and Qualification program, at temperatures ranging from 1600 to 1800 °C to determine fission product release at temperatures that bound reactor accident conditions. The PARFUME (PARticle FUel ModEl) code was used to predict the release of fission products silver, cesium, strontium, and krypton from fuel compacts containing tristructural isotropic (TRISO) coated particles during 15 of these safety tests. Comparisons between PARFUME predictions and post-irradiation examination results of the safety tests were conducted on two types of AGR-1 compacts: compactsmore » containing only intact particles and compacts containing one or more particles whose SiC layers failed during safety testing. In both cases, PARFUME globally over-predicted the experimental release fractions by several orders of magnitude: more than three (intact) and two (failed SiC) orders of magnitude for silver, more than three and up to two orders of magnitude for strontium, and up to two and more than one orders of magnitude for krypton. The release of cesium from intact particles was also largely over-predicted (by up to five orders of magnitude) but its release from particles with failed SiC was only over-predicted by a factor of about 3. These over-predictions can be largely attributed to an over-estimation of the diffusivities used in the modeling of fission product transport in TRISO-coated particles. The integral release nature of the data makes it difficult to estimate the individual over-estimations in the kernel or each coating layer. Nevertheless, a tentative assessment of correction factors to these diffusivities was performed to enable a better match between the modeling predictions and the safety testing results. The method could only be successfully applied to silver and cesium. In the case of strontium, correction factors could not be assessed

The Agr quorum-sensing system regulates fibronectin binding but not hemolysis in the absence of a functional electron transport chain.

PubMed

Pader, Vera; James, Ellen H; Painter, Kimberley L; Wigneshweraraj, Sivaramesh; Edwards, Andrew M

2014-10-01

Staphylococcus aureus is responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain of S. aureus genetically (hemB and menD) or chemically, using 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in both hemB mutant strains and S. aureus grown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression in hemB mutant strains or S. aureus grown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Agr Quorum-Sensing System Regulates Fibronectin Binding but Not Hemolysis in the Absence of a Functional Electron Transport Chain

PubMed Central

Pader, Vera; James, Ellen H.; Painter, Kimberley L.; Wigneshweraraj, Sivaramesh

2014-01-01

Staphylococcus aureus is responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain of S. aureus genetically (hemB and menD) or chemically, using 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in both hemB mutant strains and S. aureus grown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression in hemB mutant strains or S. aureus grown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain. PMID:25092909

Initial results from safety testing of US AGR-2 irradiation test fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, Robert Noel; Hunn, John D.; Baldwin, Charles A.

Two cylindrical compacts containing tristructural isotropic (TRISO)-coated particles with kernels that contained a mixture of uranium carbide and uranium oxide (UCO) and two compacts with UO 2-kernel TRISO particles have undergone 1600°C safety testing. These compacts were irradiated in the US Advanced Gas Reactor Fuel Development and Qualification Program's second irradiation test (AGR-2). The time-dependent releases of several radioisotopes ( 110mAg, 134Cs, 137Cs, 154Eu, 155Eu, 90Sr, and 85Kr) were monitored while heating the fuel specimens to 1600°C in flowing helium for 300 h. The UCO compacts behaved similarly to previously reported 1600°C-safety-tested UCO compacts from the AGR-1 irradiation. No failedmore » TRISO or failed SiC were detected (based on krypton and cesium release), and cesium release through intact SiC was very low. Release behavior of silver, europium, and strontium appeared to be dominated by inventory originally released through intact coating layers during irradiation but retained in the compact matrix until it was released during safety testing. Both UO 2 compacts exhibited cesium release from multiple particles whose SiC failed during the safety test. Europium and strontium release from these two UO 2 compacts appeared to be dominated by release from the particles with failed SiC. Silver release was characteristically like the release from the UCO compacts in that an initial release of the majority of silver trapped in the matrix occurred during ramping to 1600°C. However, additional silver release was observed later in the safety testing due to the UO 2 TRISO with failed SiC. Failure of the SiC layer in the UO 2 fuel appears to have been dominated by CO corrosion, as opposed to the palladium degradation observed in AGR-1 UCO fuel.« less

Initial results from safety testing of US AGR-2 irradiation test fuel

DOE PAGES

Morris, Robert Noel; Hunn, John D.; Baldwin, Charles A.; ...

2017-08-18

Two cylindrical compacts containing tristructural isotropic (TRISO)-coated particles with kernels that contained a mixture of uranium carbide and uranium oxide (UCO) and two compacts with UO 2-kernel TRISO particles have undergone 1600°C safety testing. These compacts were irradiated in the US Advanced Gas Reactor Fuel Development and Qualification Program's second irradiation test (AGR-2). The time-dependent releases of several radioisotopes ( 110mAg, 134Cs, 137Cs, 154Eu, 155Eu, 90Sr, and 85Kr) were monitored while heating the fuel specimens to 1600°C in flowing helium for 300 h. The UCO compacts behaved similarly to previously reported 1600°C-safety-tested UCO compacts from the AGR-1 irradiation. No failedmore » TRISO or failed SiC were detected (based on krypton and cesium release), and cesium release through intact SiC was very low. Release behavior of silver, europium, and strontium appeared to be dominated by inventory originally released through intact coating layers during irradiation but retained in the compact matrix until it was released during safety testing. Both UO 2 compacts exhibited cesium release from multiple particles whose SiC failed during the safety test. Europium and strontium release from these two UO 2 compacts appeared to be dominated by release from the particles with failed SiC. Silver release was characteristically like the release from the UCO compacts in that an initial release of the majority of silver trapped in the matrix occurred during ramping to 1600°C. However, additional silver release was observed later in the safety testing due to the UO 2 TRISO with failed SiC. Failure of the SiC layer in the UO 2 fuel appears to have been dominated by CO corrosion, as opposed to the palladium degradation observed in AGR-1 UCO fuel.« less

Osteogenesis imperfecta type III/Ehlers-Danlos overlap syndrome in a Chinese man.

PubMed

Lu, Yanqin; Wang, Yanzhou; Rauch, Frank; Li, Hu; Zhang, Yao; Zhai, Naixiang; Zhang, Jian; Ren, Xiuzhi; Han, Jinxiang

2018-02-01

Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are rare genetic disorders that are typically inherited in an autosomal dominant manner. Few cases of OI/EDS overlap syndrome have been documented. Described here is a 30-year-old Chinese male with OI type III and EDS. Sequencing of genomic DNA revealed a heterozygous COL1A1 mutation (c.671G>A, p.Gly224Asp) that affected the N-anchor domain of the alpha 1 chain of collagen type I. Ultrastructural analysis of a skin biopsy specimen revealed thin collagen fibers with irregular alignment of collagen fibers. These findings have expanded the genotypic spectrum of the OI/EDS overlap syndrome.

High frequency of methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type III and spa type t030 in Karaj's teaching hospitals, Iran.

PubMed

Bayat, Bahareh; Zade, Masoumeh Hallaj; Mansouri, Samaneh; Kalantar, Enayat; Kabir, Kourosh; Zahmatkesh, Ehsan; Sepehr, Mohammad Noori; Naseri, Mohammmad Hassan; Darban-Sarokhalil, Davood

2017-09-01

Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the most important antibiotic-resistant pathogen in many parts of the world over the past decades. This cross-sectional study was conducted to investigate MRSA isolated between July 2013 and July 2014 in Karaj, Iran. All tested isolates were collected in teaching hospitals from personnel, patients, and surfaces and each MRSA was analyzed by SCCmec and spa typing. Antibiotic susceptibility testing was accomplished by disk diffusion method. Out of 49 MRSA isolates from the Karaj's teaching hospitals, 82%, 10%, and 6% of the isolates were SCCmec types III, II, and I, respectively. The main spa type in this study was spa t030 with frequency as high as 75.5% from intensive care unit (ICU) of the hospitals and high rate of resistance to rifampicin (53%) was found in MRSA isolates. In conclusion, high frequency of spa t030 with SCCmec type III and MRSA phenotype illustrated circulating of one of the antibiotic-resistant strains in ICU of Karaj's teaching hospitals and emphasizes the need for ongoing molecular surveillance, antibiotic susceptibility monitoring, and infection control.

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

DOE PAGES

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

2014-12-26

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed Central

Meinecke, P; Passarge, E

1991-01-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation. Images PMID:1770539

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

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

NASA Astrophysics Data System (ADS)

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

2017-06-01

The paper 'Spectroscopic Identification of Type 2 Quasars at z < 1 in SDSS-III/BOSS' was published in MNRAS, 462, 1603-1615 (2016). The data files in the supporting section are not successfully linked. The actual data files can be found at http://zakamska.johnshopkins.edu/data.htm.

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

USDA-ARS?s Scientific Manuscript database

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, ...

Cierny-Mader Type III chronic osteomyelitis: the results of patients treated with debridement, irrigation, vancomycin beads and systemic antibiotics

PubMed Central

Karaduman, Mert

2007-01-01

Cierny-Mader (C-M) Type III osteomyelitis is defined as a localised lesion with both medullary and cortical involvement that is stable mechanically after debridement. The treatment of C-M Type III osteomyelitisis is difficult and requires a precise protocol to achieve a disease-free long-term follow-up. We report here the results of our study on 26 patients (19 men and 7 women; average age: 34.7 years) with C-M Type III osteomylelitis who were treated with radical debridement, irrigation, vancomycin-impregnated custom-made beads and culture-specific systemic antibiotics. Those patients with metaphyseal involvement were treated with deroofing of the cortex and debridement by means of a “trough” (16 patients); those with diaphyseal involvement were treated with both intramedullary reaming and debridement from a trough (ten patients). Antibiotic cement rods were used as an additional therapy in five patients with diaphyseal involvement. Recurrence developed in three patients and was attributed to inadequate debridement; all three patients were treated again in the same manner with success. The mean follow-up is currently 3.6 years (range: 2–6 years). All of the patients have normal clinical, radiographic and laboratory parameters, and all are ambulatory and have returned to their pretreatment level of activity or better. We conclude that C-M Type III chronic osteomyelitis can be safely treated with this protocol. PMID:17375299

Deinfibulation for preventing or treating complications in women living with type III female genital mutilation: A systematic review and meta-analysis.

PubMed

Okusanya, Babasola O; Oduwole, Olabisi; Nwachuku, Nuria; Meremikwu, Martin M

2017-02-01

Deinfibulation is a surgical procedure carried out to re-open the vaginal introitus of women living with type III female genital mutilation (FGM). To assess the impact of deinfibulation on gynecologic or obstetric outcomes by comparing women who were deinfibulated with women with type III FGM or women without FGM. Major databases including CENTRAL, MEDLINE, and Scopus were searched until August 2015. We included nonrandomized studies that compared obstetric outcomes of women with deinfibulation, type III FGM (not deinfibulated during labor), and no FGM. Quality of evidence was determined following the GRADE methodology. Summary measures were calculated using odds ratios at 95% confidence intervals. We found no randomized controlled trials. We included four case-control studies. The quality of evidence was very low. Compared with women with type III FGM at delivery, deinfibulated women had a significant reduction in the risk of having a cesarean delivery or postpartum hemorrhage. Compared with women without FGM, deinfibulated women had a similar risk of episiotomy, cesarean delivery, vaginal lacerations, postpartum hemorrhage, and blood loss at vaginal delivery. The length of second stage of labor, mean maternal hospital stay, and Apgar scores less than 7 were also comparable. Low-quality evidence suggests deinfibulation improves birth outcomes for women with type III FGM. CRD42015024466. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

[Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease].

PubMed

Mantilla, Carolina; Toro, Mónica; Sepúlveda, María Elsy; Insuasty, Margarita; Di Filippo, Diana; López, Juan Álvaro; Baquero, Carolina; Navas, María Cristina; Arias, Andrés Augusto

2018-05-01

Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

PubMed

Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

2014-06-01

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease

PubMed Central

Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

2014-01-01

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ-and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. PMID:24666275

Assessing the ability of Salmonella enterica to translocate Type III effectors into plant cells

USDA-ARS?s Scientific Manuscript database

Salmonella enterica, a human enteric pathogen, has the ability to multiply and survive endophytically in plants, and mutations in genes encoding the type III secretion system (T3SS) or its effectors (T3Es) may contribute to this colonization. Two reporter plasmids for T3E translocation into plant ce...

Classification and Realizations of Type III Factor Representations of Cuntz-Krieger Algebras Associated with Quasi-Free States

NASA Astrophysics Data System (ADS)

Kawamura, Katsunori

2009-03-01

We completely classify type III factor representations of Cuntz-Krieger algebras associated with quasi-free states up to unitary equivalence. Furthermore, we realize these representations on concrete Hilbert spaces without using GNS construction. Free groups and their type II1 factor representations are used in these realizations.

Palliative treatment with radiation-emitting metallic stents in unresectable Bismuth type III or IV hilar cholangiocarcinoma.

PubMed

Lu, Jian; Guo, Jin-He; Zhu, Hai-Dong; Zhu, Guang-Yu; Wang, Yong; Zhang, Qi; Chen, Li; Wang, Chao; Pan, Tian-Fan; Teng, Gao-Jun

2017-01-01

The emerging data for stenting in combination with brachytherapy in unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma. Consecutive patients who underwent percutaneous placement with REMS or uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma between September 2011 and April 2016 were identified into this retrospective study. Data on patient demographics and overall survival, functional success, stent patency and complications were collected at the authors' hospital. A total of 59 patients were included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The median overall survival was 338 days in the REMS group and 141 days in the SEMS group (p<0.001). The median stent patency time was 385 days for REMS and 142 days for SEMS (p<0.001). The functional success rate (87.9% vs 84.6%, p=0.722) and incidence of overall complications (27.3% vs 26.9%, p=0.999) did not differ in the two groups. Placement with REMS is safe and effective in palliation for unresectable Bismuth type III or IV hilar cholangiocarcinoma, and seems to prolong survival as well as patency of stent in these patients.

Investigations into the synthesis and fluorescence properties of Eu(III), Tb(III), Sm(III) and Gd(III) complexes of a novel bis- β-diketone-type ligand

NASA Astrophysics Data System (ADS)

Luo, Yi-Ming; Chen, Zhe; Tang, Rui-Ren; Xiao, Lin-Xiang; Peng, Hong-Jian

2008-02-01

A novel bis- β-diketon ligand, 1,1'-(2,6-bispyridyl)bis-3-phenyl-1,3-propane-dione (L), was designed and synthesized and its complexes with Eu(III), Tb(III), Sm(III) and Gd(III) ions were successfully prepared. The ligand and the corresponding metal complexes were characterized by elemental analysis, and infrared, mass and proton nuclear magnetic resonance spectroscopy. Analysis of the IR spectra suggested that each of the lanthanide metal ions coordinated to the ligand via the carbonyl oxygen atoms and the nitrogen atom of the pyridine ring. The fluorescence properties of these complexes in solid state were investigated and it was discovered that all of the lanthanide ions could be sensitized by the ligand (L) to some extent. In particular, the Tb(III) complex was an excellent green-emitter and would be a potential candidate material for applications in organic light-emitting devices (OLEDs) and medical diagnosis.

^1H NMR studies of the diamagnetic gallium (III) and paramagnetic iron (III) complexes of a chiral macrobicyclic ligand of bicapped tris (binaphtol) type

NASA Astrophysics Data System (ADS)

Baret, P.; Beaujolais, V.; Bougault, C.; Gaude, D.; Pierre, J.-L.

1998-01-01

^1H NMR studies of the diamagnetic gallium (III) and paramagnetic iron (III) complexes of a chiral macrobicyclic ligand of bicapped tris (binaphtol) type are described. The study of the gallium complex emphasizes: (i) that the inversion of the octahedral center is not observed and: (ii) the absence of exchange between free ligand and complex, at room temperature. In the case of the iron complex, assignments of the hyperfine shifted resolved resonances are achieved, based on temperature-behavior studies, which evidence the D3 symmetry of the complex. These assignments are in complete agreement with measured T1 values and proton-to-iron distances obtained from molecular modelling. Les complexes du gallium (III) et du fer (III) d'un ligand macrobicyclique chiral impliquant trois sous-unités de type binaphtol sont étudiés en RMN du proton en solution méthanolique. L'étude du complexe (diamagnétique) du gallium permet de montrer que le complexe : (i) ne subit pas d'inversion de la configuration (Δ/Λ) du site octaédrique et : (ii) qu'il n'y a pas d'échange entre ligand libre et complexe à la température ambiante. L'évolution du spectre du complexe paramagnétique du fer avec la température permet une attribution des protons du ligand et met en évidence la symétrie D3 du complexe. Une bonne corrélation est obtenue entre la distance fer-proton (donnée par la modélisation moléculaire) et le T1 du proton considéré.

Pentanuclear heterometallic {Mn(III)(2)Ln(3)} (Ln = Gd, Dy, Tb, Ho) assemblies in an open-book type structural topology: appearance of slow relaxation of magnetization in the Dy(III) and Ho(III) analogues.

PubMed

Bag, Prasenjit; Chakraborty, Amit; Rogez, Guillaume; Chandrasekhar, Vadapalli

2014-07-07

The reaction of Ln(III) nitrate and Mn(ClO4)2·6H2O salts in the presence of a multidentate sterically unencumbered ligand, (E)-2,2'-(2-hydroxy-3-((2-hydroxyphenylimino)methyl)-5-methylbenzylazanediyl)diethanol (LH4) leads to the isolation of four isostructural pentanuclear hetereometallic complexes [Mn(III)2Gd3(LH)4(NO3)(HOCH3)]ClO4·NO3 (1), [Mn(III)2Dy3(LH)4(NO3)(HOCH3)]ClO4·NO3 (2), [Mn(III)2Tb3(LH)4(NO3)(HOCH3)]ClO4·NO3 (3), and [Mn(III)2Ho3(LH)4(NO3)(HOCH3)]ClO4·NO3 (4) with an open-book type structural topology. 1-4 are dicationic and crystallize in the achiral space group, P21/n. A total of four triply deprotonated ligands, [LH](3-), are involved in holding the pentameric metal framework, {Mn(III)2Ln3}. In these complexes both the lanthanide and the manganese(III) ions are doubly bridged, involving phenolate or ethoxide oxygen atoms. The magnetochemical analysis reveals the presence of global antiferromagnetic interactions among the spin centers at low temperatures in all the four compounds. AC susceptibility measurements show the presence of temperature dependent out-of-phase ac signal for compounds 2 and 4 indicating an SMM behavior.

[CrIII(NCMe)6]3+--a labile CrIII source enabling formation of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue-type magnetic materials.

PubMed

Nelson, Kendric J; Daniels, Matthew C; Reiff, William M; Troff, Shayla A; Miller, Joel S

2007-11-26

The kinetic inertness of the hexaaquachromium(III) (kH2O=2.4x10(-6) s(-1)) has led to challenges with respect to incorporating CrIII ions into Prussian blue-type materials; however, hexakis(acetonitrile)chromium(III) was shown to be substantially more labile (approximately 10(4) times) and enables a new synthetic route for the synthesis of these materials via nonaqueous solvents. The synthesis, spectroscopic, and physical properties of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue analogues synthesized from [CrIII(NCMe)6]3+ and the corresponding [MIII(CN)6]3- are described. All these compounds {(NEt4)0.02CrIII[VIII(CN)6]0.98(BF4)(0.08).0.10MeCN (1), CrIII[CrIII(CN)6].0.16MeCN (2), CrIII[MnIII(CN)6].0.10MeCN (3), and (NEt4)0.04CrIII0.64CrIV0.40[FeII(CN)6]0.40[FeIII(CN)6]0.60(BF4)(0.16).1.02MeCN (4)} are ferrimagnets exhibiting cluster-glass behavior. Strong antiferromagnetic coupling was observed for M=V, Cr, and Mn with Weiss constants (theta) ranging from -132 to -524 K; and in 2, where the strongest coupling is observed (theta=-524 K), the highest Tc (110 K) value was observed. Weak antiferromagnetic coupling was observed for M=Fe (theta=-12 K) leading to the lowest Tc (3 K) value in this series. Weak coupling and the low Tc value observed in 4 were additionally contributed by the presence of both [FeII(CN)6]4- and [FeIII(CN)6]3- as confirmed by 57Fe-Mössbauer spectroscopy.

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Mash1-expressing cells could differentiate to type III cells in adult mouse taste buds.

PubMed

Takagi, Hiroki; Seta, Yuji; Kataoka, Shinji; Nakatomi, Mitsushiro; Toyono, Takashi; Kawamoto, Tatsuo

2018-03-10

The gustatory cells in taste buds have been identified as paraneuronal; they possess characteristics of both neuronal and epithelial cells. Like neurons, they form synapses, store and release transmitters, and are capable of generating an action potential. Like epithelial cells, taste cells have a limited life span and are regularly replaced throughout life. However, little is known about the molecular mechanisms that regulate taste cell genesis and differentiation. In the present study, to begin to understand these mechanisms, we investigated the role of Mash1-positive cells in regulating adult taste bud cell differentiation through the loss of Mash1-positive cells using the Cre-loxP system. We found that the cells expressing type III cell markers-aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase 4 (CA4), glutamate decarboxylase 67 (GAD67), neural cell adhesion molecule (NCAM), and synaptosomal-associated protein 25 (SNAP25)-were significantly reduced in the circumvallate taste buds after the administration of tamoxifen. However, gustducin and phospholipase C beta2 (PLC beta2)-markers of type II taste bud cells-were not significantly changed in the circumvallate taste buds after the administration of tamoxifen. These results suggest that Mash1-positive cells could be differentiated to type III cells, not type II cells in the taste buds.

Surgical treatment of Ideberg type III glenoid fractures with associated superior shoulder suspensory complex injury.

PubMed

Qin, Hui; Hu, Chuan-Zhen; Zhang, Xian-Long; Shen, Long-Xiang; Xue, Zi-Chao; An, Zhi-Quan

2013-10-01

Ideberg type III glenoid fractures with associated superior shoulder suspensory complex (SSSC) injuries are rare, and related treatments have not been reported in the literature. The purpose of this study was to evaluate the clinical outcomes of such injuries treated with open reduction and internal fixation (ORIF). Between July 2007 and April 2012, ten patients with Ideberg type III glenoid fractures were surgically treated using ORIF with 2 cannulated screws or a screw combined with a metacarpal plate through an anterior approach. Patients with associated SSSC injuries underwent ORIF with K-wires or plates. Information was available for 9 patients with a mean follow-up of 24.1±18.2 months. Mean bone-healing time was 8.4±2.2 weeks. At last follow-up, mean forward flexion of the operative shoulder was 157.8°±7.5°, mean external rotation was 62.9°±7.9°, and mean internal rotation was thoracic level T6±0.8. Mean Constant score was 84.1±3.7 points, which was a mean of 92.7%±3.4% of that seen in the contralateral shoulder. Mean UCLA score and Disabilities of the Arm, Shoulder and Hand score were 33.6±1.7 and 16.6±7.7, respectively. The results show that Ideberg type III glenoid fractures with associated SSSC injuries can be successfully treated using ORIF through an anterior approach. Glenoid fractures and SCCC injuries should be treated simultaneously. Copyright 2013, SLACK Incorporated.

The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse.

PubMed

Kataoka, Shinji; Yang, Ruibiao; Ishimaru, Yoshiro; Matsunami, Hiroaki; Sévigny, Jean; Kinnamon, John C; Finger, Thomas E

2008-03-01

The transient receptor potential channel, PKD2L1, is reported to be a candidate receptor for sour taste based on molecular biological and functional studies. Here, we investigated the expression pattern of PKD2L1-immunoreactivity (IR) in taste buds of the mouse. PKD2L1-IR is present in a few elongate cells in each taste bud as reported previously. The PKD2L1-expressing cells are different from those expressing PLCbeta2, a marker of Type II cells. Likewise PKD2L1-immunoreactive taste cells do not express ecto-ATPase which marks Type I cells. The PKD2L1-positive cells are immunoreactive for neural cell adhesion molecule, serotonin, PGP-9.5 (ubiquitin carboxy-terminal transferase), and chromogranin A, all of which are present in Type III taste cells. At the ultrastructural level, PKD2L1-immunoreactive cells form synapses onto afferent nerve fibers, another feature of Type III taste cells. These results are consistent with the idea that different taste cells in each taste bud perform distinct functions. We suggest that Type III cells are necessary for transduction and/or transmission of information about "sour", but have little or no role in transmission of taste information of other taste qualities.

The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse

PubMed Central

Kataoka, Shinji; Yang, Ruibiao; Ishimaru, Yoshiro; Matsunami, Hiroaki; Kinnamon, John C.; Finger, Thomas E.

2008-01-01

The transient receptor potential (TRP) channel, PKD2L1, is reported to be a candidate receptor for sour taste based on molecular biological and functional studies. Here, we investigated the expression pattern of PKD2L1-immunoreactivity (IR) in taste buds of the mouse. PKD2L1-IR is present in a few elongate cells in each taste bud as reported previously. The PKD2L1-expressing cells are different from those expressing PLCβ2, a marker of Type II cells. Likewise PKD2L1-immunoreactive taste cells do not express ecto-ATPase which marks Type I cells. The PKD2L1 positive cells are immunoreactive for NCAM, serotonin, PGP-9.5 (ubiquitin carboxy terminal transferase) and chromogranin A, all of which are present in Type III taste cells. At the ultrastructural level, PKD2L1-immunoreactive cells form synapses onto afferent nerve fibers, another feature of Type III taste cells. These results are consistent with the idea that different taste cells in each taste bud perform distinct functions. We suggest that Type III cells are necessary for transduction and/or transmission of information about “sour”, but have little or no role in transmission of taste information of other taste qualities. PMID:18156604

Phase Coupling in Langmuir Wave Packets: Evidence for Four Wave Interactions in Solar Type III Radio Bursts

NASA Technical Reports Server (NTRS)

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

2012-01-01

The four wave interaction process, known as the oscillating two stream instability (OTSI) is considered as one of the mechanisms responsible for stabilizing the electron beams associated with solar type III radio bursts. It has been reported that (1) an intense localized Langmuir wave packet associated with a type III burst contains the spectral characteristics of the OTSI: (a) a resonant peak at the local electron plasma frequency, f(sub pe), (b) a Stokes peak at a frequency slightly lower than f(sub pe), (c) anti-Stokes peak at a frequency slightly higher than f(sub pe), and (d) a low frequency enhancement below a few hundred Hz, (2) the frequencies and wave numbers of these spectral components satisfy the resonance conditions of the OTSI, and (3) the peak intensity of the wave packet is well above the thresholds for the OTSI as well as spatial collapse of envelope solitons. Here, for the first time, applying the trispectral analysis on this wave packet, we show that the tricoherence, which measures the degree of coherent four-wave coupling amongst the observed spectral components exhibits a peak. This provides an additional evidence for the OTSI and related spatial collapse of Langmuir envelope solitons in type III burst sources.

Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium.

PubMed

Platt, James L; Kent, Nicholas A; Kimmel, Alan R; Harwood, Adrian J

2017-04-01

Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states. © 2017 Platt et al.; Published by Cold Spring Harbor Laboratory Press.

Voltage current characteristics of type III superconductors

NASA Astrophysics Data System (ADS)

Dorofejev, G. L.; Imenitov, A. B.; Klimenko, E. Yu.

1980-06-01

An adequate description of voltage-current characteristics is important in order to understand the nature of high critical current for the electrodynamic construction of type-III superconductors and for commercial superconductor specification. Homogenious monofilament and multifilament Nb-Ti, Nb-Zr, Nb 3Sn wires were investigated in different ranges of magnetic field, temperature and current. The longitudinal electric field for homogenious wires may be described by E=J ρnexp- T c/T 0+ T/T 0+ B/B 0+ J/J 0, where To, Bo, Jo are the increasing parameters, which depend weakly on B and T, of the electric field. The shape of the voltage-current characteristics of multifilament wires, and the parameter's dependence on temperature and magnetic field may be explained qualitatively by the longitudinal heterogeneous nature of the filaments. A method of attaining the complete specification of the wire's electro-physical properties is proposed. It includes the traditional description of a critical surface (ie the surface corresponding to a certain conventional effective resistivity in T, B, J - space) and a description of any increasing parameter that depends on B and T.

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…

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

DTIC Science & Technology

2014-09-01

Return to duty rates of amputee soldiers in the current conflicts in Afghanistan and Iraq. J Trauma. 2010; 68:1476–1479. 5. Johansen K, Daines M, Howey T...severity score (MESS) in combat related type III tibia fracture. J Orthop Trauma. 2013. 4. Johansen K, Daines M, Howey T, et al. Objective criteria

Production of a novel camel single-domain antibody specific for the type III mutant EGFR.

PubMed

Omidfar, K; Rasaee, M J; Modjtahedi, H; Forouzandeh, M; Taghikhani, M; Golmakani, N

2004-01-01

Camelids have a unique immune system capable of producing single-domain heavy-chain antibodies. The antigen-specific domain of these heavy-chain IgGs (VHH) are the smallest binding units produced by the immune system. In this study, we report the isolation and characterization of several binders against the epidermal growth factor receptor (EGFR) vIII retrieved from immune library of camels (Camelus bactrianus and Camelus dromedarius). The EGFRvIII is a ligand-independent, constitutively active, mutated form of the wild-type EGFR. The expression of EGFRvIII has been demonstrated in a wide range of human malignancies, including gliomas, and breast, prostate, ovarian and lung cancer. Camels were immunized with a synthetic peptide corresponding to a mutated sequence and tissue homogenates. Single-domain antibodies (VHH) were directly selected by panning a phage display library on successively decreasing amounts of synthetic peptide immobilized on magnetic beads. The anti-EGFRvIII camel single-domain antibodies selectively bound to the EGFRvIII peptide and reacted specifically with the immunoaffinity-purified antigen from a non-small cell lung cancer patient. These antibodies with affinities in the nanomolar range recognized the EGFRvIII peptide and affinity-purified mutated receptor. We concluded that using the phage display technique, antigen-specific VHH antibody fragments are readily accessible from the camelids. These antibodies may be good candidates for tumor-diagnostic and therapeutic applications. Copyright 2004 S. Karger AG, Basel.

Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-cas gene cassettes reveals 39 new cas gene families.

PubMed

Shah, Shiraz A; Alkhnbashi, Omer S; Behler, Juliane; Han, Wenyuan; She, Qunxin; Hess, Wolfgang R; Garrett, Roger A; Backofen, Rolf

2018-06-19

A study was undertaken to identify conserved proteins that are encoded adjacent to cas gene cassettes of Type III CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR associated) interference modules. Type III modules have been shown to target and degrade dsDNA, ssDNA and ssRNA and are frequently intertwined with cofunctional accessory genes, including genes encoding CRISPR-associated Rossman Fold (CARF) domains. Using a comparative genomics approach, and defining a Type III association score accounting for coevolution and specificity of flanking genes, we identified and classified 39 new Type III associated gene families. Most archaeal and bacterial Type III modules were seen to be flanked by several accessory genes, around half of which did not encode CARF domains and remain of unknown function. Northern blotting and interference assays in Synechocystis confirmed that one particular non-CARF accessory protein family was involved in crRNA maturation. Non-CARF accessory genes were generally diverse, encoding nuclease, helicase, protease, ATPase, transporter and transmembrane domains with some encoding no known domains. We infer that additional families of non-CARF accessory proteins remain to be found. The method employed is scalable for potential application to metagenomic data once automated pipelines for annotation of CRISPR-Cas systems have been developed. All accessory genes found in this study are presented online in a readily accessible and searchable format for researchers to audit their model organism of choice: http://accessory.crispr.dk .

Immunohistochemical distribution of collagens type I, III, IV and VI, of undulin and of tenascin in oral fibrous hyperplasia.

PubMed

Becker, J; Schuppan, D; Müller, S

1993-11-01

The distribution of collagens type I, IV and VI, of procollagen type III, of undulin and of tenascin was studied in 10 lesions which were clinically and histologically diagnosed as localized oral fibrous hyperplasias. The immunohistochemical distribution of these proteins was similar to that observed for normal oral mucosa. Undulin showed a pattern of parallel fibers throughout. Collagen type VI was pronounced in the subepithelial connective tissue, whereas the collagen fiber bundles were equally reactive for collagens type I and III. Tenascin was observed close to the subepithelial basement membrane and in proximity to collagen fiber bundles in the upper connective tissue. The present findings indicate that oral fibrous hyperplasias that are probably caused by inflammation or chronic irritation show the differentiated and ordered pattern of extracellular matrix proteins characteristic of normal oral mucosa.

Symbiotic implications of type III protein secretion machinery in Rhizobium.

PubMed

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

1998-06-01

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

Antepartum or intrapartum deinfibulation for childbirth in women with type III female genital mutilation: A systematic review and meta-analysis.

PubMed

Esu, Ekpereonne; Udo, Atim; Okusanya, Babasola O; Agamse, David; Meremikwu, Martin M

2017-02-01

There remains no consensus on the best timing of deinfibulation in women with type III female genital mutilation (FGM). To conduct a systematic review of the effects of antepartum or intrapartum deinfibulation on childbirth outcomes in women with type III FGM. The following major databases were searched: Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov, from inception until August 2015 without any language restrictions. Studies of pregnant women or girls with type III FGM who were deinfibulated antepartum or intrapartum were included. Two team members independently screened and collected data. Quality of evidence was assessed using GRADE. Summary odds ratios and proportions were calculated when possible. There is no evidence of a significant difference between antepartum and intrapartum deinfibulation for obstetric outcomes such as duration of labor, perineal lacerations, episiotomies, postpartum hemorrhage, and cesarean deliveries. Outcomes in women living with type III FGM and those who have undergone deinfibulation were not statistically different; however, trends show a benefit for deinfibulation. All studies were underpowered to detect statistical differences. Larger studies are required to have full confidence in these findings. CRD42015024464. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Controllable synthesis, crystal structure and magnetic properties of Monomer-Dimer Cocrystallized MnIII Salen-type composite material

NASA Astrophysics Data System (ADS)

Wu, Qiong; Wu, Wei; Wu, Yongmei; Li, Weili; Qiao, Yongfeng; Wang, Ying; Wang, Baoling

2018-04-01

By the reaction of manganese-Schiff-base complexes with penta-anionic Anderson heteropolyanion, a new supramolecular architecture [Mn2(Salen)2(H2O)2][Mn(Salen)(H2O)2]2Na[IMo6O24]·8H2O (1) (salen = N,N‧-ethylene-bis (salicylideneiminate) has been isolated. Compound 1 was characterized by the single-crystal X-ray diffraction, elemental, IR and thermal gravimetric analyses. Structural analysis reveals that the unit cell simultaneously contains MnIII-Salen dimer and monomer cation fragments, for which the Anderson-type polyanions serve as counter anions. In the packing arrangement, all the MnIII dimers are well separated by polyoxometalate units and form tertiary structure together with MnIII monomers. Interestingly, different from the previous work, in the exact same reaction conditions, we are able to template MnIII-Salen complexes into different configurations by varying the charge state of polyanions. Besides, the magnetic properties of 1 were also examined by using both dc and ac magnetic field of the superconducting quantum interference devices. Most importantly, our fitting of the experimental data to a Heisenberg-type spin model shows that there exists a ferromagnetic exchange interaction ∼5 K between the spins (S = 2) on MnIII in the dimer, while antiferromagnetic ones exist among monomers and dimer (∼2 K). This meta-magnetic state could induce a slight spin frustration at low temperature, which would in turn affect the magnetic behavior. In addition, our ac field measurement of the susceptibilities suggests a typical signature for a single-molecule magnet.

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

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

Increased nuchal translucency and short femur length as possible early signs of osteogenesis imperfecta type III.

PubMed

Vimercati, Antonella; Panzarino, Mariantonietta; Totaro, Ilaria; Chincoli, Annarosa; Selvaggi, Luigi

2013-01-01

this paper reports an association between an increased Nuchal Translucency (NT) and Osteogenesis Imperfecta (OI), a type of skeletal dysplasia. Measurement of fetal NT at 10-14 weeks of gestation is a sensitive and effective screening method for chromosomal abnormalities. a 35-year- old Caucasian woman in her fourth pregnancy was referred to our clinic for an ultrasound scan at 12 weeks of gestation, that confirmed increased Nuchal Translucency. Chorionic villi sampling was performed, showing a normal karyotype. The patient was evaluated by a team of experienced ultra sonographers for pregnancy follow-up at our Department, that is a tertiary center. in our case the ultrasound scan at 12 week of gestation revealed only an increased NT (3 mm). Cytogenetic analysis on chorionic villi demonstrated a normal male karyotype. US follow-up, performed every 3-4 weeks, confirmed normal anthropometric parameters except for shortening of both femurs, but at 23 weeks an incorrect attitude of the feet was revealed. A clinical and radiographic diagnosis of OI type III was made only at birth, and through follow-up continuing to date. NT screening was successful for chromosomal abnormalities at 11-14 weeks of gestation. An increased NT thickness is also associated with numerous fetal anomalies and genetic syndromes in a chromosomally normal fetus. In our case there were no sonographic signs of imperfect osteogenesis in the first trimester, although there was an increased NT with a normal karyotype. currently, in literature, there are not other cases of OI type III associated with an increased NT. Our report is the first to suggest an association between an increased nuchal translucency, short femur length and osteogenesis imperfecta type III.

Return to play after nonoperative management for a severe type III acromioclavicular separation in the throwing shoulder of a collegiate pitcher.

PubMed

Watson, Scott T; Wyland, Douglas J

2015-02-01

Treatment of type III acromioclavicular (AC) separations is controversial, especially in the dominant shoulder of a high-level throwing athlete. This case report describes the return to play after nonoperative management of a collegiate baseball pitcher with a severe type III AC separation in his throwing shoulder. Case report of return to play with nonoperative management of a type III AC separation in the throwing shoulder of a collegiate pitcher. A case report of a single patient. Prospective data were recorded in the case of a collegiate pitcher who suffered an acute injury to the dominant shoulder, resulting in a severe type III AC separation. He was initially treated with a figure-of-8 brace and a sling. Postinjury, strengthening of the wrist, hand, and elbow began at 3½ weeks, and shoulder range of motion (ROM) and a periscapular strengthening program began at 6 weeks. At 2 months postinjury, a deformity was still present, but the athlete was pain free, with full shoulder ROM and strength without tenderness at the AC joint. Formal physical therapy was initiated to include an accelerated interval throwing program. At 12 weeks postinjury, the athlete was pitching asymptomatically, and gradually returned to regular play. At 6 months and now through 24 months postinjury, the athlete reported full strength, full ROM, and return to his previous level of throwing and velocity without complication. He volunteered that he was 100% satisfied with the result, and feels he is the same pitcher as, if not stronger than, prior to this injury. This case demonstrates a collegiate baseball pitcher who returned to his preinjury level of pitching with nonoperative treatment of a severe type III AC separation.

High mobility and high concentration Type-III heterojunction FET

NASA Astrophysics Data System (ADS)

Tsu, R.; Fiddy, M. A.; Her, T.

2018-02-01

The PN junction was introduced in transistors by doping, resulting in high losses due to Coulomb scattering from the dopants. The MOSFET introduced carriers in the form of electrons and holes with an applied bias to the oxide barrier, resulting in carrier transfer without doping. This avoids high scattering losses and dominates the IC industries. With heterojunctions having valence-band maxima near and even above the conduction-band minimum in the formation of Type-III superlattices, very useful devices, introduced by Tsu, Sai-Halacz, and Esaki, soon followed. If the layer thicknesses are more than the carrier mean-free-path, incoherent scattering results in the formation of carrier transfer via diffusion instead of opening up new energy gaps. The exploitation of carriers without scattering represents a new and significant opportunity in what we call a Broken Gap Heterojunction FET.

Small-Molecule Type III Secretion System Inhibitors Block Assembly of the Shigella Type III Secreton▿ †

PubMed Central

Veenendaal, Andreas K. J.; Sundin, Charlotta; Blocker, Ariel J.

2009-01-01

Type III secretion systems (T3SSs) are essential virulence devices for many gram-negative bacteria that are pathogenic for plants, animals, and humans. They serve to translocate virulence effector proteins directly into eukaryotic host cells. T3SSs are composed of a large cytoplasmic bulb and a transmembrane region into which a needle is embedded, protruding above the bacterial surface. The emerging antibiotic resistance of bacterial pathogens urges the development of novel strategies to fight bacterial infections. Therapeutics that rather than kill bacteria only attenuate their virulence may reduce the frequency or progress of resistance emergence. Recently, a group of salicylidene acylhydrazides were identified as inhibitors of T3SSs in Yersinia, Chlamydia, and Salmonella species. Here we show that these are also effective on the T3SS of Shigella flexneri, where they block all related forms of protein secretion so far known, as well as the epithelial cell invasion and induction of macrophage apoptosis usually demonstrated by this bacterium. Furthermore, we show the first evidence for the detrimental effect of these compounds on T3SS needle assembly, as demonstrated by increased numbers of T3S apparatuses without needles or with shorter needles. Therefore, the compounds generate a phenocopy of T3SS export apparatus mutants but with incomplete penetrance. We discuss why this would be sufficient to almost completely block the later secretion of effector proteins and how this begins to narrow the search for the molecular target of these compounds. PMID:18996990

Search for heavy lepton partners of neutrinos in proton–proton collisions in the context of the type III seesaw mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.

A search is presented in proton-proton collisions at sqrt(s) = 7 TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 inverse femtobarns. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models.more » Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.« less

Regulation of Effector Delivery by Type III Secretion Chaperone Proteins in Erwinia amylovora.

PubMed

Castiblanco, Luisa F; Triplett, Lindsay R; Sundin, George W

2018-01-01

Type III secretion (TTS) chaperones are critical for the delivery of many effector proteins from Gram-negative bacterial pathogens into host cells, functioning in the stabilization and hierarchical delivery of the effectors to the type III secretion system (TTSS). The plant pathogen Erwinia amylovora secretes at least four TTS effector proteins: DspE, Eop1, Eop3, and Eop4. DspE specifically interacts with the TTS chaperone protein DspF, which stabilizes the effector protein in the cytoplasm and promotes its efficient translocation through the TTSS. However, the role of E. amylovora chaperones in regulating the delivery of other secreted effectors is unknown. In this study, we identified functional interactions between the effector proteins DspE, Eop1, and Eop3 with the TTS chaperones DspF, Esc1 and Esc3 in yeast. Using site-directed mutagenesis, secretion, and translocation assays, we demonstrated that the three TTS chaperones have additive roles for the secretion and translocation of DspE into plant cells whereas DspF negatively affects the translocation of Eop1 and Eop3. Collectively, these results indicate that TTS chaperone proteins exhibit a cooperative behavior to orchestrate the effector secretion and translocation dynamics in E. amylovora .

Visual impairment in Finnish Usher syndrome type III.

PubMed

Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Sankila, Eeva-Marja; Tuppurainen, Kaija; Kleemola, Leenamaija; Cremers, Cor W R J; Deutman, August F

2006-02-01

To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a). We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS*) and functional vision score (FVS*) related to age were performed for all patients. The FFS* and FVS* were calculated using the isoptre V-4 test target instead of the usual III-4 target. Statistical tests relating to regression lines and Student's t-test were used to compare between USH3 patients and the other genetic subtypes of Usher syndrome. Cross-sectional analyses revealed significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age the USH3 patients showed significantly poorer visual field function than the USH2a patients. The rate of deterioration in visual function in Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a patients. At a given age, visual field impairment in USH3 patients was similar to that in USH1b patients but poorer than in USH2a patients.

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

PubMed Central

Martinez-Becerra, Francisco J.; Kissmann, Julian M.; Diaz-McNair, Jovita; Choudhari, Shyamal P.; Quick, Amy M.; Mellado-Sanchez, Gabriela; Clements, John D.

2012-01-01

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

Five Xanthomonas type III effectors suppress cell death induced by components of immunity-associated MAP kinase cascades

PubMed Central

Teper, Doron; Sunitha, Sukumaran; Martin, Gregory B; Sessa, Guido

2015-01-01

Mitogen-activated protein kinase (MAPK) cascades play a fundamental role in signaling of plant immunity and mediate elicitation of cell death. Xanthomonas spp. manipulate plant signaling by using a type III secretion system to deliver effector proteins into host cells. We examined the ability of 33 Xanthomonas effectors to inhibit cell death induced by overexpression of components of MAPK cascades in Nicotiana benthamiana plants. Five effectors inhibited cell death induced by overexpression of MAPKKKα and MEK2, but not of MAP3Kϵ. In addition, expression of AvrBs1 in yeast suppressed activation of the high osmolarity glycerol MAPK pathway, suggesting that the target of this effector is conserved in eukaryotic organisms. These results indicate that Xanthomonas employs several type III effectors to suppress immunity-associated cell death mediated by MAPK cascades. PMID:26237448

Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander). Evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool.

PubMed

Cunha, M C; Oliveira, A S; Labronici, R H; Gabbai, A A

1996-09-01

We added hydrotherapy to 50 patients with spinal muscular atrophy (SMA) who were being treated with individual conventional physiotherapy. Hydrotherapy performed at an approximate temperature of 30 degrees Celsius, twice a week, for thirty minutes in children and forty-five minutes in adults during a 2-year period. The outcome derived from this combined modality of treatment was rated according to physiotherapeutic evaluations, the MMT (Manual Muscular Test), and the Barthel Ladder. Patients were reevaluated at 2-month intervals. After two years of ongoing treatment, we were able to observe that the deformities in hip, knee and foot were progressive in all SMA Type II patients, and in some Type III. Muscle strength stabilized in most SMA Type III patients, and improved in some. MMT was not done in SMA Type II. In all patients we were able to detect an improvement in the Barthel Ladder scale. This study suggests that a measurable improvement in the quality of daily living may be obtained in patients with SMA Types II and III subjected to conventional physiotherapy when associated with hydrotherapy.

Multiplex Real-Time PCR for Detecting and Typing Clostridium botulinum Group III Organisms and Their Mosaic Variants

PubMed Central

Auricchio, Bruna; Woudstra, Cédric; Fach, Patrick; Fiore, Alfonsina; Skarin, Hanna; Bano, Luca; Segerman, Bo; Knutsson, Rickard; De Medici, Dario

2013-01-01

Botulism is a neuroparalytic disease that can occur in all warm-blooded animals, birds, and fishes. The disease in animals is mainly caused by toxins produced by Clostridium botulinum strains belonging to group III, although outbreaks due to toxins produced by group I and II organisms have been recognized. Group III strains are capable of producing botulinum toxins of type C, D, and C/D and D/C mosaic variants. Definitive diagnosis of animal botulism is made by combining clinical findings with laboratory investigations. Detection of toxins in clinical specimens and feed is the gold standard for laboratory diagnosis. Since toxins may be degraded by organisms contained in the gastrointestinal tract or may be present at levels below the detection limit, the recovery of C. botulinum from sick animal specimens is consistent for laboratory confirmation. In this article we report the development and in-house validation of a new multiplex real-time PCR for detecting and typing the neurotoxin genes found in C. botulinum group III organisms. Validation procedures have been carried out according to ISO 16140, using strains and samples recovered from cases of animal botulism in Italy and France. PMID:23971808

Nonsurgical Management of an Immature Maxillary Central Incisor with Type III Dens Invaginatus Using MTA Plug: A Case Report

PubMed Central

Norouzi, Negar; Kazem, Majid; Gohari, Atefeh

2017-01-01

Dens invaginatus is a developmental anomaly, caused by deepening of the enamel organ into the dental papilla before calcification of the dental tissues. Teeth with dens invagination are susceptible to early caries and pulp necrosis within a few years of eruption or even before root end closure. This article reports two immature maxillary central incisors with type I and III dens invaginatus which had necrotic pulp and a large periradicular lesion, that were treated successfully by nonsurgical root canal treatment. After apical plug placement, the remaining space was backfilled using warm vertical gutta-percha technique and the crowns were restored by composite restoration. At 6 months of follow up the patient was asymptomatic and probing depths were less than 3 mm. In addition, the reduction in the size of apical radiolucencies was observed by radiographic examinations. This case report revealed that even type III des invaginatus with an open apex and large periapical lesion, can be treated non-surgically using MTA as an apical plug. Although this case report presents a favorable result, further studies with long term follow-up periods are encouraged to support the use of nonsurgical endodontic treatment for type III dens invaginatus. PMID:29225653

Identification and characterization of a type III secretion-associated chaperone in the type III secretion system 1 of Vibrio parahaemolyticus.

PubMed

Akeda, Yukihiro; Okayama, Kanna; Kimura, Tomomi; Dryselius, Rikard; Kodama, Toshio; Oishi, Kazunori; Iida, Tetsuya; Honda, Takeshi

2009-07-01

Vibrio parahaemolyticus causes human gastroenteritis. Genomic sequencing of this organism has revealed that it has two sets of type III secretion systems, T3SS1 and T3SS2, both of which are important for its pathogenicity. However, the mechanism of protein secretion via T3SSs is unknown. A characteristic of many effectors is that they require specific chaperones for efficient delivery via T3SSs; however, no chaperone has been experimentally identified in the T3SSs of V. parahaemolyticus. In this study, we identified candidate T3SS1-associated chaperones from genomic sequence data and examined their roles in effector secretion/translocation and binding to their cognate substrates. From these experiments, we concluded that there is a T3S-associated chaperone, VecA, for a cytotoxic T3SS1-dependent effector, VepA. Further analysis using pulldown and secretion assays characterized the chaperone-binding domain encompassing the first 30-100 amino acids and an amino terminal secretion signal encompassing the first 5-20 amino acids on VepA. These findings will provide a strategy to clarify how the T3SS1 of V. parahaemolyticus secretes its specific effectors.

Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?

PubMed

Hu, Hai-Jie; Jin, Yan-Wen; Zhou, Rong-Xing; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

2018-03-06

The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

Genetic tracing of the gustatory neural pathway originating from Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae

PubMed Central

Yamamoto, Kurumi; Ishimaru, Yoshiro; Ohmoto, Makoto; Matsumoto, Ichiro; Asakura, Tomiko; Abe, Keiko

2011-01-01

Polycystic kidney disease 1-like 3 (Pkd1l3) is expressed specifically in sour-sensing type III taste cells that have synaptic contacts with afferent nerve fibers in circumvallate and foliate papillae located in the posterior region of the tongue, though not in fungiform papillae or the palate. To visualize the gustatory neural pathways that originate from type III taste cells in circumvallate and foliate papillae, we established transgenic mouse lines that express the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse Pkd1l3 gene promoter/enhancer. The WGA transgene was accurately expressed in Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae. Punctate WGA protein signals appeared to be detected specifically in type III taste cells but not in other types of taste cells. WGA protein was transferred primarily to a subset of neurons located in close proximity to the glossopharyngeal nerve bundles in the nodose/petrosal ganglion. WGA signals were also observed in a small population of neurons in the geniculate ganglion. This result demonstrates the anatomical connection between taste receptor cells in the foliate papillae and the chorda tympani nerves. WGA protein was further conveyed to neurons in a rostro-central subdivision of the nucleus of the solitary tract. These findings demonstrate that the approximately 10 kb 5’-flanking region of the mouse Pkd1l3 gene functions as a type III taste cell-specific promoter/enhancer. In addition, experiments using the pkd1l3-WGA transgenic mice reveal a sour gustatory pathway that originates from taste receptor cells in the posterior region of the tongue. PMID:21883212

HIGH-TEMPERATURE SAFETY TESTING OF IRRADIATED AGR-1 TRISO FUEL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stempien, John D.; Demkowicz, Paul A.; Reber, Edward L.

High-Temperature Safety Testing of Irradiated AGR-1 TRISO Fuel John D. Stempien, Paul A. Demkowicz, Edward L. Reber, and Cad L. Christensen Idaho National Laboratory, P.O. Box 1625 Idaho Falls, ID 83415, USA Corresponding Author: john.stempien@inl.gov, +1-208-526-8410 Two new safety tests of irradiated tristructural isotropic (TRISO) coated particle fuel have been completed in the Fuel Accident Condition Simulator (FACS) furnace at the Idaho National Laboratory (INL). In the first test, three fuel compacts from the first Advanced Gas Reactor irradiation experiment (AGR-1) were simultaneously heated in the FACS furnace. Prior to safety testing, each compact was irradiated in the Advanced Testmore » Reactor to a burnup of approximately 15 % fissions per initial metal atom (FIMA), a fast fluence of 3×1025 n/m2 (E > 0.18 MeV), and a time-average volume-average (TAVA) irradiation temperature of about 1020 °C. In order to simulate a core-conduction cool-down event, a temperature-versus-time profile having a peak temperature of 1700 °C was programmed into the FACS furnace controllers. Gaseous fission products (i.e., Kr-85) were carried to the Fission Gas Monitoring System (FGMS) by a helium sweep gas and captured in cold traps featuring online gamma counting. By the end of the test, a total of 3.9% of an average particle’s inventory of Kr-85 was detected in the FGMS traps. Such a low Kr-85 activity indicates that no TRISO failures (failure of all three TRISO layers) occurred during the test. If released from the compacts, condensable fission products (e.g., Ag-110m, Cs-134, Cs-137, Eu-154, Eu-155, and Sr-90) were collected on condensation plates fitted to the end of the cold finger in the FACS furnace. These condensation plates were then analyzed for fission products. In the second test, five loose UCO fuel kernels, obtained from deconsolidated particles from an irradiated AGR-1 compact, were heated in the FACS furnace to a peak temperature of 1600 °C. This test

A Repulsive Electrostatic Mechanism for Protein Export through the Type III Secretion Apparatus

PubMed Central

Rathinavelan, Thenmalarchelvi; Zhang, Lingling; Picking, Wendy L.; Weis, David D.; De Guzman, Roberto N.; Im, Wonpil

2010-01-01

Abstract Many Gram-negative bacteria initiate infections by injecting effector proteins into host cells through the type III secretion apparatus, which 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. The trajectories reveal a screwlike rotation motion during the export of nativelike helix-turn-helix conformations. Interestingly, the channel interior with excessive electronegative potential creates an energy barrier for MxiH to enter the channel, whereas the same may facilitate the ejection of the effectors into host cells. Structurally known basal regions and ATPase underneath the basal region also have electronegative interiors. Effector proteins also have considerable electronegative potential patches on their surfaces. From these observations, we propose a repulsive electrostatic mechanism for protein translocation through the type III secretion apparatus. Based on this mechanism, the ATPase activity and/or proton motive force could be used to energize the protein translocation through these nanomachines. A similar mechanism may be applicable to macromolecular channels in other secretion systems or viruses through which proteins or nucleic acids are transported. PMID:20141759

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Corrigan, Abigail L.; Peterson, Elena S.

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 onmore » 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.« less

Minifilament Eruption as the Source of a Blowout Jet, C-class Flare, and Type-III Radio Burst

NASA Astrophysics Data System (ADS)

Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Li, Haidong; Xu, Zhe

2017-01-01

We report a strong minifilament eruption associated with Geostationary Operational Environmental Satellite C1.6 flare and WIND type-III radio burst. The minifilament, which lies at the periphery of active region 12259, is detected by Hα images from the New Vacuum Solar Telescope. The minifilament undergoes a partial and then a full eruption. Simultaneously, two co-spatial jets are successively observed in extreme ultraviolet images from the Solar Dynamic Observatory. The first jet exhibits a typical fan-spine geometry, suggesting that the co-spatial minifilament is possibly embedded in magnetic fields with a fan-spine structure. However, the second jet displays blowout morphology when the entire minifilament erupts upward, leaving behind a hard X-ray emission source in the base. Differential emission measure analyses show that the eruptive region is heated up to about 4 MK during the fan-spine jet, while up to about 7 MK during the blowout jet. In particular, the blowout jet is accompanied by an interplanetary type-III radio burst observed by WIND/WAVES in the frequency range from above 10 to 0.1 MHz. Hence, the minifilament eruption is correlated with the interplanetary type-III radio burst for the first time. These results not only suggest that coronal jets can result from magnetic reconnection initiated by erupting minifilaments with open fields, but also shed light on the potential influence of minifilament eruption on interplanetary space.

MINIFILAMENT ERUPTION AS THE SOURCE OF A BLOWOUT JET, C-CLASS FLARE, AND TYPE-III RADIO BURST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Junchao; Jiang, Yunchun; Yang, Jiayan

We report a strong minifilament eruption associated with Geostationary Operational Environmental Satellite C1.6 flare and WIND type-III radio burst. The minifilament, which lies at the periphery of active region 12259, is detected by H α images from the New Vacuum Solar Telescope. The minifilament undergoes a partial and then a full eruption. Simultaneously, two co-spatial jets are successively observed in extreme ultraviolet images from the Solar Dynamic Observatory . The first jet exhibits a typical fan-spine geometry, suggesting that the co-spatial minifilament is possibly embedded in magnetic fields with a fan-spine structure. However, the second jet displays blowout morphology whenmore » the entire minifilament erupts upward, leaving behind a hard X-ray emission source in the base. Differential emission measure analyses show that the eruptive region is heated up to about 4 MK during the fan-spine jet, while up to about 7 MK during the blowout jet. In particular, the blowout jet is accompanied by an interplanetary type-III radio burst observed by WIND /WAVES in the frequency range from above 10 to 0.1 MHz. Hence, the minifilament eruption is correlated with the interplanetary type-III radio burst for the first time. These results not only suggest that coronal jets can result from magnetic reconnection initiated by erupting minifilaments with open fields, but also shed light on the potential influence of minifilament eruption on interplanetary space.« less

A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation

PubMed Central

Pearson, Jaclyn S; Riedmaier, Patrice; Marchès, Olivier; Frankel, Gad; Hartland, Elizabeth L

2011-01-01

Many bacterial pathogens utilize a type III secretion system (T3SS) to inject virulence effector proteins into host cells during infection. Previously, we found that enteropathogenic Escherichia coli (EPEC) uses the type III effector, NleE, to block the inflammatory response by inhibiting IκB degradation and nuclear translocation of the p65 subunit of NF-κB. Here we screened further effectors with unknown function for their capacity to prevent p65 nuclear translocation. We observed that ectopic expression of GFP–NleC in HeLa cells led to the degradation of p65. Delivery of NleC by the T3SS of EPEC also induced degradation of p65 in infected cells as well as other NF-κB components, c-Rel and p50. Recombinant His6-NleC induced p65 and p50 cleavage in HeLa cell lysates and mutation of a consensus zinc metalloprotease motif, HEIIH, abrogated NleC proteolytic activity. NleC inhibited IL-8 production during prolonged EPEC infection of HeLa cells in a protease activity-dependent manner. A double nleE/nleC mutant was further impaired for its ability to inhibit IL-8 secretion than either a single nleE or a single nleC mutant. We conclude that NleC is a type III effector protease that degrades NF-κB thereby contributing the arsenal of bacterial effectors that inhibit innate immune activation. PMID:21306441

Prevalence of type III secretion system in effective biocontrol pseudomonads.

PubMed

Almario, Juliana; Gobbin, Davide; Défago, Geneviève; Moënne-Loccoz, Yvan; Rezzonico, Fabio

2014-05-01

Functional type III secretion system (T3SS) genes are needed for effective biocontrol of Pythium damping-off of cucumber by Pseudomonas fluorescens KD, but whether biocontrol Pseudomonas strains with T3SS genes display overall a higher plant-protecting activity is unknown. The assessment of 198 biocontrol fluorescent pseudomonads originating from 60 soils worldwide indicated that 32% harbour the ATPase-encoding T3SS gene hrcN, which was most often found in tomato isolates. The hrcN(+) biocontrol strains (and especially those also producing 2,4-diacetylphloroglucinol and displaying 1-aminocyclopropane-1-carboxylate deaminase activity) displayed higher plant-protecting ability in comparison with hrcN(-) biocontrol strains, both in the Pythium/cucumber and Fusarium/cucumber pathosystems. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report.

PubMed

Smaili, W; Elalaoui, S Chafai; Meier, S; Zerkaoui, M; Sefiani, A; Heinimann, K

2017-05-03

Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation. We report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain. Our observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

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

PubMed

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

2016-10-04

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

AGR-2: The first irradiation of French HTR fuel in Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. Lambert; B. Grover; P. Guillermier

AGR-2, the second irradiation of the US program for qualification of the NGNP fuel, is open to international participation within the scope of the Generation IV International Forum. In this frame, it includes in its multi-capsule irradiation rig an irradiation of French HTR fuel manufactured in the CAPRI line (GAIA facility at CEA/Cadarache and AREVA/CERCA compacting line at Romans). The AGR-2 irradiation is designed to place our first fabrications of HTR particles under operating conditions that are representative of ANTARES project while keeping close to the test range of the German fuel as much as possible, which is the referencemore » in terms of irradiation behavior. A few batches of particles and 12 fuel compacts were produced and characterized in 2009 by CEA and CERCA. The fuel main characteristics are in conformity with our specifications and in compliance with INL requirements. The AGR-2 experiment is based on the design and devices used in the first experiment of the AGR program. The design makes it possible to monitor the irradiation conditions and in particular, the temperature, the power and the fission products released from fuel particles. The in pile equipment consists of a multi-capsule device designed to simultaneously irradiate six independent capsules with temperature control. The out-of-core part consists of the equipment for actively controlling temperature and measuring the fission products release on-line. The target conditions for the irradiation experiment were defined with the aim of comparing the results obtained under irradiation with German particles along with the objectives of reaching burn-up and fluence targets to validate the behavior of our fuel in a significant range (15% FIMA – 5 × 1025 n/m2 at 600 EFPD with centerline fuel temperature about 1100 degrees C). These conditions have to be representative of ANTARES project characteristics. These target conditions were compared with final results from neutron and thermal design

Interplanetary baseline observations of type III solar radio bursts

NASA Technical Reports Server (NTRS)

Weber, R. R.; Fitzenreiter, R. J.; Novaco, J. C.; Fainberg, J.

1977-01-01

Simultaneous observations of type III radio bursts from spacecraft separated by 0.43 AU have been made using the solar orbiters Helios-A and Helios-B. The burst beginning at 19:22 UT on March 28, 1976, has been located from the intersection of the source directions measured at each spacecraft and from burst arrival-time differences. The source positions range from 0.03 AU from the sun at 3000 kHz to 0.08 AU at 585 kHz. The electron density along the burst trajectory and the exciter velocity (0.13c) were determined directly without the need to assume a density model, as has been done with single-spacecraft observations. The separation of Helios-A and -B has also provided measurements of burst directivity at low frequencies. For the March 28 burst the intensity observed from near the source longitude (Helios-B) was 3-10dB greater than that from 60 deg west of the source (Helios-A)

Low frequency spectra of type III solar radio bursts

NASA Technical Reports Server (NTRS)

Weber, R. R.

1978-01-01

Flux density spectra have been determined for 91 simple type III solar bursts observed by the Goddard Space Flight Center radio astronomy experiment on the IMP-6 spacecraft during 1971 and 1972. Spectral peaks were found to occur at frequencies ranging from 44 kHz up to 2500 kHz. Half of the bursts peaked between 250 kHz and 900 kHz, corresponding to emission at solar distances of about 0.3 to 0.1 AU. Maximum burst flux density sometimes exceeds 10 to the -14th W/sq m/Hz. The primary factor controlling the spectral peak frequency of these bursts appears to be a variation in intrinsic power radiated by the source as the exciter moves outward from the sun, rather than radio propagation effects between the source and IMP-6. Thus, a burst spectrum strongly reflects the evolution of the properties of the exciting electron beam, and according to current theory, beam deceleration could help account for the observations.

Colorado's AgrAbility Project's Effects on KASA and Practice Changes with Agricultural Producers and Professionals

ERIC Educational Resources Information Center

Fetsch, Robert J.; Jackman, Danielle M.

2015-01-01

Disability rates resulting from work-related injuries remain steadily high among farmers and ranchers. To address the gap in services within this population, USDA implemented AgrAbility nationally. Using part of Bennett's hierarchical model, the current study evaluated the KASA and practice change levels of 401 farmers and ranchers and compared…

Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types III and IV hilar cholangiocarcinoma.

PubMed

Wang, Yu; Cui, Wei; Fan, Wenzhe; Zhang, Yingqiang; Yao, Wang; Huang, Kunbo; Li, Jiaping

2016-08-16

To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for unresectable Bismuth types III and IV hilar cholangiocarcinoma. Percutaneous intraductal RFA combined with metal stent placement was successful in all patients without any technical problems; the technical success rate was 100%. Chemotherapy was administered to two patients. After treatment, serum direct bilirubin levels were notably decreased. Six patients died during the follow-up period. Median stent patency from the time of the first RFA and survival from the time of diagnosis were 100 days (95% confidence interval (CI), 85-115 days) and 5.3 months (95% CI, 2.5-8.1 months), respectively. No acute pancreatitis, bile duct bleeding and perforation, bile leakage, or other severe complications occurred. Four cases of procedure-related cholangitis, three cases of postoperative abdominal pain, and five cases of asymptomatic transient increase in serum amylase were observed. One patient who presented with stent blockage 252 days' post-procedure underwent repeat ablation. Between September 2013 and May 2015, nine patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma who were treated with percutaneous intraductal RFA combined with metal stent placement after the percutaneous transhepatic cholangial drainage were included in the retrospective analysis. Procedure-related complications, stent patency, and survival after treatment were investigated. Percutaneous intraductal RFA combined with metal stent placement is a technically safe and feasible therapeutic option for the palliative treatment of unresectable Bismuth types III and IV hilar cholangiocarcinoma. Its long-term efficacy and safety is promising, but needs further study via randomized and prospective trials that include a greater number of patients.

Structural Studies of E. coli Topoisomerase III-DNA Complexes Reveal A Novel Type IA Topoisomerase-DNA Conformational Intermediate

PubMed Central

Changela, Anita; DiGate, Russell J.; Mondragón, Alfonso

2007-01-01

Summary E. coli DNA topoisomerase III belongs to the type IA family of DNA topoisomerases, which transiently cleave single-stranded DNA (ssDNA) via a 5′ phosphotyrosine intermediate. We have solved crystal structures of wild-type E. coli topoisomerase III bound to an 8-base ssDNA molecule in three different pH environments. The structures reveal the enzyme in three distinct conformational states while bound to DNA. One conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site. Another conformation represents a novel intermediate in which DNA is bound along the ssDNA-binding groove but does not enter the active site, which remains in a catalytically inactive, closed state. A third conformation shows an intermediate state where the enzyme is still in a closed state, but the ssDNA is starting to invade the active site. For the first time, the active site region in the presence of both the catalytic tyrosine and ssDNA substrate is revealed for a type IA DNA topoisomerase, although there is no evidence of ssDNA cleavage. Comparative analysis of the various conformational states suggests a sequence of domain movements undertaken by the enzyme upon substrate binding. PMID:17331537

In situ hybridization reveals that type I and III collagens are produced by pericytes in the anterior pituitary gland of rats.

PubMed

Fujiwara, Ken; Jindatip, Depicha; Kikuchi, Motoshi; Yashiro, Takashi

2010-12-01

Type I and III collagens widely occur in the rat anterior pituitary gland and are the main components of the extracellular matrix (ECM). Although ECM components possibly play an important role in the function of the anterior pituitary gland, little is known about collagen-producing cells. Type I collagen is a heterotrimer of two α1(I) chains (the product of the col1a1 gene) and one α2(I) chain (the product of the col1a2 gene). Type III collagen is a homotrimer of α1(III) chains (the product of the col3a1 gene). We used in situ hybridization with digoxigenin-labeled cRNA probes to examine the expression of col1a1, col1a2, and col3a1 mRNAs in the pituitary gland of adult rats. mRNA expression for these collagen genes was clearly observed, and cells expressing col1a1, col1a2, and col3a1 mRNA were located around capillaries in the gland. We also investigated the possible double-staining of collagen mRNA and pituitary hormones, S-100 protein (a marker of folliculo-stellate cells), or desmin (a marker of pericytes). Col1a1 and col3a1 mRNA were identified in desmin-immunopositive cells. Thus, only pericytes produce type I and III collagens in the rat anterior pituitary gland.

[Recurrent pulmonary infarction associated with familial protein S deficiency type III].

PubMed

Ide, K; Chida, K; Suda, T; Imokawa, S; Tsukamoto, K; Todate, A; Sato, J; Yonekawa, O; Nakamura, H

1999-05-01

A 38-year-old woman was admitted to our hospital because of recurrent chest pain and fever. Chest X-ray films and computed tomograms showed subpleural consolidation containing small cavity-like opacities. Open lung biopsy revealed non-infectious abscess and vessels with organizing thrombus. The patient was given a diagnosis of pulmonary infarction due to the existence of deep venous thrombosis. Coagulation studies demonstrated that she had decreased plasma protein S activity, whereas her free and total protein S antigen levels were normal. Because her mother and maternal uncle and aunt also demonstrated decreased protein S activity with normal plasma protein S antigen levels, the patient was considered to be affected by familial protein S deficiency type III.

VraR Binding to the Promoter Region of agr Inhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.

PubMed

Dai, Yuanyuan; Chang, Wenjiao; Zhao, Changcheng; Peng, Jing; Xu, Liangfei; Lu, Huaiwei; Zhou, Shusheng; Ma, Xiaoling

2017-05-01

Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene ( vraR ) and decreased expression of virulence genes ( hla , hlb , and coa ) and virulence-regulated genes (RNAIII, agrA , and saeR ). These results suggested that VraR might have a direct or indirect effect on virulence in S. aureus In electrophoretic mobility shift assays, VraR did not bind to promoter sequences of hla , hlb , and coa genes, but it did bind to the agr promoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between the agr P2 and P3 promoters. These results indicated that when S. aureus is subject to induction by vancomycin, expression of vraR is upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR in S. aureus is involved not only in the regulation of vancomycin resistance but also in the regulation of virulence. Copyright © 2017 American Society for Microbiology.

Deinfibulation for treating urologic complications of type III female genital mutilation: A systematic review.

PubMed

Effa, Emmanuel; Ojo, Olumuyiwa; Ihesie, Austin; Meremikwu, Martin M

2017-02-01

Women and girls who have undergone type III female genital mutilation (FGM) may suffer urologic complications such as recurrent urinary tract infections, obstruction, stones, and incontinence. To assess the effectiveness of deinfibulation for preventing and treating urologic complications in women and girls living with FGM. The following major databases were searched from inception to August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, SCOPUS, Web of Science, and ClinicalTrials.gov without language restrictions. Randomized controlled studies (RCTs) or observational studies with controls were considered. We screened the results of the search independently for potentially relevant studies and applied inclusion and exclusion criteria for the full texts of the relevant studies. No RCTs were found. We found three case reports and a retrospective case review, all of which were excluded. There is no evidence on the use of deinfibulation to improve urologic complications among women with type III FGM. Current clinical practice may be informed by anecdotal evidence from case reports. Appropriate RCTs and observational studies with comparison groups in countries where FGM is common are needed. PROSPERO registration: CRD42015024901. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

PubMed Central

Qiu, Jing-Xin; Kim, Edward J.; Yu, Ai-Ming

2016-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. PMID:27322206

Die another day: molecular mechanisms of effector-triggered immunity elicited by type III secreted effector proteins

USDA-ARS?s Scientific Manuscript database

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 ...

[Triple no loop Endobutton plate combined with Orthcord line for the treatment of acromioclavicular dislocation of Tossy type III].

PubMed

Xia, Ming-Hua; Xie, Shui-Hua; Wu, Jun; Zhang, Wen-Qing; Chen, Wei-Dong; He, Jian-Hua; Ding, Hao; Hu, Qian-Qin; Wang, Xiao-Peng

2016-07-25

To explore the clinical effects of the triple no loop Endobutton plate combined with Orthcord line in treating acromioclavicular dislocation of Tossy type III. Between February 2011 and September 2013, 36 patients with acromioclavicular dislocation of Tossy type III were treated with triple no loop Endobutton plate and Orthcord line. There were 21 males and 15 females, aged from 9 to 48 years old with an average of (26.41±14.05) years. Couse of disease was from 2 to 7 days in the patients. The patients had the clinical manifestations such as shoulder pain, extension limited, acromioclavicular tenderness, positive organ point sign. Clinical effects were assessed by acromioclavicular scoring system. Thirty six patients were followed up from 8 to 15 months with an average of (12.2±4.3) months. All incisions got primary healing. At the final follow up, all shoulder pain vanished, acromioclavicular joints without tenderness, negative organ point sign. No redislocation and steel plate loosening were found. According to the acromioclavicular scoring system, 31 cases obtained excellent results, 5 good. The method of triple no loop Endobutton plate combined with Orthcord line for acromioclavicular dislocation of Tossy type III has advantage of less risk and complication, good functional rehabilitation and is an ideal method.

Multiple activities of the plant pathogen type III effector proteins WtsE and AvrE require WxxxE motifs.

PubMed

Ham, Jong Hyun; Majerczak, Doris R; Nomura, Kinya; Mecey, Christy; Uribe, Francisco; He, Sheng-Yang; Mackey, David; Coplin, David L

2009-06-01

The broadly conserved AvrE-family of type III effectors from gram-negative plant-pathogenic bacteria includes important virulence factors, yet little is known about the mechanisms by which these effectors function inside plant cells to promote disease. We have identified two conserved motifs in AvrE-family effectors: a WxxxE motif and a putative C-terminal endoplasmic reticulum membrane retention/retrieval signal (ERMRS). The WxxxE and ERMRS motifs are both required for the virulence activities of WtsE and AvrE, which are major virulence factors of the corn pathogen Pantoea stewartii subsp. stewartii and the tomato or Arabidopsis pathogen Pseudomonas syringae pv. tomato, respectively. The WxxxE and the predicted ERMRS motifs are also required for other biological activities of WtsE, including elicitation of the hypersensitive response in nonhost plants and suppression of defense responses in Arabidopsis. A family of type III effectors from mammalian bacterial pathogens requires WxxxE and subcellular targeting motifs for virulence functions that involve their ability to mimic activated G-proteins. The conservation of related motifs and their necessity for the function of type III effectors from plant pathogens indicates that disturbing host pathways by mimicking activated host G-proteins may be a virulence mechanism employed by plant pathogens as well.

Molecular Typing and Virulence Characteristic of Methicillin-Resistant Staphylococcus Aureus Isolates from Pediatric Patients in Bucaramanga, Colombia

PubMed Central

Machuca, Mayra Alejandra; Sosa, Luis Miguel; González, Clara Isabel

2013-01-01

Background Staphylococcus aureus is among the most common global nosocomial pathogens. The emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide that causes nosocomial and community infections. The goals of this study were to establish the clonal complexes (CC) of the isolates of MRSA obtained from pediatric patients in a university hospital in Colombia and to investigate its molecular characteristics based on the virulence genes and the genes of staphylococcal toxins and adhesins. Methods A total of 53 MRSA isolates from pediatric patients with local or systemic infections were collected. The MRSA isolates were typed based on the SCCmec, MLST, spa and agr genes. The molecular characterization included the detection of Panton-Valentine Leukocidin, superantigenic and exfoliative toxins, and adhesin genes. The correlation between the molecular types identified and the profile of virulence factors was determined for all isolates. Results Four CC were identified, including CC8, CC5, CC80 and CC78. The ST8-MRSA-IVc-agrI was the predominant clone among the isolates, followed by the ST5-MRSA-I-agrII and ST5-MRSA-IVc-agrII clones. Twelve spa types were identified, of which t10796 and t10799 were new repeat sequences. The isolates were carriers of toxin genes, and hlg (100%), sek (92%) and pvl (88%) were the most frequent. Ten toxin gene profiles were observed, and the most frequent were seq-sek-hlg (22.6%), sek-hlg (22.6%), seb-seq-sek-hlg (18.9%) and seb-sek-hlg (15.1%). The adhesion genes were present in most of the MRSA isolates, including the following: clf-A (89%), clf-B (87%), fnb-A (83%) and ica (83%). The majority of the strains carried SCCmec-IVc and were identified as causing nosocomial infection. No significant association between a molecular type and the virulence factors was found. Conclusion Four major MRSA clone complexes were identified among the isolates. ST8-MRSA-IVc-agrI pvl+ (USA300-LV) was the

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.

Peroral endoscopic myotomy (POEM) vs laparoscopic Heller myotomy (LHM) for the treatment of Type III achalasia in 75 patients: a multicenter comparative study.

PubMed

Kumbhari, Vivek; Tieu, Alan H; Onimaru, Manabu; El Zein, Mohammad H; Teitelbaum, Ezra N; Ujiki, Michael B; Gitelis, Matthew E; Modayil, Rani J; Hungness, Eric S; Stavropoulos, Stavros N; Shiwaku, Hiro; Kunda, Rastislav; Chiu, Philip; Saxena, Payal; Messallam, Ahmed A; Inoue, Haruhiro; Khashab, Mouen A

2015-06-01

Type III achalasia is characterized by rapidly propagating pressurization attributable to spastic contractions. Although laparoscopic Heller myotomy (LHM) is the current gold standard management for type III achalasia, peroral endoscopic myotomy (POEM) is conceivably superior because it allows for a longer myotomy. Our aims were to compare the efficacy and safety of POEM with LHM for type III achalasia patients. A retrospective study of 49 patients who underwent POEM for type III achalasia across eight centers were compared to 26 patients who underwent LHM at a single institution. Procedural data were abstracted and pre- and post-procedural symptoms were recorded. Clinical response was defined by improvement of symptoms and decrease in Eckardt stage to ≤ 1. Secondary outcomes included length of myotomy, procedure duration, length of hospital stay, and rate of adverse events. Clinical response was significantly more frequent in the POEM cohort (98.0 % vs 80.8 %; P = 0.01). POEM patients had significantly shorter mean procedure time than LHM patients (102 min vs 264 min; P < 0.01) despite longer length of myotomy (16 cm vs 8 cm; P < 0.01). There was no significant difference between POEM and LHM in the length of hospital stay (3.3 days vs 3.2 days; P = 0.68), respectively. Rate of adverse events was significantly less in the POEM group (6 % vs 27 %; P < 0.01). POEM allows for a longer myotomy than LHM, which may result in improved clinical outcomes. POEM appears to be an effective and safe alternative to LHM in patients with type III achalasia.

A case of bilateral vocal fold mucosal bridges, bilateral trans-vocal fold type III sulci vocales, and an intracordal polyp.

PubMed

Tan, Melin; Pitman, Michael J

2011-07-01

We present a patient with a novel finding of bilateral mucosal bridges, bilateral type III trans-vocal fold sulci vocales, and a vocal fold polyp. Although sulci and mucosal bridges occur in the vocal folds, it is rare to find multiples of these lesions in a single patient, and it is even more uncommon when they occur in conjunction with a vocal fold polyp. To our knowledge, this is the first description of a vocal fold polyp in combination with multiple vocal fold bridges and multiple type III sulci vocales in a single patient. To describe and visually present the diagnosis and treatment of a patient with an intracordal polyp, bilateral mucosal bridges, as well as bilateral type III trans-vocal fold sulci vocales. Presentation of a set of high definition intraoperative photos displaying the extent of the vocal fold lesions and the resection of the intracordal polyp. This patient presented with only 6 months of significant dysphonia. It was felt that the recent change in voice was because of the polyp and not the bridges or sulci vocales. Considering the patient's presentation and the possible morbidity of resection of mucosal bridges and sulci, only the polyp was excised. Postoperatively, the patient's voice returned to his acceptable mild baseline dysphonia, and the benefit has persisted 6 months postoperatively. The combination of bilateral mucosal bridges, bilateral type III sulcus vocalis, and an intracordal polyp in one patient is rare if not novel. Treatment of the polyp alone returned the patient's voice to his lifelong baseline of mild dysphonia. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Low- and high-threshold primary afferent inputs to spinal lamina III antenna-type neurons.

PubMed

Fernandes, Elisabete C; Santos, Ines C; Kokai, Eva; Luz, Liliana L; Szucs, Peter; Safronov, Boris V

2018-06-21

and non-nociceptive sensory information. Antenna-type neurons with cell bodies located in lamina III and large dendritic trees extending from the superficial lamina I to deep lamina IV are best shaped for the integration of a wide variety of inputs arising from primary afferent fibers and intrinsic spinal circuitries. While the somatodendritic morphology, the hallmark of antenna neurons, has been well studied, little is still known about the axon structure and basic physiological properties of these cells. Here we did whole-cell recordings in a rat (P9-P12) spinal cord preparation with attached dorsal roots to examine the axon course, intrinsic firing properties and primary afferent inputs of antenna cells. Nine antenna cells were identified from a large sample of biocytin-filled lamina III neurons (n = 46). Axon of antenna cells showed intensive branching in laminae III-IV and, in half of the cases, issued dorsally directed collaterals reaching lamina I. Antenna cells exhibited tonic and rhythmic firing patterns; single spikes were followed by hyper- or depolarization. The neurons received monosynaptic inputs from the low-threshold Aβ afferents, Aδ afferents as well as from the high-threshold Aδ and C afferents. When selectively activated, C-fiber-driven mono- and polysynaptic EPSPs were sufficiently strong to evoke firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold and nociceptive high-threshold primary afferent inputs, and can function as wide-dynamic-range neurons able to directly connect deep dorsal horn with the major nociceptive projection area lamina I.

[The characteristics of type I, III collagen and LN in pulmonary fibrosis induced by uranium ore dust in rats].

PubMed

Hu, Ying-chun; Luo, Zhen-hua; Yuan, Xing-jiang; Yang, Li-ping; Wang, Shou-feng; Li, Guang-yue; He, Xing-peng

2011-02-01

To explore the characteristics of LN and type I, III collagen in pulmonary fibrosis induced by uranium ore dust in rats. 60 adult Wistar rats were divided randomly into two groups, control group (30 rats) and uranium ore dust group (30 rats). Non-exposed intratracheal instillation method was used. Uranium ore dust group was exposed 20 mg/ml uranium ore dust suspension 1ml per rat, meanwhile control group was exposed normal saline 1ml per rat. Post-exposed the 7, 14, 21, 30 and 60 d, 6 rats in each group were killed randomly, lung tissue were collected. The pathological changes in lung tissue were observed by microscope using HE staining, the collagen I and III in lungs were observed by polarizing microscope using Biebrich scarlet staining. The expression of LN protein in lung tissue was observed by immunohistochemistry-SP. During lung fibrosis, a large amount of the proliferated I and III collagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were type I collagen deposited in lung interstitium mainly in the early stage. The area percentage of collagen I and III was increased significantly at 7, 14, 21, 30 and 60d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). The over expression of LN in the lung tissue were observed. The expression of LN was distributed in the lung tissue as thickening of the linear or cluster. The integral optical density of LN was increased significantly at 21, 30 and 60 d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). After exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type of I collagen deposited in lung interstitium mainly in the early stage, while the type of III collagen increase significantly at the later period. The overexpression of LN exists in the process of pulmonary fibrosis. It suggests that LN has a role effect in the process of

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

PubMed Central

Gaona-López, Carlos; Julián-Sánchez, Adriana

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Evidence for an extensive collagen type III/VI proximal domain in the rat femur. I. Diminution with ovariectomy.

PubMed

Luther, F; Saino, H; Carter, D H; Aaron, J E

2003-06-01

Collagenous proteins other than Type I have received little attention in hypogonadal bone loss. Using femora from 25 young (2.5 months) and older (11 months) control and ovariectomized adult rats killed 1-4 months postoperation, cancellous atrophy was histologically confirmed, and the immunolocalization of collagen Type III was examined. This occurred as numerous immunofluorescent Sharpey-like fibers, 5-25 microm thick, regularly associated with collagen Type VI, which ramified the femoral cortex. Sequential transverse cryosections enabled the mapping of the fibers in three-dimensions, demonstrating that they constituted an extensive subperiosteal domain which may be a lasting legacy of early skeletal development. Fiber density was greatest in the trochanters and femoral neck. The domain tapered distally and was apparently anchored into the mid-shaft by intracortical cartilaginous islands, staining for collagen Type VI (as well as Type II and fibronectin). Ovariectomy caused disconnection of the fibers and reduced the proximal domain of both young and older animals, previously positive areas of the cortex becoming negative. It is concluded that collagen Type III/VI occupies a substantial, discrete domain in the rat proximal femur as a complex extension of the periosteum. Diminution of this cortical domain with trabecular atrophy suggests that it has a proactive or reactive role in determining bone mass and strength by facilitating musculoskeletal exchange in a form that is disengaged by ovariectomy.

Type II and III Taste Bud Cells Preferentially Expressed Kainate Glutamate Receptors in Rats.

PubMed

Lee, Sang-Bok; Lee, Cil-Han; Kim, Se-Nyun; Chung, Ki-Myung; Cho, Young-Kyung; Kim, Kyung-Nyun

2009-12-01

Glutamate-induced cobalt uptake reveals that non-NMDA glutamate receptors (GluRs) are present in rat taste bud cells. Previous studies involving glutamate induced cobalt staining suggest this uptake mainly occurs via kainate type GluRs. It is not known which of the 4 types of taste bud cells express subunits of kainate GluR. Circumvallate and foliate papillae of Sprague-Dawley rats (45~60 days old) were used to search for the mRNAs of subunits of non-NMDA GluRs using RT-PCR with specific primers for GluR1-7, KA1 and KA2. We also performed RT-PCR for GluR5, KA1, PLCbeta2, and NCAM/SNAP 25 in isolated single cells from taste buds. Taste epithelium, including circumvallate or foliate papilla, express mRNAs of GluR5 and KA1. However, non-taste tongue epithelium expresses no subunits of non-NMDA GluRs. Isolated single cell RT-PCR reveals that the mRNAs of GluR5 and KA1 are preferentially expressed in Type II and Type III cells over Type I cells.

Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients

PubMed Central

Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

2017-01-01

Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials. PMID:28122039

Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients.

PubMed

Chen, Xing; Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

2017-01-01

Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials.

Peroral endoscopic myotomy (POEM) vs laparoscopic Heller myotomy (LHM) for the treatment of Type III achalasia in 75 patients: a multicenter comparative study

PubMed Central

Kumbhari, Vivek; Tieu, Alan H; Onimaru, Manabu; El Zein, Mohammad H.; Teitelbaum, Ezra N.; Ujiki, Michael B.; Gitelis, Matthew E.; Modayil, Rani J.; Hungness, Eric S.; Stavropoulos, Stavros N.; Shiwaku, Hiro; Kunda, Rastislav; Chiu, Philip; Saxena, Payal; Messallam, Ahmed A.; Inoue, Haruhiro; Khashab, Mouen A.

2015-01-01

Background and study aims: Type III achalasia is characterized by rapidly propagating pressurization attributable to spastic contractions. Although laparoscopic Heller myotomy (LHM) is the current gold standard management for type III achalasia, peroral endoscopic myotomy (POEM) is conceivably superior because it allows for a longer myotomy. Our aims were to compare the efficacy and safety of POEM with LHM for type III achalasia patients. Patients and methods: A retrospective study of 49 patients who underwent POEM for type III achalasia across eight centers were compared to 26 patients who underwent LHM at a single institution. Procedural data were abstracted and pre- and post-procedural symptoms were recorded. Clinical response was defined by improvement of symptoms and decrease in Eckardt stage to ≤ 1. Secondary outcomes included length of myotomy, procedure duration, length of hospital stay, and rate of adverse events. Results: Clinical response was significantly more frequent in the POEM cohort (98.0 % vs 80.8 %; P = 0.01). POEM patients had significantly shorter mean procedure time than LHM patients (102 min vs 264 min; P < 0.01) despite longer length of myotomy (16 cm vs 8 cm; P < 0.01). There was no significant difference between POEM and LHM in the length of hospital stay (3.3 days vs 3.2 days; P = 0.68), respectively. Rate of adverse events was significantly less in the POEM group (6 % vs 27 %; P < 0.01). Conclusions: POEM allows for a longer myotomy than LHM, which may result in improved clinical outcomes. POEM appears to be an effective and safe alternative to LHM in patients with type III achalasia. PMID:26171430

Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci

PubMed Central

Li, Jingru; Wang, Wenliang; Xu, Stacey X.; Magarvey, Nathan A.; McCormick, John K.

2011-01-01

The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(l-Phe-l-Pro) and cyclo(l-Tyr-l-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens. PMID:21282650

Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci.

PubMed

Li, Jingru; Wang, Wenliang; Xu, Stacey X; Magarvey, Nathan A; McCormick, John K

2011-02-22

The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Tyr-L-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.

Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients.

PubMed

Figueroa, Javier M; Skog, Johan; Akers, Johnny; Li, Hongying; Komotar, Ricardo; Jensen, Randy; Ringel, Florian; Yang, Isaac; Kalkanis, Steven; Thompson, Reid; LoGuidice, Lori; Berghoff, Emily; Parsa, Andrew; Liau, Linda; Curry, William; Cahill, Daniel; Bettegowda, Chetan; Lang, Frederick F; Chiocca, E Antonio; Henson, John; Kim, Ryan; Breakefield, Xandra; Chen, Clark; Messer, Karen; Hochberg, Fred; Carter, Bob S

2017-10-19

RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-associated amplifications and mutations in epidermal growth factor receptor (EGFR). CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs. EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM. Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The Pseudomonas syringae type III effector HopG1 targets mitochondria, alters plant development, and suppresses plant innate immunity

PubMed Central

Block, Anna; Guo, Ming; Li, Guangyong; Elowsky, Christian; Clemente, Thomas E.; Alfano, James R.

2009-01-01

Summary The bacterial plant pathogen Pseudomonas syringae uses a type III protein secretion system to inject type III effectors into plant cells. Primary targets of these effectors appear to be effector-triggered immunity (ETI) and pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). The type III effector HopG1 is a suppressor of ETI that is broadly conserved in bacterial plant pathogens. Here we show that HopG1 from P. syringae pv. tomato DC3000 also suppresses PTI. Interestingly, HopG1 localizes to plant mitochondria, suggesting that its suppression of innate immunity may be linked to a perturbation of mitochondrial function. While HopG1 possesses no obvious mitochondrial signal peptide, its N-terminal two-thirds was sufficient for mitochondrial localization. A HopG1-GFP fusion lacking HopG1’s N-terminal 13 amino acids was not localized to the mitochondria reflecting the importance of the N-terminus for targeting. Constitutive expression of HopG1 in Arabidopsis thaliana, Nicotiana tabacum (tobacco) and Lycopersicon esculentum (tomato) dramatically alters plant development resulting in dwarfism, increased branching and infertility. Constitutive expression of HopG1 in planta leads to reduced respiration rates and an increased basal level of reactive oxygen species. These findings suggest that HopG1’s target is mitochondrial and that effector/target interaction promotes disease by disrupting mitochondrial functions. PMID:19863557

Clinical characteristics and surgical experience of Type III Wagstaffe fractures: Pay attention to concomitant chondral injury of the talus.

PubMed

Zhang, Ming; Chen, Yun-Feng; Wang, Lei; Li, Fan; Wei, Hai-Feng; Shi, Zhong-Min

2017-04-27

The purpose of this study was to investigate clinical characteristics and surgical management of Type III Wagstaffe fracture. From August 2012 to July 2015, 13 patients with Type III Wagstaffe fractures were surgically treated. During operation, the cartilage of joint surface was explored. Wagstaffe fragment was fixed with cannulated screw or suture, Chaput fragment was fixed with cannulated screw or plate, and Cotton test was performed to evaluate the stability of syndesmosis during the operation. All the patients were followed up for 14.3 months in average. Clinical outcome was assessed with Olerud-Molander score and American Orthopedic Foot and Ankle Society (AOFAS) score. The traumatic arthritis was evaluated with osteoarthritis-score (OA-score). During the operation, chondral injury was found on the lateral top of the talus in 8 cases, as "kissing lesion" of Chaput fragment. The fractures healed uneventfully and all the patients recovered satisfactorily except two had moderate restriction in ankle movement. The average Olerud-Molander score and AOFAS score were 82.3 and 86.1, respectively. Type III Wagstaffe is a rare and often missed fracture. 61% are associated with a chondral lesion on the lateral top of the talus. Anatomical reduction and rigid fixation of both fragments are mandatory to obtain ankle stability and good results. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

An Unusual Case Report of Bertolotti's Syndrome: Extraforaminal Stenosis and L5 Unilateral Root Compression (Castellvi Type III an LSTV).

PubMed

Kapetanakis, Stylianos; Chaniotakis, Constantinos; Paraskevopoulos, Constantinos; Pavlidis, Pavlos

2017-01-01

Castellvi Type III lumbosacral transitional vertebrae (LSTV) is an unusual case of Bertolotti's syndrome (BS) due to extraforaminal stenosis, especially manifesting in elderly patients. We report a case of BS in a 62 years old Greek female. The signs of the clinical examination are low back pain, sciatica, hypoesthesia, and pain to the contribution of L5 nerve. Imaging techniques revealed an LSTV Type III a (complete sacralization between LSTV and sacrum). Despite the fact that LSTV is a congenital lesion, the clinical manifestation of BS may present in the elderly population. The accumulative effect of the gradual degeneration of intervertebral foramen (stenosis) may lead to the compression of extraforaminal portion of the nerve root.

[Medium-term outcome, follow-up, and quality of life in children treated for type III esophageal atresia].

PubMed

Lepeytre, C; De Lagausie, P; Merrot, T; Baumstarck, K; Oudyi, M; Dubus, J-C

2013-10-01

The aim of this study was to evaluate the medium-term outcome (health status, medical and surgical French National Health Authority-recommended follow-up, and quality of life) of children born with type III esophageal atresia (EA). Previous events (during the perinatal period, associated abnormalities, respiratory and digestive complications) of children treated for type III EA at the Marseille university hospitals between 1999 and 2009 were noted. Parents completed a standardized questionnaire concerning the health of their children during the previous year, and a quality-of-life questionnaire (PedsQL 4.0) was also completed by children aged more than 8 years. Among the 68 children treated, 44 responded to our solicitation (mean age, 7.6 years; range, 3-12.8 years). Previous important events were : pneumonia(s) (65%), asthma before the age of 3 years (66%), hospitalization for a respiratory event (45%), fundoplication (20%), and esophageal dilatation (45%). We noted current chronic cough (16%), asthma (30%), dysphagia (39%), and symptomatic gastroesophageal reflux (9%). National guidelines were not respected, except for the surgical indications in children aged less than 6 years. The quality-of-life scores (n=43 children) were similar to healthy controls but were negatively influenced by a gastrostomy procedure (P=0.020), pneumonia (P=0.013), and hospitalization due to a respiratory event (P=0.006) or a digestive event (P=0.010), and also by current asthma (P=0.004). In conclusion, despite recurrent respiratory or digestive symptoms and inadequate recommended follow-up, the quality of life of children treated for type III of EA is good. Copyright © 2013. Published by Elsevier SAS.

Abundant Type III Lipid Transfer Proteins in Arabidopsis Tapetum Are Secreted to the Locule and Become a Constituent of the Pollen Exine1[W][OPEN

PubMed Central

Huang, Ming-Der; Chen, Tung-Ling L.; Huang, Anthony H.C.

2013-01-01

Lipid transfer proteins (LTPs) are small secretory proteins in plants with defined lipid-binding structures for possible lipid exocytosis. Special groups of LTPs unique to the anther tapetum are abundant, but their functions are unclear. We studied a special group of LTPs, type III LTPs, in Arabidopsis (Arabidopsis thaliana). Their transcripts were restricted to the anther tapetum, with levels peaking at the developmental stage of maximal pollen-wall exine synthesis. We constructed an LTP-Green Fluorescent Protein (LTP-GFP) plasmid, transformed it into wild-type plants, and monitored LTP-GFP in developing anthers with confocal laser scanning microscopy. LTP-GFP appeared in the tapetum and was secreted via the endoplasmic reticulum-trans-Golgi network machinery into the locule. It then moved to the microspore surface and remained as a component of exine. Immuno-transmission electron microscopy of native LTP in anthers confirmed the LTP-GFP observations. The in vivo association of LTP-GFP and exine in anthers was not observed with non-type III or structurally modified type III LTPs or in transformed exine-defective mutant plants. RNA interference knockdown of individual type III LTPs produced no observable mutant phenotypes. RNA interference knockdown of two type III LTPs produced microscopy-observable morphologic changes in the intine underneath the exine (presumably as a consequence of changes in the exine not observed by transmission electron microscopy) and pollen susceptible to dehydration damage. Overall, we reveal a novel transfer pathway of LTPs in which LTPs bound or nonbound to exine precursors are secreted from the tapetum to become microspore exine constituents; this pathway explains the need for plentiful LTPs to incorporate into the abundant exine. PMID:24096413

[Characteristics of lipid metabolism and the cardiovascular system in glycogenosis types I and III].

PubMed

Polenova, N V; Strokova, T V; Starodubova, A V

Glycogen storage disease (GSD) is an inherited metabolic disorder characterized by early childhood lipid metabolic disturbances with potentially proatherogenic effects. The review outlines the characteristics of impaired lipid composition and other changes in the cardiovascular system in GSD types I and III. It analyzes the factors enabling and inhibiting the development of atherosclerosis in patients with GSD. The review describes the paradox of vascular resistance to the development of early atherosclerosis despite the proatherogenic composition of lipids in the patients of this group.

Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

PubMed Central

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

2013-01-01

The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families. PMID:24058621

Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm.

PubMed

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema

2013-01-01

The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.

Structure of the cytoplasmic domain of Yersinia pestis YscD, an essential component of the type III secretion system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lountos, George T.; Tropea, Joseph E.; Waugh, David S.

2012-09-17

The Yersinia pestis YscD protein is an essential component of the type III secretion system. YscD consists of an N-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). Both the cytoplasmic and the periplasmic domains are required for the assembly of the type III secretion system. Here, the structure of the YscD cytoplasmic domain solved by SAD phasing is presented. Although the three-dimensional structure is similar to those of forkhead-associated (FHA) domains, comparison with the structures of canonical FHA domains revealed that the cytoplasmic domain of YscD lacks the conserved residues that are requiredmore » for binding phosphothreonine and is therefore unlikely to function as a true FHA domain.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardenal-Muñoz, Elena, E-mail: e_cardenal@us.es; Gutiérrez, Gabriel, E-mail: ggpozo@us.es; Ramos-Morales, Francisco, E-mail: framos@us.es

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. Thesemore » 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.« less

Management of type III female genital mutilation in Birmingham, UK: a retrospective audit.

PubMed

Paliwal, Priya; Ali, Sarah; Bradshaw, Sally; Hughes, Alison; Jolly, Kate

2014-03-01

to audit clinical management of women with type III female genital mutilation (FGM) according to local guidelines. Secondary objectives were to describe the population that uses the service and compare obstetric outcomes of intrapartum deinfibulation and antenatal deinfibulation. retrospective audit. a hospital midwifery-led FGM specialist service in Birmingham, UK. 253 women with type III FGM who gave birth between January 2008 and December 2009 METHODS: retrospective case analysis using patient records. proportion of women managed according to locally agreed criteria for the management of FGM; obstetric outcomes including perineal tears, episiotomy rates, estimated blood loss, infant APGAR scores and indications for caesarean section. 91 (36%) women booked into antenatal care after 16 weeks gestation. Only 26 (10.3%) were managed fully according to guidelines. The area with poorest performance was child protection, where the presence of normal genitalia was documented in only 52 (38.8%) of medical notes following birth of a female infant. The majority of women (214, 84.6%) had been deinfibulated in a previous pregnancy. Of the 39 infibulated at booking, only 9 (23.1%) were deinfibulated antenatally, the rest opted for intrapartum deinfibulation. Women who had intrapartum deinfibulation had a higher average blood loss and more tears than those deinfibulated antenatally, although this was not statistically significant. alternative systems should be considered to improve documentation of child protection related information. Further research is needed to confirm or refute the adverse findings among those that delayed deinfibulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at √{s }=13 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Tomei, T. R. Fernandez Perez; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Stoykova, S.; Sultanov, G.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; El-khateeb, E.; Elgammal, S.; Ellithi Kamel, A.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ã.-.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Toriashvili, T.; Lomidze, D.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Raspereza, A.; Roland, B.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Bein, S.; Blobel, V.; Centis Vignali, M.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Evangelou, I.; Foudas, C.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Csanad, M.; Filipovic, N.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Bhowmik, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Dhingra, N.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Kumari, P.; Mehta, A.; Singh, J. B.; Walia, G.; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A.; Chauhan, S.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhardwaj, R.; Bhattacharya, R.; Bhattacharya, S.; Bhawandeep, U.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Sur, N.; Sutar, B.; Banerjee, S.; Bhattacharya, S.; Chatterjee, S.; Das, P.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Chatterjee, K.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Biggio, C.; Calvelli, V.; Ferro, F.; Robutti, E.; Tosi, S.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pauwels, K.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Fienga, F.; Iorio, A. O. M.; Khan, W. A.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; De Castro Manzano, P.; Dorigo, T.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Lujan, P.; Margoni, M.; Meneguzzo, A. T.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Zumerle, G.; Braghieri, A.; Fallavollita, F.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Manoni, E.; Mantovani, G.; Mariani, V.; Menichelli, M.; Rossi, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giannini, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. 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M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Christos, M.; Feigelis, K.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Zhou, B.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; CMS Collaboration

2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at √{s }=13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb-1 . Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.

Syntheses, crystal structures, and properties of six new lanthanide(III) transition metal tellurium(IV) oxyhalides with three types of structures.

PubMed

Shen, Yue-Ling; Mao, Jiang-Gao

2005-07-25

Solid-state reactions of lanthanide(III) oxide (and lanthanide(III) oxyhalide), transition metal halide (and transition metal oxide), and TeO(2) at high temperature lead to six new lanthanide transition metal tellurium(IV) oxyhalides with three different types of structures, namely, DyCuTe(2)O(6)Cl, ErCuTe(2)O(6)Cl, ErCuTe(2)O(6)Br, Sm(2)Mn(Te(5)O(13))Cl(2), Dy(2)Cu(Te(5)O(13))Br(2), and Nd(4)Cu(TeO(3))(5)Cl(3). Compounds DyCuTe(2)O(6)Cl, ErCuTe(2)O(6)Cl, and ErCuTe(2)O(6)Br are isostructural. The lanthanide(III) ion is eight-coordinated by eight oxygen atoms, and the copper(II) ion is five-coordinated by four oxygens and a halide anion in a distorted square pyramidal geometry. The interconnection of Ln(III) and Cu(II) ions by bridging tellurite anions results in a three-dimensional (3D) network with tunnels along the a-axis; the halide anion and the lone-pair electrons of the tellurium(IV) ions are oriented toward the cavities of the tunnels. Compounds Sm(2)Mn(Te(5)O(13))Cl(2) and Dy(2)Cu(Te(5)O(13))Br(2) are isostructural. The lanthanide(III) ions are eight-coordinated by eight oxygens, and the divalent transition metal ion is octahedrally coordinated by six oxygens. Two types of polymeric tellurium(IV) oxide anions are formed: Te(3)O(8)(4)(-) and Te(4)O(10)(4)(-). The interconnection of the lanthanide(III) and divalent transition metal ions by the above two types of polymeric tellurium(IV) oxide anions leads to a 3D network with long, narrow-shaped tunnels along the b-axis. The halide anions remain isolated and are located at the above tunnels. Nd(4)Cu(TeO(3))(5)Cl(3) features a different structure. All five of the Nd(III) ions are eight-coordinated (NdO(8) for Nd(1), Nd(2), Nd(4), and Nd(5) and NdO(7)Cl for Nd(3)), and the copper(I) ion is tetrahedrally coordinated by four chloride anions. The interconnection of Nd(III) ions by bridging tellurite anions resulted in a 3D network with large tunnels along the b-axis. The CuCl(4) tetrahedra are interconnected into

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

PubMed

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

2011-01-01

Klippel-Feil syndrome is believed to occur from failure of normal segmentation of cervical somites during gestation. We present the case of a 38-year-old primiparous woman with type III Klippel-Feil syndrome for elective cesarean delivery. Our patient had a short webbed neck, short stature, limited neck flexion and extension, and thoraco-lumbar abnormalities. A multidisciplinary approach, involving obstetrics, medical subspecialties, anesthesiology, otolaryngology, and radiology, were utilized to evaluate and manage this patient. Pulmonary function testing revealed a restrictive defect, but transthoracic echocardiography was normal without pulmonary hypertension. We planned a combined spinal-epidural technique; however, only the epidural technique was obtained. Cesarean delivery was commenced with favorable maternal and fetal outcomes. Post-operative pain management was provided with intravenous morphine patient-controlled analgesia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at s = 13 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at √s = 13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb -1. Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limitsmore » on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. Furthermore, this is the most sensitive probe to date of the type-III seesaw mechanism.« less

Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at s = 13 TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at √s = 13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb -1. Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limitsmore » on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. Furthermore, this is the most sensitive probe to date of the type-III seesaw mechanism.« less

Crystallization and preliminary crystallographic analysis of an acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morita, Hiroyuki; Kondo, Shin; Kato, Ryohei

2007-07-01

An acridone-producing novel type III polyketide synthase from H. serrata has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.0 Å. Polyketide synthase 1 (PKS1) from Huperzia serrata is a plant-specific type III polyketide synthase that shows an unusually versatile catalytic potential, producing various aromatic tetraketides, including chalcones, benzophenones, phlorogulucinols and acridones. Recombinant H. serrata PKS1 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to space group I222 or I2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 73.3, b = 85.0, c = 137.7 Å, α =more » β = γ = 90.0°. Diffraction data were collected to 2.0 Å resolution using synchrotron radiation at BL24XU of SPring-8.« less

Electron Microscopic Examination of Irradiated TRISO Coated Particles of Compact 6-3-2 of AGR-1 Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Rooyen, Isabella Johanna; Demkowicz, Paul Andrew; Riesterer, Jessica Lori

2012-12-01

The electron microscopic examination of selected irradiated TRISO coated particles of the AGR-1 experiment of fuel compact 6-3-2 are presented in this report. Compact 6-3-2 refers to the compact in Capsule 6 at level 3 of Stack 2. The fuel used in capsule 6 compacts, are called the “baseline” fuel as it is fabricated with refined coating process conditions used to fabricate historic German fuel, because of its excellent irradiation performance with UO2 kernels. The AGR-1 fuel is however made of low-enriched uranium oxycarbide (UCO). Kernel diameters are approximately 350 µm with a U-235 enrichment of approximately 19.7%. Compact 6-3-2more » has been irradiated to 11.3% FIMA compact average burn-up with a time average, volume average temperature of 1070.2°C and with a compact average fast fluence of 2.38E21 n/cm« less

Electron Microscopic Examination of Irradiated TRISO Coated Particles of Compact 6-3-2 of AGR-1 Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Rooyen, Isabella Johanna; Demkowicz, Paul Andrew; Riesterer, Jessica Lori

2012-12-01

The electron microscopic examination of selected irradiated TRISO coated particles of the AGR-1 experiment of fuel compact 6-3-2 are presented in this report. Compact 6-3-2 refers to the compact in Capsule 6 at level 3 of Stack 2. The fuel used in capsule 6 compacts, are called the “baseline” fuel as it is fabricated with refined coating process conditions used to fabricate historic German fuel, because of its excellent irradiation performance with UO 2 kernels. The AGR-1 fuel is however made of low-enriched uranium oxycarbide (UCO). Kernel diameters are approximately 350 µm with a U-235 enrichment of approximately 19.7%. Compactmore » 6-3-2 has been irradiated to 11.3% FIMA compact average burn-up with a time average, volume average temperature of 1070.2°C and with a compact average fast fluence of 2.38E21 n/cm« less

Multiple-locus variable number of tandem repeats fingerprinting (MLVF) and virulence factor analysis of methicillin resistant Staphylococcus aureus SCCmec type III.

PubMed

Emaneini, Mohammad; Jabalameli, Leila; Iman-Eini, Hossein; Aligholi, Marzieh; Ghasemi, Amir; Nakhjavani, Farrokh Akbari; Taherikalani, Morovat; Khoramian, Babak; Asadollahi, Parisa; Jabalameli, Fereshteh

2011-01-01

Methicillin resistant Staphylococcus aureus (MRSA), particularly strains with type III staphylococcal cassette chromosome mec (SCCmec), represent a serious human pathogen in Tehran, Iran. The disease-causing capability depends on their ability to produce a wide variety of virulent factors. The prevalence of exotoxin genes and multiple-locus variable number of tandem repeats fingerprinting (MLVF) profile among MRSA isolates, from patients in Tehran, was evaluated by PCR and Multiplex-PCR. The MLVF typing of 144 MRSA isolates with type III SCCmec produced 5 different MLVF types. Generally, 97.2% (140/144) of all the isolates were positive for at least one of the tested exotoxin genes. The most prevalent genes were hld, found in 87.5% (126/144) of the isolates followed by lukE-lukD and hla found in 72.9% (105/144) and 70.1% (101/144) of the isolates, respectively. The tst gene, belonging to MLVF types I, IV and V, was found among three of the isolates from blood and wound samples. The sea gene was detected in 58.3% (84/144) of the isolates and the sed and see genes were found in one isolate with MLVF type V. The coexistence of genes was observed in the 87.5% (126/144) of the isolates. The rate of coexistence of hld with lukE-lukD, hla with lukE-lukD and sea with lukE-lukD were 66.7% (96/144), 44.4% (64/144) and 44.4% (64/144), respectively. The present study demonstrated that MRSA strains with type III SCCmec show different MLVF patterns and exotoxin profiles.

Phe71 in Type III Trypanosomal Protein Arginine Methyltransferase 7 (TbPRMT7) Restricts the Enzyme to Monomethylation.

PubMed

Cáceres, Tamar B; Thakur, Abhishek; Price, Owen M; Ippolito, Nicole; Li, Jun; Qu, Jun; Acevedo, Orlando; Hevel, Joan M

2018-02-27

Protein arginine methyltransferase 7 (PRMT7) is unique within the PRMT family as it is the only isoform known to exclusively make monomethylarginine (MMA). Given its role in epigenetics, the mechanistic basis for the strict monomethylation activity is under investigation. It is thought that PRMT7 enzymes are unable to add a second methyl group because of steric hindrance in the active site that restricts them to monomethylation. To test this, we probed the active site of trypanosomal PRMT7 (TbPRMT7) using accelerated molecular dynamics, site-directed mutagenesis, kinetic, binding, and product analyses. Both the dynamics simulations and experimental results show that the mutation of Phe71 to Ile converts the enzyme from a type III methyltransferase into a mixed type I/II, that is, an enzyme that can now perform dimethylation. In contrast, the serine and alanine mutants of Phe71 preserve the type III behavior of the native enzyme. These results are inconsistent with a sterics-only model to explain product specificity. Instead, molecular dynamics simulations of these variants bound to peptides show hydrogen bonding between would-be substrates and Glu172 of TbPRMT7. Only in the case of the Phe71 to Ile mutation is this interaction between MMA and the enzyme maintained, and the geometry for optimal S N 2 methyl transfer is obtained. The results of these studies highlight the benefit of combined computational and experimental methods in providing a better understanding for how product specificity is dictated by PRMTs.

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

PubMed Central

Guan, Jing; Wang, Wanying

2017-01-01

ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

PubMed

Guan, Jing; Wang, Wanying; Sun, Baolin

2017-01-01

CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive

Distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin PSM-mec in methicillin-resistant Staphylococcus aureus.

PubMed

Chatterjee, Som S; Chen, Liang; Joo, Hwang-Soo; Cheung, Gordon Y C; Kreiswirth, Barry N; Otto, Michael

2011-01-01

The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.

A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing's Syndrome

PubMed Central

Liu, Guanghua; Wang, Fen; Jiang, Jun; Yan, Zhaoli; Zhang, Dianxi; Zhang, Yinsheng

2016-01-01

Context: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities. Objective: This study characterized a novel phenotype of FH-III and explored the possible pathogenesis. Patients and Methods: A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing's syndrome at 20 years. He was diagnosed with PA and Cushing's syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro. Results: A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and β-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR. Conclusions: We presented the first FH-III patient who had both severe PA and Cushing's syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+ channels. PMID:27403928

Collagen type I and III synthesis by Tenon's capsule fibroblasts in culture: individual patient characteristics and response to mitomycin C, 5-fluorouracil, and ascorbic acid.

PubMed Central

Gross, R L

1999-01-01

PURPOSE: This study was performed to better understand the differences between patients in specific components of wound healing as it may pertain to glaucoma filtration surgery, including the use of antimetabolites. METHODS: Human Tenon's capsule fibroblasts were obtained at the time of glaucoma filtering surgery and established in individual cell cultures from 35 glaucoma patients. The dose-response to 5-fluorouracil (5FU) and mitomycin C (MMC) was determined. The individual cell lines were exposed to the antimetabolites and ascorbic acid with measurement of collagen type I and III production by an ELISA-type dot blot assay. These results were then statistically compared to the individual patient characteristics including age, race, previous surgery and medications, and type of glaucoma. RESULTS: 5-FU had little effect on collagen type I and III production or protein synthesis. MMC had an inhibitory effect on collagen secretion and total protein synthesis with increasing concentration. Photomicrographs of the cells after each treatment condition revealed characteristic morphologic changes when compared to controls. There was a large range of collagen type I and III production with correlation between the amounts of each collagen type secreted in response to the antimetabolites. However, there was no correlation with accepted risk factors for filtration failure. CONCLUSION: These antimetabolites act similarly on different cell lines in a nonspecific manner. The results suggest that the increased risk of filtration failure due to age, race, diagnosis, and previous conjunctival surgery is not due to differences in secretion of collagen types I and III by Tenon's capsule fibroblasts. Images FIGURE 3 PMID:10703140

Skeletal anteroposterior discrepancy and vertical type effects on lower incisor preoperative decompensation and postoperative compensation in skeletal Class III patients.

PubMed

Ahn, Hyo-Won; Baek, Seung-Hak

2011-01-01

To determine the initial compensation, preoperative decompensation, and postoperative compensation of the lower incisors according to the skeletal anteroposterior discrepancy and vertical type in skeletal Class III patients. The samples consisted of 68 skeletal Class III patients treated with two-jaw surgery and orthodontic treatment. Lateral cephalograms were taken before preoperative orthodontic treatment (T0) and before surgery (T1) and after debonding (T2). According to skeletal anteroposterior discrepancy/vertical type (ANB, criteria  =  -4°; SN-GoMe, criteria  =  35°) at the T0 stage, the samples were allocated into group 1 (severe anteroposterior discrepancy/hypodivergent vertical type, N  =  17), group 2 (moderate anteroposterior discrepancy/hypodivergent vertical type, N  =  17), group 3 (severe anteroposterior discrepancy/hyperdivergent vertical type, N  =  17), or group 4 (moderate anteroposterior discrepancy/hyperdivergent vertical type, N  =  17). After measurement of variables, one-way analysis of variance with Duncan's multiple comparison test, crosstab analysis, and Pearson correlation analysis were performed. At T0, groups 3 and 2 exhibited the most and least compensated lower incisors. In group 2, good preoperative decompensation and considerable postoperative compensation resulted in different values for T0, T1, and T2 (IMPA, T0 < T2 < T1; P < .001). However, group 3 did not show significant changes in IMPA between stages. Therefore, groups 2 and 3 showed different decompensation achievement ratios (P < .05). Group 3 exhibited the worst ratios of decompensation and stability (24% and 6%, respectively, P < .001). Anteroposterior discrepancy/vertical type (ANB: P < .01 at T0 and T1, P < .001 at T2; SN-GoMe: P < .01, all stages) were strongly correlated with relative percentage ratio of IMPA to norm value. Skeletal anteroposterior discrepancy/vertical type results in differences in the amount and pattern of initial

miRNA-29a targets COL3A1 to regulate the level of type III collagen in pig.

PubMed

Chuan-Hao, Li; Wei, Chen; Jia-Qing, Hu; Yan-Dong, Wang; Shou-Dong, Wang; Yong-Qing, Zeng; Hui, Wang

2016-10-30

COL3A1 encodes the protein, collagen type III alpha 1, which is an important component of collagen. Collagen can have a considerable effect on the processing quality of meat, and is nutritious. Bioinformatic analysis using Targetscan showed that COL3A1 could be a target gene of miRNA-29a. Moreover, we found that Laiwu pigs have higher levels of type III collagen and lower levels of miRNA-29a than Landrace pigs. Therefore, we hypothesized that miRNA-29a suppresses the expression of COL3A1 by targeting its 3'-UTR. miRNA-29a appears to play an inhibitory role in the regulation of COL3A1 in PK15 cells because of the following: (1) overexpression of miRNA-29a resulted in a significant down-regulation of COL3A1 protein levels (2) overexpression of miRNA-29a significantly decreased the level of COL3A1 mRNA. (3) The activity of a COL3A1 luciferase reporter was significant reduced by miRNA-29a. Furthermore, the levels of miRNA-29a and collagen type III in four tissues in Laiwu and Landrace pigs were consistent with the above observations. In this study, we identified COL3A1 as a direct target for miRNA-29a, which will inform further studies of meat quality. Copyright © 2016 Elsevier B.V. All rights reserved.

Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci.

PubMed Central

Vallejo, J G; Baker, C J; Edwards, M S

1996-01-01

Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-alpha) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-alpha production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-alpha. III-PS, GB-PS, LTA, and PG each induced TNF-alpha in a time- and concentration-dependent manner. However, TNF-alpha release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-alpha release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis. PMID:8945544

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

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.

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

Acceptance Test Data for the AGR-5/6/7 Irradiation Test Fuel Composite Defective IPyC Fraction and Pyrocarbon Anisotropy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmreich, Grant W.; Hunn, John D.; Skitt, Darren J.

Coated particle composite J52R-16-98005 was produced by Babcock and Wilcox Technologies (BWXT) as fuel for the Advanced Gas Reactor Fuel Development and Qualification (AGR) Program’s AGR-5/6/7 irradiation test in the Idaho National Laboratory (INL) Advanced Test Reactor (ATR). This composite was comprised of four coated particle fuel batches J52O-16-93165B (26%), 93168B (26%), 93169B (24%), and 93170B (24%), chosen based on the Quality Control (QC) data acquired for each individual candidate AGR-5/6/7 batch. Each batch was coated in a 150-mm-diameter production-scale fluidized-bed chemical vapor deposition (CVD) furnace. Tristructural isotropic (TRISO) coatings were deposited on 425-μm-nominal-diameter spherical kernels from BWXT Lot J52R-16-69317more » containing a mixture of 15.5%-enriched uranium carbide and uranium oxide (UCO). The TRISO coatings consisted of four consecutive CVD layers: a ~50% dense carbon buffer layer with 100-μm-nominal thickness, a dense inner pyrolytic carbon (IPyC) layer with 40-μm-nominal thickness, a silicon carbide (SiC) layer with 35-μm-nominal thickness, and a dense outer pyrolytic carbon (OPyC) layer with 40-μm-nominal thickness. The TRISO-coated particle batches were sieved to upgrade the particles by removing over-sized and under-sized material, and the upgraded batches were designated by appending the letter A to the end of the batch number (e.g., 93165A). Secondary upgrading by sieving was performed on the A-designated batches to remove particles with missing or very-thin buffer layers that were identified during previous analysis of the individual batches for defective IPyC, as reported in the acceptance test data report for the AGR-5/6/7 production batches [Hunn et al. 2017]. The additionally-upgraded batches were designated by appending the letter B to the end of the batch number (e.g., 93165B).« less

Study on competitive adsorption mechanism among oxyacid-type heavy metals in co-existing system: Removal of aqueous As(V), Cr(III) and As(III) using magnetic iron oxide nanoparticles (MIONPs) as adsorbents

NASA Astrophysics Data System (ADS)

Lin, Sen; Lian, Cheng; Xu, Meng; Zhang, Wei; Liu, Lili; Lin, Kuangfei

2017-11-01

The adsorption and co-adsorption of As(V), Cr(VI) and As(III) onto the magnetic iron oxide nanoparticles (MIONPs) surface were investigated comprehensively to clarify the competitive processes. The results reflected that the MIONPs had remarkable preferential adsorption to As(V) compared with Cr(VI) and As(III). And it was determined, relying on the analysis of heavy metals variations on the MIONPs surface at different co-adsorption stages using FTIR and XPS, that the inner-sphere complexation made vital contribution to the preferential adsorption for As(V), corresponding with the replacement experiments where As(V) could grab extensively active sites on the MIONPs pre-occupied by As(III) or Cr(V) uniaxially. The desorption processes displayed that the strongest affinity between the MIONPs and As(V) where As(III) and Cr(VI) were more inclined to wash out. It is wish to provide a helpful direction with this study for the wastewater treatment involving multiple oxyacid-type heavy metals using MIONPs as adsorbents.

Staphylococcus aureus isolated from wastewater treatment plants in Tunisia: occurrence of human and animal associated lineages.

PubMed

Ben Said, Meriam; Abbassi, Mohamed Salah; Gómez, Paula; Ruiz-Ripa, Laura; Sghaier, Senda; Ibrahim, Chourouk; Torres, Carmen; Hassen, Abdennaceur

2017-08-01

The objective was to characterize Staphylococcus aureus isolated from two wastewater treatment plants (WWTPs) located in Tunis City (Tunisia), during the period 2014-2015. Genetic lineages, antibiotic resistance mechanisms and virulence factors were determined for the recovered isolates. S. aureus isolates were recovered from 12 of the 62 wastewater samples tested (19.35%), and one isolate/sample was characterized, all of them being methicillin-susceptible (MSSA). Six spa types (t587, t674, t224, t127, t701 and t1534) were found among the 12 isolates, and the spa-t587, associated with the new sequence type ST3245, was the most predominant one (7 isolates). The remaining isolates were assigned to five clonal complexes (CC5, CC97, CC1, CC6 and CC522) according to the sequence-type determined and/or the spa-type detected. S. aureus isolates were ascribed to agrI (n = 3), agrII (n = 7) and agrIII (n = 1); however, one isolate was non-typeable. S. aureus showed resistance to (number of isolates): penicillin (12), erythromycin (7), tetracycline (one) and clindamycin (one). Among the virulence factors investigated, only one isolate harboured the tst gene, encoding the TSST-1 (toxic shock syndrome toxin 1). Despite the low number of studied isolates, the present study reports the occurrence of both human- and animal-associated S. aureus clonal complexes in WWTPs in Tunisia.

Procollagen type III amino terminal peptide and myocardial fibrosis: A study in hypertensive patients with and without left ventricular hypertrophy.

PubMed

dos Santos Moreira, Carlos; Serejo, Fátima; Alcântara, Paula; Ramalhinho, Vítor; Braz Nogueira, J

2015-05-01

An exaggerated accumulation of type I and type III fibrillar collagens occurs throughout the free wall and interventricular septum of patients with primary hypertension and left ventricular hypertrophy (LVH). In the present study the serum concentration of procollagen type III amino terminal peptide (PIIIP) was measured to determine the value of this peptide as a potential marker of ventricular fibrosis in hypertensive patients, particularly those with LVH. The study population consisted of patients with never-treated mild to moderate essential hypertension and 30 normotensive control subjects. Clinical, echocardiographic, electrocardiographic and biochemical parameters were assessed in all patients. Heart rate, body mass index and levels of blood pressure were increased in hypertensives, particularly those with LVH, compared to normotensive controls. Posterior wall thickness, left ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also increased in hypertensives, with significant differences between the two hypertensive groups. The ratio between maximal early and late transmitral flow velocity measured during diastole was lower in hypertensives, particularly those with LVH, than in normotensive controls. The increase in PIIIP indicates that type III collagen synthesis increases in hypertensives, particularly those with LVH, implying that alterations in the heart in hypertension are the result not solely of hypertrophied LV muscle, but also of increased collagen deposition within the ventricular wall and around the coronary vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in the non-invasive assessment of myocardial remodeling in hypertension. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Functional and computational analysis of amino acid patterns predictive of type III secretion system substrates in Pseudomonas syringae

USDA-ARS?s Scientific Manuscript database

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...

Crystal structure of the second fibronectin type III (FN3) domain from human collagen α1 type XX.

PubMed

Zhao, Jingfeng; Ren, Jixia; Wang, Nan; Cheng, Zhong; Yang, Runmei; Lin, Gen; Guo, Yi; Cai, Dayong; Xie, Yong; Zhao, Xiaohong

2017-12-01

Collagen α1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen α1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen α1 type XX, the crystal structure of the FN#2 domain from human collagen α1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at 2.5 Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a β-sandwich structure, which is formed by a three-stranded β-sheet (β1, β2 and β5) packed onto a four-stranded β-sheet (β3, β4, β6 and β7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen α1 type XX cannot be identified.

Human Protein Arginine Methyltransferase 7 (PRMT7) Is a Type III Enzyme Forming ω-NG-Monomethylated Arginine Residues*

PubMed Central

Zurita-Lopez, Cecilia I.; Sandberg, Troy; Kelly, Ryan; Clarke, Steven G.

2012-01-01

Full-length human protein arginine methyltransferase 7 (PRMT7) expressed as a fusion protein in Escherichia coli was initially found to generate only ω-NG-monomethylated arginine residues in small peptides, suggesting that it is a type III enzyme. A later study, however, characterized fusion proteins of PRMT7 expressed in bacterial and mammalian cells as a type II/type I enzyme, capable of producing symmetrically dimethylated arginine (type II activity) as well as small amounts of asymmetric dimethylarginine (type I activity). We have sought to clarify the enzymatic activity of human PRMT7. We analyzed the in vitro methylation products of a glutathione S-transferase (GST)-PRMT7 fusion protein with robust activity using a variety of arginine-containing synthetic peptides and protein substrates, including a GST fusion with the N-terminal domain of fibrillarin (GST-GAR), myelin basic protein, and recombinant human histones H2A, H2B, H3, and H4. Regardless of the methylation reaction conditions (incubation time, reaction volume, and substrate concentration), we found that PRMT7 only produces ω-NG-monomethylarginine with these substrates. In control experiments, we showed that mammalian GST-PRMT1 and Myc-PRMT5 were, unlike PRMT7, able to dimethylate both peptide P-SmD3 and SmB/D3 to give the expected asymmetric and symmetric products, respectively. These experiments show that PRMT7 is indeed a type III human methyltransferase capable of forming only ω-NG-monomethylarginine, not asymmetric ω-NG,NG-dimethylarginine or symmetric ω-NG,NG′-dimethylarginine, under the conditions tested. PMID:22241471

Composition, formation, and regulation of the cytosolic c-ring, a dynamic component of the type III secretion injectisome.

PubMed

Diepold, Andreas; Kudryashev, Mikhail; Delalez, Nicolas J; Berry, Richard M; Armitage, Judith P

2015-01-01

Many gram-negative pathogens employ a type III secretion injectisome to translocate effector proteins into eukaryotic host cells. While the structure of the distal "needle complex" is well documented, the composition and role of the functionally important cytosolic complex remain less well understood. Using functional fluorescent fusions, we found that the C-ring, an essential and conserved cytosolic component of the system, is composed of ~22 copies of SctQ (YscQ in Yersinia enterocolitica), which require the presence of YscQC, the product of an internal translation initiation site in yscQ, for their cooperative assembly. Photoactivated localization microscopy (PALM) reveals that in vivo, YscQ is present in both a free-moving cytosolic and a stable injectisome-bound state. Notably, fluorescence recovery after photobleaching (FRAP) shows that YscQ exchanges between the injectisome and the cytosol, with a t½ of 68 ± 8 seconds when injectisomes are secreting. In contrast, the secretin SctC (YscC) and the major export apparatus component SctV (YscV) display minimal exchange. Under non-secreting conditions, the exchange rate of YscQ is reduced to t½ = 134 ± 16 seconds, revealing a correlation between C-ring exchange and injectisome activity, which indicates a possible role for C-ring stability in regulation of type III secretion. The stabilization of the C-ring depends on the presence of the functional ATPase SctN (YscN). These data provide new insights into the formation and composition of the injectisome and present a novel aspect of type III secretion, the exchange of C-ring subunits, which is regulated with respect to secretion.

[Does prenatal diagnosis modify neonatal management and early outcome of children with esophageal atresia type III?].

PubMed

Garabedian, C; Sfeir, R; Langlois, C; Bonnard, A; Khen-Dunlop, N; Gelas, T; Michaud, L; Auber, F; Piolat, C; Lemelle, J-L; Fouquet, V; Habonima, É; Becmeur, F; Polimerol, M-L; Breton, A; Petit, T; Podevin, G; Lavrand, F; Allal, H; Lopez, M; Elbaz, F; Merrot, T; Michel, J-L; Buisson, P; Sapin, E; Delagausie, P; Pelatan, C; Gaudin, J; Weil, D; de Vries, P; Jaby, O; Lardy, H; Aubert, D; Borderon, C; Fourcade, L; Geiss, S; Breaud, J; Pouzac, M; Echaieb, A; Laplace, C; Gottrand, F; Houfflin-Debarge, V

2015-11-01

Evaluate neonatal management and outcome of neonates with either a prenatal or a post-natal diagnosis of EA type III. Population-based study using data from the French National Register for EA from 2008 to 2010. We compared children with prenatal versus post-natal diagnosis in regards to prenatal, maternal and neonatal characteristics. We define a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and mortality at 1 year. Four hundred and eight live births with EA type III were recorded with a prenatal diagnosis rate of 18.1%. Transfer after birth was lower in prenatal subset (32.4% versus 81.5%, P<0.001). Delay between birth and first intervention was not significantly different. Defect size (2cm vs 1.4cm, P<0.001), gastrostomy (21.6% versus 8.7%, P<0.001) and length in neonatal unit care were higher in prenatal subset (47.9 days versus 33.6 days, P<0.001). The composite variables were higher in prenatal diagnosis subset (38.7% vs 26.1%, P=0.044). Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity related to the EA type (longer gap). Even if it does not modify neonatal management and 1-year outcome, prenatal diagnosis allows antenatal parental counseling and avoids post-natal transfer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effect of Cortical Screw Diameter on Reduction and Stabilization of Type III Distal Phalanx Fractures: An Equine Cadaveric Study.

PubMed

Kay, Alastair T; Durgam, Sushmitha; Stewart, Matthew; Joslyn, Stephen; Schaeffer, David J; Horn, Gavin; Kesler, Richard; Chew, Peter

2016-11-01

To compare reduction of type III distal phalangeal fractures using 4.5 and 5.5 mm cortical screws placed in lag fashion and an intact hoof capsule model. Cadaveric experimental study. Hooves from 12 adult horses (n=24). Sagittal fractures were created in pairs of distal phalanges after distal interphalangeal joint disarticulation and were reduced with either 4.5 or 5.5 mm cortical screws placed in lag fashion. Contralateral phalanges served as non-reduced controls. Fracture reduction following screw placement was assessed by comparing pre-reduction and post-reduction fracture gap measurements from radiographs using paired t-tests. Effects of incremental loading (0, 135, 270, 540, 800, 1070, and 1335 kg) on fracture gaps in 6 phalanges reduced with 4.5 mm screws and 5 phalanges reduced with 5.5 mm screws were measured from fluoroscopic images and assessed by 2-way ANOVA. Significance was set at P<.05. Type III distal phalanx fractures were reliably created. Only 5.5 mm cortical screws, not 4.5 mm screws, significantly reduced fracture gaps and constrained fracture gap expansion 3 cm distal to the articular surface. Compressive loading closed the fracture gaps at the articular surface in both non-reduced control groups and those reduced with either 5.5 or 4.5 mm screws. The 5.5 mm cortical screws were more effective than 4.5 mm screws in reducing type III distal phalanx fractures and restricting distal fracture gap expansion under load. © Copyright 2016 by The American College of Veterinary Surgeons.

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.…

Readiness Review of BWXT for Fabrication of AGR-5/6/7 TRISO Particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Douglas William; Sharp, Michelle Tracy

2016-02-01

INL readiness review assessment of BWXT readiness to commence fabrication of low-enriched TRISO coated fuel particles for the AGR-5/6/7 irradiation experiments. BWXT self-identified equipment issues preventing operation. INL identified two findings. The first was that disposition codes had not been assigned and documented on BWXT forms to ensure that off-specification materials could not be used in the fabrication of TRISO particles. The second was that chemical purity specifications were not reliably passed on to chemical suppliers, which resulted in the receipt of one acetylene cylinder with suspect impurity levels.

An Unusual Case Report of Bertolotti’s Syndrome: Extraforaminal Stenosis and L5 Unilateral Root Compression (Castellvi Type III an LSTV)

PubMed Central

Kapetanakis, Stylianos; Chaniotakis, Constantinos; Paraskevopoulos, Constantinos; Pavlidis, Pavlos

2017-01-01

Introduction: Castellvi Type III lumbosacral transitional vertebrae (LSTV) is an unusual case of Bertolotti’s syndrome (BS) due to extraforaminal stenosis, especially manifesting in elderly patients. Case Report: We report a case of BS in a 62 years old Greek female. The signs of the clinical examination are low back pain, sciatica, hypoesthesia, and pain to the contribution of L5 nerve. Imaging techniques revealed an LSTV Type III a (complete sacralization between LSTV and sacrum). Conclusion: Despite the fact that LSTV is a congenital lesion, the clinical manifestation of BS may present in the elderly population. The accumulative effect of the gradual degeneration of intervertebral foramen (stenosis) may lead to the compression of extraforaminal portion of the nerve root. PMID:29051870

Characteristics of type III exciters derived from low frequency radio observations

NASA Technical Reports Server (NTRS)

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

1973-01-01

Low-frequency radio observations (2.8 MHz to 67 kHz) from the RAE-1 and IMP-6 satellites allow the tracking of type III solar burst exciters out to large distances from the sun (of the order of 1 AU). A study of the interaction processes between the exciter and the interplanetary medium was made using the time-intensity profiles of the radio emission. The change in exciter length with distance from the sun, and the resulting exciter velocity dispersion which can be deduced from this change are investigated. From detailed measurements on 35 simple bursts it is found that the exciter length increases at a faster rate than a constant velocity dispersion would give. The damping of the radio emission is also investigated, and it is concluded that some current theories of the damping mechanism give results which are not consistent with the low-frequency observations.

New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.

PubMed

Jukkola, A; Kauppila, S; Risteli, L; Vuopala, K; Risteli, J; Leisti, J; Pajunen, L

1998-06-01

We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The child died because of failure of the connective tissue structures joining the skull and the spine, leading to progressive spinal stenosis. The aortic valve was translucent and insufficient. The clinical symptoms and signs, together with histological findings, suggested a collagen defect. Studies on both skin fibroblast cultures and the patient's serum showed reduced synthesis of collagen types I and III at the protein and RNA levels. The sizes of the mRNAs and newly synthesised proteins were normal, excluding gross structural abnormalities. These findings are not in accordance with any other collagen defect characterised so far.

Lubrication studies of some type III deep eutectic solvents (DESs)

NASA Astrophysics Data System (ADS)

Ahmed, Essa. I.; Abbott, Andrew. P.; Ryder, Karl S.

2017-09-01

It has previously been shown that eutectic mixtures of quaternary ammonium salts and hydrogen bond donors form liquids with properties similar to ionic liquids [1; 2]. These so-called deep eutectic solvents (DESs) have been shown to have physical properties which would make them useful as base lubricants. The base lubricant needs to show specific properties, including high viscosity index (VI), low friction coefficient (μ), low pour point and corrosivity. To determine the applicability of DESs as base lubricants, physical properties, corrosion and lubrication properties for four type III DESs have been studied and the results have been compared with mineral base oil. The data show that the lubrication properties of DESs are superior to mineral base oil for short distances. All DESs assessed here have higher VI (191, 147, 121 for Ethaline, Glyceline and Reline respectively compared with 100 for mineral base oil), lower pour points than mineral base oil and most of the liquids studied have shown very low corrosion rates (< 3 µm year-1 for mild steel).

Expression of synaptogyrin-1 in T1R2-expressing type II taste cells and type III taste cells of rat circumvallate taste buds.

PubMed

Kotani, Takeshi; Toyono, Takashi; Seta, Yuji; Kitou, Ayae; Kataoka, Shinji; Toyoshima, Kuniaki

2013-09-01

Synaptogyrins are conserved components of the exocytic apparatus and function as regulators of Ca(2+)-dependent exocytosis. The synaptogyrin family comprises three isoforms: two neuronal (synaptogyrin-1 and -3) and one ubiquitous (synaptogyrin-2) form. Although the expression patterns of the exocytic proteins synaptotagmin-1, SNAP-25, synaptobrevin-2 and synaptophysin have been elucidated in taste buds, the function and expression pattern of synaptogyrin-1 in rat gustatory tissues have not been determined. Therefore, we examined the expression patterns of synaptogyrin-1 and several cell-specific markers of type II and III cells in rat gustatory tissues. Reverse transcription/polymerase chain reaction assays and immunoblot analysis revealed the expression of synaptogyrin-1 mRNA and its protein in circumvallate papillae. In fungiform, foliate and circumvallate papillae, the antibody against synaptogyrin-1 immunolabeled a subset of taste bud cells and intra- and subgemmal nerve processes. Double-labeling experiments revealed the expression of synaptogyrin-1 in most taste cells immunoreactive for aromatic L-amino acid decarboxylase and the neural cell adhesion molecule. A subset of synaptogyrin-1-immunoreactive taste cells also expressed phospholipase Cβ2, gustducin, or sweet taste receptor (T1R2). In addition, most synaptogyrin-1-immunoreactive taste cells expressed synaptobrevin-2. These results suggest that synaptogyrin-1 plays a regulatory role in transmission at the synapses of type III cells and is involved in exocytic function with synaptobrevin-2 in a subset of type II cells in rat taste buds.

AGR-5/6/7 LEUCO Kernel Fabrication Readiness Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, Douglas W.; Bailey, Kirk W.

2015-02-01

In preparation for forming low-enriched uranium carbide/oxide (LEUCO) fuel kernels for the Advanced Gas Reactor (AGR) fuel development and qualification program, Idaho National Laboratory conducted an operational readiness review of the Babcock & Wilcox Nuclear Operations Group – Lynchburg (B&W NOG-L) procedures, processes, and equipment from January 14 – January 16, 2015. The readiness review focused on requirements taken from the American Society Mechanical Engineers (ASME) Nuclear Quality Assurance Standard (NQA-1-2008, 1a-2009), a recent occurrence at the B&W NOG-L facility related to preparation of acid-deficient uranyl nitrate solution (ADUN), and a relook at concerns noted in a previous review. Topicmore » areas open for the review were communicated to B&W NOG-L in advance of the on-site visit to facilitate the collection of objective evidences attesting to the state of readiness.« less

Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming ω-NG-monomethylated arginine residues.

PubMed

Zurita-Lopez, Cecilia I; Sandberg, Troy; Kelly, Ryan; Clarke, Steven G

2012-03-09

Full-length human protein arginine methyltransferase 7 (PRMT7) expressed as a fusion protein in Escherichia coli was initially found to generate only ω-N(G)-monomethylated arginine residues in small peptides, suggesting that it is a type III enzyme. A later study, however, characterized fusion proteins of PRMT7 expressed in bacterial and mammalian cells as a type II/type I enzyme, capable of producing symmetrically dimethylated arginine (type II activity) as well as small amounts of asymmetric dimethylarginine (type I activity). We have sought to clarify the enzymatic activity of human PRMT7. We analyzed the in vitro methylation products of a glutathione S-transferase (GST)-PRMT7 fusion protein with robust activity using a variety of arginine-containing synthetic peptides and protein substrates, including a GST fusion with the N-terminal domain of fibrillarin (GST-GAR), myelin basic protein, and recombinant human histones H2A, H2B, H3, and H4. Regardless of the methylation reaction conditions (incubation time, reaction volume, and substrate concentration), we found that PRMT7 only produces ω-N(G)-monomethylarginine with these substrates. In control experiments, we showed that mammalian GST-PRMT1 and Myc-PRMT5 were, unlike PRMT7, able to dimethylate both peptide P-SmD3 and SmB/D3 to give the expected asymmetric and symmetric products, respectively. These experiments show that PRMT7 is indeed a type III human methyltransferase capable of forming only ω-N(G)-monomethylarginine, not asymmetric ω-N(G),N(G)-dimethylarginine or symmetric ω-N(G),N(G')-dimethylarginine, under the conditions tested.

Re-evaluating the kinetics of ATP hydrolysis during initiation of DNA sliding by Type III restriction enzymes

PubMed Central

Tóth, Júlia; Bollins, Jack; Szczelkun, Mark D.

2015-01-01

DNA cleavage by the Type III restriction enzymes requires long-range protein communication between recognition sites facilitated by thermally-driven 1D diffusion. This ‘DNA sliding’ is initiated by hydrolysis of multiple ATPs catalysed by a helicase-like domain. Two distinct ATPase phases were observed using short oligoduplex substrates; the rapid consumption of ∼10 ATPs coupled to a protein conformation switch followed by a slower phase, the duration of which was dictated by the rate of dissociation from the recognition site. Here, we show that the second ATPase phase is both variable and only observable when DNA ends are proximal to the recognition site. On DNA with sites more distant from the ends, a single ATPase phase coupled to the conformation switch was observed and subsequent site dissociation required little or no further ATP hydrolysis. The overall DNA dissociation kinetics (encompassing site release, DNA sliding and escape via a DNA end) were not influenced by the second phase. Although the data simplifies the ATP hydrolysis scheme for Type III restriction enzymes, questions remain as to why multiple ATPs are hydrolysed to prepare for DNA sliding. PMID:26538601

Dissociation from DNA of Type III Restriction–Modification enzymes during helicase-dependent motion and following endonuclease activity

PubMed Central

Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D.

2012-01-01

DNA cleavage by the Type III Restriction–Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can ‘turnover’, albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. ‘DNA sliding’). PMID:22523084

Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

2009-04-24

The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, aftermore » eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.« less

N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

USDA-ARS?s Scientific Manuscript database

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...

Search for Evidence of the Type-III Seesaw Mechanism in Multilepton Final States in Proton-Proton Collisions at sqrt[s]=13  TeV.

PubMed

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2017-12-01

A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at sqrt[s]=13  TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9  fb^{-1}. Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.

Ostéogenèse imparfaite type III de découverte tardive: à propos d'un cas

PubMed Central

Rachidi, Wafae; Nassar, Kawtar; Janani, Saadia; Mkinsi, Ouafa

2015-01-01

Patient âgé de 52 ans, était admis dans notre établissement pour des polyarthralgies chroniques, plutôt mécaniques, touchant spécialement les articulations du membre inférieur. L'interrogatoire retrouvait l'antécédent de fractures répétées depuis l'enfance, pour des traumatismes minimes, suite à des chutes par glissement. Les signes cliniques et radiologiques, notamment, les fractures récurrentes, sclérotiques bleues, hyperlaxité ligamentaire, dentinogenèse imparfaite, syndrome dysmorphique, ostéoporose densitométrique importante, plaidaient tous en faveur d'une ostéogénèse imparfaite type III. Le patient a initié le traitement, par prise régulière du calcium (1g/jour), supplémentation en vitamine D, et il est programmé pour perfusion de Bisphosphonate (Pamidronate 60mg). Ce cas illustre une forme rare de découverte tardive d'ostéogénèse imparfaite type III. PMID:25995811