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Sample records for mannheimia haemolytica a1

  1. Two outer membrane proteins are bovine lactoferrin-binding proteins in Mannheimia haemolytica A1.

    PubMed

    Samaniego-Barrón, Luisa; Luna-Castro, Sarahí; Piña-Vázquez, Carolina; Suárez-Güemes, Francisco; de la Garza, Mireya

    2016-01-01

    Mannheimia haemolytica is a Gram negative bacterium that is part of the bovine respiratory disease, which causes important economic losses in the livestock industry. In the present work, the interaction between M. haemolytica A1 and bovine lactoferrin (BLf) was studied. This iron-chelating glycoprotein is part of the mammalian innate-immune system and is present in milk and mucosal secretions; Lf is also contained in neutrophils secondary granules, which release this glycoprotein at infection sites. It was evidenced that M. haemolytica was not able to use iron-charged BLf (BholoLf) as a sole iron source; nevertheless, iron-lacked BLf (BapoLf) showed a bactericidal effect against M. haemolytica with MIC of 4.88 ± 1.88 and 7.31 ± 1.62 μM for M. haemolytica strain F (field isolate) and M. haemolytica strain R (reference strain), respectively. Through overlay assays and 2-D electrophoresis, two OMP of 32.9 and 34.2 kDa with estimated IP of 8.18 and 9.35, respectively, were observed to bind both BapoLf and BholoLf; these OMP were identified by Maldi-Tof as OmpA (heat-modifiable OMP) and a membrane protein (porin). These M. haemolytica BLf binding proteins could be interacting in vivo with both forms of BLf depending on the iron state of the bovine. PMID:27599994

  2. Mannheimia haemolytica A1-induced fibrinosuppurative meningoencephalitis in a naturally-infected Holstein-Friesian calf.

    PubMed

    Aschenbroich, S; Nemeth, N; Rech, R; Briggs, R; Sanchez, S; Brown, C

    2013-01-01

    Mannheimia haemolytica is an opportunistic bacterium that is widely recognized among the bovine respiratory disease complex as the predominant pathogen causing broncho- and pleuropneumonia in cattle. Among the characterized M. haemolytica serotypes, A1 is the major cause of severe pulmonary lesions in cattle. This report describes post-mortem findings in a Holstein-Friesian calf with fibrinosuppurative meningoencephalitis and fibrinonecrotizing, haemorrhagic broncho- and pleuropneumonia, from which M. haemolytica and bovine viral diarrhoea virus (BVDV) were isolated. Microscopical evaluation showed expansion of the brainstem and cerebellar leptomeninges by neutrophils and fibrin, associated with gram-negative coccobacilli. Occasional blood vessels within the midbrain and cerebellum contained fibrin thrombi. Bacterial culture of cerebellum and lung yielded M. haemolytica with unusually high haemolytic activity. The isolates were confirmed as serotype A1 by rapid plate agglutination. Lung tissue was positive for BVDV by polymerase chain reaction. The broncho- and pleuropneumonia in this calf were consistent with typical mannheimiosis due to serotype A1; however, extrapulmonary infections due to M. haemolytica, as seen in this case, are rarely reported. To our knowledge, this is the first documentation of a natural BVDV and M. haemolytica co-infection associated with fibrinosuppurative meningoencephalitis in a calf.

  3. Genome sequences of Mannheimia haemolytica serotype A1 strains D153 and D193 from bovine pneumonia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we report two genomes, one complete and one draft, from virulent bovine strains of Mannheimia haemolytica(strains D171 and D35)serotype A2 recovered prior to the field usage of modern antimicrobial drugs....

  4. Complete closed genome sequences of a Mannheimia haemolytica serotype A1 leukotoxin deletion mutant and its wild type parent strain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia haemolytica is a bacterial pathogen associated with bovine respiratory disease complex (BRDC). It secretes a leukotoxin that binds to CD18 on leukocyte membranes and causes acute inflammation and lung injury characteristic of BRDC. We report the complete closed genome sequences of a leu...

  5. Complete closed genome sequences of Mannheimia haemolytica serotypes A1 and A6 isolated from cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannhemimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with Bovine Respiratory Disease Complex (BRDC), a polymicrobial, multifactorial disease. We present the first two complete closed genomes of this species using a...

  6. Genome Sequence of a Presumptive Mannheimia haemolytica Strain with an A1/A6-Cross-Reactive Serotype from a White-Tailed Deer (Odocoileus virginianus).

    PubMed

    Lawrence, Paulraj K; Bey, Russell F; Wiener, Brittanny; Kittichotirat, Weerayuth; Bumgarner, Roger E

    2014-03-27

    Mannheimia haemolytica is a Gram-negative bacterium and the principal etiological agent associated mostly with bovine respiratory disease complex. However, we report here the sequence of a strain with the novel A1/A6-cross-reactive serotype, strain PKL10, isolated from white-tailed deer. PKL10 was isolated from the spleen of farmed white-tailed deer showing clinical signs of pneumonia. The genome structure of PKL10 is dramatically different from that of previously sequenced isolates, which was demonstrated by genome alignments. In addition, the coding sequences in PKL10 share approximately 86% sequence identity with the coding sequences in other fully sequenced M. haemolytica strains. This suggests that PKL10 is a novel Mannheimia species.

  7. Mannheimia haemolytica vegetative endocarditis in a Suffolk wether.

    PubMed

    LaHue, Nathaniel; Parish, Steven

    2015-05-01

    A 12-week-old Suffolk wether was diagnosed with bacterial endocarditis associated with Mannheimia haemolytica. The wether had shown signs of lethargy, inappetance, fever, and a grade 5 of 6 holosystolic murmur. Mannheimia haemolytica was cultured from blood premortem and the valvular lesion postmortem.

  8. Mannheimia haemolytica vegetative endocarditis in a Suffolk wether

    PubMed Central

    LaHue, Nathaniel; Parish, Steven

    2015-01-01

    A 12-week-old Suffolk wether was diagnosed with bacterial endocarditis associated with Mannheimia haemolytica. The wether had shown signs of lethargy, inappetance, fever, and a grade 5 of 6 holosystolic murmur. Mannheimia haemolytica was cultured from blood premortem and the valvular lesion postmortem. PMID:25969581

  9. A Multivalent Mannheimia-Bibersteinia Vaccine Protects Bighorn Sheep against Mannheimia haemolytica Challenge ▿

    PubMed Central

    Subramaniam, Renuka; Shanthalingam, Sudarvili; Bavananthasivam, Jegarubee; Kugadas, Abirami; Potter, Kathleen A.; Foreyt, William J.; Hodgins, Douglas C.; Shewen, Patricia E.; Barrington, George M.; Knowles, Donald P.; Srikumaran, Subramaniam

    2011-01-01

    Bighorn sheep (BHS) are more susceptible than domestic sheep (DS) to Mannheimia haemolytica pneumonia. Although both species carry M. haemolytica as a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalent Mannheimia-Bibersteinia vaccine will protect them upon M. haemolytica challenge. Four BHS were vaccinated with a culture supernatant vaccine prepared from M. haemolytica serotypes A1 and A2 and Bibersteinia trehalosi serotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens against M. haemolytica were 1:160 and 1:4,000, respectively. Following intranasal challenge with M. haemolytica A2 (1 × 105 CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic of M. haemolytica infection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to survive M. haemolytica challenge which is likely to reduce the BHS population decline due to pneumonia. PMID:21832104

  10. Serum IgG response in calves to the putative pneumonic virulence factor Gs60 of Mannheimia haemolytica A1.

    PubMed

    Orouji, Shahriar; Hodgins, Douglas C; Lo, Reggie Y C; Shewen, Patricia E

    2012-10-01

    Bovine pneumonic pasteurellosis vaccines incorporate various antigens of Mannheimia haemolytica, including the acknowledged virulence factor leukotoxin (Lkt), and Gs60, a surface lipoprotein. To examine the role of antibodies to Gs60 in protection, an enzyme-linked immunosorbent assay (ELISA) was developed for retrospective analysis of serum samples from previous trials in which vaccines containing native or recombinant Gs60 were administered parenterally. The analysis revealed a positive correlation between the titer of antibodies to Gs60 and protection against experimental challenge in both vaccinates and naturally exposed controls. There was a strong correlation between production of IgG antibodies to Gs60 and Lkt neutralizing antibodies. Analysis of the relationship between the serum antibody titers and resistance to experimental challenge using linear statistical models revealed a significant association between prechallenge titers of serum antibodies to Lkt and protection. Further analysis suggested that antibodies against Gs60 were beneficial when Lkt neutralizing antibody titers were low.

  11. Complete Closed Genome Sequences of a Mannheimia haemolytica Serotype A1 Leukotoxin Deletion Mutant and Its Wild-Type Parent Strain

    PubMed Central

    Harhay, Gregory P.; Smith, Timothy P. L.; Bono, James L.; Chitko-McKown, Carol G.

    2015-01-01

    Mannheimia haemolytica is a bacterial pathogen that secretes leukotoxin (LktA) which binds to leukocyte membranes via CD18, causing bacterial pneumonia in ruminants. We report the complete closed genome sequences of a leukotoxin mutant and its parent strain that are frequently used in respiratory disease studies. PMID:25953160

  12. Characterization of Mannheimia haemolytica biofilm formation in vitro.

    PubMed

    Boukahil, Ismail; Czuprynski, Charles J

    2015-01-30

    Mannheimia haemolytica is the primary bacterial agent in the bovine respiratory disease complex. It is thought that M. haemolytica colonizes the tonsillar crypts of cattle as a commensal and subsequently descends into the lungs to cause disease. Many bacterial species persist in the host as biofilms. There is limited information about the ability of M. haemolytica to form biofilms. The aim of this study was to develop an in vitro model for M. haemolytica biofilm formation. We found that M. haemolytica required at least 36 h to form robust biofilms on plastic in vitro when incubated in RPMI-1640 tissue culture medium at 37 °C, with maximal biofilm formation being evident at 48 h. Biofilm formation was inhibited by adding the monosaccharides d(+) galactose and d(+) mannose to the growth medium. Addition of antibodies to the M. haemolytica surface protein OmpA also reduced biofilm formation. Upon evaluating the macromolecules within the biofilm extracellular polymeric substance we found it contained 9.7 μg/cm(2) of protein, 0.81 μg/cm(2) of total carbohydrate, and 0.47 μg/cm(2) of extracellular DNA. Furthermore, proteinase K treatment significantly decreased biofilms (P<0.05) while α-amylase and micrococcal nuclease decreased biofilms to a lesser extent. M. haemolytica biofilm cells were more resistant than planktonic cells to the antibiotics florfenicol, gentamicin, and tulathromycin. These results provide evidence that M. haemolytica can form biofilms, which could contribute to its ability to persist as a commensal in the bovine upper respiratory tract.

  13. Genome sequences of mannheimia haemolytica serotype A2: ovine and bovine isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report describes the genome sequences of Mannheimia haemolytica, serotype A2 isolated from pneumonic lungs of two different ruminant species, one from Ovis aries, designated as Ovine (O) and the other from Bos taurus, designated as Bovine (B)....

  14. Bibersteinia trehalosi Inhibits the Growth of Mannheimia haemolytica by a Proximity-Dependent Mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis canadensis) under experimental conditions. Paradoxically, Bibersteinia (Pasteurella) trehalosi and occasionally Pasteurella multocida have been isola...

  15. Bibersteinia trehalosi inhibits the growth of mannheimia haemolytica by a proximity-dependent mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis canadensis) under experimental conditions. Paradoxically, Bibersteinia (Pasteurella) trehalosi and Pasteurella multocida have been isolated from BHS ...

  16. Non-haemolytic Mannheimia haemolytica as a cause of pleuropneumonia and septicemia in a calf.

    PubMed

    Mahu, Maxime; Valgaeren, Bonnie; Pardon, Bart; Deprez, Piet; Haesebrouck, Freddy; Boyen, Filip

    2015-10-22

    Pure cultures of non-haemolytic Mannheimia haemolytica, were cultivated from pleural effusion fluid and blood from a 1-month old Belgian Blue bull calf that was presented with apathy and anorexia. The isolates were identified as M. haemolytica by 16S rRNA gene sequencing and MALDI-TOF-MS. Since haemolysis on blood agar plates is considered a hallmark of M. haemolytica we wanted to elucidate the unusual phenotype of the isolated strain. Therefore the leukotoxin operon (lktCABD), responsible for the haemolytic phenotype of M. haemolytica and regarded as the most important virulence factor, was completely sequenced. The leukotoxin operon of the isolated strain showed a deletion in the lktA gene, resulting in a truncated LktA protein. The absence of a complete LktA protein is responsible for the non-haemolytic phenotype of the strain. To the best of our knowledge, this is the first report of a well-characterized non-haemolytic M. haemolytica isolate causing disease in cattle. PMID:26344042

  17. Identification of a mannheimia haemolytica genetic subtype that causes bovine respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is a serious health and economic problem that costs the United States cattle industry over a billion dollars annually. Mannheimia haemolytica is a major bacterial component of BRDC. An opportunistic pathogen, M. haemolytica resides within the upper respira...

  18. Proximity-dependent inhibition of growth of mannheimia haemolytica by pasteurella multocida.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. hae...

  19. Comparative Genomic Analysis of Mannheimia haemolytica from Bovine Sources.

    PubMed

    Klima, Cassidy L; Cook, Shaun R; Zaheer, Rahat; Laing, Chad; Gannon, Vick P; Xu, Yong; Rasmussen, Jay; Potter, Andrew; Hendrick, Steve; Alexander, Trevor W; McAllister, Tim A

    2016-01-01

    Bovine respiratory disease is a common health problem in beef production. The primary bacterial agent involved, Mannheimia haemolytica, is a target for antimicrobial therapy and at risk for associated antimicrobial resistance development. The role of M. haemolytica in pathogenesis is linked to serotype with serotypes 1 (S1) and 6 (S6) isolated from pneumonic lesions and serotype 2 (S2) found in the upper respiratory tract of healthy animals. Here, we sequenced the genomes of 11 strains of M. haemolytica, representing all three serotypes and performed comparative genomics analysis to identify genetic features that may contribute to pathogenesis. Possible virulence associated genes were identified within 14 distinct prophage, including a periplasmic chaperone, a lipoprotein, peptidoglycan glycosyltransferase and a stress response protein. Prophage content ranged from 2-8 per genome, but was higher in S1 and S6 strains. A type I-C CRISPR-Cas system was identified in each strain with spacer diversity and organization conserved among serotypes. The majority of spacers occur in S1 and S6 strains and originate from phage suggesting that serotypes 1 and 6 may be more resistant to phage predation. However, two spacers complementary to the host chromosome targeting a UDP-N-acetylglucosamine 2-epimerase and a glycosyl transferases group 1 gene are present in S1 and S6 strains only indicating these serotypes may employ CRISPR-Cas to regulate gene expression to avoid host immune responses or enhance adhesion during infection. Integrative conjugative elements are present in nine of the eleven genomes. Three of these harbor extensive multi-drug resistance cassettes encoding resistance against the majority of drugs used to combat infection in beef cattle, including macrolides and tetracyclines used in human medicine. The findings here identify key features that are likely contributing to serotype related pathogenesis and specific targets for vaccine design intended to reduce the

  20. Comparative Genomic Analysis of Mannheimia haemolytica from Bovine Sources

    PubMed Central

    Klima, Cassidy L.; Cook, Shaun R.; Zaheer, Rahat; Laing, Chad; Gannon, Vick P.; Xu, Yong; Rasmussen, Jay; Potter, Andrew; Hendrick, Steve; Alexander, Trevor W.; McAllister, Tim A.

    2016-01-01

    Bovine respiratory disease is a common health problem in beef production. The primary bacterial agent involved, Mannheimia haemolytica, is a target for antimicrobial therapy and at risk for associated antimicrobial resistance development. The role of M. haemolytica in pathogenesis is linked to serotype with serotypes 1 (S1) and 6 (S6) isolated from pneumonic lesions and serotype 2 (S2) found in the upper respiratory tract of healthy animals. Here, we sequenced the genomes of 11 strains of M. haemolytica, representing all three serotypes and performed comparative genomics analysis to identify genetic features that may contribute to pathogenesis. Possible virulence associated genes were identified within 14 distinct prophage, including a periplasmic chaperone, a lipoprotein, peptidoglycan glycosyltransferase and a stress response protein. Prophage content ranged from 2–8 per genome, but was higher in S1 and S6 strains. A type I-C CRISPR-Cas system was identified in each strain with spacer diversity and organization conserved among serotypes. The majority of spacers occur in S1 and S6 strains and originate from phage suggesting that serotypes 1 and 6 may be more resistant to phage predation. However, two spacers complementary to the host chromosome targeting a UDP-N-acetylglucosamine 2-epimerase and a glycosyl transferases group 1 gene are present in S1 and S6 strains only indicating these serotypes may employ CRISPR-Cas to regulate gene expression to avoid host immune responses or enhance adhesion during infection. Integrative conjugative elements are present in nine of the eleven genomes. Three of these harbor extensive multi-drug resistance cassettes encoding resistance against the majority of drugs used to combat infection in beef cattle, including macrolides and tetracyclines used in human medicine. The findings here identify key features that are likely contributing to serotype related pathogenesis and specific targets for vaccine design intended to reduce the

  1. Genome sequences of serotype A6 Mannheimia haemolytica isolates D174 and D38 recovered from bovine pneumonia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we report two genomes, one complete and one draft, from virulent bovine strains of Mannheimia haemolytica(strains D174 and D38)serotype A2 recovered prior to the field usage of modern antimicrobial drugs....

  2. Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

    PubMed Central

    Bavananthasivam, Jegarubee; Dassanayake, Rohana P.; Kugadas, Abirami; Shanthalingam, Sudarvili; Call, Douglas R.; Knowles, Donald P.

    2012-01-01

    Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. haemolytica has been isolated by culture less frequently than the other bacteria. We hypothesized that the growth of M. haemolytica is inhibited by other bacteria in the lungs of BHS. The objective of this study was to determine whether P. multocida inhibits the growth of M. haemolytica. Although in monoculture both bacteria exhibited similar growth characteristics, in coculture with P. multocida there was a clear inhibition of growth of M. haemolytica. The inhibition was detected at mid-log phase and continued through the stationary phase. When cultured in the same medium, the growth of M. haemolytica was inhibited when both bacteria were separated by a membrane that allowed contact (pore size, 8.0 μm) but not when they were separated by a membrane that limited contact (pore size, 0.4 μm). Lytic bacteriophages or bactericidal compounds could not be detected in the culture supernatant fluid from monocultures of P. multocida or from P. multocida-M. haemolytica cocultures. These results indicate that P. multocida inhibits the growth of M. haemolytica by a contact- or proximity-dependent mechanism. If the inhibition of growth of M. haemolytica by P. multocida occurs in vivo as well, it could explain the inconsistent isolation of M. haemolytica from the lungs of pneumonic BHS. PMID:22798357

  3. LKTA and PlpE small fragments fusion protein protect against Mannheimia haemolytica challenge.

    PubMed

    Guzmán-Brambila, Carolina; Quintero-Fabián, Saray; González-Castillo, Celia; de Obeso-Fernández del Valle, Álvaro; Flores-Samaniego, Beatriz; de la Mora, Germán; Rojas-Mayorquín, Argelia E; Ortuño-Sahagún, Daniel

    2012-12-01

    Bovine respiratory disease (BRD) complex is a major cause of economic losses for the cattle backgrounding and feedlot industries. Mannheimia haemolytica is considered the most important pathogen associated with this disease. Vaccines against M. haemolytica have been prepared and used for many decades, but traditional bacterins have failed to demonstrate effective protection and their use has often exacerbated disease in vaccinated animals. Thus, the BRD complex continues to exert a strong adverse effect on the health and wellbeing of stocker and feeder cattle. Therefore, generation of recombinant proteins has been helpful in formulating enhanced vaccines against M. haemolytica, which could confer better protection against BRD. In the present study, we formulated a vaccine preparation enriched with recombinant small fragments of leukotoxin A (LKTA) and outer-membrane lipoprotein (PlpE) proteins, and demonstrated its ability to generate high antibody titers in rabbits and sheep, which protected against M. haemolytica bacterial challenge in mice. PMID:22840333

  4. Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils.

    PubMed

    Aulik, Nicole A; Hellenbrand, Katrina M; Klos, Heather; Czuprynski, Charles J

    2010-11-01

    Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktC mutant of M. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or M. haemolytica cells. Further investigation revealed that NETs formed in response to M. haemolytica are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica cells in bovine NETs. Understanding NET formation in response to M. haemolytica and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease. PMID:20823211

  5. Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages

    PubMed Central

    Aulik, Nicole A.; Hellenbrand, Katrina M.

    2012-01-01

    Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M. haemolytica or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an lktC mutant of M. haemolytica) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the M. haemolytica cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to M. haemolytica cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to Escherichia coli hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the M. haemolytica leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins. PMID:22354029

  6. Mannheimia haemolytica and its leukotoxin cause macrophage extracellular trap formation by bovine macrophages.

    PubMed

    Aulik, Nicole A; Hellenbrand, Katrina M; Czuprynski, Charles J

    2012-05-01

    Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M. haemolytica or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an lktC mutant of M. haemolytica) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the M. haemolytica cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to M. haemolytica cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to Escherichia coli hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the M. haemolytica leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins. PMID:22354029

  7. Identification of immunodominant proteins from Mannheimia haemolytica and Histophilus somni by an immunoproteomic approach.

    PubMed

    Alvarez, Angel H; Gutiérrez-Ortega, Abel; Hernández-Gutiérrez, Rodolfo

    2015-10-01

    Mannheimia haemolytica and Histophilus somni are frequently isolated from diseased cattle with bovine respiratory disease (BRD). They compromise animal lung function and the immune responses generated are not sufficient to limit infection. Identification of specific immunogenic antigens for vaccine development represents a great challenge. Immunogenic proteins were identified by immunoproteomic approach with sera from cattle immunized with a commercial cellular vaccine of M. haemolytica and H. somni. Proteins of M. haemolytica were identified as solute ABC transporter, iron-binding protein, and hypothetical protein of capsular biosynthesis. Histophilus somni proteins correspond to porin, amino acid ABC transporter, hypothetical outer membrane protein, cysteine synthase, and outer membrane protein P6. Although these antigens share strong similarities with other proteins from animal pathogens, the ABC system proteins have been associated with virulence and these proteins could be considered as potential vaccine candidates for BRD.

  8. Identification of immunodominant proteins from Mannheimia haemolytica and Histophilus somni by an immunoproteomic approach

    PubMed Central

    Alvarez, Angel H.; Gutiérrez-Ortega, Abel; Hernández-Gutiérrez, Rodolfo

    2015-01-01

    Mannheimia haemolytica and Histophilus somni are frequently isolated from diseased cattle with bovine respiratory disease (BRD). They compromise animal lung function and the immune responses generated are not sufficient to limit infection. Identification of specific immunogenic antigens for vaccine development represents a great challenge. Immunogenic proteins were identified by immunoproteomic approach with sera from cattle immunized with a commercial cellular vaccine of M. haemolytica and H. somni. Proteins of M. haemolytica were identified as solute ABC transporter, iron-binding protein, and hypothetical protein of capsular biosynthesis. Histophilus somni proteins correspond to porin, amino acid ABC transporter, hypothetical outer membrane protein, cysteine synthase, and outer membrane protein P6. Although these antigens share strong similarities with other proteins from animal pathogens, the ABC system proteins have been associated with virulence and these proteins could be considered as potential vaccine candidates for BRD. PMID:26424916

  9. Susceptibility to tulathromycin in Mannheimia haemolytica isolated from feedlot cattle over a 3-year period

    PubMed Central

    Alexander, Trevor W.; Cook, Shaun; Klima, Cassidy L.; Topp, Ed; McAllister, Tim A.

    2013-01-01

    Mannheimia haemolytica isolated from feedlot cattle were tested for tulathromycin resistance. Cattle were sampled over a 3-year period, starting 12 months after approval of tulathromycin for prevention and treatment of bovine respiratory disease. Nasopharyngeal samples from approximately 5,814 cattle were collected when cattle entered feedlots (N = 4) and again from the same cattle after ≥60 days on feed. The antimicrobial use history for each animal was recorded. Mannheimia haemolytica was isolated from 796 (13.7%) entry samples and 1,038 (20.6%) ≥ 60 days samples. Of the cattle positive for M. haemolytica, 18.5, 2.9, and 2.4% were administered therapeutic concentrations of tulathromycin, tilmicosin, or tylosin tartrate, respectively. In addition, 13.2% were administered subtherapeutic concentrations of tylosin phosphate in feed. In years one and two, no tulathromycin-resistant M. haemolytica were detected, whereas five isolates (0.4%) were resistant in year three. These resistant isolates were collected from three cattle originating from a single pen, were all serotype 1, and were genetically related (≥89% similarity) according to pulsed-field gel electrophoreses patterns. The five tulathromycin-resistant isolates were multi-drug resistant also exhibiting resistance to oxytetracycline, tilmicosin, ampicillin, or penicillin. The macrolide resistance genes erm(42), erm(A), erm(B), erm(F), erm(X) and msr(E)-mph(E), were not detected in the tulathromycin-resistant M. haemolytica. This study showed that tulathromycin resistance in M. haemolytica from a general population of feedlot cattle in western Canada was low and did not change over a 3-year period after tulathromycin was approved for use in cattle. PMID:24130555

  10. Susceptibility to tulathromycin in Mannheimia haemolytica isolated from feedlot cattle over a 3-year period.

    PubMed

    Alexander, Trevor W; Cook, Shaun; Klima, Cassidy L; Topp, Ed; McAllister, Tim A

    2013-01-01

    Mannheimia haemolytica isolated from feedlot cattle were tested for tulathromycin resistance. Cattle were sampled over a 3-year period, starting 12 months after approval of tulathromycin for prevention and treatment of bovine respiratory disease. Nasopharyngeal samples from approximately 5,814 cattle were collected when cattle entered feedlots (N = 4) and again from the same cattle after ≥60 days on feed. The antimicrobial use history for each animal was recorded. Mannheimia haemolytica was isolated from 796 (13.7%) entry samples and 1,038 (20.6%) ≥ 60 days samples. Of the cattle positive for M. haemolytica, 18.5, 2.9, and 2.4% were administered therapeutic concentrations of tulathromycin, tilmicosin, or tylosin tartrate, respectively. In addition, 13.2% were administered subtherapeutic concentrations of tylosin phosphate in feed. In years one and two, no tulathromycin-resistant M. haemolytica were detected, whereas five isolates (0.4%) were resistant in year three. These resistant isolates were collected from three cattle originating from a single pen, were all serotype 1, and were genetically related (≥89% similarity) according to pulsed-field gel electrophoreses patterns. The five tulathromycin-resistant isolates were multi-drug resistant also exhibiting resistance to oxytetracycline, tilmicosin, ampicillin, or penicillin. The macrolide resistance genes erm(42), erm(A), erm(B), erm(F), erm(X) and msr(E)-mph(E), were not detected in the tulathromycin-resistant M. haemolytica. This study showed that tulathromycin resistance in M. haemolytica from a general population of feedlot cattle in western Canada was low and did not change over a 3-year period after tulathromycin was approved for use in cattle.

  11. Bighorn sheep × domestic sheep hybrids survive Mannheimia haemolytica challenge in the absence of vaccination.

    PubMed

    Subramaniam, R; Shanthalingam, S; Bavananthasivam, J; Kugadas, A; Raghavan, B; Batra, S A; Herndon, C N; Rodriguez, J; Tibary, A; Nelson, D; Potter, K A; Foreyt, W J; Srikumaran, S

    2014-06-01

    Bighorn sheep (BHS, Ovis canadensis) are much more susceptible than domestic sheep (DS, Ovis aries) to pneumonia caused by leukotoxin (Lkt)-producing members of the Family Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi. Leukotoxin is widely accepted as the critical virulence factor of these bacteria since Lkt-negative mutants do not cause death of BHS. Typically, DS carry Lkt-positive M. haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most BHS do not carry Lkt-positive M. haemolytica or B. trehalosi, or carry Lkt-negative strains in their nasopharynx. In previous studies, we demonstrated that unimmunized DS resist M. haemolytica challenge while BHS succumb to it. We hypothesized that Lkt-neutralizing antibodies, induced by Lkt-positive M. haemolytica and/or B. trehalosi innately carried by DS in their nasopharynx, render them less susceptible to infection by these bacteria. In this study we developed BHS×DS F1 hybrids by artificial insemination of domestic ewes with BHS semen. F1 hybrids were fertile, and produced F2 hybrids and back-crosses. The F1, F2, and back-crosses were raised together with domestic ewes. All these animals acquired Lkt-positive M. haemolytica and/or B. trehalosi, and developed high titers of Lkt-neutralizing antibodies in the absence of vaccination. Furthermore, all of these animals resisted challenge with lethal dose of M. haemolytica. These results suggest that lack of previous exposure to Lkt is at least partially responsible for fatal pneumonia in BHS when they acquire Lkt-positive M. haemolytica and/or B. trehalosi from DS when the two species commingle.

  12. Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia.

    PubMed

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Herndon, Caroline N; Subramaniam, Renuka; Lawrence, Paulraj K; Bavananthasivam, Jegarubee; Cassirer, E Frances; Haldorson, Gary J; Foreyt, William J; Rurangirwa, Fred R; Knowles, Donald P; Besser, Thomas E; Srikumaran, Subramaniam

    2010-10-26

    Mycoplasma ovipneumoniae has been isolated from the lungs of pneumonic bighorn sheep (BHS). However experimental reproduction of fatal pneumonia in BHS with M. ovipneumoniae was not successful. Therefore the specific role, if any, of M. ovipneumoniae in BHS pneumonia is unclear. The objective of this study was to determine whether M. ovipneumoniae alone causes fatal pneumonia in BHS, or predisposes them to infection by Mannheimia haemolytica. We chose M. haemolytica for this study because of its isolation from pneumonic BHS, and its consistent ability to cause fatal pneumonia under experimental conditions. Since in vitro culture could attenuate virulence of M. ovipneumoniae, we used ceftiofur-treated lung homogenates from pneumonic BHS lambs or nasopharyngeal washings from M. ovipneumoniae-positive domestic sheep (DS) as the source of M. ovipneumoniae. Two adult BHS were inoculated intranasally with lung homogenates while two others received nasopharyngeal washings from DS. All BHS developed clinical signs of respiratory infection, but only one BHS died. The dead BHS had carried leukotoxin-positive M. haemolytica in the nasopharynx before the onset of this study. It is likely that M. ovipneumoniae colonization predisposed this BHS to fatal infection with the M. haemolytica already present in this animal. The remaining three BHS developed pneumonia and died 1-5 days following intranasal inoculation with M. haemolytica. On necropsy, lungs of all four BHS showed lesions characteristic of bronchopneumonia. M. haemolytica and M. ovipneumoniae were isolated from the lungs. These results suggest that M. ovipneumoniae alone may not cause fatal pneumonia in BHS, but can predispose them to fatal pneumonia due to M. haemolytica infection.

  13. Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease

    PubMed Central

    Klima, Cassidy L.; Alexander, Trevor W.; Hendrick, Steve; McAllister, Tim A.

    2014-01-01

    Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), blaROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P < 0.001) in M. haemolytica collected from cattle with BRD (37%) compared with those that were healthy (2%). Overall, tetracycline resistance (18%) was the most prevalent resistant phenotype. All tetracycline-resistant M. haemolytica encoded tet(H). Ampicillin resistance (6%) and neomycin resistance (15%) were detected and corresponded to the presence of the blaROB-1 and aphA-1 genes, respectively. Tilmicosin resistance (6%) was also detected, but the resistance genes responsible were not identified. The virulence genes lktC, ahs, gs60, and gcp

  14. Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease.

    PubMed

    Klima, Cassidy L; Alexander, Trevor W; Hendrick, Steve; McAllister, Tim A

    2014-01-01

    Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), bla ROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P < 0.001) in M. haemolytica collected from cattle with BRD (37%) compared with those that were healthy (2%). Overall, tetracycline resistance (18%) was the most prevalent resistant phenotype. All tetracycline-resistant M. haemolytica encoded tet(H). Ampicillin resistance (6%) and neomycin resistance (15%) were detected and corresponded to the presence of the bla ROB-1 and aphA-1 genes, respectively. Tilmicosin resistance (6%) was also detected, but the resistance genes responsible were not identified. The virulence genes lktC, ahs, gs60, and

  15. Diversity of Mannheimia haemolytica and pasteurella trehalosi serotypes from apparently healthy sheep and abattoir specimens in the highlands of Wollo, North East Ethiopia.

    PubMed

    Sisay, T; Zerihun, A

    2003-01-01

    The prevalence and serotypic diversity of Mannheimia [Pasteurella] haemolytica and Pasteurella trehalosi from nasal swabs, sera and abattoir specimens from sheep in the highlands of Wollo, North East Ethiopia was investigated. Prevalence rates of 83% and 75% of these microorganisms were found in the serum samples and nasal swabs, respectively, from apparently healthy sheep. In a local abattoir, 205 lungs were investigated, 34% of which showed pneumonia, from which samples were collected from 51 lungs and the same number of corresponding tonsils. Mannheimia and Pasteurella species were isolated from 59% of these pneumonic lungs and 69% of the respective tonsils. M. haemolytica serotypes accounted for 41 (59%) and P. trehalosi for 11 (32%) of the isolates from the abattoir specimens. The majority (67%) of isolates from nasal swabs were P. trehalosi, M. haemolytica being isolated f rom 4 (13%) of the swabs. M. glucosida was isolated only from the tonsils. The predominant serotypes of the isolates from both the nasal swabs and the abattoir specimens were M. haemolytica A1 (17%) and P. trehalosi T4 (16%) and T3 (13%). P. trehalosi T15 was less commonly encountered, while M. haemolytica A9 and A13 were not isolated. Studies on sera from 100 sheep indicated that antibodies against M. haemolytica serotype A1 (14%) were most common, followed by A5 and A8 (each 10%) and A9 and P. trehalosi T3 (each 9%) and T4 (8%). Antibodies against M. glucosida or serotype All occurred in 2% of the sera. Multiple serotypes were common in all types of samples. The importance of including in vaccines the most prevalent serotypes involved in the pneumonia of sheep in the area is discussed. PMID:12625399

  16. Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella multocida.

    PubMed

    Potter, T; Illambas, J; Pelligand, L; Rycroft, A; Lees, P

    2013-01-01

    The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration-time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller-Hinton broth (MHB) and calf serum. Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK-PD data established C(max)/MIC ratios of 45.0 and AUC(24h)/MIC values of 174.7 h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK-PD modelling established three levels of growth inhibition: AUC(24 h)/MIC ratios for no reduction, 3 log(10) and 4 log(10) reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0 h for M. haemolytica and 48.6, 64.9 and 74.8 h for P. multocida, on average respectively. Inter-strain variability for 3 log(10) and 4 log(10) reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC(90) values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition.

  17. Multiplex PCR To Identify Macrolide Resistance Determinants in Mannheimia haemolytica and Pasteurella multocida

    PubMed Central

    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet; Wilhelm, Cornelia; Warrass, Ralf

    2012-01-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLSB (macrolide, lincosamide, and streptogramin B) phenotype; msr(E), which encodes a macrolide efflux pump; and mph(E), which encodes a macrolide-inactivating phosphotransferase. Here, we describe a multiplex PCR assay that detects the presence of erm(42), msr(E), and mph(E) and differentiates between these genes. In addition, the assay distinguishes P. multocida from M. haemolytica by amplifying distinctive fragments of the 23S rRNA (rrl) genes. One rrl fragment acts as a general indicator of gammaproteobacterial species and confirms whether the PCR assay has functioned as intended on strains that are negative for erm(42), msr(E), and mph(E). The multiplex system has been tested on more than 40 selected isolates of P. multocida and M. haemolytica and correlated with MICs for the veterinary macrolides tulathromycin and tilmicosin, and the newer compounds gamithromycin and tildipirosin. The multiplex PCR system gives a rapid and robustly accurate determination of macrolide resistance genotypes and bacterial genus, matching results from microbiological methods and whole-genome sequencing. PMID:22564832

  18. Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries...

  19. A three-way comparative genomic analysis of Mannheimia haemolytica isolates

    PubMed Central

    2010-01-01

    Background Mannhemia haemolytica is a Gram-negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen, during stress such as viral infection and transportation to feedlots and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually due to shipping fever. Despite its enormous economic importance there are no specific and accurate genetic markers, which will aid in understanding the pathogenesis and epidemiology of M. haemolytica at molecular level and assist in devising an effective control strategy. Description During our comparative genomic sequence analysis of three Mannheimia haemolytica isolates, we identified a number of genes that are unique to each strain. These genes are "high value targets" for future studies that attempt to correlate the variable gene pool with phenotype. We also identified a number of high confidence single nucleotide polymorphisms (hcSNPs) spread throughout the genome and focused on non-synonymous SNPs in known virulence genes. These SNPs will be used to design new hcSNP arrays to study variation across strains, and will potentially aid in understanding gene regulation and the mode of action of various virulence factors. Conclusions During our analysis we identified previously unknown possible type III secretion effector proteins, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated sequences (Cas). The presence of CRISPR regions is indicative of likely co-evolution with an associated phage. If proven functional, the presence of a type III secretion system in M. haemolytica will help us re-evaluate our approach to study host-pathogen interactions. We also identified various adhesins containing immuno-dominant domains, which may interfere with host-innate immunity and which could potentially serve as effective vaccine

  20. Transcriptome profile of a bovine respiratory disease pathogen: Mannheimia haemolytica PHL213

    PubMed Central

    2012-01-01

    Background Computational methods for structural gene annotation have propelled gene discovery but face certain drawbacks with regards to prokaryotic genome annotation. Identification of transcriptional start sites, demarcating overlapping gene boundaries, and identifying regulatory elements such as small RNA are not accurate using these approaches. In this study, we re-visit the structural annotation of Mannheimia haemolytica PHL213, a bovine respiratory disease pathogen. M. haemolytica is one of the causative agents of bovine respiratory disease that results in about $3 billion annual losses to the cattle industry. We used RNA-Seq and analyzed the data using freely-available computational methods and resources. The aim was to identify previously unannotated regions of the genome using RNA-Seq based expression profile to complement the existing annotation of this pathogen. Results Using the Illumina Genome Analyzer, we generated 9,055,826 reads (average length ~76 bp) and aligned them to the reference genome using Bowtie. The transcribed regions were analyzed using SAMTOOLS and custom Perl scripts in conjunction with BLAST searches and available gene annotation information. The single nucleotide resolution map enabled the identification of 14 novel protein coding regions as well as 44 potential novel sRNA. The basal transcription profile revealed that 2,506 of the 2,837 annotated regions were expressed in vitro, at 95.25% coverage, representing all broad functional gene categories in the genome. The expression profile also helped identify 518 potential operon structures involving 1,086 co-expressed pairs. We also identified 11 proteins with mutated/alternate start codons. Conclusions The application of RNA-Seq based transcriptome profiling to structural gene annotation helped correct existing annotation errors and identify potential novel protein coding regions and sRNA. We used computational tools to predict regulatory elements such as promoters and terminators

  1. Effect of subtherapeutic vs. therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

    PubMed Central

    Zaheer, Rahat; Cook, Shaun R.; Klima, Cassidy L.; Stanford, Kim; Alexander, Trevor; Topp, Edward; Read, Ron R.; McAllister, Tim A.

    2013-01-01

    Macrolides are the first-line treatment against bovine respiratory disease (BRD), and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic) or continuously in-feed (subtherapeutic), on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05) the prevalence of M. haemolytica, whereas subtherapeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica from the nasopharynx included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., Escherichia coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05) the proportion of erythromycin resistant enterococci within the population, which was comprised almost exclusively of Enterococcus hirae. Injectable macrolides impacted both respiratory and enteric microbes, whereas orally administered macrolides only influenced enteric bacteria. PMID:23750157

  2. Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves.

    PubMed

    Ismail, M; El-Kattan, Y A

    2007-06-01

    The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.

  3. PCR assay detects Mannheimia haemolytica in culture-negative pneumonic lung tissues of bighorn sheep (Ovis canadensis) from outbreaks in the western USA, 2009-2010.

    PubMed

    Shanthalingam, Sudarvili; Goldy, Andrea; Bavananthasivam, Jegarubee; Subramaniam, Renuka; Batra, Sai Arun; Kugadas, Abirami; Raghavan, Bindu; Dassanayake, Rohana P; Jennings-Gaines, Jessica E; Killion, Halcyon J; Edwards, William H; Ramsey, Jennifer M; Anderson, Neil J; Wolff, Peregrine L; Mansfield, Kristin; Bruning, Darren; Srikumaran, Subramaniam

    2014-01-01

    Mannheimia haemolytica consistently causes severe bronchopneumonia and rapid death of bighorn sheep (Ovis canadensis) under experimental conditions. However, Bibersteinia trehalosi and Pasteurella multocida have been isolated from pneumonic bighorn lung tissues more frequently than M. haemolytica by culture-based methods. We hypothesized that assays more sensitive than culture would detect M. haemolytica in pneumonic lung tissues more accurately. Therefore, our first objective was to develop a PCR assay specific for M. haemolytica and use it to determine if this organism was present in the pneumonic lungs of bighorns during the 2009-2010 outbreaks in Montana, Nevada, and Washington, USA. Mannheimia haemolytica was detected by the species-specific PCR assay in 77% of archived pneumonic lung tissues that were negative by culture. Leukotoxin-negative M. haemolytica does not cause fatal pneumonia in bighorns. Therefore, our second objective was to determine if the leukotoxin gene was also present in the lung tissues as a means of determining the leukotoxicity of M. haemolytica that were present in the lungs. The leukotoxin-specific PCR assay detected leukotoxin gene in 91% of lung tissues that were negative for M. haemolytica by culture. Mycoplasma ovipneumoniae, an organism associated with bighorn pneumonia, was detected in 65% of pneumonic bighorn lung tissues by PCR or culture. A PCR assessment of distribution of these pathogens in the nasopharynx of healthy bighorns from populations that did not experience an all-age die-off in the past 20 yr revealed that M. ovipneumoniae was present in 31% of the animals whereas leukotoxin-positive M. haemolytica was present in only 4%. Taken together, these results indicate that culture-based methods are not reliable for detection of M. haemolytica and that leukotoxin-positive M. haemolytica was a predominant etiologic agent of the pneumonia outbreaks of 2009-2010.

  4. Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica

    PubMed Central

    Lhermie, Guillaume; Ferran, Aude A.; Assié, Sébastien; Cassard, Hervé; El Garch, Farid; Schneider, Marc; Woerhlé, Frédérique; Pacalin, Diane; Delverdier, Maxence; Bousquet-Mélou, Alain; Meyer, Gilles

    2016-01-01

    The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.107 CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2–4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35–39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5–4 and 5.5–6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia. PMID:26973615

  5. Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.

    PubMed

    Lhermie, Guillaume; Ferran, Aude A; Assié, Sébastien; Cassard, Hervé; El Garch, Farid; Schneider, Marc; Woerhlé, Frédérique; Pacalin, Diane; Delverdier, Maxence; Bousquet-Mélou, Alain; Meyer, Gilles

    2016-01-01

    The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.10(7) CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2-4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35-39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5-4 and 5.5-6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia.

  6. Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida▿

    PubMed Central

    Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

    2011-01-01

    Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants. PMID:21709086

  7. Outer Membrane Protein A of Bovine and Ovine Isolates of Mannheimia haemolytica Is Surface Exposed and Contains Host Species-Specific Epitopes ▿

    PubMed Central

    Hounsome, Jonathan D. A.; Baillie, Susan; Noofeli, Mojtaba; Riboldi-Tunnicliffe, Alan; Burchmore, Richard J. S.; Isaacs, Neil W.; Davies, Robert L.

    2011-01-01

    Mannheimia haemolytica is the etiological agent of pneumonic pasteurellosis of cattle and sheep; two different OmpA subclasses, OmpA1 and OmpA2, are associated with bovine and ovine isolates, respectively. These proteins differ at the distal ends of four external loops, are involved in adherence, and are likely to play important roles in host adaptation. M. haemolytica is surrounded by a polysaccharide capsule, and the degree of OmpA surface exposure is unknown. To investigate surface exposure and immune specificity of OmpA among bovine and ovine M. haemolytica isolates, recombinant proteins representing the transmembrane domain of OmpA from a bovine serotype A1 isolate (rOmpA1) and an ovine serotype A2 isolate (rOmpA2) were overexpressed, purified, and used to generate anti-rOmpA1 and anti-rOmpA2 antibodies, respectively. Immunogold electron microscopy and immunofluorescence techniques demonstrated that OmpA1 and OmpA2 are surface exposed, and are not masked by the polysaccharide capsule, in a selection of M. haemolytica isolates of various serotypes and grown under different growth conditions. To explore epitope specificity, anti-rOmpA1 and anti-rOmpA2 antibodies were cross-absorbed with the heterologous isolate to remove cross-reacting antibodies. These cross-absorbed antibodies were highly specific and recognized only the OmpA protein of the homologous isolate in Western blot assays. A wider examination of the binding specificities of these antibodies for M. haemolytica isolates representing different OmpA subclasses revealed that cross-absorbed anti-rOmpA1 antibodies recognized OmpA1-type proteins but not OmpA2-type proteins; conversely, cross-absorbed anti-rOmpA2 antibodies recognized OmpA2-type proteins but not OmpA1-type proteins. Our results demonstrate that OmpA1 and OmpA2 are surface exposed and could potentially bind to different receptors in cattle and sheep. PMID:21896777

  8. The relationship between the occurrence of undifferentiated bovine respiratory disease and titer changes to Haemophilus somnus and Mannheimia haemolytica at 3 Ontario feedlots.

    PubMed

    O'Connor, A; Martin, S W; Harland, R; Shewen, P; Menzies, P

    2001-07-01

    The association between exposure to Haemophilus somnus and Mannheimia haemolytica (formerly Pasteurella haemolytica) and the risk of undifferentiated bovine respiratory disease (UBRD) was investigated using serological evidence of exposure coupled with a factorial design vaccine field trial. Measures of previous exposure (titer at arrival) and current exposure (titer increase in the study period) to these agents were used. The vaccine field trial involved systematic allocation of animals into groups that received either a M. haemolytica vaccine, an H. somnus vaccine, a combined M. haemolytica and H. somnus vaccine, and an unvaccinated control group. Serum was collected from the 852 animals enrolled to determine titers to H. somnus, M. haemolytica, bovine coronavirus and bovine viral diarrhea virus. Vaccination with H. somnus in combination with M. haemolytica and with M. haemolytica alone reduced the risk of UBRD. The odds ratio for vaccination with H. somnus alone and UBRD risk suggested some sparing effect, but the 95% confidence limits included unity. There was no association between serological evidence of concurrent exposure to M. haemolytica and UBRD occurrence. There was an association between titer change to H. somnus and UBRD risk. However, the association changed with time of BRD treatment; animals diagnosed and treated for UBRD on or after day 10 showed little evidence of exposure to H. somnus, despite evidence of natural H. somnus exposure in the unvaccinated group. The association between titer change to H. somnus and UBRD occurrence seen in this study may be a consequence of prolonged exposure to antibiotics, rather than a causal association.

  9. An ecologic study comparing distribution of Pasteurella trehalosi and Mannheimia haemolytica between Sierra Nevada bighorn sheep, White Mountain bighorn sheep, and domestic sheep.

    PubMed

    Tomassini, Letizia; Gonzales, Ben; Weiser, Glen C; Sischo, William

    2009-10-01

    The prevalence and phenotypic variability of Pasteurella and Mannheimia isolates from Sierra Nevada bighorn sheep (Ovis canadensis sierrae), White Mountain bighorn sheep (Ovis canadensis nelsoni), and domestic sheep (Ovis aries) from California, USA, were compared. The White Mountain bighorn sheep population had a recent history of pneumonia-associated mortality, whereas the Sierra Nevada bighorn sheep population had no recent history of pneumonia-associated mortality. The domestic sheep flocks were pastured in areas geographically near both populations but were not known to have direct contact with either bighorn sheep population. Oropharyngeal swab samples were collected from healthy domestic and bighorn sheep and cultured to characterize bacterial species, hemolysis, biogroups, and biovariants. Pasteurella trehalosi and Mannheimia haemolytica were detected in all of the study populations, but the relative proportion of each bacterial species differed among sheep populations. Pasteurella trehalosi was more common than M. haemolytica in the bighorn sheep populations, whereas the opposite was true in domestic sheep. Mannheimia haemolytica was separated into 11 biogroups, and P. trehalosi was characterized into two biogroups. Biogroup distributions for M. haemolytica and P. trehalosi differed among the three populations; however, no difference was detected for the distribution of P. trehalosi biogroups between the Sierra Nevada bighorn sheep and domestic sheep. The prevalence odds ratios (pOR) for the distribution of M. haemolytica biogroups suggested little difference between White Mountain bighorn sheep and domestic sheep compared with Sierra Nevada bighorn sheep and domestic sheep, although these comparisons had relatively large confidence intervals for the point estimates. Hemolytic activity of the isolates was not different among the sheep populations for M. haemolytica but was different for P. trehalosi. No clear evidence of association was found in the

  10. Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep

    PubMed Central

    Batra, Sai A.; Shanthalingam, Sudarvili; Munske, Gerhard R.; Raghavan, Bindu; Kugadas, Abirami; Bavanthasivam, Jegarubee; Highlander, Sarah K.

    2015-01-01

    Mannheimia haemolytica causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene lktCABD operon: lktA encodes the structural protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktB and lktD. It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are highly susceptible to M. haemolytica infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but that it enhances the potency of the toxin. PMID:26216418

  11. A Three-way Comparative Genomic Analysis of Mannheimia haemolytica Isolates

    SciTech Connect

    Lawrence, Paulraj; Kittichotirat, Weerayuth; McDermott, Jason E.; Bumgarner, Roger E.

    2010-10-04

    Mannhemia haemolytica is a Gram- negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen during stress such as viral infection and transportation to feedlots, and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually to shipping fever and despite its enormous economic importance there are no specific and accurate genetic markers, which would aid in understanding M. haemolytica pathogenesis and epidemiology at molecular level and assist in devising an effective control strategy.

  12. Tilmicosin does not inhibit interleukin-8 gene expression in the bovine lung experimentally infected with Mannheimia (Pasteurella) haemolytica.

    PubMed

    Goubau, S; Morck, D W; Buret, A

    2000-10-01

    The expression of the interleukin-8 (IL-8) gene was examined by in situ hybridization in lung tissues from calves experimentally infected with Mannheimia (Pasteurella) haemolytica and treated with tilmicosin. Interleukin-8 mRNA expression was detected in alveolar areas, particularly along interlobular septa, in the lumen, and in the epithelial cells of some bronchioles. In lesional lung tissues from animals that had received tilmicosin, we found large areas with limited inflammation. There was no staining for IL-8 mRNA in these areas. In contrast, in strongly inflamed areas, the same patterns and intensities of staining for IL-8 mRNA were detected in tilmicosin- and sham-treated animals. We conclude that tilmicosin does not affect the expression of IL-8 mRNA in tissue showing microscopic signs of inflammation. Together with previous reports, this supports the view that the pro-apoptotic properties of tilmicosin on neutrophils do not compromise the host defense mechanisms required to control the infection.

  13. Molecular epidemiology of an outbreak of clinical mastitis in sheep caused by Mannheimia haemolytica.

    PubMed

    Omaleki, Lida; Browning, Glenn F; Allen, Joanne L; Markham, Philip F; Barber, Stuart R

    2016-08-15

    The aetiology and epidemiology of outbreaks of clinical mastitis in sheep under extensive pastoral conditions are incompletely understood. The objective of this study was to conduct a detailed investigation of a clinical mastitis outbreak that affected more than 10% of 230 at-risk ewes on a sheep and grain producing property in south east Australia during drought conditions in 2009. Milk samples were collected aseptically from all affected ewes and plated on sheep blood agar for bacterial identification. M. haemolytica was isolated from 80% of the samples that yielded cultivable microorganisms and thus was the main microorganism responsible for the outbreak. Analysis of the restriction endonuclease cleavage patterns of the isolates using pulsed field gel electrophoresis revealed some evidence of clonality, suggesting the possibility of horizontal transmission, but there was also considerable diversity between the clusters of closely related isolates. Multilocus sequence typing of the M. haemolytica isolates revealed most of the isolates belonged to ST1 with no association between the PFGE and MLST fingerprints of the isolates. Resistance to neomycin, streptomycin and sulphafurazole was detected in some of the isolates, but they were all susceptible to penicillin, ampicillin, ceftiofur, amoxycillin/clavulanic acid, ciprofloxacin, tetracycline, erythromycin and trimethoprim. This is the first published record of a comparison of the strains of M. haemolytica involved in a clinical mastitis outbreak in sheep and demonstrates the importance of this pathogen in sheep production systems, particularly during adverse climatic conditions and increased stocking rate. PMID:27374911

  14. Transmission of Mannheimia haemolytica from domestic sheep (Ovis aries) to bighorn sheep (Ovis canadensis): unequivocal demonstration with green fluorescent protein-tagged organisms.

    PubMed

    Lawrence, Paulraj K; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Subramaniam, Renuka; Herndon, Caroline N; Knowles, Donald P; Rurangirwa, Fred R; Foreyt, William J; Wayman, Gary; Marciel, Ann Marie; Highlander, Sarah K; Srikumaran, Subramaniam

    2010-07-01

    Previous studies demonstrated that bighorn sheep (Ovis canadensis) died of pneumonia when commingled with domestic sheep (Ovis aries) but did not conclusively prove that the responsible pathogens were transmitted from domestic to bighorn sheep. The objective of this study was to determine, unambiguously, whether Mannheimia haemolytica can be transmitted from domestic to bighorn sheep when they commingle. Four isolates of M. haemolytica were obtained from the pharynx of two of four domestic sheep and tagged with a plasmid carrying the genes for green fluorescent protein (GFP) and ampicillin resistance (AP(R)). Four domestic sheep, colonized with the tagged bacteria, were kept about 10 m apart from four bighorn sheep for 1 mo with no clinical signs of pneumonia observed in the bighorn sheep during that period. The domestic and bighorn sheep were then allowed to have fence-line contact for 2 mo. During that period, three bighorn sheep acquired the tagged bacteria from the domestic sheep. At the end of the 2 mo of fence-line contact, the animals were allowed to commingle. All four bighorn sheep died 2 days to 9 days following commingling. The lungs from all four bighorn sheep showed gross and histopathologic lesions characteristic of M. haemolytica pneumonia. Tagged M. haemolytica were isolated from all four bighorn sheep, as confirmed by growth in ampicillin-containing culture medium, PCR-amplification of genes encoding GFP and Ap(R), and immunofluorescent staining of GFP. These results unequivocally demonstrate transmission of M. haemolytica from domestic to bighorn sheep, resulting in pneumonia and death of bighorn sheep.

  15. Immunogenicity of Mannheimia haemolytica Recombinant Outer Membrane Proteins Serotype 1-Specific Antigen, OmpA, OmpP2, and OmpD15▿

    PubMed Central

    Ayalew, Sahlu; Shrestha, Binu; Montelongo, Marie; Wilson, Amanda E.; Confer, Anthony W.

    2011-01-01

    We previously identified Mannheimia haemolytica outer membrane proteins (OMPs) that may be important immunogens by using immunoproteomic analyses. Genes for serotype 1-specific antigen (SSA-1), OmpA, OmpP2, and OmpD15 were cloned and expressed, and recombinant proteins were purified. Objective 1 of this study was to demonstrate immunogenicity of the four recombinant OMPs in mice and cattle. Objective 2 was to determine if the addition of individual recombinant OMPs or combinations of them would modify immune responsiveness of mice to the recombinant chimeric protein SAC89, containing the main epitope from M. haemolytica outer membrane lipoprotein PlpE and the neutralizing epitope of M. haemolytica leukotoxin. Mice vaccinated with recombinant OmpA (rOmpA), rSSA-1, rOmpD15, and rOmpP2 developed significant antibody responses to M. haemolytica outer membranes and to the homologous recombinant OMP. Cattle vaccinated with rOmpA and rSSA-1 developed significant antibodies to M. haemolytica outer membranes by day 28, whereas cattle vaccinated with rOmpD15 and rOmpP2 developed only minimal responses. Sera from cattle vaccinated with each of the recombinant proteins stimulated complement-mediated killing of the bacterium. Concurrent vaccination with SAC89 plus any of the four rOMPs singly resulted in increased endpoint anti-SAC89 titers, and for the SAC89/rSSA-1 vaccinees, the response was increased significantly. In contrast, the SAC89/P2/SSA-1 and SAC89/OmpA/P2/D15/SSA-1 combination vaccines resulted in significant decreases in anti-SAC89 antibodies compared to SAC89 vaccination alone. In conclusion, under the conditions of these experiments, vaccination of mice and cattle with rOmpA and rSSA-1 stimulated high antibody responses and may have protective vaccine potential. PMID:21976226

  16. Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

    PubMed

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

    2012-11-01

    Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin. PMID:22677482

  17. The effects of danofloxacin and tilmicosin on neutrophil function and lung consolidation in beef heifer calves with induced Pasteurella (Mannheimia) haemolytica pneumonia.

    PubMed

    Fajt, V R; Apley, M D; Roth, J A; Frank, D E; Brogden, K A; Skogerboe, T L; Shostrom, V K; Chin, Y-L

    2003-06-01

    Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged-treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged-treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged-treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolytica infection.

  18. Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

    PubMed

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

    2012-11-01

    Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

  19. Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

    PubMed Central

    McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

  20. Efficacy of recombinant leukotoxin in protection against pneumonic challenge with live Pasteurella haemolytica A1.

    PubMed Central

    Conlon, J A; Shewen, P E; Lo, R Y

    1991-01-01

    The recombinant leukotoxin (rLKT) of the bacterium Pasteurella haemolytica A1 was examined for its ability to protect cattle from experimental challenge with logarithmic-phase P. haemolytica. Six different vaccines were utilized in the experiment: P. haemolytica culture supernatant, P. haemolytica culture supernatant enriched with rLKT, rLKT alone, P. haemolytica culture supernatant enriched with Escherichia coli supernatant not containing LKT, E. coli supernatant alone, and phosphate-buffered saline. rLKT alone showed no protective capacity against development of clinical signs of respiratory disease or against development of postmortem lung lesions after experimental challenge. It was, however, shown to enhance the efficacy of the culture supernatant vaccine and decrease clinical signs and pneumonic lesions. The complexity of protective immunity in this disease is emphasized in this study, and, although LKT is an important virulence factor of the organism, an immune response to LKT alone does not protect animals against disease. PMID:1987075

  1. Bivalent vaccination against pneumonic pasteurellosis in domestic sheep and goats with modified-live in-frame lktA deletion mutants of Mannheimia haemolytica.

    PubMed

    Briggs, Robert E; Hauglund, Melissa J; Maheswaran, Samuel K; Tatum, Fred M

    2013-11-01

    A temperature-sensitive shuttle vector, pBB80C, was utilized to generate in-frame deletion mutants of the leukotoxin structural gene (lktA) of Mannheimia haemolytica serotypes 1, 2, 5, 6, 7, 8, 9, and 12. Culture supernatants from the mutants contained a truncated protein with an approximate molecular weight of 66 kDa which was reactive to anti-leukotoxin monoclonal antibody. No protein reactive to anti-LktA monoclonal antibody was detected at the molecular weight 100-105 kDa of native LktA. Sheep and goats vaccinated intramuscularly with a mixture of serotypes 5 and 6 mutants were resistant to virulent challenge with a mixture of the wild-type parent strains. These vaccinates responded serologically to both vaccine serotypes and exhibited markedly-reduced lung lesion volume and pulmonary infectious load compared to control animals. Control animals yielded a mixture of serotypes from lung lobes, but the proportion even within an individual animal varied widely from 95% serotype 5-95% serotype 6. Cultures recovered from liver were homogeneous, but two animals yielded serotype 5 and the other two yielded serotype 6 in pure culture.

  2. Effects of exposure to calves persistently infected with bovine viral diarrhea virus type 1b and Mannheimia haemolytica challenge on animal performance, nitrogen balance, and visceral organ mass in beef steers.

    PubMed

    Burciaga-Robles, L O; Krehbiel, C R; Step, D L; Holland, B P; Richards, C J; Montelongo, M A; Confer, A W; Fulton, R W

    2010-06-01

    Bovine viral diarrhea viruses (BVDV) have been isolated alone or in combination with other viral and bacterial pathogens in animals diagnosed with bovine respiratory disease (BRD), a disease causing major economic loss to the feedlot industry. The objective of this experiment was to determine the effects of Mannheimia haemolytica challenge after short-term exposure (72 h) to bovine viral diarrhea virus type 1b (BVDV1b) persistently infected (PI) calves on performance, N balance, and organ mass in finishing cattle. Treatments (6 steers/treatment; initial BW = 314 +/- 31 kg) were 1) steers not exposed to steers PI with BVDV nor challenged with M. haemolytica (control; CON); 2) steers exposed to 2 steers PI with BVDV1b (BVD) for 72 h; 3) steers intratracheally challenged with M. haemolytica (MH); or 4) steers exposed to 2 steers PI with BVDV1b for 72 h and challenged with M. haemolytica (BVD+MH). There were 12 h between exposure to PI steers and challenge with M. haemolytica. Steers were housed in metabolism stanchions during the first 5 d after the M. haemolytica challenge and on d 7 to 11, 28 to 32, and for 5 d before slaughter (average 119 d on feed) to determine N balance and were weighed every 28 d. At slaughter, carcass and organ mass data were collected. Data were analyzed as a randomized complete block design with a 2 x 2 factorial arrangement of treatments, and steer was used as the experimental unit. From d -3 (beginning of PI steer exposure) to 4, steers challenged with M. haemolytica had less (P = 0.04) ADG than steers not challenged with M. haemolytica. In addition, steers exposed to steers PI with BVDV tended (P = 0.09) to have less ADG and G:F across the entire finishing period than steers not exposed to BVDV. Before slaughter, retained N expressed as grams per day (P = 0.03) and as a percentage of N intake (P = 0.04) was less in BVD steers compared with steers not exposed to BVDV. There were no effects (P > 0.10) of BVDV exposure or M. haemolytica

  3. Cloning of a serotype-specific antigen from Pasteurella haemolytica A1.

    PubMed Central

    Gonzalez-Rayos, C; Lo, R Y; Shewen, P E; Beveridge, T J

    1986-01-01

    Recombinant plasmids coding for a soluble (or surface) antigen of Pasteurella haemolytica A1 were identified. Two plasmids, both containing the same 5.4 kilobase pairs of insert DNA, were recovered independently by screening a clone band of P. haemolytica A1 genomic DNA in Escherichia coli for the expression of P. haemolytica A1 soluble antigens (R. Y. C. Lo and L.A. Cameron, Can. J. Biochem. Cell Biol. 64:73-76, 1986). E. coli cells carrying the plasmids were found to be agglutinated by an antiserum raised against the P. haemolytica A1 soluble antigens. Analysis of the E. coli clones by electron microscopy revealed patches of amorphous material on the surface of the cells which were not present on the controls. Further characterization with protein A-colloidal gold labeled both these patches and the outer membranes of these cloned cells pretreated with the specific antiserum. These results indicated that the cloned antigen was expressed on the surface of the E. coli cells. The cloned antigen was found to be specific for serotype 1 when tested by slide agglutination against a collection of P. haemolytica typing antisera. Southern blot hybridization, using the cloned DNA as a probe, labeled the genomic DNA from P. haemolytica serotype 1 as well as the cross-agglutinating serotypes 2 and 7, but not DNA from the non-cross-agglutinating serotypes 3 and 4 and Pasteurella multocida. These results demonstrated that serotype specificity could be attributed to the particular antigenic determinants in the genome of the organism. Images PMID:3527985

  4. Molecular studies of Ssa1, a serotype-specific antigen of Pasteurella haemolytica A1.

    PubMed Central

    Lo, R Y; Strathdee, C A; Shewen, P E; Cooney, B J

    1991-01-01

    A serotype-specific antigen of Pasteurella haemolytica A1 encoded on the recombinant plasmid pSSA1 is characterized. Nucleotide sequence analysis of the insert DNA in pSSA1 identified the gene ssaI, which codes for a protein of approximately 100 kDa. In vivo labeling of pSSA1-encoded protein in Escherichia coli maxicells showed the expression of a 100-kDa protein from the insert DNA on the recombinant plasmid. Northern blot and primer extension analyses were used to identify the mRNA transcript in P. haemolytica A1 and the putative promoter of ssaI. The antigen (designated Ssa1) could be localized to the outer membrane of P. haemolytica A1 and E. coli clones carrying pSSA1. A rabbit serum against Ssa1 was produced by using whole cells of E. coli expressing Ssa1 on the surface as the immunogen, demonstrating that Ssa1 is immunogenic in rabbits. The results from colony immunoblot analysis with calf serum from animals that were resistant to P. haemolytica A1-induced pneumonia suggest indirectly that Ssa1 is also immunogenic in the animals. Images PMID:1840576

  5. Transmission of mannheimia haemolytica from domestic sheep (ovis aries) to bighorn sheep (ovis canadensis) : Unequivocal demonstration with green fluorescent protien-tagged organisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have demonstrated that bighorn sheep (BHS) die of pneumonia when they commingle with domestic sheep (DS). However, these studies did not conclusively prove the transmission of pathogens from DS to BHS. The objective of this study was to determine unambiguously whether Mannheimia hae...

  6. Sialoglycoprotease of Pasteurella haemolytica A1: detection of antisialoglycoprotease antibodies in sera of calves.

    PubMed Central

    Lee, C W; Shewen, P E; Cladman, W M; Conlon, J A; Mellors, A; Lo, R Y

    1994-01-01

    Log phase culture supernate from Pasteurella haemolytica biotype A, serotype 1 contains a proteolytic enzyme specific for O-sialoglycoproteins. Using two methods, Western immunoblotting and enzyme neutralization assay, it was demonstrated that certain bovine sera from two previous P. haemolytica A1 vaccination and challenge trials contained antibodies (Ab) (isotypes IgG1 and IgG2 on Western immunoblot) to the sialoglycoprotease (Gcp). In these trials, selected calves were vaccinated twice with either the commercial culture supernate vaccine Presponse or given phosphate-buffered saline (PBS). One trial was conducted during spring, P. haem XIX, and the other during the winter, P. haem XXI. Although there was no clear evidence for induction of anti-Gcp in response to vaccination, several calves seroconverted following intrapulmonary challenge with live P. haemolytica A1. This is the first report of anti-Gcp Ab in bovine sera. The results indicated that the Gcp is immunogenic and that the bacterium produces the enzyme in vivo. Further, animals with an anti-Gcp response had less pneumonia at necropsy, suggesting the Gcp may induce protective immunity. Images Fig. 1. Fig. 2. PMID:8004547

  7. Cloning and expression of the leukotoxin gene of Pasteurella haemolytica A1 in Escherichia coli K-12.

    PubMed Central

    Lo, R Y; Shewen, P E; Strathdee, C A; Greer, C N

    1985-01-01

    A clone bank of Pasteurella haemolytica A1 was constructed by partial digestion of the genomic DNA with Sau3A and ligation of 5- to 10-kilobase-pair fragments into the BamHI site of the plasmid vector pBR322. After transformation into Escherichia coli K-12, a total of 4 X 10(3) recombinant clones was obtained. These were screened for the production of P. haemolytica soluble antigens by a colony enzyme-linked immunosorbent assay blot method with a rabbit antiserum raised against the soluble antigens. The clones producing P. haemolytica soluble antigens were then analyzed for the production of the leukotoxin by a cytotoxicity assay with cells from a bovine leukemia-derived B-lymphocyte cell line as the target cells. Positive clones were identified, and subsequent restriction analysis of the recombinant plasmids showed that the same 6.3 kilobase pairs of insert DNA was cloned in either of the two orientations into the plasmid vector pBR322. One of the clones was selected for further characterization of the leukotoxin as produced in E. coli. Tests for heat lability and target cell species specificity with canine, porcine, and human peripheral blood lymphocytes indicated that the activity of the cloned leukotoxin was identical to that of the P. haemolytica leukotoxin. Furthermore, the E. coli-produced leukotoxin was also neutralized by bovine or rabbit antiserum known to have antitoxic activity. When cellular proteins from the E. coli clones were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis, a 100,000-dalton protein was identified which corresponded to one of the soluble antigens found in the leukotoxic culture supernatant of P. haemolytica. These results demonstrated that the gene(s) for the P. haemolytica leukotoxin have been cloned and that the leukotoxin was expressed in E. coli. Images PMID:3905610

  8. Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene.

    PubMed Central

    Abdullah, K M; Lo, R Y; Mellors, A

    1991-01-01

    Pasteurella haemolytica serotype A1 secretes a glycoprotease which is specific for O-sialoglycoproteins such as glycophorin A. The gene encoding the glycoprotease enzyme has been cloned in the recombinant plasmid pH1, and its nucleotide sequence has been determined. The gene (designated gcp) codes for a protein of 35.2 kDa, and an active enzyme protein of this molecular mass can be observed in Escherichia coli clones carrying pPH1. In vivo labeling of plasmid-encoded proteins in E. coli maxicells demonstrated the expression of a 35-kDa protein from pPH1. The amino-terminal sequence of the heterologously expressed protein corresponds to that predicted from the nucleotide sequence. The glycoprotease is a neutral metalloprotease, and the predicted amino acid sequence of the glycoprotease contains a putative zinc-binding site. The gene shows no significant homology with the genes for other proteases of procaryotic or eucaryotic origin. However, there is substantial homology between gcp and an E. coli gene, orfX, whose product is believed to function in the regulation of macromolecule biosynthesis. Images PMID:1885539

  9. Sequence diversity, cytotoxicity and antigenic similarities of the leukotoxin of isolates of Mannheimia species from mastitis in domestic sheep.

    PubMed

    Omaleki, Lida; Browning, Glenn F; Barber, Stuart R; Allen, Joanne L; Srikumaran, Subramaniam; Markham, Philip F

    2014-11-01

    Species within the genus Mannheimia are among the most important causes of ovine mastitis. Isolates of these species can express leukotoxin A (LktA), a primary virulence factor of these bacteria. To examine the significance of variation in the LktA, the sequences of the lktA genes in a panel of isolates from cases of ovine mastitis were compared. The cross-neutralising capacities of rat antisera raised against LktA of one Mannheimia glucosida, one haemolytic Mannheimia ruminalis, and two Mannheimia haemolytica isolates were also examined to assess the effect that variation in the lktA gene can have on protective immunity against leukotoxins with differing sequences. The lktA nucleotide distance between the M. haemolytica isolates was greater than between the M. glucosida isolates, with the M. haemolytica isolates divisible into two groups based on their lktA sequences. Comparison of the topology of phylogenetic trees of 16S rDNA and lktA sequences revealed differences in the relationships between some isolates, suggesting horizontal gene transfer. Cross neutralisation data obtained with monospecific anti-LktA rat sera were used to derive antigenic similarity coefficients for LktA from the four Mannheimia species isolates. Similarity coefficients indicated that LktA of the two M. haemolytica isolates were least similar, while LktA from M. glucosida was most similar to those for one of the M. haemolytica isolates and the haemolytic M. ruminalis isolate. The results suggested that vaccination with the M. glucosida leukotoxin would generate the greatest cross-protection against ovine mastitis caused by Mannheimia species with these alleles.

  10. Evidence of bovine immunoglobulin G1 (IgG1) protease activity in partially purified culture supernate of Pasteurella haemolytica A1.

    PubMed Central

    Lee, C W; Shewen, P E

    1996-01-01

    In the bovine respiratory tract, IgG1 is a major secretory immunoglobulin (Ig), and both IgG1 and IgG2 are believed to be important in defense against pneumonic pasteurellosis (shipping fever) in calves. Here we provide evidence for hydrolysis of IgG1 in the presence of partially purified culture supernate (ppCS) from the respiratory pathogen Pasteurella haemolytica A1. Bovine IgG1 was hydrolysed sequentially into three distinct bands (approximately 39, 12, and 7 kDa respectively). Furthermore, partial hydrolysis of bovine IgG2 was observed, but neither bovine IgA nor IgM were affected by incubation with ppCS. These findings suggest that the production of an IgG1-specific protease by P. haemolytica A1 may be a virulence mechanism contributing to the pathogenesis of bovine pneumonic pasteurellosis. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. PMID:8785718

  11. Occurrence of haemolytic Mannheimia spp. in apparently healthy sheep in Norway

    PubMed Central

    Poulsen, Louise L; Reinert, Turið M; Sand, Rikke L; Bisgaard, Magne; Christensen, Henrik; Olsen, John E; Stuen, Snorre; Bojesen, Anders M

    2006-01-01

    Background The occurrence of Mannheimia species in healthy sheep has only been investigated to a very limited extend since the genus and its five named species were established. The aim of the present study was to evaluate the occurrence of haemolytic Mannheimia species in apparently healthy sheep originating from four sheep flocks in South-Western Norway. Methods Typical β-haemolytic Pasteurellaceae were isolated from nasal swabs and subsequently subjected to bacteriological examination. A total of 57 Mannheimia isolates were obtained in pure culture. All isolates were genotyped by amplified fragment length polymorphisms (AFLP) analysis and compared to six reference strains. The 16S rRNA gene sequences of two isolates were also determined. Results β-haemolytic Mannheimia species were isolated from 24% to 64% of the sheep in the four flocks. A total of 26 haemolytic M. ruminalis-like strains were isolated among which, a considerable genetic diversity was found. Eighteen M. glucosida isolates were obtained from three flocks, whereas M. haemolytica was only isolated from two flocks, 16 of them being from only one of the flocks. Conclusion We demonstrate that a relatively high number of apparently healthy sheep in Norway seem to carry the potentially pathogenic M. haemolytica and M. glucosida in the upper respiratory tract. An unexpectedly high number of haemolytic M. ruminalis-like organisms were also obtained in all four flocks. The usually non-haemolytic M. ruminalis are typically isolated from healthy ruminants. The significance of β-haemolytic M. ruminalis-like organisms is unknown and should be investigated in a future study.

  12. Occurrence of haemolytic Mannheimia spp. in apparently healthy sheep in Norway

    PubMed Central

    Poulsen, Louise L; Reinert, Turið M; Sand, Rikke L; Bisgaard, Magne; Christensen, Henrik; Olsen, John E; Stuen, Snorre; Bojesen, Anders M

    2006-01-01

    Background The occurrence of Mannheimia species in healthy sheep has only been investigated to a very limited extend since the genus and its five named species were established. The aim of the present study was to evaluate the occurrence of haemolytic Mannheimia species in apparently healthy sheep originating from four sheep flocks in South-Western Norway. Methods Typical β-haemolytic Pasteurellaceae were isolated from nasal swabs and subsequently subjected to bacteriological examination. A total of 57 Mannheimia isolates were obtained in pure culture. All isolates were genotyped by amplified fragment length polymorphisms (AFLP) analysis and compared to six reference strains. The 16S rRNA gene sequences of two isolates were also determined. Results β-haemolytic Mannheimia species were isolated from 24% to 64% of the sheep in the four flocks. A total of 26 haemolytic M. ruminalis-like strains were isolated among which, a considerable genetic diversity was found. Eighteen M. glucosida isolates were obtained from three flocks, whereas M. haemolytica was only isolated from two flocks, 16 of them being from only one of the flocks. Conclusion We demonstrate that a relatively high number of apparently healthy sheep in Norway seem to carry the potentially pathogenic M. haemolytica and M. glucosida in the upper respiratory tract. An unexpectedly high number of haemolytic M. ruminalis-like organisms were also obtained in all four flocks. The usually non-haemolytic M. ruminalis are typically isolated from healthy ruminants. The significance of β-haemolytic M. ruminalis-like organisms is unknown and should be investigated in a future study. PMID:17076903

  13. Increase of glycocalyx and altered lectin agglutination profiles of Pasteurella haemolytica A1 after incubation in bovine subcutaneous tissue chambers in vivo or in ruminant serum in vitro.

    PubMed Central

    Brogden, K; Clarke, C

    1997-01-01

    Pasteurella haemolytica serotype A1 (bovine strain OK) was incubated for 2 and 6 h in bovine subcutaneous tissue chambers in vivo, and ovine strain 82-25 and bovine strain L011 were incubated in vitro for 2 h in heat-inactivated ovine or bovine serum from which gamma globulin had been depleted by protein G affinity chromatography to assess changes in morphology and lectin agglutination profiles (strains 82-25 and L101 only). Cells, removed from chambers after 2 h, were covered with an extensive, dense glycocalyx extending approximately 0.5 microm from the cell surface. In many cells, the glycocalyx was separated from the cell surface by a clear, electron-transparent area. Cells, removed at 6 h, were covered with a sparse glycocalyx of fine fibers 0.2 to 0.3 microm from the cell surface. Strains 82-25 and L101, incubated for 2 h in heat-inactivated ovine or bovine serum or in heat-inactivated ovine or bovine serum depleted of gamma globulin by protein G affinity chromatography, were also covered with a glycocalyx. The glycocalyx did not bind protein A-colloidal gold and therefore did not contain aggregates of accumulated antibody. Strains 82-25 and L101 were incubated individually for 2 h in 10 mM sodium phosphate buffer (pH 7.2) containing 0.14 M NaCl, 0.5 mM CaCl2, and 0.15 mM MgCl2 or with this buffer and either 25% heat-inactivated, gamma globulin-depleted ovine serum or 25% heat-inactivated, gamma globulin-depleted bovine serum. Agglutination profiles were then determined with 17 lectins in 10 mM HEPES-buffered saline (pH 8.4) with 0.1 mM CaCl2 and 0.08% sodium azide. Profiles did not vary with 10 of 17 lectins. However, profiles did vary with peanut agglutinin, Phaseolus vulgaris leucoagglutinin, Sophora japonica agglutinin, Maackia amurensis lectin II, Narcissus pseudonarcissus (daffodil) lectin, Griffonia simplicifolia lectin I, and Pisum sativum agglutinin. Altered profiles indicate a change in the bacterial cell surface, possibly by adsorption or

  14. Isolation of Pasteurella haemolytica leukotoxin mutants.

    PubMed Central

    Chidambaram, M; Sharma, B; Petras, S F; Reese, C P; Froshauer, S; Weinstock, G M

    1995-01-01

    Two mutants of Pasteurella haemolytica A1 that do not produce leukotoxin were isolated. Following mutagenesis, colonies were screened with antiserum by a filter assay for absence of the secreted leukotoxin. The two mutants both appeared to produce normal amounts of other antigens, as judged by reactivity with polyclonal serum from an animal with pasteurellosis, and were not altered in beta-hemolytic activity as seen on blood agar plates. There was no evidence of either cell-associated or secreted leukotoxin protein when Western blots (immunoblots) were carried out with the polyclonal serum or with a monoclonal antibody directed against the leukotoxin. Southern blots revealed that both mutants show the wild-type restriction pattern at the leukotoxin locus, although the strain with the lktA2 mutation showed differences in other regions of the chromosome on analysis by pulsed-field gel electrophoresis. The strain with the lktA2 mutation grew more slowly than did the wild-type strain, while the strain with the lktA1 mutation was indistinguishable from the wild-type strain in its growth properties. The strain with the lktA1 mutation should be valuable in determining the role of the leukotoxin in virulence as well as in identifying other virulence factors of P. haemolytica. PMID:7868223

  15. Isolation and Characterization of Lytic Properties of Bacteriophages Specific for M. haemolytica Strains

    PubMed Central

    Urban-Chmiel, Renata; Wernicki, Andrzej; Stęgierska, Diana; Dec, Marta; Dudzic, Anna; Puchalski, Andrzej

    2015-01-01

    Aim of Study The objective of this study was isolation and morphological characterization of temperate bacteriophages obtained from M. haemolytica strains and evaluation of their lytic properties in vitro against M. haemolytica isolated from the respiratory tract of calves. Material and Methods The material for the study consisted of the reference strain M. haemolytica serotype 1 (ATCC®) BAA-410™, reference serotypes A1, A2, A5, A6, A7, A9 and A11, and wild-type isolates of M. haemolytica. Bacteriophages were induced from an overnight bacterial starter culture of all examined M. haemolytica strains treated with mitomycin C. The lytic properties and host ranges were determined by plaque assays. The morphology of the bacteriophages was examined in negative-stained smears with 5% uranyl acetate solution using a transmission electron microscope. The genetic analysis of the bacteriophages was followed by restriction analysis of bacteriophage DNA. This was followed by analysis of genetic material by polymerase chain reaction (PCR). Results Eight bacteriophages were obtained, like typical of the families Myoviridae, Siphoviridae and Podoviridae. Most of the bacteriophages exhibited lytic properties against the M. haemolytica strains. Restriction analysis revealed similarities to the P2-like phage obtained from the strain M. haemolytica BAA-410. The most similar profiles were observed in the case of bacteriophages φA1 and φA5. All of the bacteriophages obtained were characterized by the presence of additional fragments in the restriction profiles with respect to the P2-like reference phage. In the analysis of PCR products for the P2-like reference phage phi-MhaA1-PHL101 (DQ426904) and the phages of the M. haemolytica serotypes, a 734-bp phage PCR product was obtained. The primers were programmed in Primer-Blast software using the structure of the sequence DQ426904 of reference phage PHL101. Conclusions The results obtained indicate the need for further research aimed

  16. Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycoplasma ovipneumoniae has been isolated from the lungs of pneumonic bighorn sheep (BHS). However experimental reproduction of fatal pneumonia in BHS with M. ovipneumoniae was not successful. Therefore the specific role, if any, of M. ovipneumoniae in BHS pneumonia is unclear. The objective of th...

  17. Enlightened Mannhemia haemolytica lung inflammation in bovinized mice

    PubMed Central

    2014-01-01

    Polymorphonuclear cells diapedesis has an important contribution to the induced Mannhemia haemolytica (M. haemolytica) infection lung inflammation and IL-8 is the primary polymorphonuclear chemoattractant. Using a bovine IL-8/luciferase transiently transgenized mouse model, the orchestration among M. haemolytica, IL-8 promoter activation and neutrophilia was followed in real time by in vivo image analysis. PMID:24460618

  18. Human Wound Infection with Mannheimia glucosida following Lamb Bite

    PubMed Central

    Omaleki, Lida; Turni, Conny; Barber, Stuart Richard; Browning, Glenn Francis; Francis, Michelle J.; Graham, Maryza; Korman, Tony M.

    2015-01-01

    Mannheimia spp. are veterinary pathogens that can cause mastitis and pneumonia in domestic cattle and sheep. While Mannheimia glucosida can be found as normal flora in oral and respiratory mucosa in sheep, there have been no reported cases of human infection with this organism. PMID:26202121

  19. Experimental infection of sheep with Mycoplasma ovipneumoniae and Pasteurella haemolytica.

    PubMed

    Buddle, B M; Herceg, M; Davies, D H

    1984-10-01

    A group of Caesarian-derived, colostrum-deprived lambs was inoculated intranasally and intratracheally with a virulent Mycoplasma ovipneumoniae isolate selected from ovine mammary studies and propagated in an ovine mammary gland. Other groups of lambs were inoculated with M. ovipneumoniae in combination with Pasteurella haemolytica type Al or P. haemolytica alone. The M. ovipneumoniae isolate alone did not induce any specific pneumonic lesions in the lambs and when combined with P. haemolytica type Al did not increase the severity of the P. haemolytica-type lesions. Fifty percent of lambs inoculated with P. haemolytica developed a purulent and exudative bronchopneumonia with pleurisy and high titres of P. haemolytica were recovered from these lesions.

  20. Lymphocyte function-associated antigen 1 is a receptor for Pasteurella haemolytica leukotoxin in bovine leukocytes.

    PubMed

    Jeyaseelan, S; Hsuan, S L; Kannan, M S; Walcheck, B; Wang, J F; Kehrli, M E; Lally, E T; Sieck, G C; Maheswaran, S K

    2000-01-01

    Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate that P. haemolytica Lkt binds to bovine CD18, the common subunit of all beta2 integrins. We designed experiments with the following objectives: to identify which member of the beta2 integrins is a receptor for Lkt; to determine whether Lkt binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium elevation, and cytolysis; and to determine whether a correlation exists between Lkt receptor expression and the magnitude of target cell cytolysis. We compared Lkt-induced cytolysis in neutrophils from control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced beta2 integrin expression. The results demonstrate for the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium elevation in bovine alveolar macrophages (BAMs) was inhibited by anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml; P < 0.05). Lkt-induced cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P < 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1 correlates with calcium elevation and cytolysis, and bovine LFA-1 expression correlates with the magnitude of Lkt-induced target cell cytolysis. PMID:10603370

  1. Susceptibility of Rocky Mountain bighorn sheep and domestic sheep to pneumonia induced by bighorn and domestic livestock strains of Pasteurella haemolytica.

    PubMed Central

    Onderka, D K; Rawluk, S A; Wishart, W D

    1988-01-01

    Bighorn sheep were inoculated intratracheally with suspensions of nonhemolytic Pasteurella haemolytica biotype T (10(12) organisms) unique to wild bighorns, with beta-hemolytic P. haemolytica biotype T (10(12) organisms) isolated from clinically normal domestic sheep or intradermally with half a dose of a cattle vaccine containing P. haemolytica biotype A (10(5) organisms). The bighorn strain caused lobar necrotizing bronchopneumonia whereas both domestic livestock strains precipitated fatal septicemia and fibrinous bronchopneumonia. The serotypes given were T3, T4, T15 and A1 and these were recovered from lung lesions and other organs. In three trials, domestic sheep were inoculated intratracheally with suspensions of bighorn sheep pneumonic lungs, and two concentrations of the P. haemolytica bighorn strain (10(4) and 10(12) organisms). One of these sheep was inoculated intrabronchially. The domestic sheep experienced a transient fever and elevated white blood cell counts. After six days, none of the sheep had lung lesions and inoculated organisms could not be recovered. It is suggested that bighorn sheep are very susceptible to P. haemolytica from domestic livestock and should not be allowed in contact with sheep or cattle. Images Fig. 1. Fig. 2. Fig. 3. PMID:3196974

  2. Induction of CD18-mediated passage of neutrophils by Pasteurella haemolytica in pulmonary bronchi and bronchioles.

    PubMed

    Ackermann, M R; Brogden, K A; Florance, A F; Kehrli, M E

    1999-02-01

    Pasteurella haemolytica is an important respiratory pathogen of cattle that incites extensive infiltrates of neutrophils into the lung. In addition to the parenchymal damage caused by factors released by P. haemolytica, neutrophils contribute to the pathologic changes in the lungs. Molecules which mediate neutrophil infiltration into the lungs during P. haemolytica pneumonia are poorly characterized. To determine whether the CD18 family (beta2-integrin) of leukocyte adhesion molecules mediates initial passage of neutrophils into the pulmonary bronchi and bronchioles of lungs infected with P. haemolytica, three Holstein calves homozygous for bovine leukocyte adhesion deficiency (BLAD) (CD18-deficient neutrophils), and three age- and breed-matched control calves (normal CD18 expression) were inoculated with P. haemolytica A1 via a fiberoptic bronchoscope and euthanized at 2 h postinoculation. Sections of lung were stained for neutrophils, and the intensity of neutrophilic infiltration was determined by computerized image analysis. Significantly fewer (P < 0.05) neutrophils infiltrated the lumen, epithelium, and adventitia of bronchioles and bronchi in lungs of calves with BLAD compared to normal calves, which had dense infiltrates within these sites at 2 h postinoculation. The reduced infiltration in calves with BLAD occurred despite the presence of an extremely large number of neutrophils in peripheral blood that is typical for these calves. The large number of neutrophils in the blood of calves with BLAD is probably a physiologic response that can occur without microbial colonization, since one calf with BLAD that was raised under germ-free conditions had large numbers of neutrophils in the blood that were similar to those in a calf with BLAD that was raised conventionally. Neutrophil counts in the germ-free and conventionally reared calves with BLAD were much higher than those in the three normal calves raised under germ-free conditions. The work in this study

  3. Evolutionary genetics of Pasteurella haemolytica isolates recovered from cattle and sheep.

    PubMed Central

    Davies, R L; Arkinsaw, S; Selander, R K

    1997-01-01

    Genetic diversity and relationships among 194 Pasteurella haemolytica isolates, which were recovered predominantly from cattle (39%) and sheep (58%) suffering from pneumonic pasteurellosis in the United Kingdom, Germany, and the United States, were estimated by examination of allelic variation at 18 enzyme-encoding loci detected by multilocus enzyme electrophoresis. The isolates formed two major divisions. One included 178 Pasteurella haemolytica sensu stricto strains representing serotypes A1, A2, A5 to A9, A12 to A14, and A16; the other was composed of 16 isolates belonging to the A11 taxon. P. haemolytica isolates were classified into 22 electrophoretic types (ETs) that formed three primary phylogenetic lineages. One lineage was represented by ovine serotype A2 isolates, a second lineage consisted of bovine serotype A2, together with serotype A7 and A13 isolates, and the third lineage included isolates representing all of the other serotypes, as well as a second group of serotype A7 strains. Electrophoretic types were nonrandomly associated with specific capsular serotypes, lipopolysaccharide (LPS) types, outer membrane protein (OMP) types, and host species. Bovine isolates were represented by only three serotypes (A1, A2, and A6) in 5 ETs, whereas ovine isolates were represented by all of the serotypes in 19 ETs. The majority (76%) of bovine isolates were of serotypes A1 or A6 and belonged to a single ET that marked a virulent, cattle-specific clonal group. Among the ovine isolates, 40% were of serotype A2 and belonged to two ETs that represented two virulent, sheep-specific clonal groups. Bovine A1 and A6 isolates and bovine A2 isolates were phylogenetically distinct from ovine isolates of the same serotypes, indicating that different subpopulations of these serotypes are associated with disease in cattle and sheep. Consistent differences in the OMP profiles of strains of the bovine and ovine lineages of these three serotypes suggest that certain OMPs are

  4. Detection of Mycoplasma ovipneumoniae and Pasteurella haemolytica antigens by an immunoperoxidase technique in pneumonic ovine lungs.

    PubMed

    Haziroglu, R; Diker, K S; Turkarslan, J; Gulbahar, M Y

    1996-01-01

    Four hundred twenty pneumonic lungs from lambs were examined for Mycoplasma ovipneumoniae and Pasteurella haemolytica by an immunoperoxidase technique using an extravidin-biotin-peroxidase complex method in formalin-fixed, paraffin-embedded sections. Histologic examination of tissue sections revealed strong positive reactions in 60.9% and 68.3% of the lungs against M. ovipneumoniae and P. haemolytica, respectively. M. ovipneumoniae and P. haemolytica antigens were observed at the surface and/or within the epithelial cells, macrophages, leucocytes, and bronchiolar exudate. The location of M. ovipneumoniae in the cytoplasm of the epithelial cells and P. haemolytica in the neutrophils was detected immunohistochemically.

  5. Binding of Pasteurella haemolytica leukotoxin to bovine leukocytes.

    PubMed Central

    Brown, J F; Leite, F; Czuprynski, C J

    1997-01-01

    Pasteurella haemolytica is the principal bacterial pathogen in the bovine respiratory disease complex. This organism produces an exotoxin (referred to as leukotoxin) during logarithmic-phase growth that is a potent leukocyte-modulating agent. At low concentrations, it activates neutrophils and mononuclear phagocytes to release inflammatory mediators, while at the same time making these cells destined to undergo apoptotic cell death. At higher concentrations, the toxin causes rapid swelling and loss of cell viability. In this study, we demonstrated that toxin binding can be directly evaluated by flow cytometry with biologically active biotinylated leukotoxin. Leukotoxin binding was blocked by the addition of a neutralizing anti-leukotoxin monoclonal antibody and was not detected when bovine leukocytes were incubated with culture filtrates from a mutant strain of P. haemolytica that does not produce biologically active leukotoxin. In addition, treatment of bovine leukocytes with protease K eliminated subsequent binding of leukotoxin, suggesting that there is a protein on the leukocyte surface that is either a leukotoxin binding site or is required for stabilization of leukotoxin binding. We did not detect binding of biotinylated leukotoxin to porcine or human leukocytes, which have been reported previously to be resistant to the lytic effects of the leukotoxin. These findings suggest that there may be a specific binding site for P. haemolytica leukotoxin on bovine but not on porcine or human leukocytes and that it might be involved in the activation and lytic activities of the leukotoxin. PMID:9284143

  6. Pasteurella haemolytica antigens associated with resistance to pneumonic pasteurellosis.

    PubMed Central

    Mosier, D A; Simons, K R; Confer, A W; Panciera, R J; Clinkenbeard, K D

    1989-01-01

    Antigens associated with whole Pasteurella haemolytica biotype A serotype 1, a capsular carbohydrate-protein extract of the organism, and P. haemolytica leukotoxin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antigens of the electrophoresed preparations were detected by Western blotting (immunoblotting) with sera from cattle which were either nonvaccinated or vaccinated with live or killed P. haemolytica vaccines and had variable degrees of resistance to experimental pneumonic pasteurellosis. Distinct, easily recognizable antigens of these preparations were identified, and the antibody responses to these antigens were quantified by densitometry. To determine their importance to disease resistance, we then compared antibody responses with experimental lesion scores. Antibody reactivity to surface antigens which were significantly correlated with resistance and present in two or more of the preparations were detected at 86, 66, 51, 49, 34, 31, and 16 kilodaltons (kDa). Of these, antibody responses to antigens at 86, 49, and 31 kDa appeared most important based on their concentration and significance levels. Antibody reactivity to leukotoxin antigens which were significantly correlated with resistance and common with important surface antigens were detected at 86, 66, and 49 kDa. Antibody responses to unique leukotoxin antigens which were significantly correlated with resistance were present at 92 and 58 kDa. Images PMID:2917783

  7. Antigenic and virulence properties of Pasteurella haemolytica leukotoxin mutants.

    PubMed Central

    Petras, S F; Chidambaram, M; Illyes, E F; Froshauer, S; Weinstock, G M; Reese, C P

    1995-01-01

    Antigenic properties of two mutants of Pasteurella haemolytica, strains 59B0071 and 59B0072, that do not produce detectable leukotoxin were investigated. Western blot (immunoblot) analysis with a number of polyclonal sera from animals recovering from pasteurellosis revealed that both mutants secreted a variety of antigens that were also present in cultures of several wild-type strains. These antigens ranged from about 100 to 15 kDa. Mutant strain 59B0071 was found to be totally deficient in leukotoxin, as judged not only by Western blotting but also by cytotoxicity assays with bovine lymphoma (BL-3) cells or bovine polymorphonuclear cells as targets. The mutant strain 59B0071 had normal levels of a secreted sialylglycoprotease, however. When strains were tested for virulence in goat and cattle challenge experiments, a reduction in mortality and lung lesions was observed with the mutant 59B0071 in comparison with results obtained with wild-type strains. These results are consistent with an important role for leukotoxin in P. haemolytica virulence and suggest that leukotoxin-negative mutants may be useful tools in the investigation of other virulence properties involved in P. haemolytica infections. PMID:7868224

  8. Pasteurella haemolytica bacteriophage: identification, partial characterization, and relationship of temperate bacteriophages from isolates of Pasteurella haemolytica (biotype A, serotype 1)

    SciTech Connect

    Richards, A.B.; Renshaw, H.W.; Sneed, L.W.

    1985-05-01

    Pasteurella haemolytica (biotype A, serotype 1) isolates (n = 15) from the upper respiratory tract of clinically normal cattle, as well as from lung lesions from cases of fatal bovine pasteurellosis, were examined for the presence of bacteriophage after irradiation with UV light. Treatment of all P haemolytica isolates with UV irradiation resulted in lysis of bacteria due to the induction of vegetative development of bacteriophages. The extent of growth inhibition and bacterial lysis in irradiated cultures was UV dose-dependent. Bacterial cultures exposed to UV light for 20 s reached peak culture density between 60 and 70 minutes after irradiation; thereafter, culture density declined rapidly, so that by 120 minutes, it was approximately 60% of the original value. When examined ultrastructurally, lytic cultures from each isolate revealed bacteriophages with an overall length of approximately 200 nm and that appeared to have a head with icosahedral symmetry and a contractile tail. Cell-free filtrate from each noninduced bacterial isolate was inoculated onto the other bacterial isolates in a cross-culture sensitivity assay for the presence of phages lytic for the host bacterial isolates. Zones of lysis (plaques) did not develop when bacterial lawns grown from the different isolates were inoculated with filtrates from the heterologous isolates.

  9. Exposure of calves to aerosols of parainfluenza-3 virus and Pasteurella haemolytica.

    PubMed Central

    Carrière, P D; Maxie, M G; Wilkie, B N; Savan, M; Valli, V E; Johnson, J A

    1983-01-01

    The present study was undertaken to investigate whether sequential exposure to aerosols of parainfluenza-3 virus followed by Pasteurella haemolytica, or P. haemolytica followed by parainfluenza-3 virus, could lead to the production of pulmonary lesions in conventionally-raised calves. Twenty male calves with low serum antibody titres to both organisms were placed in five equal groups. Synergism of parainfluenza-3 virus and P. haemolytica was not demonstrated in any of the sequentially infected groups and pulmonary lesions were mild in all challenged calves. Clinical signs of disease were not present after exposure to parainfluenza-3 virus although the virus was repeatedly isolated from nasal secretions of all inoculated calves. Exposure to P. haemolytica produced a transient response which consisted of increased rectal temperatures and respiratory rates, with a mild neutrophilic leukocytosis and a mild left shift present six hours postinoculation and returning to normal within 24 hours. Results from this study suggest, although do not confirm, that reduced pulmonary clearance of inhaled P. haemolytica in parainfluenza-3 virus infected calves does not necessarily lead to production of severe pulmonary lesions and that previous exposure to aerosols of P. haemolytica may not enhance secondary parainfluenza-3 virus infection. Images Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. PMID:6320999

  10. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

  11. The efficacy of oral vaccination of mice with alginate encapsulated outer membrane proteins of Pasteurella haemolytica and One-Shot.

    PubMed

    Kidane, A; Guimond, P; Ju, T R; Sanchez, M; Gibson, J; Bowersock, T L

    2001-03-21

    The goal of this study was to examine the efficacy of oral delivery of alginate encapsulated outer membrane proteins (OMP) of Pasteurella haemolytica and a commercial One-Shot vaccine in inducing protection in mice against lethal challenge with virulent P. haemolytica. We examined two alginate microsphere formulations and compared them with oral unencapsulated and subcutaneously administered vaccines. Alginate microspheres were made by the emulsion-cross-linking technique. They were examined for size, hydrophobicity, and antigen loading efficiency before they were used in the study. Mice were vaccinated by administering 200 microg of antigens in 200 microl of microspheres suspension orally or subcutaneously. One group of mice received blank microspheres and a second group was given unencapsulated antigen orally. A third and a fourth group received different formulations of alginate encapsulated antigens by oral administration. Three groups received subcutaneous inoculations (alginate encapsulated, non-adjuvanted and unencapsulated antigens, and adjuvanted One-Shot), and one group received water (naïve group). Mice were vaccinated orally for four consecutive days and challenged with P. haemolytica 5 weeks after the first vaccination. Weekly serum and feces samples were assayed for antigen specific antibodies. The number of dead mice in each group 4 days post challenge was used to compare the efficacy of the various vaccination groups. The mean volume sizes of blank alginate microsphere formulations A, and AA were 15.9, 16 and 9.2 microm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles on A and AA were 37.8 and 74.3 degrees, respectively. Antigen concentration in a 1:1 w/w suspension of microspheres in water was 0.9 mg/ml. Rate of death for the blank group was 42.8% whereas for groups vaccinated with antigens encapsulated in A and AA the death rates were 40

  12. Regulation of expression of the Pasteurella haemolytica leukotoxin determinant.

    PubMed Central

    Strathdee, C A; Lo, R Y

    1989-01-01

    The Pasteurella haemolytica leukotoxin determinant is composed of four contiguous genes encoded on the same DNA strand and denoted lktCABD, in the order of their genetic organization. To gain a better understanding of the expression and regulation of the leukotoxin, the transcripts and promoters of the lkt determinant were mapped. Northern (RNA) blot analysis revealed two sets of transcripts. One set was 3.7 and 3.4 kilobases long, encoded lktCA, and comprised approximately 90% of the transcripts, whereas the other set was 7.4 and 7.1 kilobases long and encoded lktCABD. Two promoters were present, and each had features similar to the Escherichia coli consensus promoter sequences. Both promoters were located upstream from lktC; they were separated by 258 base pairs, as mapped by primer extension analysis. These results suggest a mechanism of expression similar to that of the related E. coli hemolysin. Transcription initiated upstream from lktC at either promoter and continued through lktC and lktA to a rho-independent transcriptional termination signal in the lktA-lktB intercistronic region. This signal attenuated expression by terminating 90% of transcription to generate the 3.7- and 3.4-kilobase lktCA transcripts. The remaining readthrough transcription generated full-length 7.4- and 7.1-kilobase lktCABD transcripts. Expression of the leukotoxin was greatly reduced by growth at 30 degrees C, pH 6.5, and Fe2+ limitation. These conditions also modulated the expression of a number of other secreted proteins, which suggests that all of these secreted proteins are controlled by the same regulatory mechanism. Images PMID:2478522

  13. Pasteurella haemolytica serotype 2 contains the gene for a noncapsular serotype 1-specific antigen.

    PubMed Central

    Gonzalez, C T; Maheswaran, S K; Murtaugh, M P

    1995-01-01

    An ssa1-homologous genomic fragment cloned from Pasteurella haemolytica serotype 2 (ST2) enabled transformation of Escherichia coli DH5 alpha to a serotype 1 (ST1) phenotype through expression of the ST1-specific antigen (Ssa1). The Ssa1 protein expressed by ssa1-transformed E. coli was susceptible to heat and protease treatment and was distinct from P. haemolytica ST1-specific capsular polysaccharide. Electrophoretic analysis of in vitro-translated proteins, as well as the predicted amino acid sequence, demonstrated that Ssa1 proteins encoded from either ST1- or ST2-derived ssa1 genes were essentially identical. A comparison of the nucleotide sequences of ssa1 genes derived from P. haemolytica ST1 and ST2 revealed greater than 99% homology. Amino acid sequence homology of the predicted products of ST1- and ST2-derived ssa1 genes was greater than 98%. Northern (RNA) blot studies revealed that the presence of an increased level of ssa1 transcript in P. haemolytica ST1 grown as surface-adherent cultures on solid medium was correlated with a serologically detectable Ssa1 protein. Expression of the ssa1 transcript in ST1 was similarly upregulated by a high iron concentration in the growth medium. PMID:7890392

  14. Genetic and Immunologic Analyses of PlpE, a Lipoprotein Important in Complement-Mediated Killing of Pasteurella haemolytica Serotype 1

    PubMed Central

    Pandher, Karamjeet; Confer, Anthony W.; Murphy, George L.

    1998-01-01

    Pasteurella haemolytica serotype 1 is the bacterium most commonly associated with bovine shipping fever. The presence of antibodies against P. haemolytica outer membrane proteins (OMPs) correlates statistically with resistance to experimental P. haemolytica challenge in cattle. Until now, specific P. haemolytica OMPs which elicit antibodies that function in host defense mechanisms have not been identified. In this study, we have cloned and sequenced the gene encoding one such protein, PlpE. Analysis of the deduced amino acid sequence revealed that PlpE is a lipoprotein and that it is similar to an Actinobacillus pleuropneumoniae lipoprotein, OmlA. Affinity-purified, anti-PlpE antibodies recognize a protein in all serotypes of P. haemolytica except serotype 11. We found that intact P. haemolytica and recombinant E. coli expressing PlpE are capable of absorbing anti-PlpE antibodies from bovine immune serum, indicating that PlpE is surface exposed in P. haemolytica and assumes a similar surface-exposed conformation in E. coli. In complement-mediated killing assays, we observed a significant reduction in killing of P. haemolytica when bovine immune serum that was depleted of anti-PlpE antibodies was used as the source of antibody. Our data suggest that PlpE is surface exposed and immunogenic in cattle and that antibodies against PlpE contribute to host defense against P. haemolytica. PMID:9826333

  15. The effects of Pasteurella haemolytica lipopolysaccharide on bovine pulmonary artery endothelial cells in cell culture

    SciTech Connect

    Paulsen, D.B.

    1989-01-01

    This study examined the potential role of Pasteurella haemolytica Al lipopolysaccharide (LPS) in the pathogenesis of the vascular lesions of pneumonic pasteurellosis. Bovine pulmonary artery endothelia cells (BPAEC) were the test model. The direct toxic potential of P. Haemolytica LPS on BPAEC was examined by cell detachment assays, morphologic alterations, and membrane damage as reflected in the leakage of large internal molecules such as LDH and {sup 51}Cr-labeled molecules. LPS-induced effects having potential for causing indirect vascular damage were studied and included neutrophil-adherence to and arachidonic acid-release from BPAEC. Several substances were examined for their ability to inhibit the LPS-induced cytotoxicity. Pasteurella haemolytica LPS caused direct toxic effects in BPAEC. Cell-detachment, LDH-leakage, {sup 51}Cr-leakage, and {sup 3}H-arachidonic acid-release proceeded with similar time- and dose-dependency after exposure of BPAEC to LPS. Morphologic alterations were observed as early as one-half hour after LPS-exposure and became collectively more severe with time. Neutrophil adherence to BPAEC was increased by LPS through independent effects on both cells types. The adherence required protein synthesis in both cell types.

  16. Influence of beta(2)-integrin adhesion molecule expression and pulmonary infection with Pasteurella haemolytica on cytokine gene expression in cattle.

    PubMed

    Lee, H Y; Kehrli, M E; Brogden, K A; Gallup, J M; Ackermann, M R

    2000-07-01

    beta(2)-Integrins are leukocyte adhesion molecules composed of alpha (CD11a, -b, -c, or -d) and beta (CD18) subunit heterodimers. Genetic CD18 deficiency results in impaired neutrophil egress into tissues that varies between conducting airways and alveoli of the lung. In this study, we investigated whether CD18 deficiency in cattle affects proinflammatory cytokine (PIC) expression in pulmonary tissue after respiratory infection with Pasteurella haemolytica. Cattle were infected with P. haemolytica via fiberoptic deposition of organisms into the posterior part of the right cranial lung lobe. Animals were euthanized at 2 or 4 h postinoculation (p.i.), and tissues were collected to assess PIC gene expression using antisense RNA probes specific for bovine interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) along with the beta-actin (beta-Act) housekeeping gene. Expression of PIC was induced at 2 h p.i. in P. haemolytica-infected cattle and continued to 4 h p.i. At 2 h p.i., induction of gene expression and increase of cells that expressed PIC were observed both in CD18(+) and CD18(-) cattle after inoculation of P. haemolytica. The induction of gene expression with P. haemolytica inoculation was more prominent in CD18(-) cattle than in CD18(+) cattle by comparison to pyrogen-free saline (PFS)-inoculated control animals. At 4 h p.i., however, the induction of PIC, especially IL-1alpha, IL-6, and IFN-gamma, in the lungs of CD18(+) cattle inoculated with P. haemolytica was greater than that in lungs of the CD18(-) cattle. IFN-gamma and TNF-alpha genes were not increased in P. haemolytica-inoculated CD18(-) cattle lungs compared to the PFS-inoculated control lungs at 4 h p.i. In PFS-inoculated lungs, we generally observed a higher percentage of cells and higher level of gene expression in the lungs of CD18(-) cattle than in the lungs of CD18(+) cattle, especially at 4 h p.i. The rate of neutrophil

  17. 21 CFR 522.955 - Florfenicol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida... Haemophilus somnus. For treatment of bovine interdigital phlegmon (foot rot, acute...

  18. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida... infectious bovine keratoconjunctivitis associated with Moraxella bovis. For the treatment of bovine foot...

  19. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida... infectious bovine keratoconjunctivitis associated with Moraxella bovis. For the treatment of bovine foot...

  20. 21 CFR 522.955 - Florfenicol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida... Haemophilus somnus. For treatment of bovine interdigital phlegmon (foot rot, acute...

  1. Plane of nutrition during the preweaned period influences the pathophysiological responses to a combined intranasal bovine herpesvirus-1 and intratracheal Mannheimia haemolytica challenge in post-weaned Holstein calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine whether previous plane of milk replacer nutrition (PON) influences the pathophysiological responses to a combined viral-bacterial respiratory challenge. Thirty Holstein calves (1 day of age) were assigned to treatments in a 2 x 3 factorial arrangement with preweaned PO...

  2. Eosinophilic granuloma with Splendore-Hoeppli material caused by Mannheimia granulomatis in a calf.

    PubMed

    Kawashima, Yuuto; Takahashi, Hiroyasu; Shimoo, Megumi; Tamamura, Yukino; Ishikawa, Yoshiharu; Kadota, Koichi

    2016-07-01

    A large subcutaneous mass, formed on the left lower jaw of a 4-month-old Japanese Black male calf, was partially excised for histological and bacteriological examinations. Antibiotic treatment resulted in a good prognosis. Bacteria isolated from the excised material were characterized by weak hemolysis and positive reactions for catalase and oxidase, and were 99% identical to Mannheimia granulomatis strains. The presence of the leukotoxin gene product was demonstrated by polymerase chain reaction amplification. Histological examination showed that the excised material was composed of dense fibrous connective tissue with sparsely distributed eosinophilic granulomas or abscesses. These foci frequently contained Splendore-Hoeppli material with rod-shaped Gram-negative bacteria. Except for the absence of lymphangitis and the presence of basophils and mast cells, the histology of this lesion resembled that of lechiguana associated with coinfection of M. granulomatis and Dermatobia hominis. Leukotoxin was demonstrated by immunohistochemistry within Splendore-Hoeppli material and was judged to be responsible for its formation. PMID:26947171

  3. Eosinophilic granuloma with Splendore-Hoeppli material caused by Mannheimia granulomatis in a calf

    PubMed Central

    KAWASHIMA, Yuuto; TAKAHASHI, Hiroyasu; SHIMOO, Megumi; TAMAMURA, Yukino; ISHIKAWA, Yoshiharu; KADOTA, Koichi

    2016-01-01

    A large subcutaneous mass, formed on the left lower jaw of a 4-month-old Japanese Black male calf, was partially excised for histological and bacteriological examinations. Antibiotic treatment resulted in a good prognosis. Bacteria isolated from the excised material were characterized by weak hemolysis and positive reactions for catalase and oxidase, and were 99% identical to Mannheimia granulomatis strains. The presence of the leukotoxin gene product was demonstrated by polymerase chain reaction amplification. Histological examination showed that the excised material was composed of dense fibrous connective tissue with sparsely distributed eosinophilic granulomas or abscesses. These foci frequently contained Splendore-Hoeppli material with rod-shaped Gram-negative bacteria. Except for the absence of lymphangitis and the presence of basophils and mast cells, the histology of this lesion resembled that of lechiguana associated with coinfection of M. granulomatis and Dermatobia hominis. Leukotoxin was demonstrated by immunohistochemistry within Splendore-Hoeppli material and was judged to be responsible for its formation. PMID:26947171

  4. Use of DNA analysis of Pasteurella haemolytica biotype T isolates to monitor transmission in bighorn sheep (Ovis canadensis canadensis).

    PubMed Central

    Jaworski, M D; Ward, A C; Hunter, D L; Wesley, I V

    1993-01-01

    Pneumonia has been identified as a major cause of poor lamb survival in indigenous herds of Rocky Mountain bighorn sheep (Ovis canadensis canadensis) in central Idaho. Pasteurella haemolytica was isolated from five adult Rocky Mountain bighorn ewes captured from a free-ranging herd in central Idaho. The lambs from two of these ewes delivered by cesarean section were free of P. haemolytica until 40 days of age and after repeated contact with their dams. The lambs subsequently developed signs of pneumonia, and P. haemolytica was isolated from nasal, pharyngeal, and transtracheal wash samples from each lamb. All P. haemolytica biotype T isolates from the ewes and lambs, as well as those from a 9-month-old lamb of the same herd from which samples for culture were obtained 2 years earlier, were subjected to HaeIII restriction enzyme analysis (REA) and ribotyping. Two ribotypes and seven REA patterns were visually distinguishable by these procedures. Similarity coefficients (SAB) of 0.09 to 0.95 were calculated for the seven REA patterns. The REA patterns of the isolates from the lambs were identical (SAB = 1.0). The isolates from the lambs also had SAB values of 1.0, which was indicative of identity with one of the seven isolates cultured from the ewes at the time of capture and with the organism isolated from the 9-month-old lamb. These procedures have the discriminatory capabilities necessary to monitor the transmission of specific strains of bacteria within and between animal populations. Images PMID:8385150

  5. Highly selective production of succinic acid by metabolically engineered Mannheimia succiniciproducens and its efficient purification.

    PubMed

    Choi, Sol; Song, Hyohak; Lim, Sung Won; Kim, Tae Yong; Ahn, Jung Ho; Lee, Jeong Wook; Lee, Moon-Hee; Lee, Sang Yup

    2016-10-01

    Succinic acid (SA) is one of the fermentative products of anaerobic metabolism, and an important industrial chemical that has been much studied for its bio-based production. The key to the economically viable bio-based SA production is to develop an SA producer capable of producing SA with high yield and productivity without byproducts. Mannheimia succiniciproducens is a capnophilic rumen bacterium capable of efficiently producing SA. In this study, in silico genome-scale metabolic simulations were performed to identify gene targets to be engineered, and the PALK strain (ΔldhA and Δpta-ackA) was constructed. Fed-batch culture of PALK on glucose and glycerol as carbon sources resulted in the production of 66.14 g/L of SA with the yield and overall productivity of 1.34 mol/mol glucose equivalent and 3.39 g/L/h, respectively. SA production could be further increased to 90.68 g/L with the yield and overall productivity of 1.15 mol/mol glucose equivalent and 3.49 g/L/h, respectively, by utilizing a mixture of magnesium hydroxide and ammonia solution as a pH controlling solution. Furthermore, formation of byproducts was drastically reduced, resulting in almost homo-fermentative SA production. This allowed the recovery and purification of SA to a high purity (99.997%) with a high recovery yield (74.65%) through simple downstream processes composed of decolorization, vacuum distillation, and crystallization. The SA producer and processes developed in this study will allow economical production of SA in an industrial-scale. Biotechnol. Bioeng. 2016;113: 2168-2177. © 2016 Wiley Periodicals, Inc.

  6. Highly selective production of succinic acid by metabolically engineered Mannheimia succiniciproducens and its efficient purification.

    PubMed

    Choi, Sol; Song, Hyohak; Lim, Sung Won; Kim, Tae Yong; Ahn, Jung Ho; Lee, Jeong Wook; Lee, Moon-Hee; Lee, Sang Yup

    2016-10-01

    Succinic acid (SA) is one of the fermentative products of anaerobic metabolism, and an important industrial chemical that has been much studied for its bio-based production. The key to the economically viable bio-based SA production is to develop an SA producer capable of producing SA with high yield and productivity without byproducts. Mannheimia succiniciproducens is a capnophilic rumen bacterium capable of efficiently producing SA. In this study, in silico genome-scale metabolic simulations were performed to identify gene targets to be engineered, and the PALK strain (ΔldhA and Δpta-ackA) was constructed. Fed-batch culture of PALK on glucose and glycerol as carbon sources resulted in the production of 66.14 g/L of SA with the yield and overall productivity of 1.34 mol/mol glucose equivalent and 3.39 g/L/h, respectively. SA production could be further increased to 90.68 g/L with the yield and overall productivity of 1.15 mol/mol glucose equivalent and 3.49 g/L/h, respectively, by utilizing a mixture of magnesium hydroxide and ammonia solution as a pH controlling solution. Furthermore, formation of byproducts was drastically reduced, resulting in almost homo-fermentative SA production. This allowed the recovery and purification of SA to a high purity (99.997%) with a high recovery yield (74.65%) through simple downstream processes composed of decolorization, vacuum distillation, and crystallization. The SA producer and processes developed in this study will allow economical production of SA in an industrial-scale. Biotechnol. Bioeng. 2016;113: 2168-2177. © 2016 Wiley Periodicals, Inc. PMID:27070659

  7. Recovery of succinic acid produced by fermentation of a metabolically engineered Mannheimia succiniciproducens strain.

    PubMed

    Song, Hyohak; Huh, Yun Suk; Lee, Sang Yup; Hong, Won Hi; Hong, Yeon Ki

    2007-12-01

    There have recently been much advances in the production of succinic acid, an important four-carbon dicarboxylic acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is able to produce succinic acid with high efficiency, but also produces acetic, formic and lactic acids just like other anaerobic succinic acid producers. We recently reported the development of an engineered M. succiniciproducens LPK7 strain which produces succinic acid as a major fermentation product while producing much reduced by-products. Having an improved succinic acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of succinic acid. In this paper, we report the development of a simpler and more efficient method for the recovery of succinic acid. For the recovery of succinic acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified succinic acid (greater than 99.5% purity, wt%) with a high yield of 67.05wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of succinic acid were obtained. These results suggest that succinic acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for succinic acid production. PMID:17765349

  8. Development of a markerless gene knock-out system for Mannheimia succiniciproducens using a temperature-sensitive plasmid.

    PubMed

    Kim, Ji Mahn; Lee, Kwang Ho; Lee, Sang Yup

    2008-01-01

    A temperature-sensitive derivative of the Mannheimia varigena plasmid pMVSCS1 was constructed by hydroxylamine treatment for use in the development of a markerless gene knock-out system for Mannheimia succiniciproducens. The temperature-sensitive plasmid pMVSCS1-ts was stably maintained at 30 degrees C, but failed to replicate at 42 degrees C. DNA sequencing of the replication origin revealed a single base substitution as being responsible for its temperature sensitivity. The region of replication origin was amplified by PCR to construct an Escherichia coli-M. succiniciproducens shuttle vector pME19-ts to further examine the thermosensitivity. To make markerless mutants of M. succiniciproducens, the Cre-lox system with the variant lox66 and lox71 sites was used to prevent the instability caused by multiple loxP sites in the genome. The transient cre expression was carried out using the temperature-sensitive plasmid pCRX5, which was consequently cured after the verification of the markerless mutant by growing cells at 42 degrees C. For the demonstration of the markerless deletion of multiple genes using this method, the ldhA gene and the oadGAB operon of M. succiniciproducens encoding lactate dehydrogenase and oxaloacetate decarboxylase, respectively, were successfully deleted sequentially. This markerless deletion method should be useful for further metabolic engineering of M. succiniciproducens, which is a promising industrial bacterium for succinic acid production from renewable resources.

  9. Blood bactericidal assay (Pasteurella haemolytica) comparison of morbidity in marketed feeder calves.

    PubMed

    Purdy, C W; Richards, A B; Foster, G S

    1989-02-01

    An in vitro bactericidal assay that used bovine heparinized blood was investigated for its usefulness in detecting differences in the bactericidal immunity of calves against Pasteurella haemolytica serotype 1 (Ph1). Greater than 90% of killing occurred within 30 minutes. The substitution of fetal calf serum for autologous calf plasma caused loss of bactericidal activity of the blood. Decomplemented calf serum also was low in bactericidal activity. The blood bactericidal assay appears to be opsonin antibody-dependent and complement-dependent. The coefficient of variation (CV) that can be expected with this assay was established by use of a group of 8 calves; within-day CV maximum was 0.9, and between-day CV maximum was 2.1. The blood bactericidal assay was used to evaluate 30 calves under typical market stress from 4 farms in eastern Tennessee. All calves had decreased bactericidal activity, as they moved into a feedyard in Texas. The bactericidal activity was reduced among sick calves, based on the severity of clinical signs. Morbidity was highest during the first 14 days in the feedlot. During this period, healthy calves had a decreased bactericidal index (BI) of 4 points, and calves with clinical signs of bovine respiratory tract disease for 3 days had a decreased BI of 8 points. The average reduction in the BI of calves with clinical signs of bovine respiratory tract disease for 6 or more days was 14 points. PMID:2719384

  10. In situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in calves with acute Pasteurella haemolytica pneumonia.

    PubMed

    Radi, Z A; Register, K B; Lee, E K; Kehrli, M E; Brogden, K A; Gallup, J M; Ackermann, M R

    1999-09-01

    The in situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in normal and pneumonic lung tissues of Holstein calves with bovine leukocyte adhesion deficiency (BLAD) was compared with that of age-matched non-BLAD Holstein calves by in situ hybridization. Twenty-four Holstein calves (both BLAD and non-BLAD) were randomly assigned to one of two experimental groups and inoculated intrabronchially with Pasteurella haemolytica or pyrogen-free saline. Lung tissues were collected and fixed in 10% neutral formalin at 2 or 4 hours postinoculation (PI). The expression and distribution of ICAM-1 mRNA in the different cell types of the lung tissue was detected by in situ hybridization with a 307-base-pair bovine ICAM-1 riboprobe. In lungs of both non-BLAD and BLAD saline-inoculated calves, ICAM-1 expression was present in epithelial cells but occurred in <30% of cells in bronchi, bronchioles, and alveoli. ICAM-1 expression in vascular endothelial cells was present in <30% of cells in pulmonary arteries and veins. The expression of ICAM-1 was significantly greater (>60% of cells) in bronchiolar and alveolar epithelial cells and pulmonary endothelial cells of arteries and veins in both BLAD and non-BLAD calves inoculated with P. haemolytica. Bronchiolar epithelium had the highest intensity of mRNA expression and highest percentage of cells that were stained, whereas bronchial epithelium had the lowest intensity and percentage of cells stained. Most alveolar macrophages and neutrophils in infected lungs also expressed ICAM-1. ICAM-1 expression was generally increased in infected BLAD calves at 2 hours PI as compared with non-BLAD calves but not at 4 hours PI. The increased expression of ICAM-1 during acute P. haemolytica pneumonia in calves suggests that ICAM-1 is upregulated and may play a role in leukocyte infiltration. The extent of ICAM-1 expression in P. haemolytica-inoculated calves with BLAD was initially enhanced but otherwise similar to that in non

  11. Tilmicosin induces apoptosis in bovine peripheral neutrophils in the presence or in the absence of Pasteurella haemolytica and promotes neutrophil phagocytosis by macrophages.

    PubMed

    Chin, A C; Lee, W D; Murrin, K A; Morck, D W; Merrill, J K; Dick, P; Buret, A G

    2000-09-01

    Pathogen virulence factors and inflammation are responsible for tissue injury associated with respiratory failure in bacterial pneumonia, as seen in the bovine lung infected with Pasteurella haemolytica. Tilmicosin is a macrolide antibiotic used for the treatment of bovine bacterial pneumonia. Recent evidence suggests that tilmicosin-induced neutrophil apoptosis may have anti-inflammatory effects. Using bovine leukocytes, we sought to define whether live P. haemolytica affected tilmicosin-induced neutrophil apoptosis, assessed the proapoptotic effects of tilmicosin in comparison with other drugs, and characterized its impact on phagocytic uptake of neutrophils by macrophages. Induction of apoptosis in the presence or absence of P. haemolytica was assessed by using an enzyme-linked immunosorbent assay for apoptotic nucleosomes. In addition, fluorescent annexin-V staining identified externalized phosphatidylserine in neutrophils treated with tilmicosin, penicillin, ceftiofur, oxytetracycline, or dexamethasone. Neutrophil membrane integrity was assessed by using propidium iodide and trypan blue exclusion. As phagocytic clearance of apoptotic neutrophils by macrophages contributes to the resolution of inflammation, phagocytosis of tilmicosin-treated neutrophils by esterase-positive cultured bovine macrophages was assessed with light microscopy and transmission electron microscopy. Unlike bovine neutrophils treated with penicillin, ceftiofur, oxytetracycline, or dexamethasone, neutrophils exposed to tilmicosin became apoptotic, regardless of the presence or absence of P. haemolytica. Tilmicosin-treated apoptotic neutrophils were phagocytosed at a significantly greater rate by bovine macrophages than were control neutrophils. In conclusion, tilmicosin-induced neutrophil apoptosis occurs regardless of the presence or absence of live P. haemolytica, exhibits at least some degree of drug specificity, and promotes phagocytic clearance of the dying inflammatory cells.

  12. Viral-bacterial pneumonia in calves: duration of the interaction between bovine herpesvirus 1 and Pasteurella haemolytica.

    PubMed Central

    Yates, W D; Babiuk, L A; Jericho, K W

    1983-01-01

    Sixteen six to eight month old beef calves were exposed individually to a five minute aerosol of bovine herpesvirus 1, isolate 108. Aerosol exposure to Pasteurella haemolytica (biotype A, serotype 1) was administered individually for five minutes at either four, ten, 20 or 30 days after the virus. Fibrinous pneumonia and pleuritis occurred in all four groups but were most extensive and severe in those exposed to the virus and bacterium four days apart (the positive controls). Fibrinous pneumonia was associated with persistence of bovine herpesvirus 1 in the respiratory tract despite resolution of virus-induced necrotic lesions of the respiratory mucosa. The results presented here suggest that, although the severity of viral-bacterial synergism may be influenced by virus-induced morphological changes, the continued presence of viral antigens after the resolution of respiratory mucosal lesions may continue to exert some effect on host defenses and disease processes. Images Fig. 2. Fig. 3. Fig. 4. PMID:6315196

  13. Capsular polysaccharide vaccine for Group B Neisseria meningitidis, Escherichia coli K1, and Pasteurella haemolytica A2

    PubMed Central

    Robbins, John B.; Schneerson, Rachel; Xie, Guilin; Hanson, Lars Å.; Miller, Mark A.

    2011-01-01

    We reviewed the literature that is the basis for our proposal that (2→8)-α-Neu5Ac conjugates will be safe and effective vaccines for Group B meningococci (GBMs), Escherichia coli K1, and Pasteurella haemolytica A2. Although (2→8)-α-Neu5Ac is a virulence factor and a protective antigen of these three pathogens, it is also a component of normal tissues (neural cell adhesion molecule). Natural, anti–(2→8)-α-Neu5Ac present in most adults, vaccine-induced antibodies, and even high levels of spontaneously appearing monoclonal anti–(2→8)-α-Neu5Ac did not cause autoimmunity. Although it is not possible to prove a null hypothesis, there are no epidemiologic, serologic, immunologic, or clinical data to indicate that (2→8)-α-Neu5Ac antibodies will induce pathology or an autoimmune disease. No increased pathology caused by these antibodies was found, even in neonates and infants of mothers recovered from GBM meningitis. The lack of pathology mediated by anti–(2→8)-α-Neu5Ac may be explained by different presentations of (2→8)-α-Neu5Ac on bacterial and mammalian cells and by the unusual physicochemical properties of anti–(2→8)-α-Neu5Ac. Based on clinical and experimental data collected over 30 y and because (2→8)-α-Neu5Ac is an essential virulence factor and a protective antigen for GBM, E. coli K1, and P. haemolytica A2, protein conjugates of it are easy to prepare using inexpensive and plentiful ingredients, and they would be compatible with routinely administered infant vaccines, clinical studies of these conjugates should proceed. PMID:22025709

  14. Passage of CD18- and CD18+ bovine neutrophils into pulmonary alveoli during acute Pasteurella haemolytica pneumonia.

    PubMed

    Ackermann, M R; Kehrli, M E; Brogden, K A

    1996-11-01

    CD18 is a subunit for three beta 2 integrin molecules (Mac-1, p150, 95, LFA-1), which are expressed on the plasma membrane of neutrophils. These molecules mediate passage of neutrophils into sites of infection. In children and animals that lack CD18 expression, neutrophil infiltration is impaired in most tissues. However, in lung, CD18- neutrophils have been identified in the airway spaces during spontaneous episodes of pneumonia. To determine whether CD18 is vital for passage through the pulmonary alveolar wall, lung lobes of cattle with neutrophils that were deficient in CD18 expression (CD18-) and cattle with normal CD18 expression (CD18+) were inoculated with Pasteurella haemolytica by fiberoptic bronchoscopy; control lobes were inoculated with pyrogen-free saline (PFS). Neutrophil passage into alveolar lumina at 4 and 6 hours postinoculation was measured by computerized image analysis. Blood levels of neutrophils for CD18- cattle ranged from 12- to 26-fold higher than for CD18+ cattle prior to inoculation, and counts in both groups rose slightly postinoculation. In P. haemolytica-inoculated lobes, total numbers of neutrophils in alveolar lumina of the two groups were similar. An increase in the number of neutrophils in the alveolar wall was fourfold greater in CD18- cattle than in CD18+ cattle. In PFS-inoculated lobes, the number of neutrophils in the alveolar wall was sixfold higher in CD18 cattle than in CD18+ cattle. This work shows that by 4 and 6 hours, CD18- neutrophils enter the alveolar lumen at a rate similar to that in CD18+ cattle. Higher numbers of CD18- neutrophils are present in the alveolar wall of control (PFS) and bacteria-inoculated lobes. Thus, the CD18- cells are increased in the walls of alveoli and numbers of neutrophils that enter the alveolar lumen are similar in CD18+ and CD18- cattle. PMID:8952022

  15. Differential induction of tumor necrosis factor alpha in ovine pulmonary alveolar macrophages following infection with Corynebacterium pseudotuberculosis, Pasteurella haemolytica, or lentiviruses.

    PubMed Central

    Ellis, J A; Lairmore, M D; O'Toole, D T; Campos, M

    1991-01-01

    Soluble mediators such as tumor necrosis factor alpha (TNF-alpha) may be important in the pathogenesis of many chronic pulmonary infections. We examined the ability of Corynebacterium pseudotuberculosis, Pasteurella haemolytica, and ovine lentiviruses (OvLV) to induce TNF-alpha secretion by pulmonary alveolar macrophages (PAM). Bronchoalveolar lavage cells, composed of greater than 90% PAM, were obtained from normal sheep. Bronchoalveolar lavage cells were cultured for 2, 24, 48, 72, or 168 h in endotoxin-free RPMI medium (with 10% autologous serum) or in medium containing one of the following additives: lipopolysaccharide, 1-micron polystyrene beads, C. pseudotuberculosis, P. haemolytica, or one of two plaque-cloned OvLV, 85/28 or 85/34. Lipopolysaccharide, C. pseudotuberculosis, and P. haemolytica induced TNF-alpha activity in PAM cultures as early as 2 h after inoculation, as assessed by a colorimetric cytotoxicity assay. This activity could be blocked by rabbit anti-recombinant bovine TNF-alpha serum. In contrast, medium alone, polystyrene beads, and productive infection by OvLV did not induce TNF-alpha activity in PAM cultures. Bacterial pathogens which infect pulmonary macrophages may elicit the secretion of TNF-alpha within the lungs and lead to the cachectic state associated with chronic pneumonia. Images PMID:1652561

  16. Complete closed genome sequences of three Bibersteinia trehalosi nasopharyngeal isolates from cattle with shipping fever

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bibersteinia trehalosi is a respiratory pathogen affecting cattle and related ruminants worldwide. B. trehalosi is closely related to Mannheimia haemolytica, and is often associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease. We present three complete clos...

  17. Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were; first, to describe gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle diagnosed with bovine respiratory disease (BRD) and previously treated with either gamithromycin for control of BRD (mass me...

  18. [Problems in the use of radioactively marked bacteria in animal experiments. 1. Labeling of Pasteurella multocida, Pasteurella haemolytica and Salmonella dublin with eH, 14C, 32P, 59Fe, 99mTc, 125J1].

    PubMed

    Flossmann, K D; Rohrmann, B; Hubald, J; Finsterbusch, L

    1977-01-01

    Several methods are suggested by which to use the radionuclides 3H, 14C, 32P, 59Fe, 99mTc, and 125J for labelling or doublelabelling of Pasteurella multocida, Pasteurella haemolytica, and Salmonella dublin, with particular reference being made to labelling ofr animal experiments. Suitable radioactive substrates for internal labelling in chemically defined or partially defined nutritive media include 3H-thymin, 3H-thymidine, 14C-glucose, 14C-mannose, 14C-aspartic acid, as well as 3H-uracil, 3H-uridine, 3H-orotic acid, 14C-orotic acid, 59Fe-III-citrate or chloride, and Na2H32PO4. The choise of the nuclide and substrate should by governed by the problem at hand. PMID:849104

  19. MHC class II DR allelic diversity in bighorn sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesized that decreased diversity and/or unique polymorphisms in MHC class II alleles of bighorn sheep (BHS, Ovis canadensis) are responsible for lower titer of antibodies against Mannheimia haemolytica leukotoxin, in comparison to domestic sheep (DS, Ovis aries). To test this hypothesis, DRA...

  20. 21 CFR 522.522 - Danofloxacin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Mannheimia (Pasteurella) haemolytica and Pasteurella multocida. (3) Limitations. Animals intended for human... dairy production. A withdrawal period has not been established for this product in pre-ruminating...

  1. A study on Ovine pneumonic pasteurellosis: Isolation and Identification of Pasteurellae and their antibiogram susceptibility pattern in Haramaya District, Eastern Hararghe, Ethiopia

    PubMed Central

    2013-01-01

    Background Sheep constitute the second major component of livestock in Ethiopia. However, efficient utilization of this potential resource is hampered by combination of health problems, poor management and feed shortage. Haramaya district is one of the remote settings in Ethiopia where information about the livestock disease is not well documented. Hence this study was conducted to determine the causative agents and their antimicrobial susceptibility pattern of bacterial Pasteurella isolates among pneumonic ovine in Haramaya district, Eastern Hararghe, Ethiopia. Results Out of 256 samples examined, Pasterurella was isolated in 64 (25%), of which 38 (59.4%) were from lungs and 26 (40.6%) were from nasal cavities. 87.5% of the isolates were Mannheimia haemolytica and 12.5% were Pasteurella multocida. All of the isolates from the lungs were Mannheimia haemolytica whereas 69% of the isolates from nasals cavities were Mannheimia haemolytica. Age and body temperature were significantly associated with Pasteurella isolates from clinic (P < 0.05). Despite diverse in the site of origins, the isolates exhibited uniformity in sensitivity to a majority of the antibacterial agents. The most effective drug was Cholramphenicol (100%) followed by Sulfamethoxazole (89.1%) and Tetracycline (84.4%). Both species were completely resistant to Gentamycin and Vancomycin. Conclusion Mannheimia haemolytica is the most common cause of ovine pneumonic pasteurellosis in the study area. The isolates were susceptible to limited antimicrobial agents. Therefore, the antimicrobial susceptibility test should be conducted before treatment, except for critical cases. PMID:24289236

  2. Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia haemolytica infection results in enhanced PMN-mediated tissue damage in the lungs of bighorn sheep (BHS) compared to that of domestic sheep (DS). SERPIN B1 is an inhibitor of PMN-derived serine proteases. It prevents lung tissue injury by inhibiting the serine proteases released as a resu...

  3. Bighorn sheep pneumonia: Sorting out the cause of a polymicrobial disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pneumonia of bighorn sheep (Ovis canadensis) is a dramatic disease of high morbidity and mortality first described more than 80 years ago. The etiology of the disease has been debated since its initial discovery, and at various times lungworms, Mannheimia haemolytica and other Pasteurellaceae, and M...

  4. Genome Sequence of Bibersteinia trehalosi Strain Y31 Isolated from the Pneumonic Lung of a Bighorn Sheep

    PubMed Central

    Kugadas, Abirami; Humann, Jodi L.; Pierlé, Sebastián Aguilar; Srikumaran, Subramaniam

    2016-01-01

    Here, we report the genome sequence for Bibersteinia trehalosi strain Y31, isolated from the lungs of a bighorn sheep (Ovis canadensis) that had succumbed to pneumonia, which exhibits proximity-dependent inhibition (PDI) of Mannheimia haemolytica. The sequence will be used to understand the mechanism of PDI for these organisms. PMID:27445392

  5. Sequence analysis of serotype-specific synthesis regions II of Haemophilus influenzae serotypes c and d: evidence for common ancestry of capsule synthesis in Pasteurellaceae and Neisseria meningitidis.

    PubMed

    Lâm, Thiên-Trí; Claus, Heike; Frosch, Matthias; Vogel, Ulrich

    2011-06-01

    Sequencing of yet unknown Haemophilus influenzae serotype c (Hic) and d (Hid) capsule synthesis regions II revealed four (ccs1-4) and five (dcs1-5) open reading frames, respectively. The inferred gene functions were in line with capsular polysaccharide structures. One or more proteins encoded by the Hic capsule synthesis region II showed similarity to Actinobacillus pleuropneumoniae serotype 1 and Actinobacillus suis K1 enzymes. Orthologues to the complete operon were observed in Actinobacillus minor strain 202, where even the gene order was conserved. Furthermore, Ccs4 was related to the capsule O-acetyltransferase of Neisseria meningitidis serogroup W-135. For the Hid locus, similarities to Hie, Mannheimia haemolytica A1 and N. meningitidis serogroup A were identified and the succession of genes was similar in the different species. The resemblance of genes and gene organization found for Hic and Hid with other species suggested horizontal gene transfer during capsule evolution across the bacterial classes.

  6. Alopecia in lambs associated with micronutrient-deficient milk replacer.

    PubMed

    2016-09-24

    ▪ Alopecia associated with micronutrient deficiency in lambs fed milk replacer▪ Idiopathic necrotising enteritis in suckler calves▪ Mannheimia haemolytica abomasitis in a five-week-old calf▪ Increased diagnoses of nematodirosis in lambs▪ Enteric and spinal listeriosis in sheepThese are among matters discussed in the disease surveillance report for June 2016 from SAC Consulting: Veterinary Services (SAC C VS). PMID:27660354

  7. Pathogens of bovine respiratory disease in North American feedlots conferring multidrug resistance via integrative conjugative elements.

    PubMed

    Klima, Cassidy L; Zaheer, Rahat; Cook, Shaun R; Booker, Calvin W; Hendrick, Steve; Alexander, Trevor W; McAllister, Tim A

    2014-02-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD.

  8. Pathogens of Bovine Respiratory Disease in North American Feedlots Conferring Multidrug Resistance via Integrative Conjugative Elements

    PubMed Central

    Klima, Cassidy L.; Zaheer, Rahat; Cook, Shaun R.; Booker, Calvin W.; Hendrick, Steve

    2014-01-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD. PMID:24478472

  9. Application of enrofloxacin and orbifloxacin disks approved in Japan for susceptibility testing of representative veterinary respiratory pathogens.

    PubMed

    Harada, Kazuki; Usui, Masaru; Asai, Tetsuo

    2014-10-01

    In this study, susceptibilities of Pasteurella multocida, Mannheimia haemolytica and Actinobacillus pleuropneumoniae to enrofloxacin and orbifloxacin were tested using an agar diffusion method with the commercial disks and a broth microdilution method. Good correlation between the 2 methods for enrofloxacin and orbifloxacin was observed for P. multocida (r = -0.743 and -0.818, respectively), M. haemolytica (r = -0.739 and -0.800, respectively) and A. pleuropneumoniae (r = -0.785 and -0.809, respectively). Based on the Clinical and Laboratory Standards Institute interpretive criteria for enrofloxacin, high-level categorical agreement between the 2 methods was found for P. multocida (97.9%), M. haemolytica (93.8%) and A. pleuropneumoniae (92.0%). Our findings indicate that the tested commercial disks can be applied for susceptibility testing of veterinary respiratory pathogens.

  10. Application of Enrofloxacin and Orbifloxacin Disks Approved in Japan for Susceptibility Testing of Representative Veterinary Respiratory Pathogens

    PubMed Central

    HARADA, Kazuki; USUI, Masaru; ASAI, Tetsuo

    2014-01-01

    ABSTRACT In this study, susceptibilities of Pasteurella multocida, Mannheimia haemolytica and Actinobacillus pleuropneumoniae to enrofloxacin and orbifloxacin were tested using an agar diffusion method with the commercial disks and a broth microdilution method. Good correlation between the 2 methods for enrofloxacin and orbifloxacin was observed for P. multocida (r = −0.743 and −0.818, respectively), M. haemolytica (r = −0.739 and −0.800, respectively) and A. pleuropneumoniae (r = −0.785 and −0.809, respectively). Based on the Clinical and Laboratory Standards Institute interpretive criteria for enrofloxacin, high-level categorical agreement between the 2 methods was found for P. multocida (97.9%), M. haemolytica (93.8%) and A. pleuropneumoniae (92.0%). Our findings indicate that the tested commercial disks can be applied for susceptibility testing of veterinary respiratory pathogens. PMID:25008965

  11. A1C test

    MedlinePlus

    HbA1C test; Glycated hemoglobin test; Glycosylated hemoglobin test; Hemoglobin glycosylated test; Glycohemoglobin test ... have recently eaten does not affect the A1C test, so you do not need to fast to ...

  12. Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases.

    PubMed

    DeDonder, Keith D; Harhay, Dayna M; Apley, Michael D; Lubbers, Brian V; Clawson, Michael L; Schuller, Gennie; Harhay, Gregory P; White, Brad J; Larson, Robert L; Capik, Sarah F; Riviere, Jim E; Kalbfleisch, Ted; Tessman, Ronald K

    2016-08-30

    The objectives of this study were; first, to describe gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle diagnosed with bovine respiratory disease (BRD) and previously treated with either gamithromycin for control of BRD (mass medication=MM) or sham-saline injected (control=CON); second, to describe the macrolide resistance genes present in genetically typed M. haemolytica isolates; third, use whole-genome sequencing (WGS) to correlate the phenotypic resistance and genetic determinants for resistance among M. haemolytica isolates. M. haemolytica (n=276), P. multocida (n=253), and H. somni (n=78) were isolated from feedlot cattle diagnosed with BRD. Gamithromycin susceptibility was determined by broth microdilution. Whole-genome sequencing was utilized to determine the presence/absence of macrolide resistance genes and to genetically type M. haemolytica. Generalized linear mixed models were built for analysis. There was not a significant difference between MM and CON groups in regards to the likelihood of culturing a resistant isolate of M. haemolytica or P. multocida. The likelihood of culturing a resistant isolate of M. haemolytica differed significantly by state of origin in this study. A single M. haemolytica genetic subtype was associated with an over whelming majority of the observed resistance. H. somni isolation counts were low and statistical models would not converge. Phenotypic resistance was predicted with high sensitivity and specificity by WGS. Additional studies to elucidate the relationships between phenotypic expression of resistance/genetic determinants for resistance and clinical response to antimicrobials are necessary to inform judicious use of antimicrobials in the context of relieving animal disease and suffering. PMID:27527782

  13. A1C

    MedlinePlus

    A1C is a blood test for type 2 diabetes and prediabetes. It measures your average blood glucose, or blood sugar, level over the past 3 ... A1C alone or in combination with other diabetes tests to make a diagnosis. They also use the ...

  14. A1C Test

    MedlinePlus

    ... to minimize the complications caused by chronically elevated glucose levels, such as progressive damage to body organs like the kidneys, eyes, cardiovascular system, and nerves. The A1c test result ...

  15. Fusobacterium necrophorum in North American Bighorn Sheep ( Ovis canadensis ) Pneumonia.

    PubMed

    Shanthalingam, Sudarvili; Narayanan, Sanjeevkumar; Batra, Sai Arun; Jegarubee, Bavananthasivam; Srikumaran, Subramaniam

    2016-07-01

    Fusobacterium necrophorum has been detected in pneumonic bighorn sheep (BHS; Ovis canadensis ) lungs, in addition to the aerobic respiratory pathogens Mannheimia haemolytica , Bibersteinia trehalosi , Pasteurella multocida , and Mycoplasma ovipneumoniae . Similar to M. haemolytica , F. necrophorum produces a leukotoxin. Leukotoxin-induced lysis and degranulation of polymorphonuclear leukocytes (PMNs) and macrophages are responsible for acute inflammation and lung tissue damage characteristic of M. haemolytica -caused pneumonia. As one approach in elucidating the role of F. necrophorum in BHS pneumonia, we determined the frequency of the presence of F. necrophorum in archived pneumonic BHS lung tissues, and susceptibility of BHS leukocytes to F. necrophorum leukotoxin. A species-specific PCR assay detected F. necrophorum in 37% of pneumonic BHS lung tissues (total tested n=70). Sequences of PCR amplicons were similar to the less virulent F. necrophorum subsp. funduliforme. Fusobacterium necrophorum leukotoxin exhibited cytotoxicity to BHS PMNs and peripheral blood mononuclear cells. As with the M. haemolytica leukotoxin, F. necrophorum leukotoxin was more toxic to BHS PMNs than domestic sheep PMNs. It is likely that F. necrophorum enters the lungs after M. haemolytica and other aerobic respiratory pathogens enter the lungs and initiate tissue damage, thereby creating a microenvironment that is conducive for anaerobic bacterial growth. In summary, Fusobacterium leukotoxin is highly toxic for BHS leukocytes; however, based on the PCR findings, it is unlikely to play a direct role in the development of BHS pneumonia.

  16. Fusobacterium necrophorum in North American Bighorn Sheep ( Ovis canadensis ) Pneumonia.

    PubMed

    Shanthalingam, Sudarvili; Narayanan, Sanjeevkumar; Batra, Sai Arun; Jegarubee, Bavananthasivam; Srikumaran, Subramaniam

    2016-07-01

    Fusobacterium necrophorum has been detected in pneumonic bighorn sheep (BHS; Ovis canadensis ) lungs, in addition to the aerobic respiratory pathogens Mannheimia haemolytica , Bibersteinia trehalosi , Pasteurella multocida , and Mycoplasma ovipneumoniae . Similar to M. haemolytica , F. necrophorum produces a leukotoxin. Leukotoxin-induced lysis and degranulation of polymorphonuclear leukocytes (PMNs) and macrophages are responsible for acute inflammation and lung tissue damage characteristic of M. haemolytica -caused pneumonia. As one approach in elucidating the role of F. necrophorum in BHS pneumonia, we determined the frequency of the presence of F. necrophorum in archived pneumonic BHS lung tissues, and susceptibility of BHS leukocytes to F. necrophorum leukotoxin. A species-specific PCR assay detected F. necrophorum in 37% of pneumonic BHS lung tissues (total tested n=70). Sequences of PCR amplicons were similar to the less virulent F. necrophorum subsp. funduliforme. Fusobacterium necrophorum leukotoxin exhibited cytotoxicity to BHS PMNs and peripheral blood mononuclear cells. As with the M. haemolytica leukotoxin, F. necrophorum leukotoxin was more toxic to BHS PMNs than domestic sheep PMNs. It is likely that F. necrophorum enters the lungs after M. haemolytica and other aerobic respiratory pathogens enter the lungs and initiate tissue damage, thereby creating a microenvironment that is conducive for anaerobic bacterial growth. In summary, Fusobacterium leukotoxin is highly toxic for BHS leukocytes; however, based on the PCR findings, it is unlikely to play a direct role in the development of BHS pneumonia. PMID:27224212

  17. Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies

    PubMed Central

    Lhermie, Guillaume; El Garch, Farid; Toutain, Pierre-Louis; Ferran, Aude A.; Bousquet-Mélou, Alain

    2015-01-01

    We investigated the antimicrobial activity of a fluoroquinolone against two genetically close bacterial species belonging to the Pasteurellaceae family. Time-kill experiments were used to measure the in vitro activity of marbofloxacin against two strains of Mannheimia haemolytica and Pasteurella multocida with similar MICs. We observed that marbofloxacin was equally potent against 105 CFU/mL inocula M. haemolytica and P. multocida. However, an inoculum effect was observed with P. multocida, meaning that marbofloxacin activity was decreased against a 108 CFU/mL inoculum, whereas no inoculum effect was observed with M. haemolytica. Marbofloxacin activity was also tested in a lung infection model with immunocompromised mice intratracheally infected with 109 CFU of each bacteria. At the same dose, the clinical and bacteriological outcomes were much better for mice infected with M. haemolytica than for those infected with P. multocida. Moreover, bacteriological eradication was obtained with a lower marbofloxacin dose for mice infected with M. haemolytica. Our results suggest that the differential in vivo marbofloxacin efficacy observed with the two bacterial species of similar MIC could be explained by a differential inoculum effect. Consequently, MICs determined on 105 CFU inocula were not predictive of the differences in antibiotic efficacies against high bacterial inocula of closely related bacterial strains. These results could stimulate further investigations on bacterial species-specific antibiotic doses in a clinical setting. PMID:26506096

  18. Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons

    PubMed Central

    Tarello, Walter

    2011-01-01

    The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis. PMID:21754937

  19. Etiologic agents and diseases found associated with clinical aspergillosis in falcons.

    PubMed

    Tarello, Walter

    2011-01-01

    The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  20. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies... used in paragraph (b)(2) of this section. Two replicate titrations shall be conducted on each...

  1. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies... used in paragraph (b)(2) of this section. Two replicate titrations shall be conducted on each...

  2. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies... used in paragraph (b)(2) of this section. Two replicate titrations shall be conducted on each...

  3. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies... used in paragraph (b)(2) of this section. Two replicate titrations shall be conducted on each...

  4. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies... used in paragraph (b)(2) of this section. Two replicate titrations shall be conducted on each...

  5. Experimental infectious respiratory disease in groups of calves:Lobar distribution, variance, and sample-size requirements for vaccine evaluation

    PubMed Central

    2004-01-01

    Abstract The distribution and variance of respiratory disease produced with aerosols of bovine herpesvirus 1 (BHV-1) and Mannheimia haemolytica in control (183 calves in 44 experiments) and vaccinated calves were studied in experiments conducted at the Animal Diseases Research Institute, Lethbridge, Alberta, from 1975 to 1989. All calves had been born and raised at this institute and exposed similarly for 5 min by means of a face mask to viral and bacterial aerosols produced by a Collison atomizer (particles < 3 μm in diameter). We summarized the macroscopic pathological responses of pneumonia (main end point), tonsillitis, tracheitis, and other microbiologic and experimental variables. We also summarized the lobar distribution of pneumonia in 202 control and 192 vaccinated calves with this disease model and in calves similarly exposed to parainfluenza 3 virus/M. haemolytica or BHV-1/Pasteurella multocida. Pneumonia in control calves began in ventral tissues of all lobes, with lobar preferences, and progressed dorsally, the dorsal parts of both large caudal lobes being least affected. A high variance of pneumonia was evident within and among experiments. From the magnitude of variance observed in the control groups, the number of calves per group required in vaccine-challenge studies using this BHV-1/M. haemolytica disease model was estimated. Such estimates are required for any disease model used in vaccine-challenge studies. PMID:15188956

  6. A1C Test and Diabetes

    MedlinePlus

    ... laboratory tests. How does the A1C relate to estimated average glucose? Estimated average glucose (eAG) is calculated from the A1C. ... levels have the A1C test twice a year. Estimated average glucose (eAG) is calculated from the A1C ...

  7. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... § 169a.1(a). 3 Copies may be obtained if needed, from the Office of Management and Budget, Executive... and Industrial Activities Cost Comparison Handbook.” 4 See footnote 1 to § 169a.1(a)....

  8. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROCEDURES General § 169a.1 Purpose. This part: (a) Reissues DoD Instruction 4100.33 1 to update policy... § 169a.1(a). 3 Copies may be obtained if needed, from the Office of Management and Budget, Executive... and Industrial Activities Cost Comparison Handbook.” 4 See footnote 1 to § 169a.1(a)....

  9. 22 CFR 3a.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Definitions. 3a.1 Section 3a.1 Foreign Relations DEPARTMENT OF STATE GENERAL ACCEPTANCE OF EMPLOYMENT FROM FOREIGN GOVERNMENTS BY MEMBERS OF THE UNIFORMED SERVICES § 3a.1 Definitions. For purposes of this part— (a) Applicant means any person...

  10. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Definitions. 213a.1 Section 213a.1 Aliens... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... intention to maintain that residence for the foreseeable future. Federal poverty line means the level...

  11. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Definitions. 213a.1 Section 213a.1 Aliens... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... intention to maintain that residence for the foreseeable future. Federal poverty line means the level...

  12. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes...

  13. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes...

  14. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes...

  15. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes...

  16. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401...

  17. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401...

  18. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401...

  19. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401...

  20. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401...

  1. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes...

  2. Bactericidal activity of tracheal antimicrobial peptide against respiratory pathogens of cattle.

    PubMed

    Taha-Abdelaziz, Khaled; Perez-Casal, José; Schott, Courtney; Hsiao, Jason; Attah-Poku, Samuel; Slavić, Durđa; Caswell, Jeff L

    2013-04-15

    Tracheal antimicrobial peptide (TAP) is a β-defensin produced by mucosal epithelial cells of cattle. Although effective against several human pathogens, the activity of this bovine peptide against the bacterial pathogens that cause bovine respiratory disease have not been reported. This study compared the antibacterial effects of synthetic TAP against Mannheimia haemolytica, Histophilus somni, Pasteurella multocida, and Mycoplasma bovis. Bactericidal activity against M. bovis was not detected. In contrast, the Pasteurellaceae bacteria showed similar levels of susceptibility to that of Escherichia coli, with 0.125μg TAP inhibiting growth in a radial diffusion assay and minimum inhibitory concentrations of 1.56-6.25μg/ml in a bactericidal assay. Significant differences among isolates were not observed. Sequencing of exon 2 of the TAP gene from 23 cattle revealed a prevalent non-synonymous single nucleotide polymorphism (SNP) A137G, encoding either serine or asparagine at residue 20 of the mature peptide. The functional effect of this SNP was tested against M. haemolytica using synthetic peptides. The bactericidal effect of the asparagine-containing peptide was consistently higher than the serine-containing peptide. Bactericidal activities were similar for an acapsular mutant of M. haemolytica compared to the wild type. These findings indicate that the Pasteurellaceae bacteria that cause bovine respiratory disease are susceptible to killing by bovine TAP and appear not to have evolved resistance, whereas M. bovis appears to be resistant. A non-synonymous SNP was identified in the coding region of the TAP gene, and the corresponding peptides vary in their bactericidal activity against M. haemolytica.

  3. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of orbifloxacin in Korean Hanwoo cattle.

    PubMed

    Elias, G; Lee, J-S; Hwang, M-H; Park, Y-S; Cho, K-H; Kim, Y-H; Park, S-C

    2009-06-01

    The pharmacokinetics and pharmacodynamics of orbifloxacin were studied in six clinically healthy Hanwoo cows after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 3 mg/kg. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution and clearance of orbifloxacin after i.v. administration were 0.92 L/kg and 0.24 L/h x kg, respectively. Following i.m. administration, a slow and complete absorption with absolute bioavailability of 101.4%, and a maximum concentration (C(max)) of 1.17 microg/mL at 1.04 h were observed. The in vitro serum protein binding was 14.76%. The in vitro antibacterial activity of orbifloxacin against a pathogenic strain of Mannheimia haemolytica (M. haemolytica), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was determined. The ex vivo activity of orbifloxacin against M. haemolytica strain was also determined, and these data were integrated with the ex vivo bacterial counts to establish AUC(24h)/MIC values producing bacteriostatic action, bactericidal action and elimination of bacteria. Mean values were 32.7, 51.6 and 102.6 h, respectively. From these data, we predict that orbifloxacin, when administered i.m. at a dosage of 2.5-5 mg/kg once a day, would be effective against bovine pathogens, such as M. haemolytica. Additional studies may be needed to confirm its efficacy in a clinical setting, and to evaluate the penetration of the drug in diseased tissues.

  4. Reversibility of Intersystem Crossing in the {a}1A1(000) and {a}1A1(010) States of Methylene, CH_2

    NASA Astrophysics Data System (ADS)

    Le, Anh T.; Sears, Trevor; Hall, Gregory

    2015-06-01

    The lowest energy singlet ( {a}1A1) and triplet ( {X}3B1) electronic states of methylene, CH_2, are only separated by 3150 wn, but differ greatly in chemical reactivity. Overall methylene reaction rates and chemical behavior are therefore strongly dependent on collisionally-mediated singlet-triplet interconversion. Collisions with inert partners tend to depopulate the excited singlet state and populate vibrationally excited triplet levels in CH_2. This process is generally considered as irreversible for large molecules, however, this is not the case for small molecules such as CH_2. An investigation of the decay kinetics of CH_2 in the presence of argon and various amounts of oxygen has been carried out using transient frequency modulation (FM) absorption spectroscopy, to monitor ortho and para rotational levels in both the {a}1A1(000) and {a}1A1(010) states. In the {a}1A1(000) state, all observed rotational levels follow double exponential decay kinetics, a direct consequence of reversible intersystem crossing. The relative amplitude of the slower decay component is an indicator of how quickly the reverse crossing from excited triplet levels becomes significant during the reaction and relaxation of singlet methylene. The para rotational levels show more obvious signs of reversibility than ortho rotational levels. Adding oxygen enhances the visibility of reversibility for both ortho and para levels. However, in the {a}1A1(010) state where the FM signal is 5-10 times smaller than the {a}1A1(000) state, there is no evidence of double exponential decay kinetics. Acknowledgments: Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02-98CH10886 and DE-SC0012704 with the U.S. Department of Energy and supported by its Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences.

  5. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking... Party. The term Party means any person, employee, group of employees, labor organization, or bank as... rules and regulations, (b) named as a party in a charge, complaint, petition, application, or...

  6. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking... Party. The term Party means any person, employee, group of employees, labor organization, or bank as... rules and regulations, (b) named as a party in a charge, complaint, petition, application, or...

  7. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished...

  8. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished...

  9. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191....

  10. 8 CFR 245a.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the term such alien actually served. Under this exception, for purposes of 8 CFR part 245a, the crime... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Definitions. 245a.1 Section 245a.1 Aliens...). (c)(1) Resided continuously as used in section 245A(a)(2) of the Act, means that the alien shall...

  11. 8 CFR 245a.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the term such alien actually served. Under this exception, for purposes of 8 CFR part 245a, the crime... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Definitions. 245a.1 Section 245a.1 Aliens...). (c)(1) Resided continuously as used in section 245A(a)(2) of the Act, means that the alien shall...

  12. 8 CFR 245a.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Definitions. 245a.1 Section 245a.1 Aliens... the alien shall be regarded as having resided continuously in the United States if, at the time of filing of the application for temporary resident status: An alien who after appearing for a...

  13. 38 CFR 8a.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Insurance (VMLI) means the mortgage protection life insurance authorized for veterans under 38 U.S.C. 2106... 8a.1 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS VETERANS MORTGAGE LIFE INSURANCE § 8a.1 Definitions. (a) The term housing unit means a family dwelling or unit, together with...

  14. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Purpose. 383a.1 Section 383a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL CHARTERS... the Defense Commissary Board (DCB), with responsibilities, functions, and authorities as...

  15. 42 CFR 2a.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...(a)) provides that “ he Secretary may authorize persons engaged in research on mental health... regulations in this part establish procedures under which any person engaged in research on mental health... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 2a.1 Section 2a.1 Public...

  16. 42 CFR 2a.1 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...(a)) provides that “ he Secretary may authorize persons engaged in research on mental health... regulations in this part establish procedures under which any person engaged in research on mental health... 42 Public Health 1 2011-10-01 2011-10-01 false Applicability. 2a.1 Section 2a.1 Public...

  17. 42 CFR 54a.1 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... 290aa, et seq., which are administered by the Substance Abuse and Mental Health Services Administration. This part does not apply to direct funding under any such authorities for only mental health services... 42 Public Health 1 2012-10-01 2012-10-01 false Scope. 54a.1 Section 54a.1 Public Health...

  18. 42 CFR 54a.1 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... 290aa, et seq., which are administered by the Substance Abuse and Mental Health Services Administration. This part does not apply to direct funding under any such authorities for only mental health services... 42 Public Health 1 2011-10-01 2011-10-01 false Scope. 54a.1 Section 54a.1 Public Health...

  19. 42 CFR 54a.1 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... 290aa, et seq., which are administered by the Substance Abuse and Mental Health Services Administration. This part does not apply to direct funding under any such authorities for only mental health services... 42 Public Health 1 2010-10-01 2010-10-01 false Scope. 54a.1 Section 54a.1 Public Health...

  20. 42 CFR 54a.1 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... 290aa, et seq., which are administered by the Substance Abuse and Mental Health Services Administration. This part does not apply to direct funding under any such authorities for only mental health services... 42 Public Health 1 2013-10-01 2013-10-01 false Scope. 54a.1 Section 54a.1 Public Health...

  1. 42 CFR 54a.1 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... 290aa, et seq., which are administered by the Substance Abuse and Mental Health Services Administration. This part does not apply to direct funding under any such authorities for only mental health services... 42 Public Health 1 2014-10-01 2014-10-01 false Scope. 54a.1 Section 54a.1 Public Health...

  2. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... the person's average blood sugar levels over that time. Why It's Done Doctors use the hemoglobin A1c test to determine if your child's diabetes management plan needs to be adjusted. Typically the test ...

  3. A-1 modification work under way

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Phil Schemanski of Pratt & Whitney Rocketdyne removes equipment inside the thrust drum on the A-1 Test Stand as part of a comprehensive modification project to prepare for testing the new J-2X engine.

  4. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Stennis Space Center employees maneuver a new thrust measurement system in preparation for its installation on the A-1 Test Stand on March 3. The system was fabricated by Thrust Measurement Systems in Illinois and represents a state-of-the-art upgrade from the equipment used on the stand for more than 40 years. The A-1 Test Stand is being upgraded to provide testing for the next generation of rocket engines for America's space program.

  5. Causes of pneumonia epizootics among bighorn sheep, Western United States, 2008-2010.

    PubMed

    Besser, Thomas E; Highland, Margaret A; Baker, Katherine; Cassirer, E Frances; Anderson, Neil J; Ramsey, Jennifer M; Mansfield, Kristin; Bruning, Darren L; Wolff, Peregrine; Smith, Joshua B; Jenks, Jonathan A

    2012-03-01

    Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain etiology. To help clarify the etiology, we used culture and culture-independent methods to compare the prevalence of the bacterial respiratory pathogens Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent detected at significantly higher prevalence in animals from outbreaks (95%) than in animals from unaffected healthy populations (0%), was the most consistently detected agent and the only agent that exhibited single strain types within each outbreak. The other respiratory pathogens were frequently but inconsistently detected, as were several obligate anaerobic bacterial species, all of which might represent secondary or opportunistic infections that could contribute to disease severity. These data provide evidence that M. ovipneumoniae plays a primary role in the etiology of epizootic pneumonia of bighorn sheep.

  6. Causes of Pneumonia Epizootics among Bighorn Sheep, Western United States, 2008–2010

    PubMed Central

    Highland, Margaret A.; Baker, Katherine; Cassirer, E. Frances; Anderson, Neil J.; Ramsey, Jennifer M.; Mansfield, Kristin; Bruning, Darren L.; Wolff, Peregrine; Smith, Joshua B.; Jenks, Jonathan A.

    2012-01-01

    Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain etiology. To help clarify the etiology, we used culture and culture-independent methods to compare the prevalence of the bacterial respiratory pathogens Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent detected at significantly higher prevalence in animals from outbreaks (95%) than in animals from unaffected healthy populations (0%), was the most consistently detected agent and the only agent that exhibited single strain types within each outbreak. The other respiratory pathogens were frequently but inconsistently detected, as were several obligate anaerobic bacterial species, all of which might represent secondary or opportunistic infections that could contribute to disease severity. These data provide evidence that M. ovipneumoniae plays a primary role in the etiology of epizootic pneumonia of bighorn sheep. PMID:22377321

  7. Mastitis in sheep--The last 10 years and the future of research.

    PubMed

    Gelasakis, A I; Mavrogianni, V S; Petridis, I G; Vasileiou, N G C; Fthenakis, G C

    2015-12-14

    Bacterial mastitis is a significant welfare and financial problem in sheep flocks. This paper reviews the recently published literature, including publications that highlight the significance and virulence factors of the causal agents, especially Staphylococcus aureus and Mannheimia haemolytica, the primary causes of the disease. Research has also contributed to the understanding of risk factors, including genetic susceptibility of animals to infections, supporting future strategies for sustainable disease control. Pathogenetic mechanisms, including the role of the local defenses in the teat, have also been described and can assist formulation of strategies that induce local immune responses in the teat of ewes. Further to well-established diagnostic techniques, i.e., bacteriological tests and somatic cell counting, advanced methodologies, e.g., proteomics technologies, will likely contribute to more rapid and accurate diagnostics, in turn enhancing mastitis control efforts.

  8. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex

    PubMed Central

    Gershwin, Laurel J.; Van Eenennaam, Alison L.; Anderson, Mark L.; McEligot, Heather A.; Toaff-Rosenstein, Rachel; Taylor, Jeremy F.; Neibergs, Holly L.; Womack, James

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

  9. Demonstration of the metaphylactic use of gamithromycin against bacterial pathogens associated with bovine respiratory disease in a multicentre farm trial

    PubMed Central

    Baggott, D.; Casartelli, A.; Fraisse, F.; Manavella, C.; Marteau, R.; Rehbein, S.; Wiedemann, M.; Yoon, S.

    2011-01-01

    On five commercial cattle rearing sites across Europe, a total of 802 young cattle at high risk of developing bovine respiratory disease (BRD) associated with the bacterial pathogens Mannheimia haemolytica or Pasteurella multocida and/or Mycoplasma bovis were enrolled into a multicentre, controlled field trial. Half were treated with a single dose of gamithromycin at 6 mg/kg bodyweight by subcutaneous injection and half received an injection of a saline placebo as the control. All animals were observed daily for 14 days for signs of BRD as defined by set criteria. The proportion of metaphylactic preventive treatment successes, defined as animals surviving to day 14 without signs of BRD, in the gamithromycin-treated group (86 per cent) was significantly (P=0.0012) higher than in the saline-treated controls (61 per cent). Morbidity among the treated animals was reduced by 64 per cent compared with the controls. PMID:21493573

  10. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

    PubMed

    Gershwin, Laurel J; Van Eenennaam, Alison L; Anderson, Mark L; McEligot, Heather A; Shao, Matt X; Toaff-Rosenstein, Rachel; Taylor, Jeremy F; Neibergs, Holly L; Womack, James

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

  11. Nature of the a1(1420 )

    NASA Astrophysics Data System (ADS)

    Mikhasenko, M.; Ketzer, B.; Sarantsev, A.

    2015-05-01

    The resonancelike signal with axial-vector quantum numbers JP C=1++ at a mass of 1420 MeV and a width of 140 MeV, recently observed by the COMPASS and VES experiments in the f0(980 )π final state and tentatively called a1(1420 ), is discussed. Instead of a genuine new meson, we interpret this signal as a dynamical effect due to a singularity (branching point) in the triangle diagram formed by the processes a1(1260 )→K⋆K ¯, K⋆→K π , and K K ¯→f0(980 ) (+c .c ). The amplitude for this diagram is calculated. The result exhibits a peak in the intensity with a sharp phase motion with respect to the dominant a1(1260 )→ρ π S -wave decay, in good agreement with the data. The branching ratio of a1(1260 )→f0(980 )π via the triangle diagram is estimated and compared to the dominant decay a1(1260 )→ρ π .

  12. Methamphetamine Regulation of Sulfotransferase 1A1 and 2A1 Expression in Rat Brain Sections

    PubMed Central

    Zhou, Tianyan; Huang, Chaoqun; Chen, Yue; Xu, Jiaojiao; Shanbhag, Preeti Devaraya; Chen, Guangping

    2012-01-01

    Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7-days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum > frontal cortex, hippocampus > striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine. PMID:23026138

  13. Pneumococcal IgA1 protease subverts specific protection by human IgA1.

    PubMed

    Janoff, E N; Rubins, J B; Fasching, C; Charboneau, D; Rahkola, J T; Plaut, A G; Weiser, J N

    2014-03-01

    Bacterial immunoglobulin A1 (IgA1) proteases may sabotage the protective effects of IgA. In vitro, both exogenous and endogenously produced IgA1 protease inhibited phagocytic killing of Streptococcus pneumoniae by capsule-specific IgA1 human monoclonal antibodies (hMAbs) but not IgA2. These IgA1 proteases cleaved and reduced binding of the the effector Fcα1 heavy chain but not the antigen-binding F(ab)/light chain to pneumococcal surfaces. In vivo, IgA1 protease-resistant IgA2, but not IgA1 protease-sensitive IgA1, supported 60% survival in mice infected with wild-type S. pneumoniae. IgA1 hMAbs protected mice against IgA1 protease-deficient but not -producing pneumococci. Parallel mouse sera with human IgA2 showed more efficient complement-mediated reductions in pneumococci with neutrophils than did IgA1, particularly with protease-producing organisms. After natural human pneumococcal bacteremia, purified serum IgG inhibited IgA1 protease activity in 7 of 11 patients (64%). These observations provide the first evidence in vivo that IgA1 protease can circumvent killing of S. pneumoniae by human IgA. Acquisition of IgA1 protease-neutralizing IgG after infection directs attention to IgA1 protease both as a determinant of successful colonization and infection and as a potential vaccine candidate.

  14. Investigation of polymerase chain reaction assays to improve detection of bacterial involvement in bovine respiratory disease.

    PubMed

    Bell, Colin J; Blackburn, Paul; Elliott, Mark; Patterson, Tony I A P; Ellison, Sean; Lahuerta-Marin, Angela; Ball, Hywel J

    2014-09-01

    Bovine respiratory disease (BRD) causes severe economic losses to the cattle farming industry worldwide. The major bacterial organisms contributing to the BRD complex are Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Pasteurella multocida, and Trueperella pyogenes. The postmortem detection of these organisms in pneumonic lung tissue is generally conducted using standard culture-based techniques where the presence of therapeutic antibiotics in the tissue can inhibit bacterial isolation. In the current study, conventional and real-time polymerase chain reaction (PCR) assays were used to assess the prevalence of these 5 organisms in grossly pneumonic lung samples from 150 animals submitted for postmortem examination, and the results were compared with those obtained using culture techniques. Mannheimia haemolytica was detected in 51 cases (34%) by PCR and in 33 cases (22%) by culture, H. somni was detected in 35 cases (23.3%) by PCR and in 6 cases (4%) by culture, Myc. bovis was detected in 53 cases (35.3%) by PCR and in 29 cases (19.3%) by culture, P. multocida was detected in 50 cases (33.3%) by PCR and in 31 cases (20.7%) by culture, and T. pyogenes was detected in 42 cases (28%) by PCR and in 31 cases (20.7%) by culture, with all differences being statistically significant. The PCR assays indicated positive results for 111 cases (74%) whereas 82 cases (54.6%) were culture positive. The PCR assays have demonstrated a significantly higher rate of detection of all 5 organisms in cases of pneumonia in cattle in Northern Ireland than was detected by current standard procedures.

  15. 8 CFR 245a.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., if any, or (2) a crime treated as a misdemeanor under 8 CFR 245a.1(p). For purposes of this... CFR part 245a, the crime shall be treated as a misdemeanor. (q) Subject of an Order to Show Cause... English language competency, and attainment of these skills is measured either by successful completion...

  16. 38 CFR 8a.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 8a.1 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS VETERANS MORTGAGE LIFE... necessary land therefor, that has been or will be purchased, constructed, or remodeled with a grant to meet... eligible veteran as his or her home, or a family dwelling or unit, including the necessary land...

  17. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... which will be codified at 32 CFR part 168b. ... ENGINEERING GRADUATE FELLOWSHIPS § 168a.1 Purpose. This part: (a) Establishes guidelines for the award of National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191....

  18. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Employees at NASA's John C. Stennis Space Center complete installation of the new thrust measurement system on the A-1 Test Stand. The new TMS is a state-of-the-art upgrade from the previous system, which was installed when the testing structure was built in the 1960s. It is an advanced calibration system capable of measuring vertical and horizontal thrust loads with accuracy within 0.15 percent at 225,000 pounds. It also will allow engineers to measure thrust as they gimbal (or tilt) engines during tests. The new TMS is part of upgrades for the A-1 Test Stand in preparation for testing the next generation of American space program rocket engines.

  19. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    A new thrust measurement system is lifted onto the A-1 Test Stand deck at NASA's John C. Stennis Space Center in preparation for its installation. The new system is a state-of-the-art upgrade for the testing structure, which is being prepared for testing of next-generation rocket engines. The system was fabricated by Thrust Measurement Systems in Illinois at a cost of about $3.5 million.

  20. The nasopharyngeal microbiota of feedlot cattle that develop bovine respiratory disease.

    PubMed

    Holman, Devin B; McAllister, Tim A; Topp, Edward; Wright, André-Denis G; Alexander, Trevor W

    2015-10-22

    Bovine respiratory disease is the major cause of morbidity and mortality in feedlot cattle. The objective of this study was to compare the nasopharyngeal bacterial microbiota of healthy cattle and cattle treated for BRD in a commercial feedlot setting using a high-density 16S rRNA gene microarray (Phylochip). Samples were taken from both groups of animals (n=5) at feedlot entry (day 0) and ≥60 days after placement. Cattle diagnosed with BRD had significantly less bacterial diversity and fewer OTUs in their nasopharynx at both sampling times. The predominant phyla in both groups were Proteobacteria and Firmicutes. The relative abundance of the phylum Actinobacteria was lower in cattle treated for BRD. At the family-level there was a greater relative abundance (P<0.05) of Micrococcaceae (day 0 only), Lachnospiraceae (≥60 days), Lactobacillaceae (day 0), and Bacillaceae (day 0) in healthy cattle compared to BRD-affected cattle. The community structure of the BRD-affected and healthy cattle were also significantly different from each other at both sampling times as measured using unweighted UniFrac distances. All entry samples of cattle diagnosed with BRD had 16S rRNA gene sequences representative of the BRD-associated bacteria Mannheimia haemolytica or Pasteurella multocida, although 3/5 healthy cattle were also positive for M. haemolytica at this time point. The results also indicate that the bovine nasopharyngeal microbiota is relatively unstable during the first 60 days in the feedlot.

  1. A bighorn sheep die-off in southern Colorado involving a Pasteurellaceae strain that may have originated from syntopic cattle.

    PubMed

    Wolfe, Lisa L; Diamond, Brandon; Spraker, Terry R; Sirochman, Michael A; Walsh, Daniel P; Machin, Chandra M; Bade, Donald J; Miller, Michael W

    2010-10-01

    We investigated a pasteurellosis epizootic in free-ranging bighorn sheep (Ovis canadensis) wherein a Pasteurellaceae strain carried by syntopic cattle (Bos taurus) under severe winter conditions appeared to contribute to pneumonia in affected bighorns. Twenty-one moribund or dead bighorn sheep were found on the "Fossil Ridge" herd's winter range, Colorado, USA, between 13 December 2007 and 29 February 2008. Eight carcasses examined showed gross or microscopic evidence of acute to subacute fibrinous bronchopneumonia. All eight carcasses yielded at least one β-hemolytic Mannheimia haemolytica biogroup 1(±(G)) strain, and seven also yielded a β-hemolytic Bibersteinia trehalosi biogroup 4 (CDS) strain; evidence of Pasteurella multocida, Mycoplasma ovipneumoniae, and parainfluenza 3 and bovine respiratory syncytial viruses was also detected. Isolates of β-hemolytic Manneimia haemolytica biogroup 1(G) from a bighorn carcass and a syntopic cow showed 99.5% similarity in genetic fingerprints; B. trehalosi biogroup 4(CDS) isolates were ≥94.9% similar to an isolate from a nearby bighorn herd. Field and laboratory observations suggested that pneumonia in affected bighorns may have been caused by a combination of pathogens including two pathogenic Pasteurellaceae strains--one likely of cattle origin and one likely of bighorn origin--with infections in some cases perhaps exacerbated by other respiratory pathogens and severe weather conditions. Our and others' findings suggest that intimate interactions between wild sheep and cattle should be discouraged as part of a comprehensive approach to health management and conservation of North American wild sheep species.

  2. Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

    PubMed

    Grissett, G P; White, B J; Larson, R L

    2015-01-01

    Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure.

  3. The nasopharyngeal microbiota of feedlot cattle that develop bovine respiratory disease.

    PubMed

    Holman, Devin B; McAllister, Tim A; Topp, Edward; Wright, André-Denis G; Alexander, Trevor W

    2015-10-22

    Bovine respiratory disease is the major cause of morbidity and mortality in feedlot cattle. The objective of this study was to compare the nasopharyngeal bacterial microbiota of healthy cattle and cattle treated for BRD in a commercial feedlot setting using a high-density 16S rRNA gene microarray (Phylochip). Samples were taken from both groups of animals (n=5) at feedlot entry (day 0) and ≥60 days after placement. Cattle diagnosed with BRD had significantly less bacterial diversity and fewer OTUs in their nasopharynx at both sampling times. The predominant phyla in both groups were Proteobacteria and Firmicutes. The relative abundance of the phylum Actinobacteria was lower in cattle treated for BRD. At the family-level there was a greater relative abundance (P<0.05) of Micrococcaceae (day 0 only), Lachnospiraceae (≥60 days), Lactobacillaceae (day 0), and Bacillaceae (day 0) in healthy cattle compared to BRD-affected cattle. The community structure of the BRD-affected and healthy cattle were also significantly different from each other at both sampling times as measured using unweighted UniFrac distances. All entry samples of cattle diagnosed with BRD had 16S rRNA gene sequences representative of the BRD-associated bacteria Mannheimia haemolytica or Pasteurella multocida, although 3/5 healthy cattle were also positive for M. haemolytica at this time point. The results also indicate that the bovine nasopharyngeal microbiota is relatively unstable during the first 60 days in the feedlot. PMID:26249828

  4. Survey of marbofloxacin susceptibility of bacteria isolated from cattle with respiratory disease and mastitis in Europe.

    PubMed

    Kroemer, S; Galland, D; Guérin-Faublée, V; Giboin, H; Woehrlé-Fontaine, F

    2012-01-01

    A monitoring programme conducted in Europe since 1994 to survey the marbofloxacin susceptibility of bacterial pathogens isolated from cattle has established the susceptibility of bacterial strains isolated before any antibiotic treatment from bovine mastitis and bovine respiratory disease (BRD) cases between 2002 and 2008. Minimum inhibitory concentration (MIC) was determined by a standardised microdilution technique. For respiratory pathogens, Pasteurella multocida and Mannheimia haemolytica isolates (751 and 514 strains, respectively) were highly susceptible to marbofloxacin (MIC≤0.03 µg/ml for 77.39 per cent of the strains) and only 1.75 per cent of M haemolytica strains were resistant (MIC≥4 µg/ml). Histophilus somni isolates (73 strains) were highly susceptible to marbofloxacin (0.008 to 0.06 µg/ml). Mycoplasma bovis MIC (171 strains) ranged from 0.5 to 4 µg/ml. For mastitis pathogens, the majority of Escherichia coli isolates were highly susceptible to marbofloxacin (95.8 per cent of 617 strains). Staphylococcus aureus and coagulase-negative staphylococci (568 and 280 strains) had a homogenous population with MIC centred on 0.25 µg/ml. Streptococcus uberis and Streptococcus dysgalactiae (660 and 217 strains) were moderately susceptible with MIC centred on 1 µg/ml. Marbofloxacin MIC for these various pathogens appeared stable over the seven years of the monitoring programme and was similar to previously published MIC results.

  5. Cloning and comparison of bighorn sheep CD18 with that of domestic sheep, goats, cattle, humans and mice.

    PubMed

    Liu, Weiguo; Brayton, Kelly A; Lagerquist, John; Foreyt, William J; Srikumaran, Subramaniam

    2006-03-15

    Previously, we have shown that CD18, the beta-subunit of beta(2)-integrins, serves as a receptor for leukotoxin (Lkt) secreted by Mannheimia (Pasteurella) haemolytica on bovine leukocytes. Anti-CD18 monoclonal antibodies (mAbs) inhibit Lkt-induced cytolysis of bighorn sheep (Ovis canadensis) leukocytes suggesting that CD18 may serve as a receptor for Lkt on the leukocytes of this species as well. Confirmation of bighorn sheep CD18 as a receptor for Lkt, and elucidation of the enhanced Lkt-susceptibility of bighorn sheep polymorphonuclear leukocytes (PMNs), necessitates the cloning and sequencing of cDNA encoding bighorn sheep CD18. Hence, in this study we cloned and sequenced the cDNA encoding CD18 of bighorn sheep, and compared with that of other animal species. The cDNA of bighorn sheep CD18 has an open reading frame (ORF) of 2310bp. CD18 sequences obtained individually from peripheral blood mononuclear cells (PBMCs) and PMNs were identical to each other. Comparison of the deduced 770-amino acid sequence of CD18 of bighorn sheep with that of domestic sheep, goats, cattle, humans and mice revealed 99, 98, 95, 82 and 80% identity, respectively. Availability of cloned bighorn sheep CD18 cDNA should allow the molecular characterization of M. haemolytica Lkt-receptor interactions in bighorn sheep and other ruminants that are susceptible to this disease.

  6. Domestic sheep (Ovis aries) Pasteurellaceae isolates from diagnostic submissions to the Caine Veterinary Teaching Center (1990-2004).

    PubMed

    Miller, David S; Weiser, Glen C; Ward, Alton C S; Drew, Mark L; Chapman, Phillip L

    2011-06-01

    A retrospective study of Pasteurellaceae isolated from domestic sheep (Ovis aries) was conducted. The aim was to identify Pasteurellaceae present in animals that were clinically healthy and others with evidence of respiratory disease. The bacteria had been isolated from samples submitted to the University of Idaho Caine Veterinary Teaching Center as part of disease diagnostic testing. The 844 isolates identified mainly three species of Pasteurellaceae: Mannheimia haemolytica, Pasteurella multocida, and Pasteurella (Bibersteinia) trehalosi. A total of 114 biovariants were identified among these three species. Individual biovariants were identified 1-180 times. Two of those (M. haemolytica 1 and P. (B.) trehalosi 2) constituted 36% of the isolates, and were the only biovariants sufficiently numerous to account for >7% of the total isolates. Samples were primarily submitted from sheep with signs of respiratory disease. Eighty percent of biovariants were identified most often in animals with signs of respiratory disease, but 26% of biovariants were isolated from both sheep with respiratory disease and apparently healthy sheep. P. multocida constituted 4.7% of isolates, and were exclusively associated with animals with respiratory disease. The ability of isolates to produce beta-hemolysis on culture media was not associated with animals with respiratory disease (odds ratio 0.77, 95% CI 0.50-1.19). The inference of this study is limited due to the retrospective study design. However, it is the first study that provides an extensive baseline list of biovariants associated with respiratory disease in domestic sheep.

  7. PLC Software Program for Leak Detector Station A1 SALW-LD-ST-A1

    SciTech Connect

    KOCH, M.R.

    2001-01-25

    This document describes the software program for the programmable logic controller for the leak detector station ''SALW-LD-ST-A1''. The appendices contains a copy of the printout of the software program.

  8. An aetiopathological study of chronic bronchopneumonia in lambs in Ireland.

    PubMed

    Sheehan, Maresa; Cassidy, Joseph P; Brady, Joseph; Ball, Hywel; Doherty, Michael L; Quinn, Patrick J; Nicholas, Robin A J; Markey, Bryan K

    2007-05-01

    Chronic bronchopneumonia in lambs, also known as 'atypical' or 'chronic, non-progressive' pneumonia is a common, frequently sub-clinical disease affecting animals under 12-months-old in intensive production systems. Infection with both Mycoplasma ovipneumoniae and Mannheimia haemolytica have been implicated in the aetiology of this condition and a variety of pulmonary lesions can result. In this study, detailed laboratory examination of 30 abattoir-derived lungs with the characteristic gross features of atypical pneumonia (AP) was carried out with a view to refining and correlating the histopathological and microbiological criteria required for the diagnosis of this disease. For the first time a broad range of laboratory detection techniques including bacterial and virus isolation, fluorescent antibody tests and immunohistochemistry were used in parallel to identify potential causative pathogens such as M. ovipneumoniae, M. haemolytica, parainfluenza type-3 (PI3) virus and respiratory syncytial virus (RSV) in AP lesions. The most consistent finding was the association of gross AP lesions with M. ovipneumoniae, identified by either culture or immunohistochemistry in 27 (90%) of the 30 cases. However the presence M. ovipneumoniae organisms or antigen did not consistently correlate with particular histopathological changes. Furthermore, peri-airway lymphoid hyperplasia, intra-alveolar exudation and nodular 'hyaline scars', which are all previously reported microscopic lesions of AP, were not identified in 12 (40%) of the cases and isolation of M. haemolytica was over-represented in lungs exhibiting suppurative lesions. These findings illustrate the complex aetiopathogenesis of this disease and highlight the requirement to use a combination of diagnostic criteria in its laboratory diagnosis.

  9. A 1-D dusty plasma photonic crystal

    SciTech Connect

    Mitu, M. L.; Ticoş, C. M.; Toader, D.; Banu, N.; Scurtu, A.

    2013-09-21

    It is demonstrated numerically that a 1-D plasma crystal made of micron size cylindrical dust particles can, in principle, work as a photonic crystal for terahertz waves. The dust rods are parallel to each other and arranged in a linear string forming a periodic structure of dielectric-plasma regions. The dispersion equation is found by solving the waves equation with the boundary conditions at the dust-plasma interface and taking into account the dielectric permittivity of the dust material and plasma. The wavelength of the electromagnetic waves is in the range of a few hundred microns, close to the interparticle separation distance. The band gaps of the 1-D plasma crystal are numerically found for different types of dust materials, separation distances between the dust rods and rod diameters. The distance between levitated dust rods forming a string in rf plasma is shown experimentally to vary over a relatively wide range, from 650 μm to about 1350 μm, depending on the rf power fed into the discharge.

  10. An evaluation of the relative efficacy of tulathromycin for the treatment of undifferentiated fever in feedlot calves in Nebraska

    PubMed Central

    Schunicht, Oliver C.; Booker, Calvin W.; Guichon, P. Timothy; Jim, G. Kee; Wildman, Brian K.; Pittman, Tom J.; Perrett, Tye

    2007-01-01

    A field trial was performed under commercial feedlot conditions in central Nebraska to assess the relative efficacy of tulathromycin (TULA) to florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in feedlot calves that did not receive a metaphylactic antimicrobial or vaccines/bacterins containing Mannheimia haemolytica or Histophilus somni at feedlot arrival by comparing animal health, feedlot performance, and carcass characteristic variables. Two hundred recently weaned, auction market derived, crossbred beef calves that met the study-specific case definition of UF were randomly allocated in a 1:1 ratio to 1 of 2 experimental groups as follows: TULA, which received tulathromycin administered subcutaneously at the rate of 2.5 mg/kg body weight (BW) once at the time of allocation; or FLOR, which received florfenicol administered subcutaneously at the rate of 40 mg/kg BW once at the time of allocation. In terms of animal health, the first UF relapse (RR = 0.65), overall mortality (RR = 0.33), and BRD mortality (RR = 0.29) rates in the TULA group were significantly (P < 0.05) lower than in the FLOR group. There were no significant (P = 0.05) differences between the TULA and FLOR groups for the other animal health variables measured. There was no significant (P ≥ 0.05) difference in average daily gain between the TULA and FLOR groups. There were no significant (P ≥ 0.05) differences in the overall distributions of quality grade and yield grade between the experimental groups; however, a significantly (P < 0.05) higher proportion of carcasses in the TULA group graded yield grade USDA-4 as compared with the FLOR group. In the economic analysis, the benefits observed resulted in an economic advantage of $52.50 USD/animal in the TULA group due to lower first UF relapse and overall mortality rates, even though the occurrence of yield grade USDA-4 carcasses increased and the initial UF treatment cost was higher. PMID:17616056

  11. Architecture for a 1-GHz Digital RADAR

    NASA Technical Reports Server (NTRS)

    Mallik, Udayan

    2011-01-01

    An architecture for a Direct RF-digitization Type Digital Mode RADAR was developed at GSFC in 2008. Two variations of a basic architecture were developed for use on RADAR imaging missions using aircraft and spacecraft. Both systems can operate with a pulse repetition rate up to 10 MHz with 8 received RF samples per pulse repetition interval, or at up to 19 kHz with 4K received RF samples per pulse repetition interval. The first design describes a computer architecture for a Continuous Mode RADAR transceiver with a real-time signal processing and display architecture. The architecture can operate at a high pulse repetition rate without interruption for an infinite amount of time. The second design describes a smaller and less costly burst mode RADAR that can transceive high pulse repetition rate RF signals without interruption for up to 37 seconds. The burst-mode RADAR was designed to operate on an off-line signal processing paradigm. The temporal distribution of RF samples acquired and reported to the RADAR processor remains uniform and free of distortion in both proposed architectures. The majority of the RADAR's electronics is implemented in digital CMOS (complementary metal oxide semiconductor), and analog circuits are restricted to signal amplification operations and analog to digital conversion. An implementation of the proposed systems will create a 1-GHz, Direct RF-digitization Type, L-Band Digital RADAR--the highest band achievable for Nyquist Rate, Direct RF-digitization Systems that do not implement an electronic IF downsample stage (after the receiver signal amplification stage), using commercially available off-the-shelf integrated circuits.

  12. HDL/ApoA-1 infusion and ApoA-1 gene therapy in atherosclerosis

    PubMed Central

    Chyu, Kuang-Yuh; Shah, Prediman K.

    2015-01-01

    The HDL hypothesis stating that simply raising HDL cholesterol (HDL-C) may produce cardiovascular benefits has been questioned recently based on several randomized clinical trials using CETP inhibitors or niacin to raise HDL-C levels. However, extensive pre-clinical data support the vascular protective effects of administration of exogenous ApoA-1 containing preβ-HDL like particles. Several small proof-of-concept clinical trials using such HDL/ApoA-1 infusion therapy have shown encouraging results but definitive proof of efficacy must await large scale clinical trials. In addition to HDL infusion therapy an alternative way to exploit beneficial cardiovascular effects of HDL/ApoA-1 is to use gene transfer. Preclinical studies have shown evidence of benefit using this approach; however clinical validation is yet lacking. This review summarizes our current knowledge of the aforementioned strategies. PMID:26388776

  13. STS payloads mission control study phase A-1, volume 1, phases A and A-1

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The Space Transportation System (STS) Payloads Mission Control Phase A-1 Study results are summarized. The composite resources required to accomplish Joint STS-Payload preflight preparation for joint flight operations, including flight planning, training, and simulations are presented. The Standard Payload Operations Control Center (POCC) concept was developed.

  14. Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia

    PubMed Central

    Teh, L. K.; Hashim, H.; Zakaria, Z. A.; Salleh, M. Z.

    2012-01-01

    Background & objectives: Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). Methods: A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*6, UGT1A1*27 and UGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Results: Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). Interpretation & conclusions: There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction. PMID:22960892

  15. 26 CFR 1.666(a)-1 - Amount allocated.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Amount allocated. 1.666(a)-1 Section 1.666(a)-1... Beginning Before January 1, 1969 § 1.666(a)-1 Amount allocated. (a)(1) If a trust other than a foreign trust... had the following amounts of undistributed net income: Year Undistributed net income—portion of...

  16. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties....

  17. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties....

  18. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties....

  19. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties....

  20. Diagnostics for a 1.2 kA, 1 MeV electron induction injector

    SciTech Connect

    Houck, T.L.; Anderson, D.E.; Eylon, S.; Henestroza, E.; Lidia, S.M.; Vanecek, D.L.; Westenskow, G.A.; Yu, S.S.

    1998-05-11

    We are constructing a 1.2-kA, 1-MeV, electron induction injector as part of the RTA program, a collaborative effort between LLNL and LBNL to develop relativistic klystrons for Two-Beam Accelerator applications. The RTA injector will also be used in the development of a high-gradient, low-emittance, electron source and beam diagnostics for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility. The electron source will be a 3.5``-diameter, thermionic, flat-surface, m-type cathode with a maximum shroud field stress of approximately 165 kV/cm. Additional design parameters for the injector include a pulse length of over 150-ns flat top (1% energy variation), and a normalized edge emittance of less than 200 {pi}-mm-mr. Precise measurement of the beam parameters is required so that performance of the RTA injector can be confidently scaled to the 4-kA, 3-MeV, and 2-microsecond pulse parameters of the DARHT injector. Planned diagnostics include an isolated cathode with resistive divider for direct measurement of current emission, resistive wall and magnetic probe current monitors for measuring beam current and centroid position, capacitive probes for measuring A-K gap voltage, an energy spectrometer, and a pepper-pot emittance diagnostic. Details of the injector, beam line, and diagnostics are presented.

  1. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice.

    PubMed

    Lassen, Natalie; Bateman, J Bronwyn; Estey, Tia; Kuszak, Jer R; Nees, David W; Piatigorsky, Joram; Duester, Gregg; Day, Brian J; Huang, Jie; Hines, Lisa M; Vasiliou, Vasilis

    2007-08-31

    ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1- and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life (6-9 months of age). One- to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(-/-) and Aldh3a1(-/-)/Aldh1a1(-/-) mice compared with Aldh1a1(-/-) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal- and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic (light filtering) and enzymatic (detoxification) functions. PMID:17567582

  2. Lattice equations arising from discrete Painlevé systems. I. (A2 + A1)(1) and ( A 1 + A1 ' ) ( 1 ) cases

    NASA Astrophysics Data System (ADS)

    Joshi, Nalini; Nakazono, Nobutaka; Shi, Yang

    2015-09-01

    We introduce the concept of ω-lattice, constructed from τ functions of Painlevé systems, on which quad-equations of ABS (Adler-Bobenko-Suris) type appear. In particular, we consider the A5 ( 1 ) - and A6 ( 1 ) -surface q-Painlevé systems corresponding affine Weyl group symmetries are of (A2 + A1)(1)- and (A1 + A1)(1)-types, respectively.

  3. 26 CFR 1.501(a)-1 - Exemption from taxation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a)...

  4. 26 CFR 1.501(a)-1 - Exemption from taxation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a)...

  5. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Windchill Chart A Appendix A-1 to...

  6. [UGT1A1 Genotyping for Proper Use of Irinotecan].

    PubMed

    Matsuoka, Ayumu; Ando, Yuichi

    2015-07-01

    Irinotecan is a camptothecin analog used worldwide for a broad range of solid tumors, including colorectal and lung cancers. It can cause severe adverse drug reactions, such as neutropenia or diarrhea. Irinotecan is metabolized to form active SN-38, which is further conjugated and detoxified by the UDP-glucuronosyltransferase (UGT) 1A1 enzyme. Recent pharmacogenetic studies on irinotecan have revealed the impact of UGT1A1 polymorphisms on severe adverse effects. A variant in the promoter of the UGT1A1 gene, the UGT1A1 *28 allele, has been extensively studied, and pharmacogenetic relationships between the variant and severe toxicities of irinotecan have been reported. The US FDA and pharmaceutical companies revised the irinotecan label in 2005, and it now includes homozygosity for the UGT1A1*28 genotype as one of the risk factors for severe neutropenia. A variant in exon 1 of the UGT1A1 gene, the UGT1A1*6 allele, mainly found in East Asians, is also an important risk factor associated with severe neutropenia. The concurrence of UGT1A1*28 and UGT1A1*6, even when heterozygous, markedly alters the disposition of irinotecan, potentially increasing toxicity, which is now written on the label of irinotecan in Japan. For patients showing homozygosity for UGT1A1*28, *6, or compound heterozygosity for UGT1A1*6 and *28, dose reduction of irinotecan is strongly recommended. Genotyping tests for UGT1A1 *6 and *28 have been approved in Japan and are currently used in oncology practice. Moreover, a recent Phase 2 trial for FOLFIRINOX in Japan excluded patients who showed homozygosity for UGT1A1*28, *6, or compound heterozygosity for UGT1A1*6 and *28. At present, irinotecan chemotherapy based on a patient's UGT1A1 genetic status is scientifically reasonable. PMID:26591441

  7. Accurate identification of UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors using UGT1A1-overexpressing HeLa cells.

    PubMed

    Sun, Hua; Zhou, Xiaotong; Wu, Baojian

    2015-01-01

    1. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays an irreplaceable role in detoxification of bilirubin and many drugs (e.g., SN-38). Here we aimed to explore the potential of UGT1A1-overexpressing HeLa cells (or HeLa1A1 cells) as a tool to accurately identify UGT1A1 inhibitors. 2. Determination of glucuronidation rates (β-estradiol and SN-38 as the substrates) was performed using HeLa1A1 cells and uridine diphosphoglucuronic acid (UDPGA)-supplemented cDNA expressed UGT1A1 enzyme (or microsomes). The inhibitory effects (IC50 values) of 20 structurally diverse compounds on the UGT1A1 activity were determined using HeLa1A1 cells and microsomal incubations. 3. In HeLa1A1 cells, the IC50 values for inhibition of β-estradiol glucuronidation by the tested compounds ranged from 0.33 to 94.6 µM. In the microsomal incubations, the IC50 values ranged from 0.47 to 155 µM. It was found that the IC50 values of all test compounds derived from the cells were well consistent with those from the microsomes (deviated by less than two-fold). Further, the IC50 values from the cells were strongly correlated with those from microsomes (r = 0.944, p < 0.001). Likewise, the IC50 values (0.37-77.3 µM) for inhibition of SN-38 glucuronidation in the cells were close to those (0.42-122 µM) for glucuronidation inhibition in microsomes. A strong correlation was also observed between the two sets of IC50 values (r = 0.978, p < 0.001). 4. In conclusion, UGT1A1-overexpressing HeLa cells were an appropriate tool to accurately depict the inhibition profiles of chemicals against UGT1A1. PMID:26068529

  8. Pioneer oral streptococci produce immunoglobulin A1 protease.

    PubMed Central

    Cole, M F; Evans, M; Fitzsimmons, S; Johnson, J; Pearce, C; Sheridan, M J; Wientzen, R; Bowden, G

    1994-01-01

    As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat. Images PMID:8188337

  9. Methods for Tumor Targeting with Salmonella typhimurium A1-R.

    PubMed

    Hoffman, Robert M; Zhao, Ming

    2016-01-01

    Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor-targeting bacteria, as well. Imaging methods are described to visualize GFP-labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies. PMID:26846809

  10. An abundant dysfunctional apolipoprotein A1 in human atheroma

    PubMed Central

    Huang, Ying; DiDonato, Joseph A.; Levison, Bruce S.; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary; Gu, Xiaodong; Kadiyala, Chandra; Wang, Zeneng; Culley, Miranda K.; Hazen, Jennie E.; DiDonato, Anthony J.; Fu, Xiaoming; Berisha, Stela; Peng, Daoquan; Nguyen, Truc; Liang, Shaohong; Chuang, Chia-Chi; Cho, Leslie; Plow, Edward F.; Fox, Paul L.; Gogonea, Valentin; Tang, W.H. Wilson; Parks, John S.; Fisher, Edward A.; Smith, Jonathan D.; Hazen, Stanley L.

    2014-01-01

    Recent studies indicate high density lipoproteins (HDL) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma, are dysfunctional and extensively oxidized by myeloperoxidase (MPO), while in vitro oxidation of apoA1/HDL by MPO impairs its cholesterol acceptor function. We developed a high affinity monoclonal antibody (mAb) that specifically recognizes apoA1/HDL modified by the MPO/H2O2/Cl-system using phage display affinity maturation. An oxindolyl alanine (2-OH-Trp) moiety at tryptophan 72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirm a critical role for apoA1 Trp72 in MPO-mediated inhibition of ABCA1-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation, but accounts for 20% of the apoA1 in atherosclerotic plaque. OxTrp72-apoA1 recovered from human atheroma or plasma was lipid-poor, virtually devoid of cholesterol acceptor activity, and demonstrated both potent pro-inflammatory activities on endothelial cells and impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n=627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a pro-atherogenic process in the artery wall. PMID:24464187

  11. 26 CFR 1.666(a)-1A - Amount allocated.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Amount allocated. 1.666(a)-1A Section 1.666(a... Beginning Before January 1, 1969 § 1.666(a)-1A Amount allocated. (a) In general. In the case of a trust that....665(e)-1A(a)(1)(ii) as those beginning after December 31, 1968) according to the amount...

  12. Evidence for charged B meson decays to a1+/-(1260)pi0 and a1(0)(1260)pi+/-.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Ronan, M T; Tackmann, K; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Schroeder, T; Steinke, M; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Losecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; D'Orazio, A; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Roethel, W; Wilson, F F; Aleksan, R; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hryn'ova, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Pappagallo, M; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-12-31

    We present measurements of the branching fractions for the decays B;{+/-}-->a_{1};{+/-}(1260)pi;{0} and B;{+/-}-->a_{1};{0}(1260)pi;{+/-} from a data sample of 232x10;{6} BB[over ] pairs produced in e;{+}e;{-} annihilation through the Upsilon(4S) resonance. We measure the branching fraction B(B;{+/-}-->a_{1};{+/-}(1260)pi;{0})xB(a_{1};{+/-}(1260)-->pi;{-}pi;{+}pi;{+/-})=(13.2+/-2.7+/-2.1)x10;{-6} with a significance of 4.2sigma, and the branching fraction B(B;{+/-}-->a_{1};{0}(1260)pi;{+/-})xB(a_{1};{0}(1260)-->pi;{-}pi;{+}pi;{0})=(20.4+/-4.7+/-3.4)x10;{-6} with a significance of 3.8sigma, where the first error quoted is statistical and the second is systematic. PMID:18233566

  13. Observation and polarization measurement of B0→a1(1260)+a1(1260)- decay

    NASA Astrophysics Data System (ADS)

    Aubert, B.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.; Tackmann, K.; Tanabe, T.; Hawkes, C. M.; Soni, N.; Watson, A. T.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Fulsom, B. G.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Barrett, M.; Khan, A.; Randle-Conde, A.; Blinov, V. E.; Bukin, A. D.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Bondioli, M.; Curry, S.; Eschrich, I.; Kirkby, D.; Lankford, A. J.; Lund, P.; Mandelkern, M.; Martin, E. C.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Yasin, Z.; Sharma, V.; Campagnari, C.; Hong, T. M.; Kovalskyi, D.; Mazur, M. A.; Richman, J. D.; Beck, T. W.; Eisner, A. M.; Heusch, C. A.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Wang, L.; Winstrom, L. O.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Fang, F.; Hitlin, D. G.; Narsky, I.; Ongmongkolkul, P.; Piatenko, T.; Porter, F. C.; Andreassen, R.; Mancinelli, G.; Meadows, B. T.; Mishra, K.; Sokoloff, M. D.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Hirschauer, J. F.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Wilson, R. J.; Feltresi, E.; Hauke, A.; Jasper, H.; Karbach, T. M.; Merkel, J.; Petzold, A.; Spaan, B.; Wacker, K.; Kobel, M. J.; Nogowski, R.; Schubert, K. R.; Schwierz, R.; Volk, A.; Bernard, D.; Latour, E.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Andreotti, M.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cecchi, A.; Cibinetto, G.; Fioravanti, E.; Franchini, P.; Luppi, E.; Munerato, M.; Negrini, M.; Petrella, A.; Piemontese, L.; Santoro, V.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Tosi, S.; Chaisanguanthum, K. S.; Morii, M.; Adametz, A.; Marks, J.; Schenk, S.; Uwer, U.; Bernlochner, F. U.; Klose, V.; Lacker, H. M.; Bard, D. J.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Charles, M. J.; Mallik, U.; Cochran, J.; Crawley, H. B.; Dong, L.; Eyges, V.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gao, Y. Y.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Béquilleux, J.; D'Orazio, A.; Davier, M.; Derkach, D.; Firmino da Costa, J.; Grosdidier, G.; Le Diberder, F.; Lepeltier, V.; Lutz, A. M.; Malaescu, B.; Pruvot, S.; Roudeau, P.; Schune, M. H.; Serrano, J.; Sordini, V.; Stocchi, A.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Burke, J. P.; Chavez, C. A.; Fry, J. R.; Gabathuler, E.; Gamet, R.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; Clarke, C. K.; di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Wren, A. C.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; West, T. J.; Yi, J. I.; Anderson, J.; Chen, C.; Jawahery, A.; Roberts, D. A.; Simi, G.; Tuggle, J. M.; Dallapiccola, C.; Salvati, E.; Cowan, R.; Dujmic, D.; Fisher, P. H.; Henderson, S. W.; Sciolla, G.; Spitznagel, M.; Yamamoto, R. K.; Zhao, M.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Gandini, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Bauer, J. M.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Zhao, H. W.; Simard, M.; Taras, P.; Nicholson, H.; de Nardo, G.; Lista, L.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; Losecco, J. M.; Wang, W. F.; Corwin, L. A.; Honscheid, K.; Kagan, H.; Kass, R.; Morris, J. P.; Rahimi, A. M.; Regensburger, J. J.; Sekula, S. J.; Wong, Q. K.; Blount, N. L.; Brau, J.; Frey, R.; Igonkina, O.; Kolb, J. A.; Lu, M.; Rahmat, R.; Sinev, N. B.; Strom, D.; Strube, J.; Torrence, E.; Castelli, G.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Voci, C.; Del Amo Sanchez, P.; Ben-Haim, E.; Bonneaud, G. R.; Briand, H.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Perez, A.; Prendki, J.; Sitt, S.; Gladney, L.; Biasini, M.; Manoni, E.; Angelini, C.; Batignani, G.; Bettarini, S.; Calderini, G.; Carpinelli, M.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Morganti, M.; Neri, N.; Paoloni, E.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Baracchini, E.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Jackson, P. D.; Li Gioi, L.; Mazzoni, M. A.; Morganti, S.; Piredda, G.; Renga, F.; Voena, C.; Ebert, M.; Hartmann, T.; Schröder, H.; Waldi, R.; Adye, T.; Franek, B.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Esteve, L.; de Monchenault, G. Hamel; Kozanecki, W.; Vasseur, G.; Yèche, Ch.; Zito, M.; Allen, M. T.; Aston, D.; Bartoldus, R.; Benitez, J. F.; Cenci, R.; Coleman, J. P.; Convery, M. R.; Dingfelder, J. C.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Field, R. C.; Franco Sevilla, M.; Gabareen, A. M.; Graham, M. T.; Grenier, P.; Hast, C.; Innes, W. R.; Kaminski, J.; Kelsey, M. H.; Kim, H.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Li, S.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; Macfarlane, D. B.; Marsiske, H.; Messner, R.; Muller, D. R.; Neal, H.; Nelson, S.; O'Grady, C. P.; Ofte, I.; Perl, M.; Ratcliff, B. N.; Roodman, A.; Salnikov, A. A.; Schindler, R. H.; Schwiening, J.; Snyder, A.; Su, D.; Sullivan, M. K.; Suzuki, K.; Swain, S. K.; Thompson, J. M.; Va'Vra, J.; Wagner, A. P.; Weaver, M.; West, C. A.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Yarritu, A. K.; Young, C. C.; Ziegler, V.; Chen, X. R.; Liu, H.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Burchat, P. R.; Edwards, A. J.; Miyashita, T. S.; Ahmed, S.; Alam, M. S.; Ernst, J. A.; Pan, B.; Saeed, M. A.; Zain, S. B.; Soffer, A.; Spanier, S. M.; Wogsland, B. J.; Eckmann, R.; Ritchie, J. L.; Ruland, A. M.; Schilling, C. J.; Schwitters, R. F.; Wray, B. C.; Drummond, B. W.; Izen, J. M.; Lou, X. C.; Bianchi, F.; Gamba, D.; Pelliccioni, M.; Bomben, M.; Bosisio, L.; Cartaro, C.; Della Ricca, G.; Lanceri, L.; Vitale, L.; Azzolini, V.; Lopez-March, N.; Martinez-Vidal, F.; Milanes, D. A.; Oyanguren, A.; Albert, J.; Banerjee, Sw.; Bhuyan, B.; Choi, H. H. F.; Hamano, K.; King, G. J.; Kowalewski, R.; Lewczuk, M. J.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Gershon, T. J.; Harrison, P. F.; Ilic, J.; Latham, T. E.; Mohanty, G. B.; Puccio, E. M. T.; Band, H. R.; Chen, X.; Dasu, S.; Flood, K. T.; Pan, Y.; Prepost, R.; Vuosalo, C. O.; Wu, S. L.

    2009-11-01

    We present measurements of the branching fraction B and longitudinal polarization fraction fL for B0→a1(1260)+a1(1260)- decays, with a1(1260)±→π-π+π±. The data sample, collected with the BABAR detector at the SLAC National Accelerator Laboratory, represents 465×106 produced BB¯ pairs. We measure B(B0→a1(1260)+a1(1260)-)×[B(a1(1260)+→π-π+π+)]2=(11.8±2.6±1.6)×10-6 and fL=0.31±0.22±0.10, where the first uncertainty is statistical and the second systematic. The decay mode is measured with a significance of 5.0 standard deviations including systematic uncertainties.

  14. 26 CFR 31.6402(a)-1 - Credits or refunds.

    Code of Federal Regulations, 2010 CFR

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    Code of Federal Regulations, 2011 CFR

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    Code of Federal Regulations, 2014 CFR

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    Code of Federal Regulations, 2012 CFR

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    Code of Federal Regulations, 2010 CFR

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  11. Observation of B+-->a1+(1260)K0 and B0-->a1-(1260)K+.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Bailey, D; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2008-02-01

    We present branching fraction measurements of the decays B(+)-->a(1)(+)(1260)K(0) and B(0)-->a(1)(-)(1260)K(+) with a(1)(+/-)(1260)-->pi(-/+)pi(+/-)pi(+/-). The data sample corresponds to 383 x 10(6) BB pairs produced in e(+)e(-) annihilation through the Upsilon(4S) resonance. We measure the products of the branching fractions B(B(+)-->a(1)(+)(1260)K(0)B(a(1)(+)(1260)-->pi(-)pi(+)pi(+))=(17.4+/-2.5+/-2.2) x 10(-6) and B(B(0)-->a(1)(-)(1260)K(+)B(a(1)(-)(1260)-->pi(+)pi(-)pi(-)) = (8.2+/-1.5+/-1.2) x 10(-6). We also measure the charge asymmetries A(ch)(B(+)-->a(1)(+)(1260)K(0) = 0.12+/-0.11+/-0.02 and A(ch)(B(0)-->a(1)(-)(1260)K+) = -0.16+/-0.12+/-0.01. The first uncertainty quoted is statistical and the second is systematic. PMID:18352360

  12. Tumor-Targeting Salmonella typhimurium A1-R: An Overview.

    PubMed

    Hoffman, Robert M

    2016-01-01

    The present chapter reviews the development of the tumor-targeting amino-acid auxotrophic strain S. typhimurium A1 and the in vivo selection and characterization of the high-tumor-targeting strain S. typhimurium A1-R. Efficacy of S. typhimurium A1-R in nude-mouse models of prostate, breast, pancreatic, and ovarian cancer, as well as sarcoma and glioma in orthotopic mouse models is described. Also reviewed is efficacy of S. typhimurium A1-R targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma, breast-cancer brain metastasis, and experimental breast-cancer bone metastasis in orthotopic mouse models. The efficacy of S. typhimurium A1-R on pancreatic cancer stem cells, on pancreatic cancer in combination with anti-angiogenic agents, as well as on cervical cancer, soft-tissue sarcoma, and pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse models, is also described.

  13. Aldehyde dehydrogenase 1A1 in stem cells and cancer

    PubMed Central

    Tomita, Hiroyuki; Tanaka, Kaori; Tanaka, Takuji; Hara, Akira

    2016-01-01

    The human genome contains 19 putatively functional aldehyde dehydrogenase (ALDH) genes, which encode enzymes critical for detoxification of endogenous and exogenous aldehyde substrates through NAD(P)+-dependent oxidation. ALDH1 has three main isotypes, ALDH1A1, ALDH1A2, and ALDH1A3, and is a marker of normal tissue stem cells (SC) and cancer stem cells (CSC), where it is involved in self-renewal, differentiation and self-protection. Experiments with murine and human cells indicate that ALDH1 activity, predominantly attributed to isotype ALDH1A1, is tissue- and cancer-specific. High ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis, though high ALDH1 and ALDH1A1 levels do not always correlate with highly malignant phenotypes and poor clinical outcome. In cancer therapy, ALDH1A1 provides a useful therapeutic CSC target in tissue types that normally do not express high levels of ALDH1A1, including breast, lung, esophagus, colon and stomach. Here we review the functions and mechanisms of ALDH1A1, the key ALDH isozyme linked to SC populations and an important contributor to CSC function in cancers, and we outline its potential in future anticancer strategies. PMID:26783961

  14. [Glycosylated hemoglobin (HbA1) in pregnancy].

    PubMed

    Partida Hernández, G; Gómez García, A; Arreola Ortíz, J F

    2000-10-01

    The life style, genetic predisposition and metabolic changes occurring during pregnancy can modify the percent value of glycated hemoglobins (HbA1 and HbA1c). In addition, research papers from different laboratories in the world have reported contradictory results on this respect. The purpose of this trial was to know the percent value of HbA1 in healthy women, during the different trimesters of pregnancy. 206 pregnant (E) healthy women who came over for prenatal control to UMF No 80 IMSS in Morelia, Michoacan with no previous history of Diabetes mellitus or Essential Hypertension were classified by trimesters of pregnancy (1T, 2T, 3T) and chronological age (I, 18-24; 11, 25-30; III, 31-35 years). Their chronological and gestational ages, weight, height, body mass index and parity were recorded. % HbA1 (ion exchange chromatography) was determined on each patient. Control group was formed by 187 non pregnant healthy women (NE) chosen with same criterion that pregnant women. % HbA1 was lower in E during pregnancy (7.11 +/- 1.53 vs 7.78 +/- 1.12%, p < 0.0001) than NE group. % HbA1 in E group was lower in the 1T and 2T than in the 3T (p < 0.001), same situation was observed in 18 to 24 (group I) and 25 to 30 (group II) years old. In the other hand, in E from group II on the 2T the weeks of gestation were correlated with % HbA1 (r = 0.72, p < 0.05). This results show a diminished HbA1 percent in E group with a lower values in the 1T and 2T. Moreover, these results will allow us to know HbA1 appearance in diabetic pregnant women and to evaluate the degree of metabolic control.

  15. Selecting an A1C Point-of-Care Instrument

    PubMed Central

    Yong, Ee Vonn; Rasinen, Casey

    2015-01-01

    A1C point-of-care (POC) instruments benefit patients with diabetes by facilitating clinician decision making that results in significant glycemic improvements. Three National Glycohemoglobin Standardization Program (NGSP)–certified POC products are available in the United States: the handheld A1CNow (formerly manufactured by Bayer Diabetes Care but now made by Chek Diagnostics) and two bench-top models called the Axis-Shield Afinion Analyzer and the Siemens DCA Vantage. This article compares the three available NGSP-certified POC products in terms of accuracy, precision, ease of use, cost, and additional features. Its goal is to aid health care facilities in conveniently identifying the A1C POC product that best meets their needs. It additionally reviews evidence that supports the continued use of A1C POC instruments in the clinical arena. PMID:26300614

  16. 26 CFR 48.4222(a)-1 - Registration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Exemptions, Registration, Etc. § 48.4222(a)-1... section of the regulations, tax-free sales may not be made, except as indicated in § 48.4222(b)-1....

  17. A 1K Shadow RAM for circumvention applications

    SciTech Connect

    Murray, J.R.

    1991-01-01

    A 1K bit Shadow RAM has been developed for storage of critical data in a high transient radiation environment. The circuit includes a 1K bit (128 {times} 8) static RAM with two non-volatile (NV) shadows. The NV shadows are used to back-up the data in the static RAM allowing the circuit to be powered down during transient radiation without losing critical data. This paper will describe the circuit's operation and characterization results.

  18. Aldehyde dehydrogenase 7A1 (ALDH7A1) attenuates reactive aldehyde and oxidative stress induced cytotoxicity

    PubMed Central

    Brocker, Chad; Cantore, Miriam; Failli, Paola; Vasiliou, Vasilis

    2012-01-01

    Mammalian aldehyde dehydrogenase 7A1 (ALDH7A1) is homologous to plant ALDH7B1 which protects against various forms of stress such as increased salinity, dehydration and treatment with oxidants or pesticides. Deleterious mutations in human ALDH7A1 are responsible for pyridoxine-dependent and folinic acid-responsive seizures. In previous studies, we have shown that human ALDH7A1 protects against hyperosmotic stress presumably through the generation of betaine, an important cellular osmolyte, formed from betaine aldehyde. Hyperosmotic stress is coupled to an increase in oxidative stress and lipid peroxidation (LPO). In this study, cell viability assays revealed that stable expression of mitochondrial ALDH7A1 in Chinese hamster ovary (CHO) cells provides significant protection against treatment with the LPO-derived aldehydes hexanal and 4-hydroxy-2-nonenal (4HNE) implicating a protective function for the enzyme during oxidative stress. A significant increase in cell survival was also observed in CHO cells expressing either mitochondrial or cytosolic ALDH7A1 treated with increasing concentrations of hydrogen peroxide (H2O2) or 4HNE, providing further evidence for anti-oxidant activity. In vitro enzyme activity assays indicate that human ALDH7A1 is sensitive to oxidation and that efficiency can be at least partially restored by incubating recombinant protein with the thiol reducing agent β-mercaptoethanol (BME). We also show that after reactivation with BME, recombinant ALDH7A1 is capable of metabolizing the reactive aldehyde 4HNE. In conclusion, ALDH7A1 mechanistically appears to provide cells protection through multiple pathways including the removal of toxic LPO-derived aldehydes in addition to osmolyte generation. PMID:21338592

  19. Nuclear receptor 4A1 (NR4A1) as a drug target for treating rhabdomyosarcoma (RMS)

    PubMed Central

    Lacey, Alexandra; Hedrick, Erik; Li, Xi; Patel, Ketan; Doddapaneni, Ravi; Singh, Mandip; Safe, Stephen

    2016-01-01

    The orphan nuclear receptor NR4A1 is expressed in tumors from rhabdomyosarcoma (RMS) patients and Rh30 and RD RMS cell lines, and we used RNA interference (RNAi) to investigate the role of this receptor in RMS cells. Knockdown of NR4A1 in Rh30 cells decreased cell proliferation, induced Annexin V staining and induced polyADPribose polymerase (PARP) cleavage and these results were similar to those observed in other solid tumors. Previous studies show that NR4A1 regulates expression of growth promoting/pro-survival genes with GC-rich promoters, activates mTOR through suppression of p53, and maintains low oxidative stress by regulating expression of isocitrate dehydrogenase 1 (IDH1) and thioredoxin domain containing 5 (TXNDC5). Results of RNAi studies demonstrated that NR4A1 also regulates these pathways and associated genes in RMS cells and thereby exhibits pro-oncogenic activity. 1,1-Bis(3-indolyl)-1-(p-substituted phenyl)methane (C-DIM) analogs containing p-hydroxyl (DIM-C-pPhOH) and p-carboxymethyl (DIM-C-pPhCO2Me) substituents are NR4A1 ligands that decreased NR4A1-dependent transactivation in RMS cells and inhibited RMS cell and tumor growth and induced apoptosis. Moreover, the effects of NR4A1 knockdown and the C-DIM/NR4A1 antagonists were comparable as inhibitors of NR4A1-dependent genes/pathways. Both NR4A1 knockdown and treatment with DIM-C-pPhOH and DIM-C-pPhCO2Me also induced ROS which activated stress genes and induced sestrin 2 which activated AMPK and inhibited mTOR in the mutant p53 RMS cells. Since NR4A1 regulates several growth-promoting/pro-survival pathways in RMS, the C-DIM/NR4A1 antagonists represent a novel mechanism-based approach for treating this disease alone or in combination and thereby reducing the adverse effects of current cytotoxic therapies. PMID:27144436

  20. Insufficient Sensitivity of Hemoglobin A1C (A1C) Determination in Diagnosis or Screening of Early Diabetic States

    PubMed Central

    Fajans, Stefan S.; Herman, William H.; Oral, Elif A.

    2010-01-01

    An International Expert Committee made recommendations for using the hemoglobin A1C (A1C) assay as the preferred method for diagnosis of diabetes in nonpregnant individuals. A concentration of ≥ 6.5% was considered as diagnostic. It is the aim of this study to compare the sensitivity of A1C with that of plasma glucose concentrations in subjects with early diabetes or IGT. We chose two groups of subjects who had A1C of ≤ 6.4%. The first group of 89 subjects had family histories of diabetes (MODY or T2DM) and had OGTT and A1C determinations. They included 36 subjects with diabetes or IGT and 53 with normal OGTT. The second group of 58 subjects was screened for diabetes in our Diabetes Clinic by FPG or 2HPG or OGTT and A1C and similar comparisons were made. Subjects with diabetes or IGT, including those with fasting hyperglycemia, had A1C ranging from 5.0 – 6.4%, mean 5.8%. The subjects with normal OGTT had A1C of 4.2 – 6.3%, mean 5.4% or 5.5% for the two groups. A1C may be in the normal range in subjects with diabetes or IGT, including those with fasting hyperglycemia. Approximately one third of subjects with early diabetes and IGT have A1C <5.7%, the cut-point that ADA recommends as indicating the onset of risk of developing diabetes in the future. The results of our study are similar to those obtained by a large Dutch epidemiological study. If our aim is to recognize early diabetic states to apply effective prophylactic procedures to prevent or delay progression to more severe diabetes, A1C is not sufficiently sensitive or reliable for diagnosis of diabetes or IGT. A combination of A1C and plasma glucose determinations, where necessary, are recommended for diagnosis or screening of diabetes or IGT. PMID:20723948

  1. Microbial diversity and dynamics during the production of May bryndza cheese.

    PubMed

    Pangallo, Domenico; Saková, Nikoleta; Koreňová, Janka; Puškárová, Andrea; Kraková, Lucia; Valík, Lubomír; Kuchta, Tomáš

    2014-01-17

    Diversity and dynamics of microbial cultures were studied during the production of May bryndza cheese, a traditional Slovak cheese produced from unpasteurized ewes' milk. Quantitative culture-based data were obtained for lactobacilli, lactococci, total mesophilic aerobic counts, coliforms, E. coli, staphylococci, coagulase-positive staphylococci, yeasts, fungi and Geotrichum spp. in ewes' milk, curd produced from it and ripened for 0 - 10 days, and in bryndza cheese produced from the curd, in three consecutive batches. Diversity of prokaryotes and eukaryotes in selected stages of the production was studied by non-culture approach based on amplification of 16S rDNA and internal transcribed spacer region, coupled to denaturing gradient gel electrophoresis and sequencing. The culture-based data demonstrated an overall trend of growth of the microbial population contributing to lactic acid production and to ripening of the cheese, lactobacilli, lactococci and Geotrichum spp. growing up to densities of 10(8) CFU/g, 10(9) CFU/g and 10(5) CFU/g, respectively, in all three consecutive batches of bryndza cheese. The diversity of bacteria encompassed Acinetobacter calcoaceticus, Acinetobacter guillouiae, Acinetobacter sp., Acinetobacter johnsonii, Citrobacter braakii, Clostridium bartlettii, Corynebacterium callunae, Corynebacterium maris, Enterobacter aerogenes, Enterobacter asburiae, Enterobacter hormaechei, Enterococcus faecium, Enterococcus pallens, Escherichia coli, Haemophilus haemolyticus, Hafnia alvei, Kluyvera cryocrescens, Lactobacillus helveticus, Lactococcus garvieae, Lc. lactis subsp. cremoris, Lc. lactis subsp. lactis, "Leuconostoc garlicum", Mannheimia glucosida, Mannheimia haemolytica, Pseudomonas sp., Ps. fluorescens, "Ps. reactans", Raoultella ornithinolytica, R. terrigena, "Rothia arfidiae", Staphylococcus aureus, Staph. epidermidis, Staph. felis, Staph. pasteuri, Staph. sciuri, Staph. xylosus, Streptococcus parauberis, Str. thermophilus and Variovorax

  2. Glycated haemoglobin (HbA1c): today and tomorrow.

    PubMed

    Roszyk, L; Faye, B; Sapin, V; Somda, F; Tauveron, I

    2007-10-01

    The assay of glycated haemoglobin (HbA1c) is a gold standard in bioanalysis, and is essential to ensure the optimal care of diabetic patients. Accordingly, the principal scientific societies in diabetology and clinical chemistry have made efforts to standardize this assay in order to select and validate certain analytical methods and achieve consistency in the results obtained therewith. However, clinicians have to be aware of the caution required when interpreting HbA1c assay results owing to modified lifetime and (or) abnormal synthesis of haemoglobin. Although this biological examination has now become an essential part of diabetes monitoring, its status as a screening tool is still controversial, even after 30 years of debate. Other uses of HbA1c assay are currently being assessed in cardiology (coronary syndromes), vascular diseases (arteriopathy), nephrology (renal insufficiency), haematology (anaemia) and oncology (factors of predisposition). PMID:17904515

  3. MybA1 gene diversity across the Vitis genus.

    PubMed

    Péros, Jean-Pierre; Launay, Amandine; Berger, Gilles; Lacombe, Thierry; This, Patrice

    2015-06-01

    The MybA1 gene in the genus Vitis encodes a transcription factor, belonging to the R2R3 Myb family, that controls the last steps in the anthocyanins biosynthesis pathway. Polymorphism within MybA1 has been associated with color variation in berries of V. vinifera and other Vitis species. In this work, we analyzed the sequence variation in MybA1 both in the subg. Muscadinia and in an extended set of Asian, American and European genotypes of subg. Vitis. Our aims were to infer the evolution of this gene during the speciation process and to identify polymorphisms that could potentially generate changes in gene regulation. The results show that MybA1 experienced many insertions and deletions in non-coding regions but also in the third exon sequence. Owing to the larger set of Vitis species compared here, new indels were identified and the origin of previously described indels was reconsidered. A large number of single nucleotide polymorphisms were found in non-coding regions but also in the sequence coding for the R2R3 domain and the C terminal part of the protein. Some of these changes led to amino acid substitutions and therefore could have modified MybA1 protein activity. Bayesian phylogenetic analysis of all polymorphisms did not provide a consensus tree depicting the geographical partitioning of the species but allowed highlighting several species relationships within subgenus Vitis. Finally, the evolutionary events described could be useful to gain more insight into the role of MybA1 for anthocyanin biosynthesis in grapevine.

  4. Establishment of Salmonella strain expressing catalytically active human UDP-glucuronosyltransferase 1A1 (UGT1A1).

    PubMed

    Fujita, K; Mogami, A; Hayashi, A; Kamataki, T

    2000-04-01

    Human uridinediphosphate-glucuronosyltransferase 1A1 (UGT1A1) was expressed in Salmonella typhimurium TA1535 cells by transfection of the cells with plasmids carrying the UGT1A1 cDNA. UGT1A1 cDNA was isolated by a polymerase chain reaction from human liver total RNA and was inserted into the pSE420 plasmid, linked to the trc promoter and terminator. The plasmid thus constructed was introduced into Salmonella TA1535 cells. The expression of human UGT1A1 protein was confirmed by Western blot analysis. The maximal expression was observed at 24 h after the addition of isopropyl-beta-D-thiogalactopyranoside, an inducer. However, the bilirubin conjugation activity of the membrane fraction from the Salmonella cells was not detectable. When a beta-glucuronidase inhibitor such as saccharic acid 1,4-lactone, glycyrrhizin or 1-naphtyl-beta-D-glucuronide was added to the reaction mixture, the bilirubin conjugation activity of the human UGT1A1 was detected. When geniposide was added to the reaction mixture, the bilirubin conjugation activity of UGT1A1 was not seen. Taking these results into account, the established Salmonella strain possesses the beta-glucuronidase activity. Since the beta-glucuronidase activity of the Salmonella was lower than that of E. coli, it was concluded that Salmonella seemed to be a good host to express UGT protein. This is the first study to demonstrate the establishment of a bacterial strain expressing native human UGT protein showing catalytic activity. PMID:10821120

  5. Bighorn sheep pneumonia: sorting out the cause of a polymicrobial disease.

    PubMed

    Besser, Thomas E; Frances Cassirer, E; Highland, Margaret A; Wolff, Peregrine; Justice-Allen, Anne; Mansfield, Kristin; Davis, Margaret A; Foreyt, William

    2013-02-01

    Pneumonia of bighorn sheep (Ovis canadensis) is a dramatic disease of high morbidity and mortality first described more than 80 years ago. The etiology of the disease has been debated since its initial discovery, and at various times lungworms, Mannheimia haemolytica and other Pasteurellaceae, and Mycoplasma ovipneumoniae have been proposed as primary causal agents. A multi-factorial "respiratory disease complex" has also been proposed as confirmation of causation has eluded investigators. In this paper we review the evidence for each of the candidate primary agents with regard to causal criteria including strength of association, temporality, plausibility, experimental evidence, and analogy. While we find some degree of biological plausibility for all agents and strong experimental evidence for M. haemolytica, we demonstrate that of the alternatives considered, M. ovipneumoniae is the best supported by all criteria and is therefore the most parsimonious explanation for the disease. The strong but somewhat controversial experimental evidence implicating disease transmission from domestic sheep is consistent with this finding. Based on epidemiologic and microbiologic data, we propose that healthy bighorn sheep populations are naïve to M. ovipneumoniae, and that its introduction to susceptible bighorn sheep populations results in epizootic polymicrobial bacterial pneumonia often followed by chronic infection in recovered adults. If this hypothesized model is correct, efforts to control this disease by development or application of vectored vaccines to Pasteurellaceae are unlikely to provide significant benefits, whereas efforts to ensure segregation of healthy bighorn sheep populations from M. ovipneumoniae-infected reservoir hosts are crucial to prevention of new disease epizootics. It may also be possible to develop M. ovipneumoniae vaccines or other management strategies that could reduce the impact of this devastating disease in bighorn sheep.

  6. Estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in Australian live export cattle.

    PubMed

    Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; O'Hara, Amanda J

    2015-01-01

    The prevalence of organisms known to be associated with bovine respiratory disease (BRD) was investigated in cattle prior to export. A quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: Bovine coronavirus (BoCV; Betacoronavirus 1), Bovine herpesvirus 1 (BoHV-1), Bovine viral diarrhea virus 1 (BVDV-1), Bovine respiratory syncytial virus (BRSV), Bovine parainfluenza virus 3 (BPIV-3), Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. Between 2010 and 2012, nasal swabs were collected from 1,484 apparently healthy cattle destined for export to the Middle East and Russian Federation. In addition, whole blood samples from 334 animals were tested for antibodies to BoHV-1, BRSV, BVDV-1, and BPIV-3 using enzyme-linked immunosorbent assay. The nasal prevalence of BoCV at the individual animal level was 40.1%. The nasal and seroprevalence of BoHV-1, BRSV, BVDV-1, and BPIV-3 was 1.0% and 39%, 1.2% and 46%, 3.0% and 56%, and 1.4% and 87%, respectively. The nasal prevalence of H. somni, M. bovis, M. haemolytica, and P. multocida was 42%, 4.8%, 13.4%, and 26%, respectively. Significant differences in nasal and seroprevalence were detected between groups of animals from different geographical locations. The results of the current study provide baseline data on the prevalence of organisms associated with BRD in Australian live export cattle in the preassembly period. This data could be used to develop strategies for BRD prevention and control prior to loading.

  7. Purification and structural characterisation of phospholipase A1 (Vespapase, Ves a 1) from Thai banded tiger wasp (Vespa affinis) venom.

    PubMed

    Sukprasert, Sophida; Rungsa, Prapenpuksiri; Uawonggul, Nunthawun; Incamnoi, Paroonkorn; Thammasirirak, Sompong; Daduang, Jureerut; Daduang, Sakda

    2013-01-01

    The Thai banded tiger wasp (Vespa affinis) is one of the most dangerous vespid species in Southeast Asia, and stinging accidents involving this species still cause fatalities. In the present study, four forms of V. affinis phospholipase A(1) were identified through a proteomics approach. Two of these enzymes were purified by reverse-phase chromatography, and their biochemical properties were characterised. These enzymes, designated Ves a 1s, are not glycoproteins and exist as 33441.5 and 33474.4 Da proteins, which corresponded with the 34-kDa band observed via SDS-PAGE. The thermal stabilities of these enzymes were stronger than snake venom. Using an in vivo assay, no difference was found in the toxicities of the different isoforms. Furthermore, the toxicity of these enzymes does not appear to be correlated with their PLA(1) activity. The cDNAs of the full-length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005-bp ORF, which encodes 334 amino acid residues, and 67- and 227-bp 5' and 3' UTRs, respectively. The two isoforms are different by three nucleotide substitutions, resulting in the replacement of two amino acids. Through sequence alignment, these enzymes were classified as members of the pancreatic lipase family. The structural modelling of Ves a 1 used the rat pancreatic lipase-related protein 2 (1bu8A) as a template because it has PLA(1) activity, which demonstrated that this enzyme belongs to the α/β hydrolase fold family. The Ves a 1 structure, which is composed of seven α-helixes and eleven β-strands, contains the β-strand/ɛSer/α-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence. The typical surface structures that play important roles in substrate selectivity (the lid domain and the β9 loop) were shortened in the Ves a 1 structure, which suggests that this enzyme may only exhibit phospholipase activity. Moreover, the observed insertion of proline into the lid domain of the Ves a 1 structure is rare

  8. PTSD and Sexual Orientation: An Examination of Criterion A1 and Non-Criterion A1 Events

    PubMed Central

    Alessi, Edward J.; Meyer, Ilan H.; Martin, James I.

    2015-01-01

    This large-scale cross-sectional study compared posttraumatic stress disorder (PTSD) prevalence among White, Black, and Latino lesbian, gay and bisexual individuals (LGBs; n = 382) and compared them with heterosexual individuals (n = 126). Building on previous research, we relaxed the criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM–IV; American Psychiatric Association, 1994), allowing non-Criterion A1 events such as ending a relationship, unemployment, homelessness, and separation from parents to qualify, and we assessed differences in PTSD prevalence between standard DSM–IV criteria and the relaxed criteria. Findings revealed that participants reporting a non-Criterion A1 event were more likely than those reporting a Criterion A1 event to have symptoms diagnosable as PTSD. There was no significant difference in either DSM–IV or relaxed Criterion A1 PTSD prevalence between lesbian and gay, and heterosexual individuals or between bisexual and heterosexual individuals. Compared with White LGBs, Black and Latino LGBs had higher prevalence of PTSD with the relaxed Criterion A1 definition, but this was statistically significant only for Latinos. PMID:26113955

  9. Characterization of the COL2A1 VNTR polymorphism

    SciTech Connect

    Berg, E.S.; Olaisen, B.

    1993-05-01

    The variable number of tandem repeat (VNTR) region 3{prime} to the collagen type II gene (COL2A1) was amplified in vitro by the polymerase chain reaction. Subsequent high-resolution gel electrophoresis showed that the five earlier reported alleles could be further subtyped. A total of 17 allelic variants with a heterozygosity of 73.0% were found in 202 unrelated Norwegians. DNA sequencing of 19 COL2A1 alleles has been performed. The internal organization of the VNTR was common for all alleles, as previously shown for a few alleles. Moreover, the polymorphism in the COL2A1 locus is mainly due to variation in the numbers of copies of two repeat units, containing 34 and 31 bp, respectively, and/or to small deletions in either of the two units. DNA sequencing of alleles with the same electrophoretic size revealed no heterogeneity such as an alternating order of the different units, a feature that might have been expected to be the result of unequal crossing-over events. The observed ordered structure of the VNTR and the possibility of single-stranded DNA from the cores in the VNTR forming hairpins and loops suggest that the COL2A1 polymorphism may have evolved mainly by replication slippage mechanisms. 23 refs., 2 figs., 3 tabs.

  10. Dynamics and phase transitions in A 1C 60 compounds

    NASA Astrophysics Data System (ADS)

    Schober, H.; Renker, B.; Heid, R.; Tölle, A.

    1997-02-01

    We present an overview of extensive inelastic neutron scattering experiments carried out on powders of A 1C 60. The various phases leave strong fingerprints in the microscopic dynamics confirming the solid-state chemical reactions. The strong kinetic phase transitions can be followed in real time and turn out to be highly complex.

  11. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the plan. Q-13. Does a transaction or accounting methodology involving an employee's designated Roth... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate... § 1.403(b)-3(c) (in the case of a section 403(b) plan). Q-2. How is a distribution from a...

  12. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the plan. Q-13. Does a transaction or accounting methodology involving an employee's designated Roth... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate... § 1.403(b)-3(c) (in the case of a section 403(b) plan). Q-2. How is a distribution from a...

  13. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the plan. Q-13. Does a transaction or accounting methodology involving an employee's designated Roth... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate... § 1.403(b)-3(c) (in the case of a section 403(b) plan). Q-2. How is a distribution from a...

  14. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the plan. Q-13. Does a transaction or accounting methodology involving an employee's designated Roth.... Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate account under a... case of a section 403(b) plan). Q-2. How is a distribution from a designated Roth account taxed?...

  15. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the plan. Q-13. Does a transaction or accounting methodology involving an employee's designated Roth... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate... § 1.403(b)-3(c) (in the case of a section 403(b) plan). Q-2. How is a distribution from a...

  16. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., consult with, and make recommendations to the Secretary of Labor and the Secretary of Health, Education... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope....

  17. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., consult with, and make recommendations to the Secretary of Labor and the Secretary of Health, Education... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope....

  18. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., consult with, and make recommendations to the Secretary of Labor and the Secretary of Health, Education... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope....

  19. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., consult with, and make recommendations to the Secretary of Labor and the Secretary of Health, Education... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope....

  20. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., consult with, and make recommendations to the Secretary of Labor and the Secretary of Health, Education... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope....

  1. 26 CFR 31.3306(a)-1 - Who are employers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE.... (a) Definition—(1) For calendar years 1956 through 1969, inclusive. Every person who employs 4...

  2. Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

    PubMed Central

    Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

    2007-01-01

    Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

  3. 26 CFR 1.167(a)-1 - Depreciation in general.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Depreciation in general. 1.167(a)-1 Section 1... Depreciation in general. (a) Reasonable allowance. Section 167(a) provides that a reasonable allowance for the exhaustion, wear and tear, and obsolescence of property used in the trade or business or of property held...

  4. 7 CFR 15a.1 - Purpose and effective date.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FROM FEDERAL FINANCIAL ASSISTANCE Introduction § 15a.1 Purpose and effective date. The purpose of this part is to effectuate title IX of the Education Amendments of 1972, as amended by Public Law 93-568, 88 Stat. 1855 and Public Law 94-482, 90 Stat. 2234 (except sections 904 and 906 of those Amendments)...

  5. The Heart of a 1:1 Classroom

    ERIC Educational Resources Information Center

    Tulbert, Carrie Ann

    2012-01-01

    Many educators believe that the act of building relationships is the core of learning. When technology is integrated into every classroom, do relationships improve or disintegrate among the key stakeholders in an educational environment? The purpose of this study is to determine the extent to which technology in a 1:1 school district can alter…

  6. Dietary Lecithin Decreases Skeletal Muscle COL1A1 and COL3A1 Gene Expression in Finisher Gilts

    PubMed Central

    Akit, Henny; Collins, Cherie; Fahri, Fahri; Hung, Alex; D’Souza, Daryl; Leury, Brian; Dunshea, Frank

    2016-01-01

    Simple Summary In this study, the effect of dietary lecithin on skeletal muscle gene expression of collagen precursors and enzymes was investigated in gilts. Thirty-six finisher gilts were fed with diets containing either 0, 4, 20 or 80 g/kg soybean lecithin for six weeks. Then, rectus abdominis muscle was sampled and analyzed for eight genes involved in collagen synthesis and degradation (COL1A1, COL3A1, MMP-1, MMP-13, TIMP-1, TIMP-3, lysyl oxidase and α-subunit P4H) using quantitative real-time PCR. The results showed that lecithin down-regulated COL1A1 and COL3A1 as well as tended to down-regulate α-subunit P4H expression. Abstract The purpose of this study was to investigate the effect of dietary lecithin on skeletal muscle gene expression of collagen precursors and enzymes involved in collagen synthesis and degradation. Finisher gilts with an average start weight of 55.9 ± 2.22 kg were fed diets containing either 0, 4, 20 or 80 g/kg soybean lecithin prior to harvest for six weeks and the rectus abdominis muscle gene expression profile was analyzed by quantitative real-time PCR. Lecithin treatment down-regulated Type I (α1) procollagen (COL1A1) and Type III (α1) procollagen (COL3A1) mRNA expression (p < 0.05, respectively), indicating a decrease in the precursors for collagen synthesis. The α-subunit of prolyl 4-hydroxylase (P4H) mRNA expression also tended to be down-regulated (p = 0.056), indicating a decrease in collagen synthesis. Decreased matrix metalloproteinase-1 (MMP-1) mRNA expression may reflect a positive regulatory response to the reduced collagen synthesis in muscle from the pigs fed lecithin (p = 0.035). Lecithin had no effect on tissue inhibitor metalloproteinase-1 (TIMP-1), matrix metalloproteinase-13 (MMP-13) and lysyl oxidase mRNA expression. In conclusion, lecithin down-regulated COL1A1 and COL3A1 as well as tended to down-regulate α-subunit P4H expression. However, determination of muscle collagen content and solubility are required

  7. Differential binding characteristics of native monomeric and polymeric immunoglobulin A1 (IgA1) on human mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules.

    PubMed

    Gao, Y-H; Xu, L-X; Zhang, J-J; Zhang, Y; Zhao, M-H; Wang, H-Y

    2007-06-01

    Recent studies had demonstrated that serum and mesangial immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) were polymeric and deglycosylated. The current study was to investigate the binding characteristics of monomeric and polymeric normal human IgA1 on mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules. The normal human IgA1 was desialylated and degalactosylated with specific enzymes, respectively. The monomeric IgA1 (mIgA1) and polymeric IgA1 (pIgA1) were separated by Sephacryl S-300 chromatography. The binding capacities of the mIgA1 and pIgA1 to primary human mesangial cells (HMC) were evaluated by classical radioligand assay. Both the native mIgA1 and pIgA1 could bind to HMC in a dose-dependent and saturable manner. The maximal binding capacity of the native pIgA1 were significantly higher than that of the native mIgA1 (P < 0.05). However, the affinity of the native mIgA1 was almost 100 times higher than that of the native pIgA1. After deglycosylation, binding of the two deglycosylated mIgA1 to HMC could not be detected. However, the maximal binding capacities of the two deglycosylated pIgA1 to HMC were increased significantly compared with that of native pIgA1. The affinity of the two deglycosylated pIgA1 was similar to that of native pIgA1 (P > 0.05). The current study suggests differential binding characteristics of native monomeric and polymeric IgA1 on mesangial cells. Glycosylation of IgA1 molecules could significantly affect the binding of IgA1 on HMC.

  8. Differential binding characteristics of native monomeric and polymeric immunoglobulin A1 (IgA1) on human mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules

    PubMed Central

    Gao, Y-H; Xu, L-X; Zhang, J-J; Zhang, Y; Zhao, M-H; Wang, H-Y

    2007-01-01

    Recent studies had demonstrated that serum and mesangial immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) were polymeric and deglycosylated. The current study was to investigate the binding characteristics of monomeric and polymeric normal human IgA1 on mesangial cells and the influence of in vitro deglycosylation of IgA1 molecules. The normal human IgA1 was desialylated and degalactosylated with specific enzymes, respectively. The monomeric IgA1 (mIgA1) and polymeric IgA1 (pIgA1) were separated by Sephacryl S-300 chromatography. The binding capacities of the mIgA1 and pIgA1 to primary human mesangial cells (HMC) were evaluated by classical radioligand assay. Both the native mIgA1 and pIgA1 could bind to HMC in a dose-dependent and saturable manner. The maximal binding capacity of the native pIgA1 were significantly higher than that of the native mIgA1 (P < 0·05). However, the affinity of the native mIgA1 was almost 100 times higher than that of the native pIgA1. After deglycosylation, binding of the two deglycosylated mIgA1 to HMC could not be detected. However, the maximal binding capacities of the two deglycosylated pIgA1 to HMC were increased significantly compared with that of native pIgA1. The affinity of the two deglycosylated pIgA1 was similar to that of native pIgA1 (P > 0·05). The current study suggests differential binding characteristics of native monomeric and polymeric IgA1 on mesangial cells. Glycosylation of IgA1 molecules could significantly affect the binding of IgA1 on HMC. PMID:17386074

  9. SPICE macromodel for a 1-megawatt power MOSFET switch

    SciTech Connect

    Helms, C.; Ackermann, M.; Fischer, T.; Deveney, M.

    1993-08-01

    This paper presents a SPICE macromodel for a 1-megawatt high power electrical switch which uses power MOSFETs as the active switching elements. The model accurately predicts the time dependent switching current and provides a reasonable representation of the time dependent switch resistance and voltage drop across the switch. Techniques for extracting model parameters for commercial power MOSFETs are discussed along with suggestions for extending the model to spark gaps and other high power switches.

  10. X-ray variability observed with HEAO A-1

    NASA Technical Reports Server (NTRS)

    Friedman, H.

    1979-01-01

    Results from the HEAO A-1 instrument which observed X-ray source variability over a wide range of accessible timescales are surveyed. The objects observed include quasars, BL Lacertae, and active galactic nuclei. A high sensitivity search for X-ray pulsars, known black hole candidates, period fluctuation in binary pulsars, and X-ray and gamma ray bursts are among the topics covered.

  11. C/2013 A1 (Siding Spring vs. Mars)

    NASA Technical Reports Server (NTRS)

    Moorhead, Althea; Cooke, William

    2013-01-01

    Comet C/2013 A1 (Siding Spring): recently discovered long period comet. Will have close encounter with Mars on October 19, 2014. Collision is extremely unlikely. Passing through the coma and/or tail is likely. Increases risk to Martian spacecraft. Meteoroids (100 microns or larger): approx. or <20% chance of impact per square meter due to coma and tail. Gas may also a ect Martian atmosphere.

  12. Elucidating hydroxylation and methylation steps tailoring piericidin A1 biosynthesis.

    PubMed

    Chen, Yaolong; Zhang, Wenjun; Zhu, Yiguang; Zhang, Qingbo; Tian, Xinpeng; Zhang, Si; Zhang, Changsheng

    2014-02-01

    The piericidin A1 (1) gene cluster was identified from the deep-sea derived Streptomyces sp. SCSIO 03032. Our in vivo and in vitro experiments verified PieE as a 4'-hydroxylase and PieB2 as a 4'-O-methyltransferase, allowing the elucidation of the post-PKS modification steps involved in 1 biosynthesis. In addition, the shunt metabolite piericidin E1 (7) was identified as a novel analogue featuring a C-2/C-3 epoxy ring.

  13. The A1Σu+ system of Mg2

    NASA Astrophysics Data System (ADS)

    Knöckel, Horst; Rühmann, Steffen; Tiemann, Eberhard

    2014-10-01

    The A1Σu+-X1Σg+ UV spectrum of Mg2 has been investigated with high resolution employing Fourier-transform spectroscopy and laser excitation. Computer simulation and fit of line positions to the overlapping structures in the spectra yield precise transition frequencies. Starting with the well characterized ground state X1Σg+ from former work, we derived excited energy levels and report on the evaluation of the A1Σu+ excited state, which is found to interact with another electronic state, which we identify as the lower part of the (1)1Πu state. A coupled channels fit to the level energies of the upper state yields a reliable potential energy curve for the A1Σu+ state for the range of vibrational levels 1 ≤ v' ≤ 46. A potential energy curve for the (1)1Πu state is proposed, but the (1)1Πu state is only characterized by its coupling to the A state, and no direct transition to a level of the (1)1Πu state could be uniquely identified due to the overlapping spectral structures. Supplementary material in the form of one dat file available from the Journal web page at http://dx.doi.org/10.1140/epjd/e2014-50289-9

  14. Dietary Lecithin Decreases Skeletal Muscle COL1A1 and COL3A1 Gene Expression in Finisher Gilts.

    PubMed

    Akit, Henny; Collins, Cherie; Fahri, Fahri; Hung, Alex; D'Souza, Daryl; Leury, Brian; Dunshea, Frank

    2016-01-01

    The purpose of this study was to investigate the effect of dietary lecithin on skeletal muscle gene expression of collagen precursors and enzymes involved in collagen synthesis and degradation. Finisher gilts with an average start weight of 55.9 ± 2.22 kg were fed diets containing either 0, 4, 20 or 80 g/kg soybean lecithin prior to harvest for six weeks and the rectus abdominis muscle gene expression profile was analyzed by quantitative real-time PCR. Lecithin treatment down-regulated Type I (α1) procollagen (COL1A1) and Type III (α1) procollagen (COL3A1) mRNA expression ( p < 0.05, respectively), indicating a decrease in the precursors for collagen synthesis. The α-subunit of prolyl 4-hydroxylase (P4H) mRNA expression also tended to be down-regulated ( p = 0.056), indicating a decrease in collagen synthesis. Decreased matrix metalloproteinase-1 (MMP-1) mRNA expression may reflect a positive regulatory response to the reduced collagen synthesis in muscle from the pigs fed lecithin ( p = 0.035). Lecithin had no effect on tissue inhibitor metalloproteinase-1 (TIMP-1), matrix metalloproteinase-13 (MMP-13) and lysyl oxidase mRNA expression. In conclusion, lecithin down-regulated COL1A1 and COL3A1 as well as tended to down-regulate α-subunit P4H expression. However, determination of muscle collagen content and solubility are required to support the gene functions. PMID:27338483

  15. Catechol-O-methyltransferase association with hemoglobin A1c

    PubMed Central

    Hall, Kathryn T.; Jablonski, Kathleen A.; Chen, Ling; Harden, Maegan; Tolkin, Benjamin R.; Kaptchuk, Ted J.; Bray, George A.; Ridker, Paul M.; Florez, Jose C.; Chasman, Daniel I.

    2016-01-01

    Aims Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes. Methods We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women’s Genome Health Study (WGHS), and Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), and with susceptibility to type 2 diabetes in WGHS, DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the Diabetes Prevention Program (DPP). Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment. Results COMT rs4680 high-activity G-allele was associated with lower HbA1c in WGHS (β = −0.032% [0.012], p = 0.008) and borderline significant in MAGIC (β = −0.006% [0.003], p = 0.07). Combined COMT per val allele effects on type 2 diabetes were significant (OR = 0.98 [0.96–0.998], p = 0.03) in fixed-effects analyses across WGHS, DIAGRAM, and DPP. Similar results were obtained for 2 other COMT SNPs rs4818 and rs4633. In the DPP, the rs4680 val allele was borderline associated with lower diabetes incidence among participants randomized to metformin (HR = 0.81 [0.65–1.00], p = 0.05). Conclusions COMT rs4680 high-activity G-allele was associated with lower HbA1c and modest protection from type 2 diabetes. The directionality of COMT associations was concordant with those previously observed for cardiometabolic risk factors and CVD. PMID:27282867

  16. Anisotropice superfluid fraction of3He A1 phase

    NASA Astrophysics Data System (ADS)

    Bastea, M.; Kojima, H.

    1995-11-01

    The superfluid fraction of3He a1 phase is computed from measurements of the velocity of spin/entropy waves induced in a cylindrical chamber, for two different directions of the magnetic field: parallel and perpendicular to the axis of the chamber. The ratio of the superfluid fractions in the parallel and perpendicular orientations is 1.85, and does not depend on the field between 1 and 5 Tesla. We adapt a theoretical texture model to account for the superfluid flow, and the results are consistent with the above ratio and direct estimates of superfluid velocity.

  17. CYP1A1 genetic polymorphisms in Ecuador, South America.

    PubMed

    Paz-y-Miño, César; Arévalo, Melissa; Muñoz G, María José; Leone, Paola E

    2005-01-01

    A total of 108 individuals from the Ecuadorian population from rural and urban places were analyzed for two CYP1A1 gene polymorphisms. The frequency of the val allele at codon 462 was 0.50, while the frequency of the Msp I restriction site, m2 allele at the T6235C position was 0.70. These polymorphisms in Ecuador have higher frequencies if we compare with others around the world, with the exception of some South American population in Brazil and Chile.

  18. Phylogenetic diversity of Pasteurellaceae and horizontal gene transfer of leukotoxin in wild and domestic sheep.

    PubMed

    Kelley, Scott T; Cassirer, E Frances; Weiser, Glen C; Safaee, Shirin

    2007-01-01

    Wild and domestic animal populations are known to be sources and reservoirs of emerging diseases. There is also a growing recognition that horizontal genetic transfer (HGT) plays an important role in bacterial pathogenesis. We used molecular phylogenetic methods to assess diversity and cross-transmission rates of Pasteurellaceae bacteria in populations of bighorn sheep, Dall's sheep, domestic sheep and domestic goats. Members of the Pasteurellaceae cause an array of deadly illnesses including bacterial pneumonia known as "pasteurellosis", a particularly devastating disease for bighorn sheep. A phylogenetic analysis of a combined dataset of two RNA genes (16S ribosomal RNA and RNAse P RNA) revealed remarkable evolutionary diversity among Pasteurella trehalosi and Mannheimia (Pasteurella) haemolytica bacteria isolated from sheep and goats. Several phylotypes appeared to associate with particular host species, though we found numerous instances of apparent cross-transmission among species and populations. Statistical analyses revealed that host species, geographic locale and biovariant classification, but not virulence, correlated strongly with Pasteurellaceae phylogeny. Sheep host species correlated with P. trehalosi isolates phylogeny (PTP test; P=0.002), but not with the phylogeny of M. haemolytica isolates, suggesting that P. trehalosi bacteria may be more host specific. With regards to populations within species, we also discovered a strong correlation between geographic locale and isolate phylogeny in the Rocky Mountain bighorn sheep (PTP test; P=0.001). We also investigated the potential for HGT of the leukotoxin A (lktA) gene, which produces a toxin that plays an integral role in causing disease. Comparative analysis of the combined RNA gene phylogeny and the lktA phylogenies revealed considerable incongruence between the phylogenies, suggestive of HGT. Furthermore, we found identical lktA alleles in unrelated bacterial species, some of which had been isolated

  19. Standardization of HbA1c: good or bad?

    PubMed

    Marshall, Sally M

    2010-07-01

    The development of a true reference measurement system by the International Federation for Clinical Chemistry (IFCC) for the first time allows reporting of true HbA(1c) results, standardized to an absolute value, worldwide. Regression equations between the IFCC assay and current harmonization assays, including the Diabetes Control and Complications Trial (DCCT) assay, are linear, tight, and stable over time. National and international setting of targets, audit and benchmarking of services will be easier than before, as will translation of research into clinical practice. Nevertheless, the main disadvantage of the IFCC assay is that the numbers and units reported (mmol/mol) are very different from the DCCT value (percentage). An extensive education program for patients and health-care professionals is, therefore, needed to prevent confusion and consequent deterioration in glycemic control. Furthermore, the IFCC system does not overcome difficulties inherent in the measurement and interpretation of HbA(1c), such as in the presence of abnormal turnover of red blood cells and hemoglobinopathies. PMID:20440288

  20. Dysspondyloenchondromatosis: Another COL2A1-Related Skeletal Dysplasia?

    PubMed Central

    Nakane, T.; Tando, T.; Aoyagi, K.; Hatakeyama, K.; Nishimura, G.; Coucke, I.P.J.; Mortier, G.; Sugita, K.

    2011-01-01

    Dysspondyloenchondromatosis (DSC) is a rare skeletal dysplasia that has currently been classified into the group of spondylometaphyseal dysplasias. To date, only 12 affected individuals have been reported. All cases are sporadic, and the etiology remains unknown. Distinctive features of DSC are anisospondyly and enchondroma-like lesions in the metaphyseal and diaphyseal portions of the long tubular bones. Affected individuals usually develop kyphoscoliosis and asymmetric limb shortening at an early age. Interestingly, some of the skeletal changes overlap with spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, a rare type II collagen disorder. Based on this resemblance we postulated that DSC may be allelic to SEMD Strudwick type and therefore performed a COL2A1 analysis in an affected boy who was diagnosed as having DSC at the age of 3 years. The identification of a novel heterozygous COL2A1 missense mutation (p.Gly753Asp) in the proband confirms our hypothesis and suggests that DSC may be another type II collagen disorder. PMID:22570642

  1. COL2A1 Mutation in Spondylometaphyseal Dysplasia Algerian Type

    PubMed Central

    Matsubayashi, S.; Ikema, M.; Ninomiya, Y.; Yamaguchi, K.; Ikegawa, S.; Nishimura, G.

    2013-01-01

    Spondylometaphyseal dysplasia Algerian type (SMD-A) is an autosomal dominant disorder that was first reported in an Algerian family by Kozlowski et al. [Pediatr Radiol 1988;18:221-226]. Kozlowski's group reported a sporadic case in a 12-year-old Polish boy. They proposed SMD-A as a distinctive skeletal dysplasia and also suggested that a case of SMD reported by Schmidt et al. [J Pediatr 1963;63:106-112] might have had the same disorder. Afterwards, however, no additional report has emerged to date. In addition, the question whether SMD-A belongs to type II collagenopathy (a group of disorders due to a heterozygous mutation of COL2A1) has been continuously under debate. Here we report a 7-year-old Japanese boy with a heterozygous missense mutation in COL2A1, 2582G>T (Gly861Val), whose phenotype matched that of SMD-A. Our observation supports the hypothesis that SMD-A is a variant of type II collagenopathy. PMID:23653587

  2. Concept of a (1-. cap alpha. ) performance confidence interval

    SciTech Connect

    Leong, H.H.; Johnson, G.R.; Bechtel, T.N.

    1980-01-01

    A multi-input, single-output system is assumed to be represented by some model. The distribution functions of the input and the output variables are considered to be at least obtainable through experimental data. Associated with the computer response of the model corresponding to given inputs, a conditional pseudoresponse set is generated. This response can be constructed by means of the model by using the simulated pseudorandom input variates from a neighborhood defined by a preassigned probability allowance. A pair of such pseudoresponse values can then be computed by a procedure corresponding to a (1-..cap alpha..) probability for the conditional pseudoresponse set. The range defined by such a pair is called a (1-..cap alpha..) performance confidence interval with respect to the model. The application of this concept can allow comparison of the merit of two models describing the same system, or it can detect a system change when the current response is out of the performance interval with respect to the previously identified model. 6 figures.

  3. Collisionally-Mediated Singlet-Triplet Crossing in ˜{a}1A1 CH_2 Revisited: (010) Coupling

    NASA Astrophysics Data System (ADS)

    Le, Anh T.; Hall, Gregory; Sears, Trevor

    2014-06-01

    Methylene, CH2, possesses a ground ˜{X}3B1 ground electronic state and an excited ˜{a}1A1 state only 3150cm-1 higher in energy. The collision-induced singlet-triplet crossing in the gaseous mixtures is important in determining overall reaction rates and chemical behavior. Accidental near-degeneracies between rotational levels of the singlet state and the vibrationally excited triplet state result in a few gateway rotational levels that mediate collision-induced intersystem crossing. The mixed states can be recognized and quantified by deperturbation, knowing the zero-order singlet and triplet energy levels. Hyperfine structure can be used as alternative indicator of singlet-triplet mixing. Non-zero mixing will induce hyperfine splittings intermediate between the unresolved hyperfine structure of pure singlet and the resolvable (≈50MHz) splittings of pure triplet, arising from the (I\\cdotS) interaction in the ortho states, where nuclear spin I=1. Collision-induced intersystem crossing rates from the (010) state are comparable to those for (000), yet the identities and characters of the presumed gateway states are unknown. A new spectrometer is under construction to investigate triplet mixing rotational levels of ˜{a}1A1(010) by sub-Doppler measurements of perturbation-induced hyperfine splittings. Their observation will permit the identification of gateway states and quantification of the degree of triplet contamination of the singlet wavefunction. Progress in the measurements and the analysis of rotational energy transfer in (010) will be reported. Acknowledgments: Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy and supported by its Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. C.-H. Chang, G. E. Hall, T. J. Sears, J. Chem. Phys 133, 144310(2010) G. E. Hall, A. V. Komissarov, and T. J. Sears, J. Phys. Chem. A 108 7922-7927 (2004)

  4. [Microsurgical anatomy importance of A1-anterior communicating artery complex].

    PubMed

    Monroy-Sosa, Alejandro; Pérez-Cruz, Julio César; Reyes-Soto, Gervith; Delgado-Hernández, Carlos; Macías-Duvignau, Mario Alberto; Delgado-Reyes, Luis

    2013-01-01

    Antecedentes: la arteria cerebral anterior se origina de la bifurcación de la arteria carótida interna lateral al quiasma óptico, posteriormente se une con su homóloga contralateral mediante la arteria comunicante anterior. El complejo precomunicante(A1)-arteria comunicante anterior es el lugar más frecuente de variantes anatómicas y el sitio con mayor cantidad de aneurismas (30 a 37%). Objetivo: conocer la anatomía microquirúrgica, las variantes anatómicas y la importancia del complejo segmento precomunicante-arteria comunicante anterior en cirugía neurológica de la patología vascular, principalmente aneurismas, en población mexicana. Material y métodos: estudio prospectivo y descriptivo efectuado en el Departamento de Anatomía de la Facultad de Medicina (UNAM) en 30 encéfalos inyectados. Se estudió la anatomía microquirúrgica (longitud y calibre) del complejo segmento precomunicante-arteria comunicante anterior de la arteria cerebral anterior y sus variantes. Resultados: se encontraron 60 segmentos precomunicantes. La longitud promedio del lado izquierdo fue de 11.35 mm y del derecho de 11.84 mm. El calibre medio en el lado izquierdo fue de 1.67 mm y en el derecho de 1.64 mm. El número promedio de perforantes en el lado izquierdo fue de 7.9 y en el derecho de 7.5. La arteria comunicante anterior se encontró en 29 encéfalos sobre el quiasma óptico, su trayecto dependió de la longitud del segmento A1. La longitud media del segmento fue de 2.84 mm, el calibre fue de 1.41 mm y el número promedio de perforantes de 3.27. En 18 encéfalos (60%) se encontraron variantes del complejo A1-arteria comunicante anterior y dos aneurismas tipo blíster. Conclusión: es necesario entender la anatomía microquirúrgica del complejo segmento precomunicante-arteria comunicante anterior y conocer las variantes para tener una visión en tercera dimensión durante la cirugía de aneurismas.

  5. Pulmonary toxicity of cyclophosphamide: a 1-year study

    SciTech Connect

    Morse, C.C.; Sigler, C.; Lock, S.; Hakkinen, P.J.; Haschek, W.M.; Witschi, H.P.

    1985-01-01

    The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure - volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion. 16 references, 5 figures, 3 tables.

  6. A 1,3-Dihydro-1,3-azaborine Debuts

    PubMed Central

    Xu, Senmiao; Zakharov, Lev N.

    2011-01-01

    We present the first synthesis and characterization of a 1,3-dihydro-1,3-azaborine, a long-sought BN isostere of benzene. 1,3-Dihydro-1,3-azaborine is a stable structural motif with considerable aromatic character as evidenced by structural analysis and its reaction chemistry. Single crystal X-ray analysis indicates bonding consistent with significant electron delocalization. 1,3-Dihydro-1,3-azaborines also undergo nucleophilic substitutions at boron and electrophilic aromatic substitution reactions. In view of the versatility and impact of aromatic compounds in the biomedical field and in materials science, the present study further expands the available chemical space of arenes via BN/CC isosterism. PMID:22091703

  7. Optical design of a 1-to-1 lithography projection

    NASA Astrophysics Data System (ADS)

    Huang, Jiun-Woei

    2016-08-01

    A 1:1 lithography projection has been designed and is fabricated for a 3D integrated circuit fabrication platform. Using a dual triplet as an initial type to form a one-to-one lens and applying a tele-centric structure, the optical common components of an optical system have been designed. The tolerance of the mechanical mounts is simulated by tilting the mounts to single and two aspheric surfaces of lens to show the degradation in the modulation transfer function; thus, the single aspheric-tilted mount in a system is suggested to reach the precision. Furthermore, Koehler illumination is used. By applying partial coherence analysis, the optimized relative numerical aperture was found. As the system is built, optimized performance should be expected.

  8. Underwater Imaging Using a 1 × 16 CMUT Linear Array

    PubMed Central

    Zhang, Rui; Zhang, Wendong; He, Changde; Zhang, Yongmei; Song, Jinlong; Xue, Chenyang

    2016-01-01

    A 1 × 16 capacitive micro-machined ultrasonic transducer linear array was designed, fabricated, and tested for underwater imaging in the low frequency range. The linear array was fabricated using Si-SOI bonding techniques. Underwater transmission performance was tested in a water tank, and the array has a resonant frequency of 700 kHz, with pressure amplitude 182 dB (μPa·m/V) at 1 m. The −3 dB main beam width of the designed dense linear array is approximately 5 degrees. Synthetic aperture focusing technique was applied to improve the resolution of reconstructed images, with promising results. Thus, the proposed array was shown to be suitable for underwater imaging applications. PMID:26938536

  9. Underwater Imaging Using a 1 × 16 CMUT Linear Array.

    PubMed

    Zhang, Rui; Zhang, Wendong; He, Changde; Zhang, Yongmei; Song, Jinlong; Xue, Chenyang

    2016-03-01

    A 1 × 16 capacitive micro-machined ultrasonic transducer linear array was designed, fabricated, and tested for underwater imaging in the low frequency range. The linear array was fabricated using Si-SOI bonding techniques. Underwater transmission performance was tested in a water tank, and the array has a resonant frequency of 700 kHz, with pressure amplitude 182 dB (μPa·m/V) at 1 m. The -3 dB main beam width of the designed dense linear array is approximately 5 degrees. Synthetic aperture focusing technique was applied to improve the resolution of reconstructed images, with promising results. Thus, the proposed array was shown to be suitable for underwater imaging applications.

  10. Optical design of a 1-to-1 lithography projection

    NASA Astrophysics Data System (ADS)

    Huang, Jiun-Woei

    2016-10-01

    A 1:1 lithography projection has been designed and is fabricated for a 3D integrated circuit fabrication platform. Using a dual triplet as an initial type to form a one-to-one lens and applying a tele-centric structure, the optical common components of an optical system have been designed. The tolerance of the mechanical mounts is simulated by tilting the mounts to single and two aspheric surfaces of lens to show the degradation in the modulation transfer function; thus, the single aspheric-tilted mount in a system is suggested to reach the precision. Furthermore, Koehler illumination is used. By applying partial coherence analysis, the optimized relative numerical aperture was found. As the system is built, optimized performance should be expected.

  11. Study of the Comet C/2013 A1 (Siding Spring)

    NASA Astrophysics Data System (ADS)

    Vodniza, Alberto Q.; Pereira, Mario R.

    2014-11-01

    The comet called C/2013 A1 (SIDING SPRING) was discovered on January 3, 2013 in Australia. In January 28/2014, NASA announced that is preparing for the close encounter that will happen between the comet C/2013 A1 and Mars on October 19-2014. The Mission called “MAVEN” will insert in Mars orbit on september 21—2014. The comet will pass just 138,000 kilometers far from the surface of Mars. The probability that the comet collides with Mars is small but the dust particles emitted by the comet can cause damage to spacecrafts and probes that are in orbit around that planet. NASA is making preparations to take all precautions. If the comet is quite active, there will be almost no time to take security measures with Mars orbiters. For that reason NASA is already ahead of the facts. According to scientists of the "JET PROPULSION LABORATORY-JPL", dust particles spewing from the comet may be traveling at 56 km / sec in relation to the orbiters, fifty times faster than the speed of a bullet. From our Observatory, located in Pasto-Colombia, we captured several pictures, videos and astrometry data during several days. The pictures of the asteroid were captured with the following equipment: CGE PRO 1400 CELESTRON (f/11 Schmidt-Cassegrain Telescope) and STL-1001 SBIG camera. Astrometry was carried out, and we calculated the orbital elements.Summary And Conclusions: We obtained the following orbital parameters: eccentricity = 1.0003983, orbital inclination = 129.03078 deg, longitude of the ascending node = 300.99538 deg, argument of perihelion = 2.42310 deg, perihelion distance = 1.40023196 A.U. The parameters were calculated based on 20 observations (Jan 21 to April 02) with mean residual = 0.334 arcseconds. We also obtained the light curve of the body with our data (January to November/2014)Acknowledgements: The authors would like to thank to University of Narino-Pasto-Colombia.

  12. Transmission of lungworms (Muellerius capillaris) from domestic goats to bighorn sheep on common pasture.

    PubMed

    Foreyt, William J; Jenkins, E J; Appleyard, G D

    2009-04-01

    Four domestic goats (Capra hircus) that were passing first-stage dorsal-spined larvae of Muellerius capillaris were copastured on a 0.82-ha pasture for 11 mo from May 2003 to April 2004 with seven Rocky Mountain bighorn sheep (Ovis canadensis) that were not passing dorsal-spined larvae. During the 11-mo experiment, two bighorn sheep died from pneumonia caused by Mannheimia (Pasteurella) haemolytica biotype A, serotype 2. The remaining five bighorn sheep and the four domestic goats remained healthy throughout the experiment. Muellerius larvae were detected from all domestic goats on a monthly basis throughout the experiment and were first detected from all five surviving bighorn sheep approximately 5 mo after the copasturing began. Once the bighorn sheep began passing Muellerius larvae, larvae were detected in low numbers from all bighorn sheep every month thereafter for the 6 mo the goats were still in the enclosure and continued to pass larvae for more than 3 yr after the goats were removed from the experiment. Six bighorn sheep in two similar enclosures that did not contain goats did not pass Muellerius larvae before, during, or after the experimental period. Results of this experiment indicate that M. capillaris from domestic goats is capable of infecting bighorn sheep when animals are copastured together on a common range. PMID:19395736

  13. Pneumonia of lambs in the Abruzzo region of Italy: anatomopathological and histopathological studies and localisation of Mycoplasma ovipneumoniae.

    PubMed

    Ettorre, Chiara; Sacchini, Flavio; Scacchia, Massimo; Della Salda, Leonardo

    2007-01-01

    The most common forms of inflammation of the lower respiratory tract in lambs are acute enzootic pneumonia, caused mainly by Mannheimia haemolytica, chronic enzootic pneumonia (defined as 'atypical' in lambs), the aetiological of which is Mycoplasma ovipneumoniae and viral inflammation principally caused by parainfluenza virus type 3. The authors conducted anatomopathological and histopathological studies of the most commonly encountered spontaneous lung inflammations in lambs slaughtered in the Abruzzo region of Italy, with special attention to 'atypical pneumonia'. Microbiological isolations and a histopathological and immunohistochemical analysis were performed to reveal any possible correlations between causal agents and lesion patterns. Positive results for M. ovipneumoniae were compared to those for Mycoplasma isolation to evaluate the sensitivity of the two techniques. Of a total of 156 samples, 31 (19.8%) demonstrated involvement of M. ovipneumoniae, 15 (9.6%) were positive on microbiological isolation confirmed by typing with biomolecular methods and, finally, histological lesions (atypical pneumonia) were observed in the remaining 16 cases (10.2%). Of these 31 samples, 23 (14.7% of the total) demonstrated postive antigen in alveolar macrophages and giant cells on immunohistochemical testing. These data revealed the presence of chronic enzootic pneumonia in the Abruzzo area and the importance of immunohistochemistry (in combination with isolation and anatomopathological and histopathological examination) for the diagnosis of pneumonia caused by M. ovipneumoniae, as well as the high sensitivity shown by antigen marker expression, even in samples where bacterial load was limited.

  14. Stress significantly increases mortality following a secondary bacterial respiratory infection

    PubMed Central

    2012-01-01

    A variety of mechanisms contribute to the viral-bacterial synergy which results in fatal secondary bacterial respiratory infections. Epidemiological investigations have implicated physical and psychological stressors as factors contributing to the incidence and severity of respiratory infections and psychological stress alters host responses to experimental viral respiratory infections. The effect of stress on secondary bacterial respiratory infections has not, however, been investigated. A natural model of secondary bacterial respiratory infection in naive calves was used to determine if weaning and maternal separation (WMS) significantly altered mortality when compared to calves pre-adapted (PA) to this psychological stressor. Following weaning, calves were challenged with Mannheimia haemolytica four days after a primary bovine herpesvirus-1 (BHV-1) respiratory infection. Mortality doubled in WMS calves when compared to calves pre-adapted to weaning for two weeks prior to the viral respiratory infection. Similar results were observed in two independent experiments and fatal viral-bacterial synergy did not extend beyond the time of viral shedding. Virus shedding did not differ significantly between treatment groups but innate immune responses during viral infection, including IFN-γ secretion, the acute-phase inflammatory response, CD14 expression, and LPS-induced TNFα production, were significantly greater in WMS versus PA calves. These observations demonstrate that weaning and maternal separation at the time of a primary BHV-1 respiratory infection increased innate immune responses that correlated significantly with mortality following a secondary bacterial respiratory infection. PMID:22435642

  15. Microbiological and histopathological findings in cases of fatal bovine respiratory disease of feedlot cattle in western Canada

    PubMed Central

    Booker, Calvin W.; Abutarbush, Sameeh M.; Morley, Paul S.; Jim, G. Kee; Pittman, Tom J.; Schunicht, Oliver C.; Perrett, Tye; Wildman, Brian K.; Fenton, R. Kent; Guichon, P. Timothy; Janzen, Eugene D.

    2008-01-01

    The aim of this study was to describe the microbiologic agents and pathologic processes in fatal bovine respiratory disease (BRD) of feedlot cattle and to investigate associations between agents and pathologic processes. Ninety feedlot calves diagnosed at necropsy with BRD and 9 control calves without BRD were examined, using immunohistochemical (IHC) staining and histopathologic studies. Mannheimia haemolytica (MH) (peracute, acute, and subacute cases) and Mycoplasma bovis (MB) (subacute, bronchiolar, and chronic cases) were the most common agents identified in fatal BRD cases. Significant associations (P < 0.10) were detected between microbiologic agents and between agents and pathologic processes. When IHC staining was used, 25/26 (96%) of animals that were positive for bovine viral diarrhea virus (BVDV) were also positive for MH; 12/15 (80 %) of animals that were positive for Histophilus somni (HS) were also positive for MB; and all of the animals that were positive for HS were negative for MH and BVDV. This quantitative pathological study demonstrates that several etiologic agents and pathologic processes are involved in fatal BRD of feedlot cattle. PMID:18512458

  16. Bovine respiratory disease research (1983-2009).

    PubMed

    Fulton, Robert W

    2009-12-01

    Bovine respiratory disease (BRD) research has provided significant understanding of the disease over the past 26 years. Modern research tools that have been used include monoclonal antibodies, genomics, polymerase chain reaction, immunohistochemistry (IHC), DNA vaccines and viral vectors coding for immunogens. Emerging/reemerging viruses and new antigenic strains of viruses and bacteria have been identified. Methods of detection and the role for cattle persistently infected bovine viral diarrhea virus (BVDV) were identified; viral subunits, cellular components and bacterial products have been characterized. Product advances have included vaccines for bovine respiratory syncytial virus, Mannheimia haemolytica and Pasteurella multocida; the addition of BVDV2 to the existing vaccines and new antibiotics. The role of Mycoplasma spp., particularly Mycoplasma bovis in BRD, has been more extensively studied. Bovine immunology research has provided more specific information on immune responses, T cell subsets and cytokines. The molecular and genetic basis for viral-bacterial synergy in BRD has been described. Attempts have been made to document how prevention of BRD by proper vaccination and management prior to exposure to infectious agents can minimize disease and serve as economic incentives for certified health programs. PMID:20003649

  17. Seven years survey of susceptibility to marbofloxacin of bovine pathogenic strains from eight European countries.

    PubMed

    Meunier, D; Acar, J-F; Martel, J-L; Kroemer, S; Vallé, M

    2004-09-01

    This study was conducted from 1994 to 2001 to determine the susceptibility of bovine pathogenic bacteria to marbofloxacin (a third generation fluoroquinolone used only in individual administration for animals). Strains originated in bovine diseases from eight European countries. They were isolated from gut infections (Escherichia coli, salmonellae), mastitis (E. coli, Staphylococcus aureus, Streptococcus uberis, S. agalactiae, S. dysgalactiae) and respiratory diseases (Mannheimia haemolytica, Pasteurella multocida, Haemophilus somnus). There was no change in the MIC distributions for each species after the launch of marbofloxacin in 1997. In E. coli, a resistant population was present before the use of marbofloxacin having been induced by co- or cross-resistance to other antibiotics used previously. Over this period the only a significant change seen was an increase in MIC(90) of E. coli from the gut (1.275 microg/ml in 1994/1995 to 5.098 microg/ml in 2001). All the salmonellae were susceptible to marbofloxacin with a MIC(90) = 0.073 microg/ml in 2001 without development of high level resistance. The use of marbofloxacin seems not to have favoured a significant increase and spreading of resistant bacteria.

  18. Transmission of lungworms (Muellerius capillaris) from domestic goats to bighorn sheep on common pasture.

    PubMed

    Foreyt, William J; Jenkins, E J; Appleyard, G D

    2009-04-01

    Four domestic goats (Capra hircus) that were passing first-stage dorsal-spined larvae of Muellerius capillaris were copastured on a 0.82-ha pasture for 11 mo from May 2003 to April 2004 with seven Rocky Mountain bighorn sheep (Ovis canadensis) that were not passing dorsal-spined larvae. During the 11-mo experiment, two bighorn sheep died from pneumonia caused by Mannheimia (Pasteurella) haemolytica biotype A, serotype 2. The remaining five bighorn sheep and the four domestic goats remained healthy throughout the experiment. Muellerius larvae were detected from all domestic goats on a monthly basis throughout the experiment and were first detected from all five surviving bighorn sheep approximately 5 mo after the copasturing began. Once the bighorn sheep began passing Muellerius larvae, larvae were detected in low numbers from all bighorn sheep every month thereafter for the 6 mo the goats were still in the enclosure and continued to pass larvae for more than 3 yr after the goats were removed from the experiment. Six bighorn sheep in two similar enclosures that did not contain goats did not pass Muellerius larvae before, during, or after the experimental period. Results of this experiment indicate that M. capillaris from domestic goats is capable of infecting bighorn sheep when animals are copastured together on a common range.

  19. Tulathromycin Exerts Proresolving Effects in Bovine Neutrophils by Inhibiting Phospholipases and Altering Leukotriene B4, Prostaglandin E2, and Lipoxin A4 Production

    PubMed Central

    Fischer, Carrie D.; Duquette, Stephanie C.; Renaux, Bernard S.; Feener, Troy D.; Morck, Douglas W.; Hollenberg, Morley D.; Lucas, Merlyn J.

    2014-01-01

    The accumulation of neutrophils and proinflammatory mediators, such as leukotriene B4 (LTB4), is a classic marker of inflammatory disease. The clearance of apoptotic neutrophils, inhibition of proinflammatory signaling, and production of proresolving lipids (including lipoxins, such as lipoxin A4 [LXA4]) are imperative for resolving inflammation. Tulathromycin (TUL), a macrolide used to treat bovine respiratory disease, confers immunomodulatory benefits via mechanisms that remain unclear. We recently reported the anti-inflammatory properties of TUL in bovine phagocytes in vitro and in Mannheimia haemolytica-challenged calves. The findings demonstrated that this system offers a powerful model for investigating novel mechanisms of pharmacological immunomodulation. In the present study, we examined the effects of TUL in a nonbacterial model of pulmonary inflammation in vivo and characterized its effects on lipid signaling. In bronchoalveolar lavage (BAL) fluid samples from calves challenged with zymosan particles (50 mg), treatment with TUL (2.5 mg/kg of body weight) significantly reduced pulmonary levels of LTB4 and prostaglandin E2 (PGE2). In calcium ionophore (A23187)-stimulated bovine neutrophils, TUL inhibited phospholipase D (PLD), cytosolic phospholipase A2 (PLA2) activity, and the release of LTB4. In contrast, TUL promoted the secretion of LXA4 in resting and A23187-stimulated neutrophils, while levels of its precursor, 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], were significantly lower. These findings indicate that TUL directly modulates lipid signaling by inhibiting the production of proinflammatory eicosanoids and promoting the production of proresolving lipoxins. PMID:24820086

  20. Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species.

    PubMed

    Subramaniam, Renuka; Dassanayake, Rohana P; Norimine, Junzo; Brown, Wendy C; Knowles, Donald P; Srikumaran, Subramaniam

    2010-10-15

    Mannheimia haemolytica infection results in enhanced PMN-mediated tissue damage in the lungs of bighorn sheep (BHS) compared to that of domestic sheep (DS). SERPIN B1 is an inhibitor of PMN-derived serine proteases. It prevents lung tissue injury by inhibiting the serine proteases released as a result of PMN lysis and degranulation. It is conceivable that PMNs of BHS exhibit decreased quantity and/or activity of SERPIN B1 which results in enhanced tissue injury and decreased bacterial clearance in pneumonic lungs of BHS. The objective of this study was to clone and express SERPIN B1 of BHS and DS, and develop antibodies to facilitate quantification of SERPIN B1. The 1,134bp cDNA of SERPIN B1 of BHS and DS encodes a polypeptide of 377 amino acids. SERPIN B1 of BHS and DS exhibits 100% identity at the nucleotide and amino acid levels. The amino acid sequence of ovine (BHS/DS) SERPIN B1 displays 69%, 71%, 74%, 78% and 80% identity with that of rats, dogs, mice, humans and horses, respectively. Ovine SERPIN B1 expressed in Escherichia coli was used to develop polyclonal antibodies in mice. Western blot analysis revealed the specificity of these antibodies for ovine rSERPIN B1.

  1. Identification of an immunogenic protein of Actinobacillus seminis that is present in microvesicles

    PubMed Central

    2006-01-01

    Abstract Actinobacillus seminis is a gram-negative bacterium of the Pasteurellaceae family that is involved in ovine epididymitis. Looking for a protein specific to this species, we determined the protein profile of subcellular fractions of A. seminis (American Type Culture Collection number 15768): proteins from the outer membrane (OMPs), inner membrane (IMPs), and cytoplasm (CPs). These profiles provide the first data, to our knowledge, regarding subcellular fractions of A. seminis. In the OMP fraction, we identified a protein with a molecular mass of 75 kDa that proved to be immunogenic and apparently specific for A. seminis. This conclusion was based on the reaction of hyperimmune serum of rabbits inoculated with whole cells of A. seminis that was tested against sonicated complete cells of reference strains and field isolates of Brucella ovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. No protein of these bacteria cross-reacted with the 75-kDa protein of A. seminis. Furthermore, when each type of hyperimmune serum was tested against the sonicated cells and each of the subcellular fractions of A. seminis, it did not recognize the A. seminis 75-kDa protein. We also isolated and identified this protein in microvesicles released to the culture supernatant. The results suggest that the 75-kDa protein could be used to establish a diagnostic test specific for ovine epididymitis caused by A. seminis. PMID:16548331

  2. Elevated CSF dynorphin A [1-8] in Tourette's syndrome.

    PubMed

    Leckman, J F; Riddle, M A; Berrettini, W H; Anderson, G M; Hardin, M; Chappell, P; Bissette, G; Nemeroff, C B; Goodman, W K; Cohen, D J

    1988-01-01

    A recent neuropathological study has reported decreased levels of dynorphin A immunoreactivity in striato-pallidal fibers in the brain of a patient with severe Gilles de la Tourette's syndrome (TS). This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. We report on the presence of elevated concentrations of dynorphin A [1-8] in the CSF of 7 TS patients, aged 20 to 45 years. The increase in CSF dynorphin was found to be associated with the severity of the obsessive compulsive symptoms but not with tic severity in these patients. Although CSF studies lack the precision necessary to address questions of selective involvement of neuronal system in specific CNS locations, these findings suggest that endogenous opioids are involved in the pathobiology of TS and related disorders. Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (OCD) (1). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case per 10,000 girls, and milder variants of the syndrome are likely to occur in a sizeable percentage of the population (2). Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consistent with an autosomal dominant form of inheritance (3,4). Neurobiologic and pharmacological data have implicated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and basal ganglia structures remain the prime candidates as the neuroanatomical origin for TS and related conditions (1). Endogenous opioids, including dynorphin and met-enkephalin are concentrated in structures of the basal ganglia (5), are known to

  3. Splicing analysis of unclassified variants in COL2A1 and COL11A1 identifies deep intronic pathogenic mutations

    PubMed Central

    Richards, Allan J; McNinch, Annie; Whittaker, Joanne; Treacy, Becky; Oakhill, Kim; Poulson, Arabella; Snead, Martin P

    2012-01-01

    UK NHS diagnostic service sequence analysis of genes generally examines and reports on variations within a designated region 5′ and 3′ of each exon, typically 30 bp up and downstream. However, because of the degenerate nature of the splice sites, intronic variants outside the AG and GT dinucleotides of the acceptor and donor splice sites (ASS and DSS) are most often classified as being of unknown clinical significance, unless there is some functional evidence of their pathogenicity. It is now becoming clear that mutations deep within introns can also interfere with normal processing of pre-mRNA and result in pathogenic effects on the mature transcript. In diagnostic laboratories, these deep intronic variants most often fall outside of the regions analysed and so are rarely reported. With the likelihood that next generation sequencing will identify more of these unclassified variants, it will become important to perform additional studies to determine the pathogenicity of such sequence anomalies. Here, we analyse variants detected in either COL2A1 or COL11A1 in patients with Stickler syndrome. These have been analysed both in silico and functionally using either RNA isolated from the patient's cells or, more commonly, minigenes as splicing reporters. We show that deep intronic mutations are not a rare occurrence, including one variant that results in multiple transcripts, where both de novo donor and ASS are created by the mutation. Another variant produces transcripts that result in either haploinsufficiency or a dominant negative effect, potentially modifying the disease phenotype. PMID:22189268

  4. Evaluation of a 1% iodophor postmilking teat sanitizer.

    PubMed

    Goldberg, J J; Murdough, P A; Howard, A B; Drechsler, P A; Pankey, J W; Ledbetter, G A; Richards, D A; Day, L L

    1994-03-01

    A natural exposure field trial a with positive control was conducted to evaluate bacteriological efficacy and teat conditioning qualities of an experimental postmilking teat dip. An experimental 1% iodine postmilking teat sanitizer with a 10% emollient system was compared with a 1% iodine plus 10% glycerin teat sanitizer. Efficacy of the two sanitizers was equivalent for all new IMI, major pathogens, and environmental pathogens. The products were not equivalent for efficacy against coliforms and coagulase-negative staphylococci. Fewer coliform IMI were diagnosed in the control group than in the treatment group. Differences were determined for efficacy against coagulase-negative staphylococci in favor of the treatment product. The products were equivalent for all clinical mastitis, including previously existing IMI that became clinical. The products were not equivalent for all or new clinical IMI with major pathogens, all environmental pathogens, or coliforms. Fewer infections were diagnosed in the control group than in the treatment group. Teat end and teat skin conditions improved with the use of the triple emollient, postmilking teat sanitizer under the winter conditions experienced during this field trial. PMID:8169282

  5. Transport of gibberellin a(1) in cowpea membrane vesicles.

    PubMed

    O'neill, S D; Keith, B; Rappaport, L

    1986-04-01

    The permeability properties of gibberellin A(1) (GA(1)) were examined in membrane vesicles isolated from cowpea hypocotyls. The rate of GA(1) uptake was progressively greater as pH decreased, indicating that the neutral molecule is more permeable than anionic GA(1). Membrane vesicles used in this study possessed a tonoplast-type H(+)-translocating ATPase as assayed by MgATP-dependent quenching of acridine orange fluorescence and methylamine uptake. However, GA(1) uptake was not stimulated by MgATP. At concentrations in excess of 1 micromolar, GA(1), GA(5), and GA, collapsed both MgATP-generated and artifically imposed pH gradients, apparently by shuttling H(+) across the membrane as neutral GA. The relatively high permeability of neutral GA and the potentially detrimental effects of GA in uncoupling pH gradients across intracellular membranes supports the view that GA(1) accumulation and compartmentation must occur by conversion of GA(1) to more polar metabolites.

  6. In Vitro Gibberellin A(1) Binding in Zea mays L.

    PubMed

    Keith, B; Rappaport, L

    1987-12-01

    The first and second leaf sheaths of Zea mays L. cv Golden Jubilee were extracted and the extract centrifuged at 100,000g to yield a supernatant or cytosol fraction. Binding of [(3)H]gibberellin A(1) (GA(1)) to a soluble macromolecular component present in the cytosol was demonstrated at 4 degrees C by Sephadex G-200 chromatography. The binding component was of high molecular weight (HMW) and greater than 500 kilodaltons. The HMW component was shown to be a protein and the (3)H-activity bound to this protein was largely [(3)H]GA(1) and not a metabolite. Binding was pH sensitive but only a small percentage (20%) appeared to be exchangeable on addition of unlabeled GA(1). Both biologically active and inactive GAs and non-GAs were able to inhibit GA(1) binding. [(3)H]GA(1) binding to an intermediate molecular weight (IMW) fraction (40-100 kilodaltons) was also detected, provided cytosol was first desalted using Sephadex G-200 chromatography. Gel filtration studies suggest that the HMW binding component is an aggregate derived from the IMW fraction. The HMW binding fraction can be separated into two components using anion exchange chromatography.

  7. Development of a 1×2 piezoelectric optical fiber switch

    NASA Astrophysics Data System (ADS)

    Leung, M.; Yue, J.; Razak, K. A.; Haemmerle, E.; Hodgson, M.; Gao, W.

    2008-03-01

    This paper presents the design, fabrication and performance of a 1×2 piezoelectric optical switch. The optical switch is developed based on the concept that the input fiber is directly moved by the deflection of a piezoelectric tube actuator. The piezoelectric tube actuator used in this switch is manufactured through an electrophoretic deposition process. The tube is inexpensive to produce and compact in size with high mechanical performance. It has a maximum deflection of 30μm which is capable to actuate the input fiber for switching. The multimode fiber optical switch has been successfully assembled. To reduce the misalignment loss between the fibers, the output fibers are precisely aligned in silicon vgrooves. Different components are bonded with low shrinkage adhesive in order to minimize their position inaccuracy. The performance characteristics of the optical switch have been measured, with an insertion loss of 1dB, crosstalk of -45dB and switching speed from 5 to 10ms. The switch also shows good reliability and requires small driving power. The development of multimode optical switch prototypes proves that the idea of piezoelectric switching is feasible. Further developments include the improvement of switching performance, reduction of the prototype size and the fabrication of multiple output prototypes.

  8. A 1-Joule laser for a 16-fiber injection system

    SciTech Connect

    Honig, J

    2004-04-06

    A 1-J laser was designed to launch light down 16, multi-mode fibers (400-{micro}m-core dia.). A diffractive-optic splitter was designed in collaboration with Digital Optics Corporation (DOC), and was delivered by DOC. Using this splitter, the energy injected into each fiber varied <1%. The spatial profile out of each fiber was such that there were no ''hot spots,'' a flyer could successfully be launched and a PETN pellet could be initiated. Preliminary designs of the system were driven by system efficiency where a pristine TEM{sub 00} laser beam would be required. The laser is a master oscillator, power amplifier (MOPA) consisting of a 4-mm-dia. Nd:YLF rod in the stable, q-switched oscillator and a 9.5-mm-dia. Nd:YLF rod in the double-passed amplifier. Using a TEM{sub 00} oscillator beam resulted in excellent transmission efficiencies through the fibers at lower energies but proved to be quite unreliable at higher energies, causing premature fiber damage, flyer plate rupture, stimulated Raman scattering (SRS), and stimulated Brillouin scattering (SBS). Upon further investigation, it was found that both temporal and spatial beam formatting of the laser were required to successfully initiate the PETN. Results from the single-mode experiments, including fiber damage, SRS and SBS losses, will be presented. In addition, results showing the improvement that can be obtained by proper laser beam formatting will also be presented.

  9. Towards a 1km resolution global flood risk model

    NASA Astrophysics Data System (ADS)

    Bates, Paul; Neal, Jeff; Sampson, Chris; Smith, Andy

    2014-05-01

    Recent advances in computationally efficient numerical algorithms and new High Performance Computing architectures now make high (1-2km) resolution global hydrodynamic models a realistic proposition. However in many areas of the world the data sets and tools necessary to undertake such modelling do not currently exist. In particular, five major problems need to be resolved: (1) the best globally available terrain data (SRTM) was generated from X-band interferometric radar data which does not penetrate vegetation canopies and which has significant problems in determining ground elevations in urban areas; (2) a global river bathymetry data set does not currently exist; (3) most river channels globally are less than the smallest currently resolvable grid scale (1km) and therefore require a sub-grid treatment; (4) a means to estimate the magnitude of the T year flood at any point along the global river network does not currently exist; and (5) a large proportion of flood losses are generated by off-floodplain surface water flows which are not well represented in current hydrodynamic modelling systems. In this paper we propose solutions to each of these five issues as part of a concerted effort to develop a 1km (or better) resolution global flood hazard model. We describe the new numerical algorithms, computer architectures and computational resources used, and demonstrate solutions to the five previously intractable problems identified above. We conduct a validation study of the modelling against satellite imagery of major flooding on the Mississippi-Missouri confluence plain in the central USA before outlining a proof-of-concept regional study for SE Asia as a step towards a global scale model. For SE Asia we simulate flood hazard for ten different flood return periods over the entire Thailand, Cambodia, Vietnam, Malaysia and Laos region at 1km resolution and show that the modelling produces coherent, consistent and sensible simulations of extent and water depth.

  10. Varicella paediatric hospitalisations in Belgium: a 1-year national survey

    PubMed Central

    Blumental, Sophie; Sabbe, Martine; Lepage, Philippe

    2016-01-01

    Background Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. Methods Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. Results Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105 person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105 person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105 person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106 and fatality ratio 0.2% among our cohort. Conclusions Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium. PMID:26130380

  11. Dynamical functions of a 1D correlated quantum liquid

    NASA Astrophysics Data System (ADS)

    Carmelo, J. M. P.; Bozi, D.; Penc, K.

    2008-10-01

    The dynamical correlation functions in one-dimensional electronic systems show power-law behaviour at low energies and momenta close to integer multiples of the charge and spin Fermi momenta. These systems are usually referred to as Tomonaga-Luttinger liquids. However, near well defined lines of the (k,ω) plane the power-law behaviour extends beyond the low-energy cases mentioned above, and also appears at higher energies, leading to singular features in the photoemission spectra and other dynamical correlation functions. The general spectral-function expressions derived in this paper were used in recent theoretical studies of the finite-energy singular features in photoemission of the organic compound tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ) metallic phase. They are based on a so-called pseudofermion dynamical theory (PDT), which allows us to systematically enumerate and describe the excitations in the Hubbard model starting from the Bethe ansatz, as well as to calculate the charge and spin object phase shifts appearing as exponents of the power laws. In particular, we concentrate on the spin-density m\\rightarrow 0 limit and on effects in the vicinity of the singular border lines, as well as close to half filling. Our studies take into account spectral contributions from types of microscopic processes that do not occur for finite values of the spin density. In addition, the specific processes involved in the spectral features of TTF-TCNQ are studied. Our results are useful for the further understanding of the unusual spectral properties observed in low-dimensional organic metals and also provide expressions for the one- and two-atom spectral functions of a correlated quantum system of ultracold fermionic atoms in a 1D optical lattice with on-site two-atom repulsion.

  12. TRAPPIST monitoring of comet C/2013 A1 (Siding Spring)

    NASA Astrophysics Data System (ADS)

    Opitom, Cyrielle; Jehin, Emmanuël; Manfroid, Jean; Hutsemékers, Damien; Gillon, Michaël

    2014-11-01

    C/2013 A1 (Siding Spring) is a long period comet discovered by Robert H McNaught at Siding Spring Observatory in Australia on January 3, 2013 at 7.2 au from the Sun. This comet will make a close encounter with Mars on October 19, 2014. At this occasion the comet will be extensively observed both from Earth and from several orbiters around Mars.On September 20, 2013 when the comet was around 5 au from the Sun, we started a monitoring with the TRAPPIST robotic telescope installed at La Silla observatory [1]. A set of narrowband cometary filters designed by the NASA for the Hale-Bopp Observing Campaign [2] is permanently mounted on the telescope along with classic Johnson-Cousins B, V, Rc, and Ic filters.We observed the comet continuously at least once a week from September 20, 2013 to April 6, 2014 with broad band filters. We then recovered the comet on May 20. At this time we could detect the gas and started the observations with narrow band filters until early November, covering the close approach to Mars and the perihelion passage.We present here our first results about comet Siding Springs. From the images in the broad band filters and in the dust continuum filters we derived A(θ)fρ values [3] and studied the evolution of the comet activity with the heliocentric distance from September 20, 2013 to early November 2014. We could also detect gas since May 20, 2014. We thus derived gas production rates using a Haser model [4]. We present the evolution of gas production rates and gas production rates ratios with the heliocentric distance.Finally, we discuss the dust and gas coma morphology.

  13. Feasibility study of a 1-MW pulsed spallation source

    SciTech Connect

    Cho, Y.; Chae, Y.C.; Crosbie, E.

    1995-12-31

    A feasibility study of a 1-MW pulsed spallation source based on a rapidly cycling proton synchrotron (RCS) has been completed. The facility consists of a 400-MeV HP{sup -} linac, a 30-Hz RCS that accelerates the 400-MeV beam to 2 GeV, and two neutron-generating target stations. The design time-averaged current of the accelerator system is 0.5 mA, or 1.04{times}1014 protons per pulse. The linac system consists of an H{sup -}ion source, a 2-MeV RFQ, a 70-MeV DTL and a 330-MeV CCL. Transverse phase space painting to achieve a Kapchinskij-Vladimirskij (K-V) distribution of the injected particles in the RCS is accomplished by charge exchange injection and programming of the closed orbit during injection. The synchrotron lattice uses FODO cells of {approx}90{degrees} phase advance. Dispersion-free straight sections are obtained by using a missing magnet scheme. Synchrotron magnets are powered by a dual-frequency resonant circuit that excites the magnets at a 20-Hz rate and de-excites them at a 60-Hz rate, resulting in an effective rate of 30 Hz, and reducing the required peak rf voltage by 1/3. A key feature, of the design of this accelerator system is that beam losses are from injection to extraction, reducing activation to levels consistent with hands-on maintenance. Details of the study are presented.

  14. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  15. Sites in the CH3 domain of human IgA1 that influence sensitivity to bacterial IgA1 proteases.

    PubMed

    Senior, Bernard W; Woof, Jenny M

    2006-09-15

    The influence of regions, other than the hinge, on the susceptibility of human IgA1 to cleavage by diverse bacterial IgA1 proteases, was examined using IgA1 mutants bearing amino acid deletions, substitutions, and domain swaps. IgA1 lacking the tailpiece retained its susceptibility to cleavage by all of the IgA1 proteases. The domain swap molecule alpha1alpha2gamma3, in which the CH3 domain of IgA1 was exchanged for that of human IgG1, was resistant to cleavage with the type 1 and 2 serine IgA1 proteases of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae, but remained sensitive to cleavage with the metallo-IgA1 proteases of Streptococcus pneumoniae, Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis. Substitution of the IgA1 Calpha3 domain motif Pro440 -Phe443 into the corresponding position in the Cgamma3 domain of alpha1alpha2gamma3 resulted now in sensitivity to the type 2 IgA1 protease of N. meningitidis, indicating the possible requirement of these amino acids for sensitivity to this protease. For the H. influenzae type 2 protease, resistance of an IgA1 mutant in which the CH3 domain residues 399-409 were exchanged with those from IgG1, but sensitivity of mutant HuBovalpha3 in which the Calpha3 domain of bovine IgA replaces that of human IgA1, suggests that CH3 domain residues Glu403, Gln406, and Thr409 influence sensitivity to this enzyme. Hence, unlike the situation with the metallo-IgA1 proteases of Streptococcus spp., the sensitivity of human IgA1 to cleavage with the serine IgA1 proteases of Neisseria and Haemophilus involves their binding to different sites specifically in the CH3 domain.

  16. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A...

  17. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A...

  18. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A...

  19. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A...

  20. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A...

  1. Differential effect of over-expressing UGT1A1 and CYP1A1 on xenobiotic assault in MCF-7 cells.

    PubMed

    Leung, Hau Y; Wang, Yun; Leung, Lai K

    2007-12-01

    Gene mutation has been considered as a major step of carcinogenesis. Some defective genes may induce spontaneous tumorigenesis, while others are required to interact with the environment to induce cancer. CYP1A1 and UGT1A1 are encoded for the respective phase I and II drug-metabolizing enzymes. Their expressions have been associated with breast cancer incidence in women, and some xenobiotics are substrates of these two enzymes. In the current study, cytochrome P450 (CYP) 1A1 and UDP-glucuronosyltransferase (UGT) 1A1 were over-expressed in the breast cancer MCF-7 cells, and potential interactions between these enzymes and estrogen or polycyclic aromatic hydrocarbon were evaluated. Compared with control cells (MCF-7(VEC)), reduced cell proliferation was seen in cells expressing UGT1A1 (MCF-7(UGT1A1)) under estradiol treatment. 7,12-Dimethylbenz[a]anthracene (DMBA) is an established breast cancer initiator in animal model. Over-expressing UGT1A1 reduced the binding of DMBA to DNA, and increased MCF-7(UGT1A1) intact cells under DMBA treatment was verified by comet assay. On the other hand, intensified DMBA binding and damages were observed in MCF-7(CYP1A1) cells. This study supported that UGT1A1 but not CYP1A1 expression could protect against xenobiotic assault. PMID:17981384

  2. Severe irinotecan-induced toxicity in a patient with UGT1A1 28 and UGT1A1 6 polymorphisms.

    PubMed

    Xu, Jian-Ming; Wang, Yan; Ge, Fei-Jiao; Lin, Li; Liu, Ze-Yuan; Sharma, Manish R

    2013-06-28

    Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing UGT1A1 28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1 28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UGT1A1 28 (TA 7/7), while UGT1A1 6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1 28 and UGT1A1 6 polymorphisms. PMID:23840132

  3. The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients.

    PubMed

    Xiao, Di; Guo, Yu; Li, Xi; Yin, Ji-Ye; Zheng, Wei; Qiu, Xin-Wen; Xiao, Ling; Liu, Rang-Ru; Wang, Sai-Ying; Gong, Wei-Jing; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-01-01

    Background. We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients. Methods. The distributions of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy. Results. No significant difference was found between T2DM patients and healthy subjects in SLC22A1 rs594709 and SLC47A1 rs2289669 allele frequencies and genotype frequencies. After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p = 0.015) and decrease in HOMA-IS (p = 0.001) and QUICKI (p = 0.002) than A allele carriers. SLC47A1 rs2289669 GG genotype patients had a higher decrease in TChol (p = 0.030) and LDL-C (p = 0.049) than A allele carriers. Among SLC22A1 rs594709 AA genotype, patients with SLC47A1 rs2289669 AA genotype showed a higher decrease in FBG (p = 0.015), PINS (p = 0.041), and HOMA-IR (p = 0.014) than G allele carriers. However, among SLC22A1 rs594709 G allele carriers, SLC47A1 rs2289669 AA genotype patients showed a higher decrease in TChol (p = 0.013) than G allele carriers. Conclusion. Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients. PMID:26977146

  4. Retinoic acid-metabolizing enzyme cytochrome P450 26a1 (cyp26a1) is essential for implantation: functional study of its role in early pregnancy.

    PubMed

    Han, Bing-Chen; Xia, Hong-Fei; Sun, Jing; Yang, Ying; Peng, Jing-Pian

    2010-05-01

    Vitamin A (VA) is required for normal fetal development and successful pregnancy. Excessive VA intake during pregnancy may lead to adverse maternal and fetal effects. Cytochrome P450 26A1 (cyp26a1), a retinoic acid (RA)-metabolizing enzyme, is involved in VA metabolism. It has been shown that cyp26a1 is expressed in female reproductive tract, especially in uterus. In order to investigate the role of cyp26a1 during pregnancy, we constructed a recombinant plasmid DNA vaccine encoding cyp26a1 protein and immunized mice with the plasmid. Compared to control groups, the pregnancy rate of the cyp26a1 plasmid-immunized mice were significantly decreased (P < 0.01). Further results showed that both cyp26a1 mRNA and protein were specifically induced in the uterus during implantation period and localized in the uterine luminal epithelium. Importantly, the number of implantation sites was also significantly reduced (P < 0.05) after the uterine injection of cyp26a1-specific antisense oligos or anti-cyp26a1 antibody on day 3 of pregnancy. Accordingly, the expression of RA-related cellular retinoic acid binding protein 1 and tissue transglutaminase was markedly increased (P < 0.05) in the uterine luminal epithelium after intrauterine injection treatments. These data demonstrate that uterine cyp26a1 activity is important for the maintenance of pregnancy, especially during the process of blastocyst implantation.

  5. Acquired thermotolerance independent of heat shock factor A1 (HsfA1), the master regulator of the heat stress response.

    PubMed

    Liu, Hsiang-chin; Charng, Yee-yung

    2012-05-01

    The heat stress (HS) response in eukaryotes is mainly regulated by heat shock factors (HSFs). Genetic disruption of the master HSF gene leads to dramatically reduced HS response and thermotolerance in several model organisms. However, it is not clear whether organisms devoid of the master regulator can still acclimate to heat. Previously, we showed that Arabidopsis HsfA1a, HsfA1b, and HsfA1d act as master regulators in the HS response. In this study, we examined the heat acclimation capacity of the Arabidopsis quadruple and triple T-DNA knockout mutants of HsfA1a, HsfA1b, HsfA1d, and HsfA1e. Our data showed that in the absence of the master regulators, a minimal but significant level of acquired thermotolerance could be attained in the Arabidopsis mutants after acclimation. The optimum acclimation temperature for the HsfA1 quadruple mutant was lower than that for the wild type plants, suggesting that plant cells have two HS-sensing mechanisms that can be distinguished genetically. The acquired thermotolerance of the quadruple mutant was likely due to the induction of a small number of HsfA1-independent HS response genes regulated by other transcription factors. Here, we discuss the possible candidates and propose a working model of the transcription network of the HS response by including the HsfA1-dependent and -independent pathways.

  6. The A1 Subunit of Shiga Toxin 2 Has Higher Affinity for Ribosomes and Higher Catalytic Activity than the A1 Subunit of Shiga Toxin 1.

    PubMed

    Basu, Debaleena; Li, Xiao-Ping; Kahn, Jennifer N; May, Kerrie L; Kahn, Peter C; Tumer, Nilgun E

    2016-01-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) infections can lead to life-threatening complications, including hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS), which is the most common cause of acute renal failure in children in the United States. Stx1 and Stx2 are AB5 toxins consisting of an enzymatically active A subunit associated with a pentamer of receptor binding B subunits. Epidemiological evidence suggests that Stx2-producing E. coli strains are more frequently associated with HUS than Stx1-producing strains. Several studies suggest that the B subunit plays a role in mediating toxicity. However, the role of the A subunits in the increased potency of Stx2 has not been fully investigated. Here, using purified A1 subunits, we show that Stx2A1 has a higher affinity for yeast and mammalian ribosomes than Stx1A1. Biacore analysis indicated that Stx2A1 has faster association and dissociation with ribosomes than Stx1A1. Analysis of ribosome depurination kinetics demonstrated that Stx2A1 depurinates yeast and mammalian ribosomes and an RNA stem-loop mimic of the sarcin/ricin loop (SRL) at a higher catalytic rate and is a more efficient enzyme than Stx1A1. Stx2A1 depurinated ribosomes at a higher level in vivo and was more cytotoxic than Stx1A1 in Saccharomyces cerevisiae. Stx2A1 depurinated ribosomes and inhibited translation at a significantly higher level than Stx1A1 in human cells. These results provide the first direct evidence that the higher affinity for ribosomes in combination with higher catalytic activity toward the SRL allows Stx2A1 to depurinate ribosomes, inhibit translation, and exhibit cytotoxicity at a significantly higher level than Stx1A1.

  7. Vibrational energies for the X1A1, A1B1, and B1A1 states of SiH2/SiD2 and related transition probabilities based on global potential energy surfaces.

    PubMed

    Tokue, Ikuo; Yamasaki, Katsuyoshi; Nanbu, Shinkoh

    2005-04-01

    Transition probabilities were evaluated for the X(1)A(1)-A(1)B(1) and A(1)B(1)-B(1)A(1) systems of SiH(2) and SiD(2) to analyze the X-->A-->B photoexcitation. The Franck-Condon factors (FCFs) and Einstein's B coefficients were computed by quantum vibrational calculations using the three-dimensional potential energy surfaces (PESs) of the SiH(2)(X(1)A(1),A(1)B(1),B(1)A(1)) electronic states and the electronic transition moments for the X-A, X-B, and A-B system. The global PESs were determined by the multireference configuration interaction calculations with the Davidson correction and the interpolant moving least-squares method combined with the Shepard interpolation. The obtained FCFs for the X-A and A-B systems exhibit that the bending mode is strongly enhanced in the excitation since the equilibrium bond angle greatly varies with the three states; the barrier to linearity is evaluated to be 21,900 cm(-1) for the X state, 6400 cm(-1) for the A state, and 230-240 cm(-1) for the B state. The theoretical lifetimes for the pure bending levels of the A and B states were calculated from the fluorescence decay rates for the A-X, B-A, and B-X emissions.

  8. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    PubMed

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  9. Binding capacity of in vitro deglycosylated IgA1 to human mesangial cells.

    PubMed

    Zhang, Jun-jun; Xu, Li-xia; Zhang, Ying; Zhao, Ming-hui

    2006-04-01

    IgA nephropathy (IgAN) is the most common glomerular disease and it is characterized by deposition of IgA1 molecules in mesangium. Recent studies had demonstrated that serum and mesangial IgA1 in IgAN were deglycosylated and IgA1 could bind to human mesangial cells (HMC) through a novel receptor. The aim of the current study is to investigate and compare the binding capacities of different in vitro deglycosylated IgA1 on human mesangial cells. Serum IgA1 was purified by jacalin affinity chromatography and then was desialylated (DesIgA1) and/or degalactosylated (Des/DeGalIgA1) with neuraminidase and/or beta-galactosidase. The efficacy of deglycosylations was assessed by Peanut agglutinin (PNA) and Vicia villosa (VV) lectin. The sizes of normal IgA1 and deglycosylated IgA1 were determined by Sephacryl S-300 chromatography and binding capacities to primary HMC were evaluated by radioligand binding assays. Normal IgA1 and deglycosylated IgA1 could bind to HMC in a dose-dependent, saturable manner. The maximal binding capacities and binding sites/cell of DesIgA1 and Des/DeGalIgA were significantly higher than that of normal IgA1. However, more aggregated IgA1 was found in DesIgA1 and Des/DeGalIgA1. Scatchard analysis revealed a similar Kd of normal IgA1 and deglycosylated IgA1. The current study suggested that the binding capacities of DesIgA1 and Des/DeGalIgA1 to HMC were significantly higher than that of normal IgA1, which at least in part was due to more macromolecular IgA1 in deglycoslated IgA1. However, there were no significant differences in the affinities of normal IgA1, DesIgA1 and Des/DeGalIgA1 with HMC. Deglycosylated IgA1 might play an important role in pathogenesis of IgAN.

  10. Development of Selective Inhibitors for Human Aldehyde Dehydrogenase 3A1 (ALDH3A1) for the Enhancement of Cyclophosphamide Cytotoxicity

    PubMed Central

    Parajuli, Bibek; Georgiadis, Taxiarchis M.; Fishel, Melissa L.; Hurley, Thomas D.

    2014-01-01

    Aldehyde dehydrogenase 3A1 (ALDH3A1) plays an important role in many cellular oxidative processes, including cancer chemo-resistance by metabolizing activated forms of oxazaphosphorine drugs such as cyclophosphamide (CP) and its analogues such as mafosfamide (MF), ifosfamide (IFM), 4-hydroperoxycyclophosphamide (4-HPCP). Compounds that can selectively target ALDH3A1 may permit delineation of its roles in these processes and could restore chemosensitivity in cancer cells that express this isoenzyme. Here we report the detailed kinetic and structural characterization of an ALDH3A1 selective inhibitor, CB29, previously identified in a high throughput screen. Kinetic and crystallographic studies demonstrate that CB29 binds within the aldehyde substrate-binding site of ALDH3A1. Cellular proliferation of ALDH3A1-expressing lung adenocarcinoma (A549) and glioblastoma (SF767) cell lines, as well as the ALDH3A1 non-expressing lung fibroblast cells, CCD-13Lu, is unaffected by treatment with CB29 and its analogues alone. However, the sensitivity toward the anti-proliferative effects of mafosfamide is enhanced by treatment with CB29 and its analogue in the tumour cells. In contrast, the sensitivity of CCD-13Lu cells toward mafosfamide was unaffected by the addition of these same compounds. CB29 is chemically distinct from the previously reported small molecule inhibitors of ALDH isoenzymes and does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1 or ALDH2 isoenzymes at concentrations up to 250 μM. Thus, CB29 is a novel small molecule inhibitor of ALDH3A1, which may be useful as a chemical tool to delineate the role of ALDH3A1 in numerous metabolic pathways, including sensitizing ALDH3A1-positive cancer cells to oxazaphosphorines. PMID:24677340

  11. Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome

    PubMed Central

    Wang, Xun; Jia, Xiaoyun; Xiao, Xueshan; Li, Shiqiang; Li, Jie; Li, Yadi; Wei, Yantao; Liang, Xiaoling

    2016-01-01

    Purpose To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome. Methods A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 and COL11A1 genes. Multiplex ligation-dependent probe amplification was performed to detect the gross indels of COL2A1 and COL11A1. Bioinformatics analysis was performed to evaluate the pathogenicity of the variants. Results Five mutations in COL2A1 were identified in six of 16 probands, including three novel (c.85C>T, c.3356delG, c.3401delG) mutations and two known mutations (c.1693C>T, c.2710C>T). Of the five mutations, three were truncated mutations, and the other two were missense mutations. Putative pathogenic mutations of the COL11A1 gene were absent in this cohort of patients. Gross indels were not found in COL2A1 or COL11A1 in any of the probands. High myopia was the most frequent initial ocular phenotype of Stickler syndrome. In this study, 12 Chinese probands lacked obvious systemic phenotypes. Conclusions In this study, three novel and two known mutations in the COL2A1 gene were identified in six of 16 Chinese patients with Stickler syndrome. This is the first study in a cohort of Chinese patients with Stickler syndrome, and the results expand the mutation spectrum of the COL2A1 gene. Analysis of the genotype-phenotype correlation showed that the early onset of high myopia with vitreous abnormalities may serve as a key indicator of Stickler syndrome, while the existence of mandibular protrusion in pediatric patients may be an efficient indicator for the absence of mutations in COL2A1 and COL11A1. PMID:27390512

  12. Knowledge of A1c Predicts Diabetes Self-Management and A1c Level among Chinese Patients with Type 2 Diabetes.

    PubMed

    Yang, Shengnan; Kong, Weimin; Hsue, Cunyi; Fish, Anne F; Chen, Yufeng; Guo, Xiaohui; Lou, Qingqing; Anderson, Robert

    2016-01-01

    This study was to identify current A1c understanding status among Chinese patients with type 2 diabetes, assess if knowledge of A1c affects their diabetes self-management and their glycemic control and recognize the factors influencing knowledge of A1c among patients with type 2 diabetes. A multi-center, cross-sectional survey was conducted between April and July 2010 in 50 medical centers in the Mainland China. Participants were recruited from inpatients and outpatients who were admitted to or visited those medical centers. The survey included core questions about their demographic characteristics, diabetes self-management behavior, and A1c knowledge. Overall, of 5957 patients, the percentage of patients with good understanding was 25.3%. In the multivariable logistic regression model, the variables related to the knowledge of A1c status are presented. We discovered that patients with longer diabetes duration (OR = 1.05; 95%CI = 1.04-1.06) and having received diabetes education (OR = 1.80; 95%CI = 1.49-2.17) were overrepresented in the good understanding of A1c group. In addition, compared to no education level, higher education level was statistically associated with good understanding of A1c (P<0.001). The percentage of patients with good understanding varied from region to region (P<0.001), with Eastern being highest (OR = 1.54; 95%CI = 1.32-1.80), followed by Central (OR = 1.25; 95%CI = 1.02-1.53), when referring to Western. Only a minority of patients with type 2 diabetes in China understood their A1c value. The patients who had a good understanding of their A1c demonstrated significantly better diabetes self-management behavior and had lower A1c levels than those who did not.

  13. Sheep lung cytochrome P4501A1 (CYP1A1): cDNA cloning and transcriptional regulation by oxygen tension.

    PubMed

    Hazinski, T A; Noisin, E; Hamon, I; DeMatteo, A

    1995-10-01

    Lung cytochrome P450 activity has been linked to neoplasia and may produce reactive oxidant species and potent arachidonic acid metabolites. In lamb lung, oxygen breathing increases lung P450 activity, and inhibition of lung cytochrome P450 activity reduces oxygen-induced lung injury. The P4501A1 (CYP1A1) isozyme is present in many lung cells, including endothelial cells, and may therefore be involved in the pathogenesis of hyperoxic injury to microvascular endothelium. Therefore, to test the hypothesis that oxygen regulates P4501A1 gene expression in the lung, we cloned the sheep P4501A1 cDNA, and examined its regulation by oxygen breathing significantly increased lung P4501A1 RNA levels and that this increase preceded the increase in isozyme activity. Oxygen exposure also promptly increased P4501A1 RNA levels in cultured lamb lung microvascular endothelial cells but not in endothelial cells isolated from the main pulmonary artery or in lung smooth muscle cells. The oxygen-stimulated increase in P4501A1 RNA levels was not serum dependent, was unaffected by cycloheximide treatment, and could not be mimicked by treatment of the cells with oxygenated medium, conditioned medium, or by chemical oxidants. By nuclear run-on assay in cultured lung endothelial cells, oxygen increased the transcription rate of P4501A1 by almost fourfold after 90 min of oxygen exposure but had no significant effect on P4501A1 RNA stability. We conclude that oxygen tension, but not chemical oxidants, increases P4501A1 gene expression pretranslationally in lung microvascular endothelial cells. We speculate that oxygen induction of P450 activity in these cells may contribute to microvascular injury during oxygen breathing. PMID:7560103

  14. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value

    PubMed Central

    Brunel, Valéry; Lahary, Agnčs; Chagraoui, Abdeslam; Thuillez, Christian

    2016-01-01

    Glycated haemoglobin (HbA1c) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA1c value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA1c. A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA1c value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA1c.
Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA1C value in patients in presence of HbJ variant. PMID:27346969

  15. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

    PubMed

    Brunel, Valéry; Lahary, Agnčs; Chagraoui, Abdeslam; Thuillez, Christian

    2016-01-01

    Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c).
 Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

  16. Sensor sensationalism? Alternative views on the nature and role of 'cytochrome a1' in bacteria.

    PubMed

    Poole, R K; Baines, B S; Williams, H D

    1985-01-01

    Replying to a recent proposal that 'cytochrome a1' functions as an oxygen sensor, we argue that this speculation is flawed by the failure to appreciate that cytochrome a1-like haemoproteins are a diverse group of haemoproteins. PMID:3939981

  17. 17 CFR 240.11a-1 - Regulation of floor trading.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., particularly sections 11(a) and 23(a) thereof, and Rule 11a-1 (17 CFR 240.11a-1) under the Act, deeming it... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Regulation of floor trading... Securities Exchange Act of 1934 Adoption of Floor Trading Regulation (rule 11a-1) § 240.11a-1 Regulation...

  18. 17 CFR 240.11a-1 - Regulation of floor trading.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., particularly sections 11(a) and 23(a) thereof, and Rule 11a-1 (17 CFR 240.11a-1) under the Act, deeming it... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Regulation of floor trading... Securities Exchange Act of 1934 Adoption of Floor Trading Regulation (rule 11a-1) § 240.11a-1 Regulation...

  19. 26 CFR 301.6231(a)(1)-1 - Exception for small partnerships.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....6231(a)(1)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Exception for small partnerships. 301.6231(a)(1)-1 Section 301.6231(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  20. 26 CFR 301.6231(a)(1)-1 - Exception for small partnerships.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....6231(a)(1)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Exception for small partnerships. 301.6231(a)(1)-1 Section 301.6231(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  1. 26 CFR 31.3121(a)(1)-1 - Annual wage limitation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Annual wage limitation. 31.3121(a)(1)-1 Section 31.3121(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... § 31.3121(a)(1)-1 Annual wage limitation. (a) In general. (1) The term “wages” does not include...

  2. 26 CFR 301.6231(a)(1)-1 - Exception for small partnerships.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....6231(a)(1)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Exception for small partnerships. 301.6231(a)(1)-1 Section 301.6231(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...

  3. 17 CFR 240.11a1-4(T) - Bond transactions on national securities exchanges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bond transactions on national securities exchanges. 240.11a1-4(T) Section 240.11a1-4(T) Commodity and Securities Exchanges SECURITIES AND....11a1-4(T) Bond transactions on national securities exchanges. A transaction in a bond, note,...

  4. 26 CFR 301.6031(a)-1 - Return of partnership income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Return of partnership income. 301.6031(a)-1....6031(a)-1 Return of partnership income. For provisions relating to the requirement of returns of partnership income, see § 1.6031(a)-1 of this chapter....

  5. 26 CFR 1.1314(a)-1 - Ascertainment of amount of adjustment in year of error.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of error. 1.1314(a)-1 Section 1.1314(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Years and Special Limitations § 1.1314(a)-1 Ascertainment of amount of adjustment in year of error. (a... ascertained the amount of the tax previously determined for the taxpayer as to whom the error was made for...

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    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of error. 1.1314(a)-1 Section 1.1314(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Years and Special Limitations § 1.1314(a)-1 Ascertainment of amount of adjustment in year of error. (a... ascertained the amount of the tax previously determined for the taxpayer as to whom the error was made for...

  7. 26 CFR 1.1314(a)-1 - Ascertainment of amount of adjustment in year of error.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of error. 1.1314(a)-1 Section 1.1314(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Years and Special Limitations § 1.1314(a)-1 Ascertainment of amount of adjustment in year of error. (a... ascertained the amount of the tax previously determined for the taxpayer as to whom the error was made for...

  8. 42 CFR 63a.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false To what programs do these regulations apply? 63a.1 Section 63a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH TRAINING GRANTS § 63a.1 To what programs do...

  9. 42 CFR 63a.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false To what programs do these regulations apply? 63a.1 Section 63a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH TRAINING GRANTS § 63a.1 To what programs do...

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    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false To what programs do these regulations apply? 63a.1 Section 63a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTES OF HEALTH TRAINING GRANTS § 63a.1 To what programs do...

  11. 26 CFR 1.1314(a)-1 - Ascertainment of amount of adjustment in year of error.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of error. 1.1314(a)-1 Section 1.1314(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Years and Special Limitations § 1.1314(a)-1 Ascertainment of amount of adjustment in year of error. (a... ascertained the amount of the tax previously determined for the taxpayer as to whom the error was made for...

  12. 26 CFR 1.6031(a)-1 - Return of partnership income.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Return of partnership income. 1.6031(a)-1 Section 1.6031(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6031(a)-1 Return of partnership income. (a) Domestic partnerships—(1)...

  13. Genetics Home Reference: COL4A1-related brain small-vessel disease

    MedlinePlus

    ... COL4A1-related brain small-vessel disease COL4A1-related brain small-vessel disease Enable Javascript to view the ... PDF Open All Close All Description COL4A1 -related brain small-vessel disease is part of a group ...

  14. 26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the...

  15. 26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the...

  16. 26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the...

  17. 26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the...

  18. 26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE....652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules in §§...

  19. 47 CFR 80.1087 - Ship radio equipment-Sea area A1.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Ship radio equipment-Sea area A1. 80.1087... Requirements for Ship Stations § 80.1087 Ship radio equipment—Sea area A1. This section contains the additional equipment requirements for ships that remain within sea area A1 at all times. (a) In addition to meeting...

  20. 47 CFR 80.1087 - Ship radio equipment-Sea area A1.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Ship radio equipment-Sea area A1. 80.1087... Requirements for Ship Stations § 80.1087 Ship radio equipment—Sea area A1. This section contains the additional equipment requirements for ships that remain within sea area A1 at all times. (a) In addition to meeting...

  1. 47 CFR 80.1087 - Ship radio equipment-Sea area A1.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Ship radio equipment-Sea area A1. 80.1087... Requirements for Ship Stations § 80.1087 Ship radio equipment—Sea area A1. This section contains the additional equipment requirements for ships that remain within sea area A1 at all times. (a) In addition to meeting...

  2. 47 CFR 80.1087 - Ship radio equipment-Sea area A1.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Ship radio equipment-Sea area A1. 80.1087... Requirements for Ship Stations § 80.1087 Ship radio equipment—Sea area A1. This section contains the additional equipment requirements for ships that remain within sea area A1 at all times. (a) In addition to meeting...

  3. 26 CFR 1.642(a)(1)-1 - Partially tax-exempt interest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Partially tax-exempt interest. 1.642(a)(1)-1 Section 1.642(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(a)(1)-1 Partially...

  4. 26 CFR 1.926(a)-1T - Temporary regulations; distributions to shareholders.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... shareholders. 1.926(a)-1T Section 1.926(a)-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...(a)-1T Temporary regulations; distributions to shareholders. (a) Treatment of distributions. Any distribution by a FSC (or former FSC) to its shareholder with respect to its stock will be includible in...

  5. Decays B(s)→a1(b1)D(s), a1(b1)D(s)* in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Zhang, Zhi-Qing

    2013-04-01

    Within the framework of the perturbative QCD approach, we study the branching ratios of the two-body charmed decays B(s)→a1(b1)D(s), a1(b1)D(s)*, which, including Cabibbo-Kobayashi-Maskawa, allowed and suppressed decays. Our calculations are consistent with the currently available data and the experimental upper limits. Certainly, many of these predicted channels have not been measured by experiments and can be confronted with the future experimental data. We also discuss the polarization factions of the decays B(s)→a1(b1)D(s)*, some of which are sensitive to the distinct Gegenbauer moments of the wave functions and the decay constants of mesons a1 and b1.

  6. Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1).

    PubMed

    Yang, Shyh-Ming; Yasgar, Adam; Miller, Bettina; Lal-Nag, Madhu; Brimacombe, Kyle; Hu, Xin; Sun, Hongmao; Wang, Amy; Xu, Xin; Nguyen, Kimloan; Oppermann, Udo; Ferrer, Marc; Vasiliou, Vasilis; Simeonov, Anton; Jadhav, Ajit; Maloney, David J

    2015-08-13

    Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiological and toxicological functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small molecule ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quantitative high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties. This chemotype exhibits highly selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isozymes as well as other dehydrogenases such as HPGD and HSD17β4. Moreover, the pharmacokinetic evaluation of selected analog 64 (NCT-501) is also highlighted. PMID:26207746

  7. Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1).

    PubMed

    Yang, Shyh-Ming; Yasgar, Adam; Miller, Bettina; Lal-Nag, Madhu; Brimacombe, Kyle; Hu, Xin; Sun, Hongmao; Wang, Amy; Xu, Xin; Nguyen, Kimloan; Oppermann, Udo; Ferrer, Marc; Vasiliou, Vasilis; Simeonov, Anton; Jadhav, Ajit; Maloney, David J

    2015-08-13

    Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiological and toxicological functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small molecule ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quantitative high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties. This chemotype exhibits highly selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isozymes as well as other dehydrogenases such as HPGD and HSD17β4. Moreover, the pharmacokinetic evaluation of selected analog 64 (NCT-501) is also highlighted.

  8. Protective role of cytochrome P450 1A1 (CYP1A1) against benzo[a]pyrene-induced toxicity in mouse aorta.

    PubMed

    Uno, Shigeyuki; Sakurai, Kenichi; Nebert, Daniel W; Makishima, Makoto

    2014-02-28

    Benzo[a]pyrene (BaP) is an environmental pollutant produced by combustive processes, such as cigarette smoke and coke ovens, and is implicated in the pathogenesis of atherosclerosis. Cytochrome P450 1A1 (CYP1A1) plays a role in both metabolic activation and detoxication of BaP in a context-dependent manner. The role of CYP1A1 in BaP-induced toxicity in aorta remains unknown. First, we fed Apoe⁻/⁻ mice an atherogenic diet plus BaP and found that oral BaP-enhanced atherosclerosis is associated with increased reactive oxygen species (ROS) and inflammatory markers, such as plasma tumor necrosis factor levels and aortic mRNA expression of vascular endothelial growth factor A (Vegfa). We next examined the effect of an atherogenic diet plus BaP on ROS and inflammatory markers in Cyp1a1⁻/⁻ mice. Although this treatment was not sufficient to induce atherosclerotic lesions in Cyp1a1⁻/⁻ mice, plasma antioxidant levels were decreased in Cyp1a1⁻/⁻ mice even in the absence of BaP treatment. The atherogenic diet plus BaP effectively elevated plasma ROS levels and expression of atherosclerosis-related genes, specifically Vegfa, in Cyp1a1⁻/⁻ mice compared with wild-type mice. BaP treatment increased Vegfa mRNA levels in mouse embryonic fibroblasts from Cyp1a1⁻/⁻ mice but not from wild-type mice. BaP-induced DNA adduct formation was increased in the aorta of Cyp1a1⁻/⁻ mice, but not wild-type or Apoe⁻/⁻ mice, and the atherogenic diet decreased BaP-induced DNA adducts in Cyp1a1⁻/⁻ mice compared with mice on a control diet. These data suggest that ROS production contributes to BaP-exacerbated atherosclerosis and that CYP1A1 plays a protective role against oral BaP toxicity in aorta.

  9. Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

    PubMed Central

    Kubota, Akira; O'Meara, Conor M.; Lamb, David C.; Tanguay, Robert L.; Goldstone, Jared V.

    2016-01-01

    Cytochrome P450 (CYP) enzymes for which there is no functional information are considered “orphan” CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including liver, heart, gonads, spleen and brain, as well as eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to “deorphanization”, that is, identifying CYP20A1 functions and its roles in health and disease. PMID:26853319

  10. Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders.

    PubMed

    Lemaire, Benjamin; Kubota, Akira; O'Meara, Conor M; Lamb, David C; Tanguay, Robert L; Goldstone, Jared V; Stegeman, John J

    2016-04-01

    Cytochrome P450 (CYP) enzymes for which there is no functional information are considered "orphan" CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including the liver, heart, gonads, spleen and brain, as well as the eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to "deorphanization", that is, identifying CYP20A1 functions and its roles in health and disease. PMID:26853319

  11. Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells.

    PubMed

    Raska, Milan; Moldoveanu, Zina; Suzuki, Hitoshi; Brown, Rhubell; Kulhavy, Rose; Andrasi, Judit; Hall, Stacy; Vu, Huong L; Carlsson, Fredric; Lindahl, Gunnar; Tomana, Milan; Julian, Bruce A; Wyatt, Robert J; Mestecky, Jiri; Novak, Jan

    2007-05-25

    Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.

  12. Identification and characterization of CMP-NeuAc:GalNAc-IgA1 α2,6-sialyltransferase in IgA1-producing cells

    PubMed Central

    Raska, Milan; Moldoveanu, Zina; Suzuki, Hitoshi; Brown, Rhubell; Kulhavy, Rose; Andrasi, Judit; Hall, Stacy; Vu, Huong L.; Carlsson, Frederic; Lindahl, Gunnar; Tomana, Milan; Julian, Bruce A.; Wyatt, Robert J.; Mestecky, Jiri; Novak, Jan

    2007-01-01

    Summary Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 α2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent β1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 α2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 α2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr. PMID:17418236

  13. Use of Fructosyl Peptide Oxidase for HbA1c Assay

    PubMed Central

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-01-01

    ARKRAY, Inc developed the world’s first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay “CinQ HbA1c” with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent. PMID:25633966

  14. IgA nephropathy and aberrant glycosylation of tonsillar, serum and glomerular IgA1.

    PubMed

    Hiki, Yoshiyuki; Ito, Akihiko; Yamamoto, Yoshihiro; Yamamoto, Koichiro; Iwase, Hitoo

    2011-01-01

    Human IgA1, which is the predominant subtype deposited in the glomeruli in IgA nephropathy (IgAN), has a unique mucin-like structure in its hinge region. Several studies suggested that the IgA1 molecules in IgAN patients had an aberrant structure of O-glycans. The paper summarizes the analyses of O-glycan structure in the IgA1 molecules taken from tonsils, sera and glomeruli of patients with IgAN. Hypoglycosylation, especially hypogalactosylation of O-glycans has been observed not only in serum and glomerular IgA1 but also in tonsillar IgA1.

  15. Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae.

    PubMed Central

    Male, C J

    1979-01-01

    Bacterial strains of Haemophilus species and Streptococcus pneumoniae were examined for synthesis of the enzyme immunoglobulin A1 (IgA1) protease. Of 36 H. influenzae strains examined, 35 produced IgA1 protease; strains included all six capsular types, unencapsulated variants of types b and d, and untypable H. influenzae. Eight Haemophilus strains (non-H. influenzae) were studied, and two produced IgA1 protease. All 10 strains of S. pneumoniae produced IgA1 protease; these strains included 9 different capsular polysaccharide types and 1 untypable strain. Both IgA1 proteases cleaved myeloma IgA1 and secretory IgA but not myeloma IgA2, IgM, or IgG as determined by immunoelectrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that both enzymes cleaved IgA1 myeloma sera, but not IgA2, into two fragments. The apparent molecular weight of the cleaved fragments was dependent both on the apparent molecular weight of the cleaved fragments was dependent both on the specific IgA1 protease assayed and the specific IgA1 substrate utilized. It is postulated that both carbohydrate variation between the IgA1 substrates studied and the ability of S. pneumoniae glycosidases to cleave carbohydrates from glycoprotein offer an explanation for the different fragment sizes observed. Images PMID:40880

  16. A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death.

    PubMed Central

    Carrió, R.; López-Hoyos, M.; Jimeno, J.; Benedict, M. A.; Merino, R.; Benito, A.; Fernández-Luna, J. L.; Núñez, G.; García-Porrero, J. A.; Merino, J.

    1996-01-01

    Members of the bcl-2 gene family are essential regulators of cell survival in a wide range of biological processes. A1, a member of the family, is known to be expressed in certain adult tissues. However, the precise tissue distribution and function of A1 remains poorly understood. We show here that A1 is expressed in multiple tissues during murine embryonic development. In the embryo, A1 was detected first at embryonic day 11.5 in liver, brain, and limbs. At day 13.5 of gestation, A1 expression was observed in the central nervous system, liver, perichondrium, and digital zones of developing limbs in a pattern different from that of bcl-X. In the central nervous system of 15.5-day embryos, A1 was expressed at high levels in the ventricular zone and cortical plate of brain cortex. Significantly, the interdigital zones of limbs and the intermediate region of the developing brain cortex, two sites associated with extensive cell death, were devoid of A1 and bcl-X. The expression of A1 was retained in many adult tissues. To assess the ability of A1 to modulate cell death, stable transfectants expressing different amounts of A1 protein were generated in K562 cells. Expression of A1 was associated with retardation of apoptotic cell death induced by actinomycin D and cycloheximide as well as by okadaic acid. Confocal microscopy showed that the A1 protein was localized to the cytoplasm in a pattern similar to that of Bcl-2. These results demonstrate that the expression of A1 is wider than previously reported in adult tissues. Furthermore, its distribution in multiple tissues of the embryo suggests that A1 plays a role in the regulation of physiological cell death during embryonic development. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:8952545

  17. Identification of Interacting Motifs Between Armadillo Repeat Containing 1 (ARC1) and Exocyst 70 A1 (Exo70A1) Proteins in Brassica oleracea.

    PubMed

    Liu, Jing; Zhang, Hecui; Lian, Xiaoping; Converse, Richard; Zhu, Liquan

    2016-02-01

    In order to identify the functional domains which regulate the interaction between the self-incompatibility proteins armadillo repeat containing 1 (ARC1) and exocyst 70 A1 (Exo70A1) in Brassica oleracea, fragments containing selected motifs of ARC1 (ARC1210, ARC1246, ARC1279, ARC1354) and site-specific mutants with substitutions at possible interaction sites (ARC1354m, ARC1664m) were PCR amplified and inserted into pGADT7, while coding sequences from Exo70A1 (Exo70A185, Exo70A1) were subcloned into pGBKT7. The interactions between the protein products produced by these constructs were then analyzed utilizing a yeast two-hybrid system. Our data indicate that both ARC1210 and ARC1246 interact strongly with Exo70A185 and Exo70A1, while ARC1279, ARC1354, ARC1354m and ARC1664m exhibited a weak interaction, indicating that the recognition sites are located within the 210 N-terminal amino acids of ARC1 and the 85 N-terminal amino acids of Exo70A1. This was further verified by GST pull-down analysis. This supports a model in which the N-terminal leucine zipper of ARC1 and the first 85 N-terminal amino acids of Exo70A1 mediate the interaction between these two proteins. Bioinformatic and phylogenetic analysis demonstrated that these motifs were highly conserved across different species, indicating that the interaction characterized in B. oleracea may operate in a wide array of cultivars. PMID:26696546

  18. Identification of Interacting Motifs Between Armadillo Repeat Containing 1 (ARC1) and Exocyst 70 A1 (Exo70A1) Proteins in Brassica oleracea.

    PubMed

    Liu, Jing; Zhang, Hecui; Lian, Xiaoping; Converse, Richard; Zhu, Liquan

    2016-02-01

    In order to identify the functional domains which regulate the interaction between the self-incompatibility proteins armadillo repeat containing 1 (ARC1) and exocyst 70 A1 (Exo70A1) in Brassica oleracea, fragments containing selected motifs of ARC1 (ARC1210, ARC1246, ARC1279, ARC1354) and site-specific mutants with substitutions at possible interaction sites (ARC1354m, ARC1664m) were PCR amplified and inserted into pGADT7, while coding sequences from Exo70A1 (Exo70A185, Exo70A1) were subcloned into pGBKT7. The interactions between the protein products produced by these constructs were then analyzed utilizing a yeast two-hybrid system. Our data indicate that both ARC1210 and ARC1246 interact strongly with Exo70A185 and Exo70A1, while ARC1279, ARC1354, ARC1354m and ARC1664m exhibited a weak interaction, indicating that the recognition sites are located within the 210 N-terminal amino acids of ARC1 and the 85 N-terminal amino acids of Exo70A1. This was further verified by GST pull-down analysis. This supports a model in which the N-terminal leucine zipper of ARC1 and the first 85 N-terminal amino acids of Exo70A1 mediate the interaction between these two proteins. Bioinformatic and phylogenetic analysis demonstrated that these motifs were highly conserved across different species, indicating that the interaction characterized in B. oleracea may operate in a wide array of cultivars.

  19. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic

  20. Annexin A1 Deficiency does not Affect Myofiber Repair but Delays Regeneration of Injured Muscles

    PubMed Central

    Leikina, Evgenia; Defour, Aurelia; Melikov, Kamran; Van der Meulen, Jack H.; Nagaraju, Kanneboyina; Bhuvanendran, Shivaprasad; Gebert, Claudia; Pfeifer, Karl; Chernomordik, Leonid V.; Jaiswal, Jyoti K.

    2015-01-01

    Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1−/−). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1−/− myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma. PMID:26667898

  1. Versatile substrates and probes for IgA1 protease activity.

    PubMed

    Choudary, Santosh K; Qiu, Jiazhou; Plaut, Andrew G; Kritzer, Joshua A

    2013-10-11

    Bacterial meningitis is a severe infectious disease with high mortality. Gram-positive and Gram-negative bacteria that cause meningitis secrete immunoglobulin A1 (IgA1) proteases to assist in mucosal colonization, invasion, and immune evasion. IgA1 proteases have unique selectivity, with few reported substrates other than IgA1 from human tissue. Here we describe the design, characterization, and application of peptide substrates for diverse IgA1 proteases from Neisseria, Haemophilus, and Streptococcus bacteria. IgA1 proteases from diverse strains showed unexpected selectivity profiles among peptide substrates derived from autoproteolytic sites. A fluorescence probe derived from one of these peptides was used to quantitate IgA1 protease activity in buffer and in human cerebrospinal fluid; it was able to detect recombinant Haemophilus influenzae type 1 IgA1 protease at less than 1 μg mL(-1) . We also used the probe to establish the first high-throughput screen for IgA1 protease inhibitors. This work provides tools that will help investigate the roles of IgA1 proteases in bacterial colonization, immune evasion, and infection.

  2. Circuit mechanisms of GluA1-dependent spatial working memory.

    PubMed

    Freudenberg, Florian; Marx, Verena; Seeburg, Peter H; Sprengel, Rolf; Celikel, Tansu

    2013-12-01

    Spatial working memory (SWM), the ability to process and manipulate spatial information over a relatively short period of time, requires an intact hippocampus, but also involves other forebrain nuclei in both in rodents and humans. Previous studies in mice showed that the molecular mechanism of SWM includes activation of AMPA receptors containing the GluA1 subunit (encoded by gria1) as GluA1 deletion in the whole brain (gria1(-/-)) results in strong SWM deficit. However, since these mice globally lack GluA1, the circuit mechanisms of GluA1 contribution to SWM remain unknown. In this study, by targeted expression of GluA1 containing AMPA receptors in the forebrain of gria1(-/-) mice or by removing GluA1 selectively from hippocampus of mice with "floxed" GluA1 alleles (gria1(fl/fl) ), we show that SWM requires GluA1 action in cortical circuits but is only partially dependent on GluA1-containing AMPA receptors in hippocampus. We further show that hippocampal GluA1 contribution to SWM is temporally restricted and becomes prominent at longer retention intervals (≥ 30 s). These findings provide a novel insight into the neural circuits required for SWM processing and argue that AMPA mediated signaling across forebrain and hippocampus differentially contribute to encoding of SWM.

  3. Interaction of atorvastatin with the human glial transporter SLC16A1.

    PubMed

    Sasaki, Shotaro; Futagi, Yuya; Ideno, Masaya; Kobayashi, Masaki; Narumi, Katsuya; Furugen, Ayako; Iseki, Ken

    2016-10-01

    Solute carrier (SLC) 16A1 is a pH-dependent carrier of 5-oxoproline, a derivative of the amino acid. SLC16A1 interacts with carboxylate group-containing substrates, which are also present in atorvastatin, and might be the reason for its ability to interact with atorvastatin. Does atorvastatin interact with the carrier? Does it also interact with the carrier via the substrate recognition site? This study was carried out to answer these questions. Polymerase chain reaction was used to determine the expression of SLC16A1 in normal human astrocytes. We induced SLC16A1 expression in a mammalian cell line and in Xenopus laevis oocytes. We used [(3)H] 5-oxoproline for direct measurement of SLC16A1-specific transport activity. SLC16A1 was clearly observed in normal human astrocytes. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors inhibited the SLC16A1-specific transport of 5-oxoproline. Atorvastatin was the most potent inhibitor, with an inhibition constant of 40μM. The drug was a non-competitive inhibitor of SLC16A1. In the present study, we showed non-competitive inhibition of SLC16A1-specific transport activity by atorvastatin. However, the affinity between the drug and the carrier was extremely low. Therefore, the interaction of atorvastatin with SLC16A1 is unlikely to be a problem in clinical practice.

  4. Annexin A1 Deficiency does not Affect Myofiber Repair but Delays Regeneration of Injured Muscles.

    PubMed

    Leikina, Evgenia; Defour, Aurelia; Melikov, Kamran; Van der Meulen, Jack H; Nagaraju, Kanneboyina; Bhuvanendran, Shivaprasad; Gebert, Claudia; Pfeifer, Karl; Chernomordik, Leonid V; Jaiswal, Jyoti K

    2015-01-01

    Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1-/-). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1-/- myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma. PMID:26667898

  5. Glycated Hemoglobin (HbA1c): Clinical Applications of a Mathematical Concept

    PubMed Central

    Leow, Melvin Khee Shing

    2016-01-01

    Background and purpose: Glycated hemoglobin (HbA1c) reflects the cumulative glucose exposure of erythrocytes over a preceding time frame proportional to erythrocyte survival. HbA1c is thus an areal function of the glucose-time curve, an educationally useful concept to aid teaching and clinical judgment. Methods: An ordinary differential equation is formulated as a parsimonious model of HbA1c. The integrated form yields HbA1c as an area-under-the-curve (AUC) of a glucose-time profile. The rate constant of the HbA1c model is then derived using the validated regression equation in the ADAG study that links mean blood glucose and HbA1c with a very high degree of goodness-of-fit. Results: This model has didactic utility to enable patients, biomedical students and clinicians to appreciate how HbA1c may be conceptually inferred from discrete blood glucose values using continuous glucose monitoring system (CGMS) or self-monitored blood glucose (SMBG) glucometer readings as shown in the examples. It can be appreciated how hypoglycemia can occur with rapid HbA1c decline despite poor glycemic control. Conclusions: Being independent of laboratory assay pitfalls, computed ‘virtual’ HbA1c serves as an invaluable internal consistency cross-check against laboratory-measured HbA1c discordant with SMBG readings suggestive of inaccurate/fraudulent glucometer records or hematologic disorders including thalassemia and hemoglobinopathy. This model could be implemented within portable glucometers, CGMS devices and even smartphone apps for deriving tentative ‘virtual’ HbA1c from serial glucose readings as an adjunct to measured HbA1c. Such predicted ‘virtual’ HbA1c readily accessible via glucometers may serve as feedback to modify behavior and empower diabetic patients to achieve better glycemic control. PMID:27708483

  6. Phylogenetic relationships among Perissodactyla: secretoglobin 1A1 gene duplication and triplication in the Equidae family.

    PubMed

    Côté, Olivier; Viel, Laurent; Bienzle, Dorothee

    2013-12-01

    Secretoglobin family 1A member 1 (SCGB 1A1) is a small anti-inflammatory and immunomodulatory protein that is abundantly secreted in airway surface fluids. We recently reported the existence of three distinct SCGB1A1 genes in the domestic horse genome as opposed to the single gene copy consensus present in other mammals. The origin of SCGB1A1 gene triplication and the evolutionary relationship of the three genes amongst Equidae family members are unknown. For this study, SCGB1A1 genomic data were collected from various Equus individuals including E. caballus, E. przewalskii, E. asinus, E. grevyi, and E. quagga. Three SCGB1A1 genes in E. przewalskii, two SCGB1A1 genes in E. asinus, and a single SCGB1A1 gene in E. grevyi and E. quagga were identified. Sequence analysis revealed that the non-synonymous nucleotide substitutions between the different equid genes coded for 17 amino acid changes. Most of these changes localized to the SCGB 1A1 central cavity that binds hydrophobic ligands, suggesting that this area of SCGB 1A1 evolved to accommodate diverse molecular interactions. Three-dimensional modeling of the proteins revealed that the size of the SCGB 1A1 central cavity is larger than that of SCGB 1A1A. Altogether, these findings suggest that evolution of the SCGB1A1 gene may parallel the separation of caballine and non-caballine species amongst Equidae, and may indicate an expansion of function for SCGB1A1 gene products.

  7. Carbon monoxide-releasing molecule-A1 (CORM-A1) improves clinical signs of experimental autoimmune uveoretinitis (EAU) in rats.

    PubMed

    Fagone, Paolo; Mangano, Katia; Mammana, Santa; Cavalli, Eugenio; Di Marco, Roberto; Barcellona, Maria Luisa; Salvatorelli, Lucia; Magro, Gaetano; Nicoletti, Ferdinando

    2015-04-01

    Uveitis is a sight-threatening inflammatory disease of the eye which represents the third leading cause of blindness in the developed countries. The conventional pharmacological treatment includes corticosteroids and immunosuppressive agents, which are limited by their side effects. New therapeutic strategies are thus strongly needed. Exogenously-administered carbon monoxide (CO) may represent an effective treatment for conditions characterized by a dysregulated inflammatory response. Carbon monoxide-releasing molecules (CORMs) are a novel group of compounds capable of carrying and liberating controlled quantities of CO. Among CORMs, CORM-A1 represents the first example of water soluble CO releaser. We show here that CORM-A1 under a late prophylactic regime is able to significantly ameliorate the natural course of experimental autoimmune uveoretinitis, a rodent model of immunoinflammatory posterior uveitis. The present study strongly supports the development of CORM-A1 as a potential new drug for treatment of patients with non-infectious posterior uveitis.

  8. Serological Analysis of Immunogenic Properties of Recombinant Meningococcus IgA1 Protease-Based Proteins.

    PubMed

    Kotelnikova, O V; Zinchenko, A A; Vikhrov, A A; Alliluev, A P; Serova, O V; Gordeeva, E A; Zhigis, L S; Zueva, V S; Razgulyaeva, O A; Melikhova, T D; Nokel, E A; Drozhzhina, E Yu; Rumsh, L D

    2016-07-01

    Using the genome sequence of IgA1 protease of N. meningitidis of serogroup B, four recombinant proteins of different structure and molecular weight were constructed. These proteins were equal in inducing the formation of specific antibodies to IgA1 protease and had protective properties against meningococci. In the sera of immunized mice, anti-IgA1 protease antibodies were detected by whole-cell ELISA, which indicated the presence of IgA1 protease on the surface of these bacteria. We hypothesized that the protective properties of IgA1 protease-based antigens and IgA1 protease analogs could be realized not only via impairment of bacterium adhesion to the mucosa, but also via suppression of this pathogen in the organism. The presented findings seem promising for using these proteins as the basis for anti-meningococcus vaccine.

  9. Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite.

    PubMed

    Rieg, Timo; Schnermann, Jürgen; Vallon, Volker

    2007-01-26

    Adenosine A1 receptor wild-type (+/+) and knockout (-/-) mice were used to elucidate the role of adenosine A1 receptors in caffeine self-administration in a two-bottle choice test and in the effect of caffeine on total fluid intake and plasma renin concentration. With access to water only, adenosine A1 receptor -/- mice showed greater basal fluid intake and greater plasma renin concentration than +/+ mice. Free access to both water and a caffeinated solution (30 mg/100 ml) for 14 days increased total fluid intake only in adenosine A1 receptor +/+ mice (by 23+/-3%), and both total fluid intake and plasma renin concentration were no longer different between genotypes. Mean intake of water and caffeinated solution was not different between adenosine A1 receptor +/+ and -/- mice. These data reveal that adenosine A1 receptors do not contribute to caffeine consumption, but determine the effects of caffeine on fluid intake and plasma renin concentration. PMID:17126319

  10. Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II

    PubMed Central

    Cochrane, Stephen A.; Findlay, Brandon; Bakhtiary, Alireza; Acedo, Jeella Z.; Rodriguez-Lopez, Eva M.; Mercier, Pascal; Vederas, John C.

    2016-01-01

    Tridecaptin A1 (TriA1) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA1 exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA1–lipid II complex. These results suggest that TriA1 kills Gram-negative bacteria by a mechanism of action using a lipid-II–binding motif. PMID:27688760

  11. [Indicators of glycemic control --hemoglobin A1c (HbA1c), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG)].

    PubMed

    Sato, Asako

    2014-01-01

    The clinical goal of diabetes management is a good quality of life that is not different from that of a healthy subjects. To fulfill the goal, prevention of complications is needed under good glycemic control. Although blood glucose measurement is essential for glycemic control, there are diurnal variations in blood glucose levels. An indicator of long-term glycemic control is necessary. HbA1c is the gold standard measurement for the assessment of glycemic control, and worldwide large scale clinical studies of diabetes complications have greatly valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c was recommended for use in the diagnosis of diabetes in Japan and in the United States. Although HbA1c is used widely and internationally, international standardization of the HbA1c value has not been achieved. In Japan, from April 2014, it has been decided to adopt the National Glycohemoglobin Standardization Program (NGSP) value, which is used by many countries globally, as the first step toward internationalization. Recently, cardiovascular disease in diabetic patients has been increasing in Japan. Relationships between postprandial hyperglycemia and cardiovascular disease have been noted. Therefore, the correction of postprandial hyperglycemia is one of the important goals of glycemic control to prevent cardiovascular disease. HbA1c or glycated albumin (GA) results from the glycation of hemoglobin or serum albumin and represents 2-month or 2-week glycemia, respectively. In addition, the glycation speed of GA is ten times faster than HbA1c, so GA is likely to reflect the variation in blood glucose and postprandial hyperglycemia in combination with HbA1c and its value. 1,5-anhydroglucitol (AG) is a marker of glycemia-induced glycosuria, since reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited by glucose. It is an indicator to identify rapid changes in hyperglycemia. Understanding the characteristics of the

  12. Catalytic and Immunochemical Detection of Hepatic and Extrahepatic Microsomal Cytochrome P450 1A1 (CYP1A1) in White-sided Dolphin (Lagenorhynchus acutus)

    PubMed Central

    Wilson, Joanna Y.; Moore, Michael J.; Stegeman, John J.

    2009-01-01

    We have characterized microsomal systems and measured the levels of microsomal cytochrome P450 1A1 (CYP1A1) and ethoxyresorufin-O-deethylase activity in multiple internal organs of male and female white-sided dolphin (Lagenorhynchus acutus) from the northwest Atlantic Ocean. Internal organs were sampled within 24 hours of death, sometimes in a period of hours, collection times which are significantly less than usually seen for marine mammals. Tissue autolysis, as assessed by histological analysis of liver, was minimal to none in all individuals. Total P420 did not correlate with time from death to sampling, suggesting that it is a poor indicator of P450 degradation in cetacean tissues where perfusion isn’t practical. The total hepatic microsomal P450 content, cytochrome b5 content, and NADPH-cytochrome c (P450) reductase (CPR) activity averaged 0.29 nmol mg−1, 0.12 nmol mg−1, and 238 nmol mg−1 min−1, respectively. Microsomal CPR activity in liver was higher than that in lung and kidney, and was higher than that reported in liver of most other cetacean species. Immunodetected CYP1A1 content was low in all organs, less than 3 pmoles CYP1A equivalents mg−1. EROD activity ranged from 9 – 376 pmoles mg−1 min−1 and was greater in liver than in other tissues. Hepatic microsomal EROD activity and CYP1A1 content did not correlate. However, hepatic EROD activity, but not CYP1A1 protein content, was well correlated with both total PCB and Σmono-ortho PCB concentrations in blubber. Length, as a proxy for age, did not correlate with hepatic EROD activity or CYP1A1 protein levels, and sex did not influence the relationship between EROD and contaminant concentrations. We cannot easily control for the extent of tissue degradation in cetacean studies nor do we have a complete history of these animals. Therefore, other factors such as degradation or hormonal state may have a role in the observed relationships. Yet, as in other mammals, hepatic tissues appear to be

  13. 26 CFR 31.6161(a)(1)-1 - Extensions of time for paying tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Extensions of time for paying tax. 31.6161(a)(1)-1 Section 31.6161(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Provisions of Subtitle F, Internal Revenue Code of 1954) § 31.6161(a)(1)-1 Extensions of time for paying...

  14. 26 CFR 31.6161(a)(1)-1 - Extensions of time for paying tax.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Extensions of time for paying tax. 31.6161(a)(1)-1 Section 31.6161(a)(1)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Provisions of Subtitle F, Internal Revenue Code of 1954) § 31.6161(a)(1)-1 Extensions of time for paying...

  15. Systemic effects of arctic pollutants in beluga whales indicated by CYP1A1 expression.

    PubMed

    Wilson, Joanna Y; Cooke, Suzy R; Moore, Michael J; Martineau, Daniel; Mikaelian, Igor; Metner, Donald A; Lockhart, W Lyle; Stegeman, John J

    2005-11-01

    Cytochrome P450 1A1 (CYP1A1) is induced by exposure to polycyclic aromatic hydrocarbons (PAHs) and planar halogenated aromatic hydrocarbons (PHAHs) such as non-ortho polychlorinated biphenyls (PCBs). In this study, we examined CYP1A1 protein expression immunohistochemically in multiple organs of beluga whales from two locations in the Arctic and from the St. Lawrence estuary. These beluga populations have some of the lowest (Arctic sites) and highest (St. Lawrence estuary) concentrations of PCBs in blubber of all cetaceans. Samples from these populations might be expected to have different contaminant-induced responses, reflecting their different exposure histories. The pattern and extent of CYP1A1 staining in whales from all three locations were similar to those seen in animal models in which CYP1A has been highly induced, indicating a high-level expression in these whales. CYP1A1 induction has been related to toxic effects of PHAHs or PAHs in some species. In St. Lawrence beluga, the high level of CYP1A1 expression coupled with high levels of contaminants (including CYP1A1 substrates, e.g., PAH procarcinogens potentially activated by CYP1A1) indicates that CYP1A1 could be involved in the development of neoplastic lesions seen in the St. Lawrence beluga population. The systemic high-level expression of CYP1A1 in Arctic beluga suggests that effects of PAHs or PHAHs may be expected in Arctic populations, as well. The high-level expression of CYP1A1 in the Arctic beluga suggests that this species is highly sensitive to CYP1A1 induction by aryl hydrocarbon receptor agonists.

  16. Evaluation of Hemoglobin A1c Criteria to Assess Preoperative Diabetes Risk in Cardiac Surgery Patients

    PubMed Central

    Saberi, Sima; Zrull, Christina A.; Patil, Preethi V.; Jha, Leena; Kling-Colson, Susan C.; Gandia, Kenia G.; DuBois, Elizabeth C.; Plunkett, Cynthia D.; Bodnar, Tim W.; Pop-Busui, Rodica

    2011-01-01

    Abstract Objective Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Methods Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. Results All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. Conclusions In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes. PMID:21854260

  17. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    PubMed Central

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  18. Type 2 Diabetes Prevention: Implications of Hemoglobin A1c Genetics.

    PubMed

    Leong, Aaron; Meigs, James B

    2015-01-01

    Hemoglobin A1c (HbA1c) is a biomarker used for population-level screening of type 2 diabetes (T2D) and risk stratification. Large-scale, genome-wide association studies have identified multiple genomic loci influencing HbA1c. We discuss the challenges of classifying these genomic loci as influencing HbA1c through glycemic or nonglycemic pathways, based on their probable biology and pleiotropic associations with erythrocyte traits. We show that putative nonglycemic genetic variants have a measurable, albeit small, impact on the classification of T2D status by HbA1c in white and Asian populations. Accounting for their effect on HbA1c may be relevant when screening populations with higher frequencies of nonglycemic HbA1c-altering alleles. As carriers of such HbA1c-altering alleles have HbA1c levels that may not accurately reflect overall glycemia, we describe how accounting for genotype may improve the performance of HbA1c in T2D prediction models and risk stratification, allowing for lifestyle intervention strategies to be directed towards those who are truly at elevated risk for developing T2D. In a Mendelian randomization framework, genetic variants can be used as instrumental variables to estimate causal relationships between HbA1c and T2D-related complications. This approach may help to support or refute HbA1c as an appropriate biomarker for long-term health outcomes in the general population. PMID:27111120

  19. 17 CFR 240.36a1-2 - Exemption from SIPA for OTC derivatives dealers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Exemption from SIPA for OTC... § 240.36a1-2 Exemption from SIPA for OTC derivatives dealers. Preliminary Note: OTC derivatives dealers... (§ 240.36a1-1), and application of the Securities Investor Protection Act of 1970 (§ 240.36a1-2)....

  20. 17 CFR 240.36a1-2 - Exemption from SIPA for OTC derivatives dealers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from SIPA for OTC... § 240.36a1-2 Exemption from SIPA for OTC derivatives dealers. Preliminary Note: OTC derivatives dealers... (§ 240.36a1-1), and application of the Securities Investor Protection Act of 1970 (§ 240.36a1-2)....

  1. Galactosylation of serum IgA1 O-glycans in celiac disease.

    PubMed

    Lindfors, Katri; Suzuki, Hitoshi; Novak, Jan; Collin, Pekka; Saavalainen, Päivi; Koskinen, Lotta L E; Mäki, Markku; Kaukinen, Katri

    2011-02-01

    In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin receptor. As IgA1 with galactose-deficient O-linked glycans has elevated affinity for the transferrin receptor, we assessed whether total serum IgA1 and IgA1 anti-TG2 autoantibodies in celiac patients are aberrantly glycosylated. We report that males with celiac disease have higher total serum levels of galactose-deficient IgA1 than non-celiac males. Furthermore, O-glycans of the disease-specific TG2 IgA1 autoantibodies in celiac patients exhibited elevated galactose deficiency. A gluten-free diet had no effect on the total serum levels of galactose-deficient IgA1, whereas the amount of galactose-deficient anti-TG2 IgA1 decreased. Thus, the undergalactosylated IgA1 molecules are not pathognomonic for celiac disease, but galactose deficiency in IgA1 could be an aggravating factor.

  2. NR4A1 Antagonists Inhibit β1-Integrin-Dependent Breast Cancer Cell Migration.

    PubMed

    Hedrick, Erik; Lee, Syng-Ook; Doddapaneni, Ravi; Singh, Mandip; Safe, Stephen

    2016-05-01

    Overexpression of the nuclear receptor 4A1 (NR4A1) in breast cancer patients is a prognostic factor for decreased survival and increased metastasis, and this has been linked to NR4A1-dependent regulation of transforming growth factor β (TGF-β) signaling. Results of RNA interference studies demonstrate that basal migration of aggressive SKBR3 and MDA-MB-231 breast cancer cells is TGF-β independent and dependent on regulation of β1-integrin gene expression by NR4A1 which can be inhibited by the NR4A1 antagonists 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) and a related p-carboxymethylphenyl [1,1-bis(3'-indolyl)-1-(p-carboxymethylphenyl)methane (DIM-C-pPhCO2Me)] analog. The NR4A1 antagonists also inhibited TGF-β-induced migration of MDA-MB-231 cells by blocking nuclear export of NR4A1, which is an essential step in TGF-β-induced cell migration. We also observed that NR4A1 regulates expression of both β1- and β3-integrins, and unlike other β1-integrin inhibitors which induce prometastatic β3-integrin, NR4A1 antagonists inhibit expression of both β1- and β3-integrin, demonstrating a novel mechanism-based approach for targeting integrins and integrin-dependent breast cancer metastasis. PMID:26929200

  3. Transcriptional regulation of human hydroxysteroid sulfotransferase SULT2A1 by LXRα.

    PubMed

    Ou, Zhimin; Jiang, Mengxi; Hu, Bingfang; Huang, Yixian; Xu, Meishu; Ren, Songrong; Li, Song; Liu, Suhuan; Xie, Wen; Huang, Min

    2014-10-01

    The nuclear receptor liver X receptor (LXR) plays an important role in the metabolism and homeostasis of cholesterol, lipids, bile acids, and steroid hormones. In this study, we uncovered a function of LXRα (NR1H3) in regulating the human hydroxysteroid sulfotransferase SULT2A1, a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens. We showed that activation of LXR induced the expression of SULT2A1 at mRNA, protein, and enzymatic levels. A combination of promoter reporter gene and chromatin immunoprecipitation assays showed that LXRα transactivated the SULT2A1 gene promoter through its specific binding to the -500- to -258-base pair region of the SULT2A1 gene promoter. LXR small interfering RNA knockdown experiments suggested that LXRα, but not LXRβ, played a dominant role in regulating SULT2A1. In primary human hepatocytes, we found a positive correlation between the expression of SULT2A1 and LXRα, which further supported the regulation of SULT2A1 by LXRα. In summary, our results established human SULT2A1 as a novel LXRα target gene. The expression of LXRα is a potential predictor for the expression of SULT2A1 in human liver. PMID:25028566

  4. FoxA1 as a lineage-specific oncogene in luminal type breast cancer

    SciTech Connect

    Yamaguchi, Noritaka; Ito, Emi; Azuma, Sakura; Honma, Reiko; Yanagisawa, Yuka; Nishikawa, Akira; Kawamura, Mika; Imai, Jun-ichi

    2008-01-25

    The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells.

  5. Observation of B0 meson decay to a 1 +/(1260)pi /+.

    PubMed

    Aubert, B; Barate, R; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Pappagallo, M; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Andreassen, R; Mancinelli, G; Meadows, B T; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Grenier, P; Latour, E; Thiebaux, Ch; Verderi, M; Bard, D J; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Gaillard, J R; Nash, J A; Nikolich, M B; Panduro Vazquez, W; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Stocchi, A; Wang, W F; Wormser, G; Cheng, C H; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Di Lodovico, F; Menges, W; Sacco, R; Brown, C L; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Kelly, M P; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Willocq, S Y; Cowan, R; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; Patel, P M; Potter, C T; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; Nardo, G De; del Re, D; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Piccolo, D; Sciacca, C; Baak, M; Bulten, H; Raven, G; Snoek, H L; Jessop, C P; LoSecco, J M; Allmendinger, T; Benelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Galeazzi, F; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F

    2006-08-01

    We present a measurement of the branching fraction of the decay B(0)-->a1 (+/)(1260)pi(/+) with a1 (+/)(1260)-->pi(/+)pi(+/)pi(+/). The data sample corresponds to 218 x 10(6) BB[over ] pairs produced in e+e- annihilation through the Upsilon(4S) resonance. We measure the branching fraction Beta(B(0)-->a1(+/)(1260)pi(/+))Beta(a1(+/)(1260)-->pi(/+)pi(+/)pi(+/)) = (16.6+/1.9+/1.5) x 10(-6), where the first error quoted is statistical and the second is systematic. PMID:17026094

  6. Observation of B0 meson decay to a 1 +/(1260)pi /+.

    PubMed

    Aubert, B; Barate, R; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Pappagallo, M; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Andreassen, R; Mancinelli, G; Meadows, B T; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Grenier, P; Latour, E; Thiebaux, Ch; Verderi, M; Bard, D J; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Gaillard, J R; Nash, J A; Nikolich, M B; Panduro Vazquez, W; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Stocchi, A; Wang, W F; Wormser, G; Cheng, C H; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Di Lodovico, F; Menges, W; Sacco, R; Brown, C L; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Kelly, M P; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Willocq, S Y; Cowan, R; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; Patel, P M; Potter, C T; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; Nardo, G De; del Re, D; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Piccolo, D; Sciacca, C; Baak, M; Bulten, H; Raven, G; Snoek, H L; Jessop, C P; LoSecco, J M; Allmendinger, T; Benelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Galeazzi, F; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Hartfiel, B L; John, M J J; Leruste, Ph; Malclès, J; Ocariz, J; Roos, L; Therin, G; Behera, P K; Gladney, L; Panetta, J; Biasini, M; Covarelli, R; Pioppi, M; Angelini, C; Batignani, G; Bettarini, S; Bucci, F; Calderini, G; Carpinelli, M; Cenci, R; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J; Haire, M; Judd, D; Wagoner, D E; Biesiada, J; Danielson, N; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Safai Tehrani, F; Voena, C; Ebert, M; Schröder, H; Waldi, R; Adye, T; De Groot, N; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Legendre, M; Mayer, B; Vasseur, G; Yèche, Ch; Zito, M; Park, W; Purohit, M V; Weidemann, A W; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Boyarski, A M; Claus, R; Coleman, J P; Convery, M R; Cristinziani, M; Dingfelder, J C; Dong, D; Dorfan, J; Dubois-Felsmann, G P; Dujmic, D; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Libby, J; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Weaver, M; Weinstein, A J R; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Roat, C; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Satpathy, A; Schilling, C J; Schwitters, R F; Izen, J M; Kitayama, I; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Grancagnolo, S; Lanceri, L; Vitale, L; Azzolini, V; Martinez-Vidal, F; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Eichenbaum, A M; Flood, K T; Hollar, J J; Johnson, J R; Kutter, P E; Li, H; Liu, R; Mellado, B; Mihalyi, A; Mohapatra, A K; Pan, Y; Pierini, M; Prepost, R; Tan, P; Wu, S L; Yu, Z; Neal, H

    2006-08-01

    We present a measurement of the branching fraction of the decay B(0)-->a1 (+/)(1260)pi(/+) with a1 (+/)(1260)-->pi(/+)pi(+/)pi(+/). The data sample corresponds to 218 x 10(6) BB[over ] pairs produced in e+e- annihilation through the Upsilon(4S) resonance. We measure the branching fraction Beta(B(0)-->a1(+/)(1260)pi(/+))Beta(a1(+/)(1260)-->pi(/+)pi(+/)pi(+/)) = (16.6+/1.9+/1.5) x 10(-6), where the first error quoted is statistical and the second is systematic.

  7. Genomic organization of SLC3A1, a transporter gene mutated in cystinuria

    SciTech Connect

    Pras, E.; Sood, R.; Raben, N.

    1996-08-15

    The SLC3A1 gene encodes a transport protein for cystine and the dibasic amino acids. Recently mutations in this gene have been shown to cause cystinuria. We report the genomic structure and organization of SLC3A1, which is composed of 10 exons and spans nearly 45 kb. Until now screening for mutations in SLC3A1 has been based on RT-PCR amplification of illegitimate mRNA transcripts from white blood cells. In this report we provide primers for amplification of exons from genomic DNA, thus simplifying the process of screening for SLC3A1 mutations in cystinuria. 20 refs., 3 figs., 2 tabs.

  8. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing

    PubMed Central

    Gammal, RS; Court, MH; Haidar, CE; Iwuchukwu, OF; Gaur, AH; Alvarellos, M; Guillemette, C; Lennox, JL; Whirl‐Carrillo, M; Brummel, SS; Ratain, MJ; Klein, TE; Schackman, BR; Caudle, KE

    2015-01-01

    The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin‐related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org). PMID:26417955

  9. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing.

    PubMed

    Gammal, R S; Court, M H; Haidar, C E; Iwuchukwu, O F; Gaur, A H; Alvarellos, M; Guillemette, C; Lennox, J L; Whirl-Carrillo, M; Brummel, S S; Ratain, M J; Klein, T E; Schackman, B R; Caudle, K E; Haas, D W

    2016-04-01

    The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org). PMID:26417955

  10. Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk

    PubMed Central

    Bethke, Lara; Webb, Emily; Sellick, Gabrielle; Rudd, Matthew; Penegar, Stephen; Withey, Laura; Qureshi, Mobshra; Houlston, Richard

    2007-01-01

    Background Cytochrome P450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones. Methods To investigate if common variants of CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1 and CYP19A1 influence CRC risk we genotyped 2,575 CRC cases and 2,707 controls for 20 single nucleotide polymorphisms (SNPs) that have not previously been shown to have functional consequence within these genes. Results There was a suggestion of increased risk, albeit insignificant after correction for multiple testing, of CRC for individuals homozygous for CYP1B1 rs162558 and heterozygous for CYP1A2 rs2069522 (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03–1.80 and OR = 1.34, 95% CI: 1.00–1.79 respectively). Conclusion This study provides some support for polymorphic variation in CYP1A2 and CYP1B1 playing a role in CRC susceptibility. PMID:17615053

  11. Homology model of human retinoic acid metabolising enzyme cytochrome P450 26A1 (CYP26A1): active site architecture and ligand binding.

    PubMed

    Gomaa, Mohamed Sayed; Yee, Sook Wah; Milbourne, Ceri Elizabeth; Barbera, Maria Chiara; Simons, Claire; Brancale, Andrea

    2006-08-01

    Homology models of cytochrome P450 RA1 (CYP26A1) were constructed using three human P450 structures, CYP2C8, CYP2C9 and CYP3A4 as templates for the model building. Using MOE software the lowest energy CYP26A1 model was then assessed for stereochemical quality and side chain environment. Further active site optimisation of the CYP26A1 model built using the CYP3A4 template was performed by molecular dynamics to generate a final CYP26A1 model. The natural substrate, all-trans-retinoic acid (atRA), and inhibitor R 15866, were docked into the model allowing further validation of the active site architecture. Using the docking studies structurally and functionally important residues were identified with subsequent characterisation of secondary structure. Multiple hydrophobic interactions, including the side chains of TRP112, PHE299, PHE222, PHE84, PHE374 and PRO371, are important for binding of atRA and R115866. Additional hydrogen bonding interactions were noted as follows: atRA-- C==O of the atRA carboxylate group and ARG86; R115866--benzothiazole nitrogen and the backbone NH of SER115.

  12. Improved method for measuring absolute O2(a1Δg) concentration by O2(a1Δg-->X3Σg-) IR radiation

    NASA Astrophysics Data System (ADS)

    Deng, Liezheng; Shi, Wenbo; Yang, Heping; Sha, Guohe; Zhang, Cunhao

    2004-11-01

    We describe an improved technique for measuring the absolute O2(a1Δ) concentration via the quantitative determination of IR radiation from O2(a1Δg→X3Σg-) transition. An exact geometrical optical model was first established, in which the influence of reflection and refraction on the radiation characteristics of a luminous volume source was given full consideration, making possible the accurate calculation of the coupling efficiency between the volume source and a receiving area. Then, an IR radiation receiving apparatus (IRRRA) was constructed and its responsivity (mV/W) to the power of IR radiation calibrated by a tungsten standard lamp. An optical detection system was, in turn, built according to the optical model with fine alignment between the IRRRA and an optical cell. We then demonstrate the procedure to obtain the absolute concentration of O2(a1Δ) flowing through the optical cell from a jet singlet oxygen generator from the signal of the IRRRA, the optical cell volume, and the coupling efficiency between the cell and the IRRRA. Moreover, to verify the accuracy of this method, the absolute O2(a1Δ) concentration was compared to that measured by an established isothermal calorimetry method. Based on the comparison of the O2(a1Δ) concentrations determined by the two methods, the Einstein A-coefficient was estimated as (2.70±0.84)×10-4 s-1, which agrees with Badger's value of 2.58×10-4, Špalek's of 2.24×10-4, Newman's of 2.19×10-4, and Miller's of 2.3×10-4 within the uncertainty of the experimental techniques. The method advanced in this article is worthwhile for the measurement of absolute O2(a1Δ) concentration in a chemical oxygen iodine laser or a singlet oxygen generator. It can also provide a general technique for the measurement of absolute concentrations of long-lifetime luminous species other than O2(a1Δ).

  13. The effect of Fasciola hepatica infection on respiratory vaccine responsiveness in calves.

    PubMed

    Krump, L; Hamilton, C M; Sekiya, M; O'Neill, R; Mulcahy, G

    2014-03-17

    Fasciola hepatica is a common parasite in cattle, and bovine fasciolosis causes significant production losses, as well as being a zoonotic disease of global importance. F. hepatica has been shown to have immunoregulatory effects and the aim of this research was to establish whether F. hepatica infection influences the response to vaccination against respiratory pathogens in calves. A total of 48 calves were randomly and equally allocated to two groups. The experimental group was infected with F. hepatica, while the other group was used as a control. At week 2 and 6 after infection calves from both groups were administered a vaccine containing inactivated PI-3, BRSV and Mannheimia haemolytica, pathogens commonly associated with bovine respiratory disease. Blood samples were taken weekly over 12 weeks to measure specific antibodies against all vaccine antigens and against F. hepatica, as well as IgG1 and IgG2 isotypes for PI-3 and BRSV specific antibodies. Faecal samples were examined for F. hepatica eggs and routine haematology and liver enzyme biochemistry were performed and cytokine production in vitro measured. Liver enzymes (GGT and GLDH) and eosinophils were significantly higher in the experimental group, whereas neutrophil numbers were higher in the control group. There was no significant difference between the groups in terms of vaccine-specific total responses to PI-3, BRSV and M. haemolytica. IgG1 levels were higher in comparison to IgG2 levels in both PI-3 and BRSV specific antibodies. IL-4 levels from stimulated and unstimulated PBMC were significantly higher in the control group. IFN-γ levels were significantly higher in PBMC from the control group when cultured in medium only. No significant differences were noted in the levels of other cytokines measured. In this work, no effect of early F. hepatica infection on the antibody responses to a range of respiratory vaccine antigens in calves was shown. However, differences in cytokine responsiveness of

  14. Methods, units and quality requirements for the analysis of haemoglobin A1c in diabetes mellitus

    PubMed Central

    Penttilä, Ilkka; Penttilä, Karri; Holm, Päivi; Laitinen, Harri; Ranta, Päivi; Törrönen, Jukka; Rauramaa, Rainer

    2016-01-01

    The formation of glycohemoglobin, especially the hemoglobin A1c (HbA1c) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970s it has been known that diabetics display higher values OF HbA1C because they have elevated blood glucose concentrations. Thus HbA1c has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement OF HbA1C, numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple mini-column technique to the very accurate automated high-pressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for HbA1c varied extensively between laboratories, therefore in United States and Canada working groups (WG) of the Diabetes Controls and Complications Trial (DCCT) were set up to standardize the HbA1c assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990s, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) appointed a new WG to plan a reference preparation and method for the HBA1c measurement. When the reference procedures were established, in 2004 IFCC recommended that all manufacturers for equipment used in HbA1c assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation (CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the HbA1c assays, analytical problems, problems with the units in which HbA1c values are expressed, reference values, quality control aspects, target requirements for HbA1c, and the relationship of the plasma glucose values to HbA1c concentrations. We also note that the acceptance

  15. Cytochrome P450 1A1 Regulates Breast Cancer Cell Proliferation and Survival

    PubMed Central

    Rodriguez, Mariangellys; Potter, David A.

    2013-01-01

    Cytochrome P450 1A1 (CYP1A1) is an extrahepatic phase I metabolizing enzyme whose expression is suppressed under physiologic conditions, but can be induced by substrates via the aryl hydrocarbon receptor (AhR). Nonetheless, recent studies show that the majority of breast tumors constitutively express CYP1A1. These findings led us to test the hypothesis that CYP1A1 promotes breast cancer progression by evaluating the effects of CYP1A1 knock down on the proliferation and survival of the MCF7 and MDA-MB-231 lines. Independently of estrogen receptor status, CYP1A1 knock down decreases cell proliferation, decreases colony formation, blocks the cell cycle at G0/G1 associated with reduction of cyclin D1, and increases apoptosis associated with reduction of survivin. CYP1A1 knock down markedly increases phosphorylation of AMP-activated protein kinase (AMPK) and decreases phosphorylation of AKT, extracellular signal-regulated kinases 1 and 2 (ERK1/2), and 70kDa ribosomal protein S6 kinase (P70S6K). AMPK inhibition by compound C partially abrogates the pro-apoptotic effects of CYP1A1siRNA, suggesting that CYP1A1siRNA effects are mediated, in part, through AMPK signaling. Consistent with CYP1A1 knock down results, pharmacologic reduction of CYP1A1 levels by the phytopolyphenol carnosol also correlates with impaired proliferation and induced AMPK phosphorylation. These results indicate that reduction of basal CYP1A1 expression is critical for inhibition of proliferation, which is not affected by alpha-naphthoflavone-mediated inhibition of CYP1A1 activity nor modulated by AhR silencing. This study supports that CYP1A1 may promote breast cancer proliferation and survival, at least in part, through AMPK signaling and that reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics. PMID:23576571

  16. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    PubMed

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis.

  17. Methods, units and quality requirements for the analysis of haemoglobin A1c in diabetes mellitus.

    PubMed

    Penttilä, Ilkka; Penttilä, Karri; Holm, Päivi; Laitinen, Harri; Ranta, Päivi; Törrönen, Jukka; Rauramaa, Rainer

    2016-06-26

    The formation of glycohemoglobin, especially the hemoglobin A1c (HbA1c) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970s it has been known that diabetics display higher values OF HbA1C because they have elevated blood glucose concentrations. Thus HbA1c has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement OF HbA1C, numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple mini-column technique to the very accurate automated high-pressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for HbA1c varied extensively between laboratories, therefore in United States and Canada working groups (WG) of the Diabetes Controls and Complications Trial (DCCT) were set up to standardize the HbA1c assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990s, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) appointed a new WG to plan a reference preparation and method for the HBA1c measurement. When the reference procedures were established, in 2004 IFCC recommended that all manufacturers for equipment used in HbA1c assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation (CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the HbA1c assays, analytical problems, problems with the units in which HbA1c values are expressed, reference values, quality control aspects, target requirements for HbA1c, and the relationship of the plasma glucose values to HbA1c concentrations. We also note that the acceptance

  18. Ultraviolet radiation decreases expression and induces aggregation of corneal ALDH3A1.

    PubMed

    Manzer, Rizwan; Pappa, Aglaia; Estey, Tia; Sladek, Norman; Carpenter, John F; Vasiliou, Vasilis

    2003-02-01

    Substantial reduction in corneal ALDH3A1 enzymatic activity associated with eye pathology was previously reported in C57BL/6J mice subjected to ultraviolet radiation (UVR). The aim of this study was to examine whether UVR diminishes corneal ALDH3A1 expression through modifications at the transcriptional, translational, or post-translational level. Adult C57BL/6J mice were subjected to UVR exposure (302 nm peak wavelength) for various periods of time, and corneal ALDH3A1 mRNA and protein levels were monitored by Northern and Western blot analysis, respectively. In addition, ALDH3A1 enzymatic activity was determined as a measure of post-translational modification. Mice exposed to 0.2 J/cm(2) UVB radiation demonstrated an extensive decrease, approximately 80%, in mRNA and protein levels, as well as enzymatic activity of corneal ALDH3A1. Significant reductions in corneal ALDH3A1 enzymatic activity were detected in mice 96 h after exposure to 0.05 and 0.1 J/cm(2) UVB radiation; no significant changes were observed in mRNA and protein levels. These data suggest that UVB down-regulates corneal ALDH3A1 expression at the transcriptional and/or post-translational level depending on the dose of UVB. Reduction in gene transcription requires UVB doses greater than or equal to 0.2 J/cm(2). In vitro experiments with human corneal epithelial cell lines stably transfected with human ALDH3A1 cDNA, and with purified recombinant human ALDH3A1 protein, indicated that ALDH3A1 undergoes post-translational modifications after UVR exposure. These modifications result in both covalent and non-covalent aggregation of the protein with no detectable precipitation. Such conformational changes may be associated with the function of ALDH3A1 as a chaperone-like molecule in the cornea. PMID:12604188

  19. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy.

    PubMed

    Gharavi, Ali G; Moldoveanu, Zina; Wyatt, Robert J; Barker, Catherine V; Woodford, Susan Y; Lifton, Richard P; Mestecky, Jiri; Novak, Jan; Julian, Bruce A

    2008-05-01

    IgA nephropathy (IgAN) is a complex trait determined by genetic and environmental factors. Most IgAN patients exhibit a characteristic undergalactosylation of the O-glycans of the IgA1 hinge region, which promotes formation and glomerular deposition of immune complexes. It is not known whether this aberrant glycosylation is the result of an acquired or inherited defect, or whether the presence of aberrant IgA1 glycoforms alone can produce IgAN. A newly validated lectin enzyme-linked immunosorbent assay (ELISA) was used to determine the serum level of galactose-deficient IgA1 (Gd-IgA1) in a cohort of 89 IgAN patients and 266 of their relatives. High Gd-IgA1 levels (> or =95th percentile for controls) were observed in all 5 available patients with familial IgAN, in 21 of 45 (47%) of their at-risk relatives (assuming autosomal dominant inheritance), and in only 1 of 19 (5%) of unrelated individuals who married into the family. This provides evidence that abnormal IgA1 glycosylation is an inherited rather than acquired trait. Similarly, Gd-IgA1 levels were high in 65 of 84 (78%) patients with sporadic IgAN and in 50 of 202 (25%) blood relatives. Heritability of Gd-IgA1 was estimated at 0.54 (P = 0.0001), and segregation analysis suggested the presence of a major dominant gene on a polygenic background. Because most relatives with abnormal IgA1 glycoforms were asymptomatic, additional cofactors must be required for IgAN to develop. The fact that abnormal IgA1 glycosylation clusters in most but not all families suggests that measuring Gd-IgA1 may help distinguish patients with different pathogenic mechanisms of disease.

  20. Epigenetic Regulation of Vitamin D 24-Hydroxylase/CYP24A1 in Human Prostate Cancer

    PubMed Central

    Luo, Wei; Karpf, Adam R.; Deeb, Kristin K.; Muindi, Josephia R.; Morrison, Carl D.; Johnson, Candace S.; Trump, Donald L.

    2010-01-01

    Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the CYP24A1 gene which is downregulated in human prostate cancer by unknown mechanisms. We found that CYP24A1 expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates CYP24A1 expression in prostate cancer cells. In vitro methylation of the CYP24A1 promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of CYP24A1 in prostate cancer cells. ChIP-qPCR reveals that specific histone modifications are associated with the CYP24A1 promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the CYP24A1 promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of VDR to the CYP24A1 promoter. RT-PCR analysis of paired human prostate samples reveals that CYP24A1 expression is down-regulated in prostate malignant lesions compared to adjacent histologically benign lesions. Bisulfite pyrosequencing shows that CYP24A1 gene is hypermethylated in malignant lesions compared to matched benign lesions. Our findings indicate that repression of CYP24A1 gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. PMID:20587525

  1. The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse.

    PubMed

    Heitzmann, Dirk; Buehler, Philipp; Schweda, Frank; Georgieff, Michael; Warth, Richard; Thomas, Joerg

    2016-02-01

    The nucleoside adenosine has been implicated in the regulation of respiration, especially during hypoxia in the newborn. In this study the role of adenosine A1 receptors for the control of respiration was investigated in vivo. To this end, respiration of unrestrained adult and neonatal adenosine A1 receptor knockout mice (A1R(-/-)) was measured in a plethysmographic device. Under control conditions (21% O2) and mild hypoxia (12-15% O2) no difference of respiratory parameters was observed between adult wildtype (A1R(+/+)) and A1R(-/-) mice. Under more severe hypoxia (6-10% O2) A1R(+/+) mice showed, after a transient increase of respiration, a decrease of respiration frequency (fR) and tidal volume (VT) leading to a decrease of minute volume (MV). This depression of respiration during severe hypoxia was absent in A1R(-/-) mice which displayed a stimulated respiration as indicated by the enhancement of MV by some 50-60%. During hypercapnia-hyperoxia (3-10% CO2/97-90 % O2), no obvious differences in respiration of A1R(-/-) and A1R(+/+) was observed. In neonatal mice, the respiratory response to hypoxia was surprisingly similar in both genotypes. However, neonatal A1R(-/-) mice appeared to have more frequently periods of apnea during hypoxia and in the post-hypoxic control period. In conclusion, these data indicate that the adenosine A1 receptor is an important molecular component mediating hypoxic depression in adult mice and it appears to stabilize respiration of neonatal mice. PMID:26593641

  2. [Analytical problems in determination of hemoglobin A1c and the different ways of its interpretation].

    PubMed

    Góth, László

    2009-04-19

    Glycated proteins are formed during the nonenzymatic reaction of glucose and amino groups of proteins. Hemoglobin A1c is formed by the condensation of glucose with the N-terminal valine residue of each beta-chain of hemoglobin A. The amount of glycated hemoglobin in blood depends on both life-span of red blood cells and blood glucose concentration. As the rate of formation of hemoglobin A1c is directly proportional to the concentration of glucose in the blood, it represent the integrated values for glucose over the preceding 6 to 8 weeks. Hemoglobin A1c determination is widely used for monitoring long-term glycemic control, and it is a risk factor for complications of diabetes. The concentration of blood hemoglobin A1c depends on further factors such as half-life of hemoglobin, blood carbohydrates, blood analytes, methods of determination and calibration. Committees were established under the auspices of the American Association of Clinical Chemistry, American Diabetes Association, International Federation of Clinical Chemistry (IFCC) to standardize HbA1c assays (DCCT: Diabetes Control and Complications Trial, NGSP: National Glycohemoglobin Standardization Program, IFCC reference method for measurement of HbA1c). The NGSP recommends to report HbA1c result in % (g HbA1c/g hemoglobin) while IFCC suggests mmol HbA1c/mol hemoglobin A. Reports are presenting mathematical relationship between HbA1c and average glucose concentration in blood, however, the clinical usefulness of estimating average serum glucose from HbA1c level is under discussion. PMID:19362928

  3. Induction of human UGT1A1 by bilirubin through AhR dependent pathway.

    PubMed

    Togawa, Hiroshi; Shinkai, Shigeko; Mizutani, Takaharu

    2008-12-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) plays a key role to conjugate bilirubin and preventing jaundice, but there is no report showing the induction of human UGT1A1 (UGT1A1) by bilirubin. In this report, we show findings of the induction of the reporter gene (-3475/+14) of UGT1A1 in HepG2 cells by bilirubin at 50 microM, 100 microM, with human aryl hydrocarbon receptor (hAhR). We confirmed that induction of the reporter gene by bilirubin is dependent on the position of the xenobiotic responsive element (XRE) (-3328/-3319) of UGT1A1, because the XRE deletion UGT1A1 gene did not respond to stimulation by a complex of bilirubin and hAhR. alpha-Naphthoflavone (alpha-NF) of a typical AhR antagonist at 50 microM inhibited induction by bilirubin, suggesting that bilirubin stimulates through binding with hAhR. Meanwhile, bilirubin itself did not stimulate the induction of AhR, because we detected no-elevation of the mRNA level of AhR by RT-PCR. These results indicate that the induction of UGT1A1 by bilirubin-AhR did not depend on the elevation of AhR but on ligand binding. From this result, we considered that high bilirubin in neonates must induce the elevation of UGT1A1 after birth to prevent jaundice, and bilirubin in adults also regulates the level of UGT1A1. This is the first report showing direct induction of UGT1A1 by a bilirubin through AhR pathway. PMID:19356098

  4. The clinical application of UGT1A1 pharmacogenetic testing: Gene-environment interactions

    PubMed Central

    2010-01-01

    Over the past decade, the number of pharmacogenetic tests has increased considerably, allowing for the development of our knowledge of their clinical application. The uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) assay is an example of a pharmacogenetic test. Numerous variants have been found in UGT1A1, the main conjugating enzyme of bilirubin and drugs such as the anticancer drug irinotecan. Recently, the US Food and Drug Administration (FDA) recommended testing for the presence of UGT1A1*28, an allele correlated with decreased transcriptional activity, to predict patients at risk of irinotecan toxicity. The administration of other drugs -- such as inhibitors of the UGT1A1 enzyme -- can clinically mimic the *28 phenotype, whereas inducers of UGT1A1 can increase the glucuronidation rate of the enzyme. The *28 polymorphism is not present in all ethnicities at a similar frequency, which suggests that it is important to study different populations to determine the clinical relevance of testing for UGT1A1*28 and to identify other clinically relevant UGT1A1 variants. Environmental factors such as lifestyle can also affect UGT1A1 activity. This review is a critical analysis of studies on drugs that can be affected by the presence of UGT1A1*28, the distribution of this polymorphism around the globe, distinct variants that may be clinically significant in African and Asian populations and how lifestyle can affect treatment outcomes that depend on UGT1A1 activity. PMID:20511137

  5. Axonal patterns and targets of dA1 interneurons in the chick hindbrain.

    PubMed

    Kohl, Ayelet; Hadas, Yoav; Klar, Avihu; Sela-Donenfeld, Dalit

    2012-04-25

    Hindbrain dorsal interneurons that comprise the rhombic lip relay sensory information and coordinate motor outputs. The progenitor dA1 subgroup of interneurons, which is formed along the dorsal-most region of the caudal rhombic lip, gives rise to the cochlear and precerebellar nuclei. These centers project sensory inputs toward upper-brain regions. The fundamental role of dA1 interneurons in the assembly and function of these brainstem nuclei is well characterized. However, the precise en route axonal patterns and synaptic targets of dA1 interneurons are not clear as of yet. Novel genetic tools were used to label dA1 neurons and trace their axonal trajectories and synaptic connections at various stages of chick embryos. Using dA1-specific enhancers, two contralateral ascending axonal projection patterns were identified; one derived from rhombomeres 6-7 that elongated in the dorsal funiculus, while the other originated from rhombomeres 2-5 and extended in the lateral funiculus. Targets of dA1 axons were followed at later stages using PiggyBac-mediated DNA transposition. dA1 axons were found to project and form synapses in the auditory nuclei and cerebellum. Investigation of mechanisms that regulate the patterns of dA1 axons revealed a fundamental role of Lim-homeodomain (HD) proteins. Switch in the expression of the specific dA1 Lim-HD proteins Lhx2/9 into Lhx1, which is typically expressed in dB1 interneurons, modified dA1 axonal patterns to project along the routes of dB1 subgroup. Together, the results of this research provided new tools and knowledge to the assembly of trajectories and connectivity of hindbrain dA1 interneurons and of molecular mechanisms that control these patterns.

  6. Attenuation of Cigarette Smoke-Induced Emphysema in Mice by Apolipoprotein A-1 Overexpression.

    PubMed

    Kim, Chorong; Lee, Ji-Min; Park, Sung-Woo; Kim, Ki-Sun; Lee, Myoung Won; Paik, Sanghyun; Jang, An Soo; Kim, Do Jin; Uh, Sootaek; Kim, Yonghoon; Park, Choon-Sik

    2016-01-01

    Chronic inflammation, oxidative stress, and proteolysis participate primarily in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. COPD is a highly prevalent smoking-related disease for which no effective therapy exists to improve the disease course. Although apolipoprotein A-1 (ApoA1) has antiinflammatory and antioxidant properties as well as cholesterol efflux potential, its role in cigarette smoke (CS)-induced emphysema has not been determined. Therefore, we investigated whether human ApoA1 transgenic (TG) mice, with conditionally induced alveolar epithelium to overexpress ApoA1, are protected against the CS-induced lung inflammatory response and development of emphysema. In this study, ApoA1 levels were significantly decreased in the lungs of patients with COPD and in the lungs of mice exposed to CS. ApoA1 TG mice did not develop emphysema when chronically exposed to CS. Compared with the control TG mice, ApoA1 overexpression attenuated lung inflammation, oxidative stress, metalloprotease activation, and apoptosis in CS-exposed mouse lungs. To explore a plausible mechanism of antiapoptotic activity of ApoA1, alveolar epithelial cells (A549) were treated with CS extract (CSE). ApoA1 prevented CSE-induced translocation of Fas and downstream death-inducing signaling complex into lipid rafts, thereby inhibiting Fas-mediated apoptosis. Taken together, the data showed that ApoA1 overexpression attenuated CS-induced lung inflammation and emphysema in mice. Augmentation of ApoA1 in the lung may have therapeutic potential in preventing smoking-related COPD/emphysema.

  7. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    PubMed

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p < 0.05) and performed worse in beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI. PMID:26608888

  8. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1.

    PubMed

    Suzuki, Hitoshi; Moldoveanu, Zina; Hall, Stacy; Brown, Rhubell; Vu, Huong L; Novak, Lea; Julian, Bruce A; Tomana, Milan; Wyatt, Robert J; Edberg, Jeffrey C; Alarcón, Graciela S; Kimberly, Robert P; Tomino, Yasuhiko; Mestecky, Jiri; Novak, Jan

    2008-02-01

    Aberrant glycosylation of IgA1 plays an essential role in the pathogenesis of IgA nephropathy. This abnormality is manifested by a deficiency of galactose in the hinge-region O-linked glycans of IgA1. Biosynthesis of these glycans occurs in a stepwise fashion beginning with the addition of N-acetylgalactosamine by the enzyme N-acetylgalactosaminyltransferase 2 and continuing with the addition of either galactose by beta1,3-galactosyltransferase or a terminal sialic acid by a N-acetylgalactosamine-specific alpha2,6-sialyltransferase. To identify the molecular basis for the aberrant IgA glycosylation, we established EBV-immortalized IgA1-producing cells from peripheral blood cells of patients with IgA nephropathy. The secreted IgA1 was mostly polymeric and had galactose-deficient O-linked glycans, characterized by a terminal or sialylated N-acetylgalactosamine. As controls, we showed that EBV-immortalized cells from patients with lupus nephritis and healthy individuals did not produce IgA with the defective galactosylation pattern. Analysis of the biosynthetic pathways in cloned EBV-immortalized cells from patients with IgA nephropathy indicated a decrease in beta1,3-galactosyltransferase activity and an increase in N-acetylgalactosamine-specific alpha2,6-sialyltransferase activity. Also, expression of beta1,3-galactosyltransferase was significantly lower, and that of N-acetylgalactosamine-specific alpha2,6-sialyltransferase was significantly higher than the expression of these genes in the control cells. Thus, our data suggest that premature sialylation likely contributes to the aberrant IgA1 glycosylation in IgA nephropathy and may represent a new therapeutic target.

  9. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1

    PubMed Central

    Suzuki, Hitoshi; Moldoveanu, Zina; Hall, Stacy; Brown, Rhubell; Vu, Huong L.; Novak, Lea; Julian, Bruce A.; Tomana, Milan; Wyatt, Robert J.; Edberg, Jeffrey C.; Alarcón, Graciela S.; Kimberly, Robert P.; Tomino, Yasuhiko; Mestecky, Jiri; Novak, Jan

    2008-01-01

    Aberrant glycosylation of IgA1 plays an essential role in the pathogenesis of IgA nephropathy. This abnormality is manifested by a deficiency of galactose in the hinge-region O-linked glycans of IgA1. Biosynthesis of these glycans occurs in a stepwise fashion beginning with the addition of N-acetylgalactosamine by the enzyme N-acetylgalactosaminyltransferase 2 and continuing with the addition of either galactose by β1,3-galactosyltransferase or a terminal sialic acid by a N-acetylgalactosamine–specific α2,6-sialyltransferase. To identify the molecular basis for the aberrant IgA glycosylation, we established EBV-immortalized IgA1-producing cells from peripheral blood cells of patients with IgA nephropathy. The secreted IgA1 was mostly polymeric and had galactose-deficient O-linked glycans, characterized by a terminal or sialylated N-acetylgalactosamine. As controls, we showed that EBV-immortalized cells from patients with lupus nephritis and healthy individuals did not produce IgA with the defective galactosylation pattern. Analysis of the biosynthetic pathways in cloned EBV-immortalized cells from patients with IgA nephropathy indicated a decrease in β1,3-galactosyltransferase activity and an increase in N-acetylgalactosamine–specific α2,6-sialyltransferase activity. Also, expression of β1,3-galactosyltransferase was significantly lower, and that of N-acetylgalactosamine–specific α2,6-sialyltransferase was significantly higher than the expression of these genes in the control cells. Thus, our data suggest that premature sialylation likely contributes to the aberrant IgA1 glycosylation in IgA nephropathy and may represent a new therapeutic target. PMID:18172551

  10. 17 CFR 275.202(a)(1)-1 - Certain transactions not deemed assignments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Certain transactions not deemed assignments. 275.202(a)(1)-1 Section 275.202(a)(1)-1 Commodity and Securities Exchanges SECURITIES...)(1)-1 Certain transactions not deemed assignments. A transaction which does not result in a change...

  11. 17 CFR 275.202(a)(1)-1 - Certain transactions not deemed assignments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certain transactions not deemed assignments. 275.202(a)(1)-1 Section 275.202(a)(1)-1 Commodity and Securities Exchanges SECURITIES...)(1)-1 Certain transactions not deemed assignments. A transaction which does not result in a change...

  12. 17 CFR 275.202(a)(1)-1 - Certain transactions not deemed assignments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Certain transactions not deemed assignments. 275.202(a)(1)-1 Section 275.202(a)(1)-1 Commodity and Securities Exchanges SECURITIES...)(1)-1 Certain transactions not deemed assignments. A transaction which does not result in a change...

  13. Genome Sequence of Bacillus cereus Strain A1, an Efficient Starch-Utilizing Producer of Hydrogen.

    PubMed

    Zhang, Ting; Bao, Meidan; Wang, Yu; Su, Haijia; Tan, Tianwei

    2014-01-01

    Bacillus cereus strain A1 is a newly isolated hydrogen producer capable of utilizing bioresources and biowaste, such as starch and starch wastewater. Here, we present a 5.67-Mb assembly of the genome sequence of strain A1, which may provide insights into the molecular mechanism of hydrogen production from bioresources and biowaste.

  14. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or required... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of...

  15. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or required... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of...

  16. Production of the allergenic protein Alt a 1 by Alternaria isolates from working environments.

    PubMed

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-02-16

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%-16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103-6.528 ng/mL) than a ATCC strain (0.551-0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

  17. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia.

    PubMed

    Coulon, Séverine; Dussiot, Michaël; Grapton, Damien; Maciel, Thiago Trovati; Wang, Pamella Huey Mei; Callens, Celine; Tiwari, Meetu Kaushik; Agarwal, Saurabh; Fricot, Aurelie; Vandekerckhove, Julie; Tamouza, Houda; Zermati, Yael; Ribeil, Jean-Antoine; Djedaini, Kamel; Oruc, Zeliha; Pascal, Virginie; Courtois, Geneviève; Arnulf, Bertrand; Alyanakian, Marie-Alexandra; Mayeux, Patrick; Leanderson, Tomas; Benhamou, Marc; Cogné, Michel; Monteiro, Renato C; Hermine, Olivier; Moura, Ivan C

    2011-10-23

    Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXXΦ. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.

  18. A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis

    PubMed Central

    Bäumer, Nicole; Bäumer, Sebastian; Haak, Miriam; Koschmieder, Steffen; Schönig, Kai; Berdel, Wolfgang E.; Müller-Tidow, Carsten

    2015-01-01

    The quest for novel therapeutic targets in acute myeloid leukemia (AML) is still ongoing. One of such targets, cyclin A1, was shown to be overexpressed in AML including AML stem cells. However, the function of cyclin A1 in AML is largely unknown, and the data on its impact on patients´ survival remain controversial. Therefore, we developed a transgenic mouse model of stem cell-directed inducible cyclin A1 overexpression and crossed these mice with PML-RARα-knockin mice, which develop an AML M3-like phenotype. To observe the effects of cyclin A1 loss-of-function, we also crossed PML-RARα-knockin mice to cyclin A1-knockout mice. Neither overexpression nor loss of cyclin A1 significantly altered leukemogenesis in PML-RARα-knockin mice. These findings imply that upregulation of cyclin A1 is not essential for leukemogenesis. Our data suggest that cyclin A1 does not represent a suitable target for AML therapy. PMID:26080083

  19. Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

    PubMed Central

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-01-01

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL) than a ATCC strain (0.551–0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein. PMID:25689994

  20. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of business... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or...

  1. Comparison of Technology Use between Biology and Physics Teachers in a 1:1 Laptop Environment

    ERIC Educational Resources Information Center

    Crook, Simon J.; Sharma, Manjula D.; Wilson, Rachel

    2015-01-01

    Using a mixed-methods approach the authors compared the associated practices of senior physics teachers (n = 7) and students (n = 53) in a 1:1 laptop environment with those of senior biology teachers (n = 10) and students (n = 125) also in a 1:1 laptop environment, in seven high schools in Sydney, NSW, Australia. They found that the physics…

  2. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or required... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of...

  3. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or required... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of...

  4. 42 CFR 63a.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for research training with respect to the human diseases, disorders, or other aspects of human health... 42 Public Health 1 2010-10-01 2010-10-01 false To what programs do these regulations apply? 63a.1 Section 63a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  5. 42 CFR 63a.1 - To what programs do these regulations apply?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... for research training with respect to the human diseases, disorders, or other aspects of human health... 42 Public Health 1 2011-10-01 2011-10-01 false To what programs do these regulations apply? 63a.1 Section 63a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  6. NEK2 mediates ALDH1A1-dependent drug resistance in multiple myeloma

    PubMed Central

    Xia, Jiliang; Gu, Zhimin; Wendlandt, Erik; Zhan, Xin; Janz, Siegfried; Tricot, Guido; Zhan, Fenghuang

    2014-01-01

    We reported previously that increased expression of aldehyde dehydrogenase 1 (ALDH1) in multiple myeloma (MM) is a marker of tumor-initiating cells (TICs) that is further associated with chromosomal instability (CIN). Here we demonstrate that member A1 of the ALDH1 family of proteins, ALDH1A1, is most abundantly expressed in myeloma. Enforced expression of ALDH1A1 in myeloma cells led to increased clonogenicity, tumor formation in mice, and resistance to myeloma drugs in vitro and in vivo. The mechanism underlying these phenotypes included the ALDH1A1-dependent activation of drug-efflux pump, ABCB1, and survival proteins, AKT and BCL2. Over expression of ALDH1A1 in myeloma cells led to increased mRNA and protein levels of NIMA-related kinase 2 (NEK2), whereas shRNA-mediated knock down of NEK2 decreased drug efflux pump activity and drug resistance. The activation of NEK2 in myeloma cells relied on the ALDH1A1-dependent generation of the retinoid X receptor α (RXRα) ligand, 9-cis retinoic acid (9CRA) – not the retinoic acid receptor α (RARα) ligand, all-trans retinoic acid (ATRA). These findings implicate the ALDH1A1-RXRα-NEK2 pathway in drug resistance and disease relapse in myeloma and suggest that specific inhibitors of ALDH1A1 are worthy of consideration for clinical development of new approaches to overcome drug resistance in myeloma. PMID:25230277

  7. FBG1 Is the Final Arbitrator of A1AT-Z Degradation

    PubMed Central

    Wen, John H.; Wen, Hsiang; Gibson-Corley, Katherine N.; Glenn, Kevin A.

    2015-01-01

    Alpha-1 antitrypsin deficiency is the leading cause of childhood liver failure and one of the most common lethal genetic diseases. The disease-causing mutant A1AT-Z fails to fold correctly and accumulates in the endoplasmic reticulum (ER) of the liver, resulting in hepatic fibrosis and hepatocellular carcinoma in a subset of patients. Furthermore, A1AT-Z sequestration in hepatocytes leads to a reduction in A1AT secretion into the serum, causing panacinar emphysema in adults. The purpose of this work was to elucidate the details by which A1AT-Z is degraded in hepatic cell lines. We identified the ubiquitin ligase FBG1, which has been previously shown to degrade proteins by both the ubiquitin proteasome pathway and autophagy, as being key to A1AT-Z degradation. Using chemical and genetic approaches we show that FBG1 degrades A1AT-Z through both the ubiquitin proteasome system and autophagy. Overexpression of FBG1 decreases the half-life of A1AT-Z and knocking down FBG1 in a hepatic cell line, and in mice results in an increase in ATAT. Finally, we show that FBG1 degrades A1AT-Z through a Beclin1-dependent arm of autophagy. In our model, FBG1 acts as a safety ubiquitin ligase, whose function is to re-ubiquitinate ER proteins that have previously undergone de-ubiquitination to ensure they are degraded. PMID:26295339

  8. Production of the allergenic protein Alt a 1 by Alternaria isolates from working environments.

    PubMed

    Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz

    2015-02-01

    The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%-16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103-6.528 ng/mL) than a ATCC strain (0.551-0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein. PMID:25689994

  9. Cytochrome P450, CYP93A1, as a defense marker in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CYP93A1 is a cytochrome P450 that is involved in the synthesis of the phytoalexin glyceollin in soybean (Glycine max L. Merr). The gene encoding CYP93A1 has been used as a defense marker in soybean cell cultures, however, little is known regarding how this gene is expressed in the intact plant. To f...

  10. NR4A1 promotes PDGF-BB-induced cell colony formation in soft agar.

    PubMed

    Eger, Glenda; Papadopoulos, Natalia; Lennartsson, Johan; Heldin, Carl-Henrik

    2014-01-01

    The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth. PMID:25269081

  11. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1 Methane 74-82-8 CH4 a...

  12. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Global Warming Potentials A Table A-1 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... A-1 to Subpart A of Part 98—Global Warming Potentials Name CAS No. Chemical formula Global...

  13. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Global Warming Potentials A Table A-1 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... A-1 to Subpart A of Part 98—Global Warming Potentials Name CAS No. Chemical formula Global...

  14. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Global Warming Potentials A Table A-1 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... A-1 to Subpart A of Part 98—Global Warming Potentials Name CAS No. Chemical formula Global...

  15. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1 Methane 74-82-8 CH4...

  16. 26 CFR 1.6050A-1 - Reporting requirements of certain fishing boat operators.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Reporting requirements of certain fishing boat operators. 1.6050A-1 Section 1.6050A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... requirements of certain fishing boat operators. (a) Requirement of reporting. The operator of a boat on...

  17. 26 CFR 1.6050A-1 - Reporting requirements of certain fishing boat operators.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Reporting requirements of certain fishing boat operators. 1.6050A-1 Section 1.6050A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... requirements of certain fishing boat operators. (a) Requirement of reporting. The operator of a boat on...

  18. 26 CFR 1.6050A-1 - Reporting requirements of certain fishing boat operators.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Reporting requirements of certain fishing boat operators. 1.6050A-1 Section 1.6050A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... certain fishing boat operators. (a) Requirement of reporting. The operator of a boat on which one or...

  19. 26 CFR 1.6050A-1 - Reporting requirements of certain fishing boat operators.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Reporting requirements of certain fishing boat operators. 1.6050A-1 Section 1.6050A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... requirements of certain fishing boat operators. (a) Requirement of reporting. The operator of a boat on...

  20. 26 CFR 1.6050A-1 - Reporting requirements of certain fishing boat operators.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Reporting requirements of certain fishing boat operators. 1.6050A-1 Section 1.6050A-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... requirements of certain fishing boat operators. (a) Requirement of reporting. The operator of a boat on...

  1. A Chemical and Structural Study of the A1N-Si Interface

    NASA Technical Reports Server (NTRS)

    George, T.; Beye, R.

    1997-01-01

    Samples of A1N grown on silicon [111] subtrates were examined using electron enery loss spectroscopy (EELS) and selected area diffraction (SAD) with high-resolution transmission electron microscopy (TEM) to determine the source of out-of-place tilts and in-plane rotations of the A1N crystallites at the Si interface.

  2. 78 FR 36440 - Approval and Promulgation of Implementation Plans; Tennessee; 110(a)(1) and (2) Infrastructure...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... AGENCY 40 CFR Part 52 Approval and Promulgation of Implementation Plans; Tennessee; 110(a)(1) and (2... conditionally approve in part, portions of the State Implementation Plan (SIP) submission, submitted by the... demonstrate that the State meets the requirements of sections 110(a)(1) and (2) of the Clean Air Act (CAA...

  3. 26 CFR 53.4941(a)-1 - Imposition of initial taxes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(a)-1 Imposition of initial taxes. (a) Tax on self-dealer—(1) In general. Section 4941(a)(1) of the code imposes an excise tax on each act of self-dealing between a disqualified person (as defined in section 4946(a))...

  4. 26 CFR 53.4941(a)-1 - Imposition of initial taxes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(a)-1 Imposition of initial taxes. (a) Tax on self-dealer—(1) In general. Section 4941(a)(1) of the code imposes an excise tax on each act of self-dealing between a disqualified person (as defined in section 4946(a))...

  5. 26 CFR 53.4941(a)-1 - Imposition of initial taxes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(a)-1 Imposition of initial taxes. (a) Tax on self-dealer—(1) In general. Section 4941(a)(1) of the code imposes an excise tax on each act of self-dealing between a disqualified person (as defined in section 4946(a))...

  6. 26 CFR 53.4941(a)-1 - Imposition of initial taxes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(a)-1 Imposition of initial taxes. (a) Tax on self-dealer—(1) In general. Section 4941(a)(1) of the code imposes an excise tax on each act of self-dealing between a disqualified person (as defined in section 4946(a))...

  7. Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors

    PubMed Central

    Morgan, Cynthia A.; Hurley, Thomas D.

    2015-01-01

    Aldehyde dehydrogenases (ALDH) catalyze the irreversible oxidation of aldehydes to their corresponding carboxylic acid. Alterations in ALDH1A1 activity are associated with such diverse diseases as cancer, Parkinson’s disease, obesity, and cataracts. Inhibitors of ALDH1A1 could aid in illuminating the role of this enzyme in disease processes. However, there are no commercially available selective inhibitors for ALDH1A1. Here we characterize two distinct chemical classes of inhibitors that are selective for human ALDH1A1 compared to eight other ALDH isoenzymes. The prototypical members of each structural class, CM026 and CM037, exhibit sub-micromolar inhibition constants, but have different mechanisms of inhibition. The crystal structures of these compounds bound to ALDH1A1 demonstrate that they bind within the aldehyde binding pocket of ALDH1A1 and exploit the presence of a unique Glycine residue to achieve their selectivity. These two novel and selective ALDH1A1 inhibitors may serve as chemical tools to better understand the contributions of ALDH1A1 to normal biology and to disease states. PMID:25634381

  8. Apolipoprotein A1/C3/A5 haplotypes and serum lipid levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels ...

  9. 26 CFR 1.642(a)(1)-1 - Partially tax-exempt interest.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Partially tax-exempt interest. 1.642(a)(1)-1...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(a)(1)-1 Partially tax-exempt interest. An estate or trust is allowed the credit against tax for partially...

  10. 40 CFR Appendix A1 to Subpart F of... - Generic Maximum Contaminant Levels

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Generic Maximum Contaminant Levels A1 Appendix A1 to Subpart F of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Recycling and Emissions Reduction Pt....

  11. 40 CFR Appendix A1 to Subpart F of... - Generic Maximum Contaminant Levels

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Generic Maximum Contaminant Levels A1 Appendix A1 to Subpart F of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Recycling and Emissions Reduction Pt....

  12. 40 CFR Appendix A1 to Subpart F of... - Generic Maximum Contaminant Levels

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Generic Maximum Contaminant Levels A1 Appendix A1 to Subpart F of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Recycling and Emissions Reduction Pt....

  13. 40 CFR Appendix A1 to Subpart F of... - Generic Maximum Contaminant Levels

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Generic Maximum Contaminant Levels A1 Appendix A1 to Subpart F of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Recycling and Emissions Reduction Pt....

  14. 40 CFR Appendix A1 to Subpart F of... - Generic Maximum Contaminant Levels

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Generic Maximum Contaminant Levels A1 Appendix A1 to Subpart F of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Recycling and Emissions Reduction Pt....

  15. 26 CFR 1.925(a)-1 - Transfer pricing rules for FSCs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Return of partnership income. 1.6031(a)-1...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6031(a)-1 Return of partnership income. (a) Domestic partnerships—(1) Return required. Except as provided in paragraphs (a)(3) and (c)...

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    Code of Federal Regulations, 2011 CFR

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    Code of Federal Regulations, 2010 CFR

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    Code of Federal Regulations, 2014 CFR

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  20. NR4A1 Promotes PDGF-BB-Induced Cell Colony Formation in Soft Agar

    PubMed Central

    Eger, Glenda; Papadopoulos, Natalia; Lennartsson, Johan; Heldin, Carl-Henrik

    2014-01-01

    The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth. PMID:25269081