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Sample records for avium complex paradigm

  1. The Mycobacterium avium complex.

    PubMed Central

    Inderlied, C B; Kemper, C A; Bermudez, L E

    1993-01-01

    Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing

  2. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms were measured. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1s-1, and the EPMs of fifteen environmental isolates ranged from -1...

  3. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms isolated from clinical and environmental sources were measured in 9.15 mM KH2PO4 buffered water. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1 ...

  4. Mechanism of Mycobacterium avium complex pathogenesis.

    PubMed

    Reddy, V M

    1998-06-08

    Mycobacterium avium complex (MAC) group of microorganisms are the most common opportunistic bacterial pathogens causing disseminated disease in HIV infected patients. These microorganisms are ubiquitous in nature, and are acquired by respiratory and oral routes. Pathogenesis of MAC depends on the ability of the organisms to colonize intestinal/respiratory mucosa, penetrate the protective barriers and resist intracellular killing by macrophages. Transient and reversible variation of colony morphology is one the characteristic feature of MAC that plays a significant role in the virulence and pathogenesis of these microorganisms. Isogenic colony variants of MAC differ in their virulence, susceptibility to antibiotics, stimulation of oxygen radicals and cytokines. The virulent smooth transparent colony variants are more frequently isolated from AIDS patients, more efficient in mucosal colonization, and adhere more efficiently to epithelial cells as compared to the less virulent smooth opaque variants. However, both the isogenic variants bind to the mucosal epithelial cells through the same multiple receptors. In addition, both the isogenic variants of MAC also bind to intestinal mucus through a single receptor. Study of the interaction of MAC with the host cells and characterization of MAC adhesins and host cell receptors facilitates the elucidation of the mechanisms involved in MAC pathogenesis.

  5. GENETIC FINGERPRINTING OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS ISOLATED FROM HOSPITAL PATIENTS AND THE ENVIRONMENT

    EPA Science Inventory

    A particularly pathogenic group of mycobacteria belong to the Mycobacterium avium complex (MAC), which includes M. avium and M. intracellulare. MAC organisms cause disease in children, the elderly, and immuno-compromised individuals. A critical step in preventing MAC infections...

  6. [Mycobacterium avium complex in water buffaloes slaughtered for consumption].

    PubMed

    Freitas, J; Panetta, J C; Curcio, M; Ueki, S Y

    2001-06-01

    Two mycobacterium strains isolated from lung tissue a apical lymph nodes of slaughtered water buffaloes were biochemically analyzed and identified as Mycobacterium avium complex strains. Association between these microorganisms and the acquired immunodeficiency syndrome, and the potential risk posed by eating infected animals and their products, was discussed.

  7. Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations.

    PubMed

    Andréjak, Claire; Almeida, Deepak V; Tyagi, Sandeep; Converse, Paul J; Ammerman, Nicole C; Grosset, Jacques H

    2015-04-01

    The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. PMID:25624335

  8. Detection of quantification of Mycobacterium avium complex organisms in drinking water

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U. S. Environmental Protection Agency’s Contaminant Candidate List 2 (CCL2) due to their association with human disease and occurrence in public dr...

  9. REAL-TIME QUANTITATIVE PCR DETECTION OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS IN DRINKING WATER

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U.S. Environmental Protection Agency's Contaminant Candidate List (CCL) due to their association with human disease and occurrence in public drinkin...

  10. Draft genome sequence of a Mycobacterium avium complex isolate from a broadbill bird

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the draft genome sequences of ten Mycobacterium avium complex isolates obtained from diverse hosts. This collection includes isolates obtained from deer, pig, elephant, ruddy duck and Red-tailed hawk species. The type strain of Mycobacterium avium subspecies silvaticum (ATCC 49884) is also...

  11. AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM AVIUM COMPLEX ISOLATES RECOVERED FROM SOUTHERN CALIFORNIA

    EPA Science Inventory

    Fine-scale genotyping methods are necessary in order to identify possible sources of human exposure to opportunistic pathogens belonging to the Mycobacterium avium complex (MAC). In this study, amplified fragment length polymorphism (AFLP) analysis was evaluated for fingerprintin...

  12. Infection of Eurasian badgers (Meles meles) with Mycobacterium avium complex (MAC) bacteria.

    PubMed

    Balseiro, Ana; Merediz, Isabel; Sevilla, Iker A; García-Castro, Carmen; Gortázar, Christian; Prieto, José M; Delahay, Richard J

    2011-05-01

    There are few reports of infection with Mycobacterium avium complex (MAC) bacteria in badgers. In this study archive data relating to the isolation of MAC organisms from badgers in the UK is presented, and information derived from recent cases of such infection in Spain is used to illustrate the associated pathology and to characterise strain types. Tissue samples were cultured for mycobacteria and, in the case of Spanish badgers, were examined both histopathologically and using immunohistochemistry, and DNA typing of M. avium isolates was also carried out. A total of 5 (7.35%) and 281 (0.51%) isolates of M. avium spp. were recovered from badgers from the studies in Spain and the UK, respectively. DNA typing of the isolates from Spain identified the sub-species M. avium hominissuis and M. avium avium. These findings provide new information on the prevalence of MAC organisms in badgers in the UK and Spain. The extent to which infected badgers may be involved in the epidemiology of M. avium in other wild or domestic hosts remains unknown.

  13. Investigation of Spa Pools Associated with Lung Disorders Caused by Mycobacterium avium Complex in Immunocompetent Adults

    PubMed Central

    Lumb, Richard; Stapledon, Richard; Scroop, Andrew; Bond, Peter; Cunliffe, David; Goodwin, Allan; Doyle, Robyn; Bastian, Ivan

    2004-01-01

    Three cases of Mycobacterium avium complex-related lung disorders were associated with two poorly maintained spa pools by genotypic investigations. Inadequate disinfection of the two spas had reduced the load of environmental bacteria to less than 1 CFU/ml but allowed levels of M. avium complex of 4.3 × 104 and 4.5 × 103 CFU/ml. Persistence of the disease-associated genotype was demonstrated in one spa pool for over 5 months until repeated treatments with greater than 10 mg of chlorine per liter for 1-h intervals eliminated M. avium complex from the spa pool. A fourth case of Mycobacterium avium complex-related lung disease was associated epidemiologically but not genotypically with another spa pool that had had no maintenance undertaken. This spa pool contained low numbers of mycobacteria by smear and was culture positive for M. avium complex, and the nonmycobacterial organism count was 5.2 × 106 CFU/ml. Public awareness about the proper maintenance of private (residential) spa pools must be promoted by health departments in partnership with spa pool retailers. PMID:15294830

  14. Phenotypic and Genomic Analyses of the Mycobacterium avium Complex Reveal Differences in Gastrointestinal Invasion and Genomic Composition

    PubMed Central

    McGarvey, Jeffery A.; Bermudez, Luiz E.

    2001-01-01

    Mycobacterium avium and Mycobacterium intracellulare are closely related organisms and comprise the Mycobacterium avium complex. These organisms share many common characteristics, including the ability to cause life-threatening respiratory infections in people with underlying lung pathology or immunological defects and occasionally in those with no known predisposing conditions. However, the ability to invade the mucosa of the gastrointestinal tract and cause disseminated disease in AIDS patients has not been epidemiologically linked to M. intracellulare and appears to be unique to M. avium. We compared the abilities of M. avium and M. intracellulare to tolerate the acidic conditions of the stomach, to resist the membrane-disrupting activity of cationic peptides, and to invade intestinal epithelial cells in vitro and in vivo. We observed that M. avium and M. intracellulare were both tolerant to the acidic conditions encountered in the stomach and resistant to cationic peptides. However, when strains of M. avium and M. intracellulare were examined for their ability to enter cultured human intestinal cells or mouse intestinal mucosa, we observed that M. avium could invade more efficiently than M. intracellulare. To elucidate the basis of this pathogenic difference and identify genes involved in the invasion of the intestinal mucosa, we performed chromosomal DNA subtractive hybridization using M. avium and M. intracellulare chromosomal DNAs. In all, 21 genes that were present in M. avium but absent in M. intracellulare were identified, including some that may be associated with the ability of M. avium to invade the intestinal mucosa. PMID:11705893

  15. Opinions Differ by Expertise in Mycobacterium avium Complex Disease

    PubMed Central

    Prevots, D. Rebecca; Jamieson, Frances B.; Winthrop, Kevin L.

    2014-01-01

    Rationale: Pulmonary Mycobacterium avium complex treatment guidelines rely largely on expert opinion. The extent to which nonexperts agree with recommendations of experts in this clinical area is unknown. Objectives: We sought to compare practices and perceptions of prognosis between experts and nonexperts. Methods: We surveyed respirologists (Ontario, Canada, “nonexperts”) and experts from nontuberculous mycobacterial disease centers of excellence (Canada and United States). Measurements and Main Results: Forty-six Ontario respirologists (29% of 160) and 19 experts (73% of 26) participated. There was agreement between nonexperts and experts regarding disease duration before diagnosis (2 yr), likelihood of spontaneous remission (7–15%), typical duration of treatment (18 mo), first choice of therapy (guideline regimens), a subgroup of patients for whom less-intensive regimens are favored (10% after recurrence), likelihood of recurrence (30%), and median survival (10 yr in most patients). Noted differences were that nonexperts estimated fewer patients with a positive culture had disease (30% vs. 50%, P = 0.02), used intensive guidelines therapy less often in new cases (50% vs. 79%, P = 0.02), and perceived a slightly lower success rate with guidelines therapy (65% vs. 75%, P = 0.047). Response ranges were wider for nonexperts, significantly so for selection of intensive guidelines therapy in new (P = 0.01) and recurrent (P = 0.04) cases. Conclusion: Experts and nonexperts agreed on many issues. However, nonexperts perceived lower rates of disease among patients with isolates, tended to use less aggressive treatment approaches, and perceived lower success rates. Significant variability was observed in responses—often wider among nonexperts. Although these results are likely biased by referral, they may identify important areas for targeted education. PMID:24083335

  16. Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases

    PubMed Central

    Deshpande, Devyani; Srivastava, Shashikant; Musuka, Sandirai

    2016-01-01

    Mycobacterium avium-intracellulare complex (MAC) causes an intractable intracellular infection that presents as chronic pulmonary disease. Currently, therapy consists of ethambutol and macrolides and takes several years to complete. The neuroleptic phenothiazine thioridazine kills mycobacteria by inhibiting the electron transport chain. In several experiments with bacterial populations of up to 1012 CFU/ml, we failed to isolate any bacteria resistant to 3 times the MIC of thioridazine, suggesting the absence of resistant mutants at bacterial burdens severalfold higher than those encountered in patients. In the hollow-fiber model of intracellular MAC (HFS-MAC), thioridazine achieved an extracellular half-life of 16.8 h and an intracellular half-life of 19.7 h. Thioridazine concentrations were >28,000-fold higher inside infected macrophages than in the HFS-MAC central compartment (equivalent to plasma). Thioridazine maximal kill was 5.20 ± 0.75 log10 CFU/ml on day 7 (r2 = 0.96) and 7.19 ± 0.31 log10 CFU/ml on day 14 (r2 = 0.99), the highest seen with any drug in the system. Dose fractionation studies revealed that thioridazine efficacy and acquired drug resistance were driven by the peak concentation-to-MIC ratio, with a 50% effective concentration (EC50) of 2.78 ± 0.44 for microbial killing. Acquired drug resistance was encountered by day 21 with suboptimal doses, demonstrating that fluctuating drug concentrations drive evolution faster than static concentrations in mutation frequency studies. However, the thioridazine EC50 changed 16.14-fold when the concentration of fetal bovine serum was changed from 0% to 50%, suggesting that intracellular potency could be heavily curtailed by protein binding. Efficacy in patients will depend on the balance between trapping of the drug in the pulmonary system and the massive intracellular concentrations versus very high protein binding of thioridazine. PMID:27216055

  17. Genetic Analysis of Mycobacterium avium Complex Strains Used for Producing Purified Protein Derivatives

    PubMed Central

    Semret, Makeda; Bakker, Douwe; Smart, Nonie; Olsen, Ingrid; Haslov, Kaare; Behr, Marcel A.

    2006-01-01

    For over a century, purified protein derivatives (PPD) have been used to detect mycobacterial infections in humans and livestock. Among these, reagents to detect infections by Mycobacterium avium complex organisms have been produced, but the utility of these reagents has not been clearly established due in part to limited biologic and immunologic standardization. Because there is little information about the strains used to produce these reagents (avian PPD, intracellulare PPD, scrofulaceum PPD, and Johnin), we have performed genetic characterizations of strains used to produce these products. Sequence analysis of 16S rRNA and the hsp65 gene provided results concordant with species designations provided for M. avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum organisms. For M. avium strains, comparative genomic hybridization was performed on a whole-genome DNA microarray, revealing one novel 7.9-kilobase genomic deletion in certain Johnin-producing strains, in addition to genomic variability inherent to the particular M. avium subspecies. Our findings indicate that considerable genomic differences exist between organisms used for reagents and the infecting organism being studied. These results serve as a baseline for potency studies of different preparations and should aid in comparative studies of newly discovered antigens for the diagnosis of infection and disease by M. avium complex organisms. PMID:16960109

  18. Assessing the effectiveness of low-pressure ultraviolet light for inactivating Mycobacterium avium complex (MAC) micro-organisms

    EPA Science Inventory

    Aims: To assess low-pressure ultraviolet light (LP-UV) inactivation kinetics of Mycobacterium avium complex (MAC) strains in a water matrix using collimated beam apparatus. Methods and Results: Strains of M. avium (n = 3) and Mycobacterium intracellulare (n = 2) were exposed t...

  19. Characterization to species level of Mycobacterium avium complex strains from human immunodeficiency virus-positive and -negative patients.

    PubMed Central

    Kyriakopoulos, A M; Tassios, P T; Matsiota-Bernard, P; Marinis, E; Tsaousidou, S; Legakis, N J

    1997-01-01

    Forty human clinical Mycobacterium avium-M. intracellulare complex strains isolated in Greece were characterized to the species level by PCR with three sets of primers specific for one or both species. M. avium predominated in both human immunodeficiency virus-positive and -negative patients, but the frequency of M. intracellulare isolation appeared to be higher in the latter. PMID:9350780

  20. Envelope protein complexes of Mycobacterium avium subsp. paratuberculosis and their antigenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic enteric disease of ruminant animals. In the present study, blue native PAGE electrophoresis and 2D SDS-PAGE were used to separate MAP envelope protein complexes, followed by mass spectrometry (MS) ...

  1. Polypoid bronchial lesions due to Scedosporium apiospermum in a patient with Mycobacterium avium complex pulmonary disease.

    PubMed

    Murayama, T; Amitani, R; Tsuyuguchi, K; Watanabe, I; Kimoto, T; Suzuki, K; Tanaka, E; Kamei, K; Nishimura, K

    1998-09-01

    A 69 yr old female was hospitalized for further examination of abnormal shadows on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid arthritis and gold-induced interstitial pneumonia. On admission she still suffered from rheumatoid arthritis. A chest computed tomography scan on admission showed clusters of small nodules in subpleural regions of both lungs combined with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the orifice of the left B4 bronchus. Cultures of the brushing specimen of the polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey mycelial colonies that were later identified as Scedosporium apiospermum. It was concluded that the polypoid bronchial lesions due to Scedosporium apiospermum were formed in the preexisting dilated bronchus caused by Mycobacterium avium complex pulmonary disease. PMID:9762808

  2. Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

    PubMed Central

    Yajko, D M; Kirihara, J; Sanders, C; Nassos, P; Hadley, W K

    1988-01-01

    Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies. PMID:3196000

  3. THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

    EPA Science Inventory

    Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

  4. Septic arthritis and granulomatous synovitis caused by infection with Mycobacterium avium complex in a horse.

    PubMed

    Hewes, Christina A; Schneider, Robert K; Baszler, Timothy V; Oaks, J Lindsay

    2005-06-15

    A 12-year-old American Saddlebred gelding was referred to a veterinary teaching hospital for evaluation of a chronic lameness problem in the right radiocarpal joint. The horse had been treated for osteoarthritis of the right radiocarpal joint with multiple injections of cortisone during the past 3 years. The horse was severely lame on the right forelimb at a trot. Radiography and computed tomography revealed a 3 x 2-cm lytic defect in the distal portion of the radius and periarticular bone proliferation around the right radiocarpal joint. Ultrasonography of the distal portion of the radius revealed a soft tissue mass in the palmarolateral aspect of the joint. Proliferative synovium with a large amount of fibrin was observed in the dorsal and palmar aspects of the joint via arthroscopic examination of the right radiocarpal joint. Histologic examination of synovial biopsy specimens revealed proliferative granulomatous synovitis with giant cells. Mycobacterium avium complex was cultured from the synovial fluid. Infection with M avium complex should be considered in horses with chronic recurring arthritis associated with granulomatous synovitis.

  5. Further analysis of VNTR and MIRU in the genome of Mycobacterium avium complex, and application to molecular epidemiology of isolates from South America.

    PubMed

    Romano, M I; Amadio, A; Bigi, F; Klepp, L; Etchechoury, I; Llana, M Noto; Morsella, C; Paolicchi, F; Pavlik, I; Bartos, M; Leão, S C; Cataldi, A

    2005-10-31

    All members of Mycobacterium avium complex are serious pathogens for humans and animals. The aim of this study was to look for and analyze VNTR-MIRU loci in the genome of M. avium complex and their preliminary application to test these isolates. In the present study, we identified 22 novel VNTR-MIRU by using Tandem Repeat software: five with a structure similar to MIRU and 17 without MIRU structure; these latter were designated as VNTR. Most VNTR were located within predicted coding regions. Most MIRU were intercistronic with their extremities overlapping the termination and initiation codons of their flanking genes. Some of these VNTR-MIRU exhibited polymorphism among M. avium complex isolates due to insertion or deletion of whole repeats and/or of nucleotide sequence degeneration. We determined the variability of six VNTR-MIRU loci in 21 M. avium subsp. hominissuis and 26 M. avium subsp. paratuberculosis. The analysis identified 15 different alleles with the combination of six VNTR-MIRU in the 21 M. avium subsp. hominissuis with 16 different IS1245 RFLP and four different profiles with PCR-restriction analysis of hsp65 (PRA). However, neither the six VNTR-MIRU loci nor the PRA were able to distinguish M. avium subsp. paratuberculosis isolates with five different IS900 RFLP profiles. In conclusion, some of the VNTR-MIRU loci identified were useful to differentiate M. avium subsp. hominissuis but not M. avium subsp. paratuberculosis isolates here included. However, we observed polymorphism in VNTR-MIRU loci between M. avium subsp. hominissuis and M. avium subsp. paratuberculosis genomes, which could be important in the understanding of the obvious differences in the pathogenic effects of these mycobacteria.

  6. Middle-aged to elderly women have a higher asymptomatic infection rate with Mycobacterium avium complex, regardless of body habitus.

    PubMed

    Nishimura, Tomoyasu; Fujita-Suzuki, Yukiko; Mori, Masaaki; Carpenter, Stephen M; Fujiwara, Hiroshi; Uwamino, Yoshifumi; Tamizu, Eiko; Yano, Ikuya; Kawabe, Hiroshi; Hasegawa, Naoki

    2016-04-01

    Mycobacterium avium complex (MAC) pulmonary disease is prevalent in middle-aged to elderly women with a thin body habitus. By comparing the rate of serologically diagnosed asymptomatic MAC infection and body mass index among 1033 healthy subjects, we find that middle-aged to elderly women became infected with MAC, regardless of their body habitus.

  7. [Rapid diagnosis of mycobacteria, especially Mycobacterium tuberculosis and Mycobacterium avium complex, using MB Check system].

    PubMed

    Saito, H; Tomioka, H; Sato, K; Inoue, K; Shigeto, E

    1992-07-01

    Fourty-five sputum specimens were subjected to isolation for mycobacteria either MB Check system (MB method; F. Hoffmann-La Roche Ltd., Basel, Switzerland) or 3% Ogawa egg medium (Ogawa method). Test sputum was treated with 4 volumes of 4% NaOH for 1-2 min and 0.1 ml of the resulting mixture was inoculated onto 3% Ogawa egg medium. The remaining portion of the mixture was neutralized with IN HCl, diluted with 1/15 M phosphate buffer (PB; pH 6.8), and subsequently centrifuged at 3,000 rpm for 20 min. The sediment was suspended in 1.5 ml of PB and 0.5 ml each was inoculated into MB Check M bottle (20 ml) supplemented with M supplement (1 ml). In MB method, bacterial growth was measured on Middlebrook 7H11 agar medium and Middlebrook 7H11 agar medium containing NAP (p-nitro-alpha-acetylamino-beta-hydroxy-propiophenone). Among 45 sputum specimens, the number of positive specimens for mycobacterial growth in the above two cultivation methods and time required for growth were as follows: 3% Ogawa egg medium; 12 specimens (26.7%) gave positive growth, including 7 of M. tuberculosis complex strains on 14-35 days (average 22 days) and 5 of M. avium complex strains on 14-21 days (average 18 days); MB method; 15 of specimens (33.3%) gave positive growth, including 8 of M. tuberculosis complex strains on 7-21 days (average 15 days), 6 of M. avium complex strains on 7-14 days (average 11 days) and 1 of M. scrofulaceum strain on 28 days. There was no specimen which was positive for mycobacterial growth on 3% Ogawa egg medium but negative on MB medium. PMID:1434318

  8. Detection of Mycobacterium tuberculosis and Mycobacterium avium Complexes by Real-Time PCR in Bovine Milk from Brazilian Dairy Farms.

    PubMed

    Bezerra, André Vinícius Andrade; Dos Reis, Emily Marques; Rodrigues, Rogério Oliveira; Cenci, Alexander; Cerva, Cristine; Mayer, Fabiana Quoos

    2015-05-01

    Foodborne diseases are a public health problem worldwide. The consumption of contaminated raw milk has been recognized as a major cause of transmission of bovine tuberculosis to humans. Other mycobacteria that may be present in raw milk and may cause diseases are those belonging to the Mycobacterium avium complex. In this study, molecular biology tools were applied to investigate raw milk contamination with Mycobacterium spp. in family dairy farms from Rio Grande do Sul, southern Brazil. Furthermore, different variables related to the source of the milk, herd characteristics, and management were evaluated for their effect on milk contamination. Five hundred and two samples were analyzed, of which 354 were from the Northwest region (102 farms with samples from 93 bulk tanks and 261 animals) and 148 from the South region of the state (22 farms with samples from 23 bulk tanks and 125 animals). Among them, 10 (1.99%) and 7 (1.39%) were positive for Mycobacterium tuberculosis (9 confirmed as Mycobacterium bovis) and M. avium complexes, respectively. There was no difference in the frequencies of positive samples between the regions or the sample sources. Of the positive samples, 4 were collected from a bulk tank (1 positive for M. avium and 3 for M. tuberculosis). Moreover, 1 sample was positive concomitantly for M. tuberculosis and M. avium complexes. On risk analysis, no variable was associated with raw milk contamination by M. tuberculosis complex species. However, washing the udders of all animals and drying them with paper towels were weakly classified as risk factors for M. avium contamination. Positive samples were obtained from both animals and bulk tanks, which emphasizes the importance of tuberculosis control programs and provides evidence that milk monitoring can be used as a control practice. Moreover, the findings of this study reinforce the need for awareness of the problems of raw milk consumption among the general population. PMID:25951404

  9. Detection of Mycobacterium tuberculosis and Mycobacterium avium Complexes by Real-Time PCR in Bovine Milk from Brazilian Dairy Farms.

    PubMed

    Bezerra, André Vinícius Andrade; Dos Reis, Emily Marques; Rodrigues, Rogério Oliveira; Cenci, Alexander; Cerva, Cristine; Mayer, Fabiana Quoos

    2015-05-01

    Foodborne diseases are a public health problem worldwide. The consumption of contaminated raw milk has been recognized as a major cause of transmission of bovine tuberculosis to humans. Other mycobacteria that may be present in raw milk and may cause diseases are those belonging to the Mycobacterium avium complex. In this study, molecular biology tools were applied to investigate raw milk contamination with Mycobacterium spp. in family dairy farms from Rio Grande do Sul, southern Brazil. Furthermore, different variables related to the source of the milk, herd characteristics, and management were evaluated for their effect on milk contamination. Five hundred and two samples were analyzed, of which 354 were from the Northwest region (102 farms with samples from 93 bulk tanks and 261 animals) and 148 from the South region of the state (22 farms with samples from 23 bulk tanks and 125 animals). Among them, 10 (1.99%) and 7 (1.39%) were positive for Mycobacterium tuberculosis (9 confirmed as Mycobacterium bovis) and M. avium complexes, respectively. There was no difference in the frequencies of positive samples between the regions or the sample sources. Of the positive samples, 4 were collected from a bulk tank (1 positive for M. avium and 3 for M. tuberculosis). Moreover, 1 sample was positive concomitantly for M. tuberculosis and M. avium complexes. On risk analysis, no variable was associated with raw milk contamination by M. tuberculosis complex species. However, washing the udders of all animals and drying them with paper towels were weakly classified as risk factors for M. avium contamination. Positive samples were obtained from both animals and bulk tanks, which emphasizes the importance of tuberculosis control programs and provides evidence that milk monitoring can be used as a control practice. Moreover, the findings of this study reinforce the need for awareness of the problems of raw milk consumption among the general population.

  10. Clinical Evaluation of COBAS TaqMan PCR for the Detection of Mycobacterium tuberculosis and M. avium Complex

    PubMed Central

    Ikegame, Satoshi; Sakoda, Yoritake; Fujino, Nao; Taguchi, Kazuhito; Kawasaki, Masayuki; Kajiki, Akira

    2012-01-01

    A retrospective observational study was performed to determine the sensitivity and limitation of PCR test for the detection of Mycobacterium tuberculosis and M. avium complex. We obtained clinical specimens collected from the respiratory tract, cultured M. tuberculosis or M. avium complex, and performed PCR analysis. A total of 299 samples (M. tuberculosis, 177; M. avium, 35; M. intracellulare, 87) were analyzed by COBAS TaqMan PCR from April 2007 to March 2011. The PCR positivity rates were 50–55%, 70–100%, 88–98%, and 100% in smear-negative, smear 1+, 2+, and 3+ groups, respectively. The PCR positivity of tuberculosis in smear 1+ was 80.6%, which was statistically significantly (P < 0.001) lower than that of smear 2+ (97.3%). From January 2005 to March 2007, we collected an additional 138 samples (M. tuberculosis, 74; M. avium, 21; M. intracellulare, 43), which were analyzed by COBAS Amplicor PCR. The PCR positivity rates obtained using COBAS TaqMan PCR and COBAS Amplicor PCR were not significantly different. The sensitivity of PCR test for mycobacteria is not sufficient in case of smear 1+. Careful consideration must be given to the interpretation of negative PCR test results in smear 1+, because smear-positive tuberculosis is the criterion for isolation. PMID:23029612

  11. Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower.

    PubMed

    Whiley, Harriet; Giglio, Steven; Bentham, Richard

    2015-07-24

    Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the "unhooking" showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation.

  12. Mycobacterium avium complex (MAC) osteomyelitis and septic arthritis in an immunocompetent host.

    PubMed

    Jones, A R; Bartlett, J; McCormack, J G

    1995-01-01

    We describe a case of Mycobacterium avium complex (MAC) osteomyelitis and septic arthritis in an immunocompetent man. Infection was derived from a chainsaw injury sustained on the lateral aspect of the ankle 13 years earlier, and had spread through the bone, joint and soft tissue emerging at the medial aspect. This was successfully treated with surgical debridement, drainage, arthrodesis and 18 months of chemotherapy consisting of clarithromycin, rifampicin, ethambutol, and ciprofloxacin with an initial 2 weeks of amikacin. Infections with this organisms are generally associated with immunocompromised states, particularly advanced AIDS. However, our patient illustrates that atypical mycobacterial infections must also be considered in immunocompetent patients who have a prolonged clinical course and an appropriate potential source of infection.

  13. Rapid susceptibility testing of Mycobacterium avium complex and Mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1994-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of HIV infection will continue to rise more rapidly worldwide than predicted earlier. The AIDS patients are susceptible to diseases called opportunistic infections of which tuberculosis and Mycobacterium avium complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, MD, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. We proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis.

  14. Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower.

    PubMed

    Whiley, Harriet; Giglio, Steven; Bentham, Richard

    2015-01-01

    Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the "unhooking" showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation. PMID:26213977

  15. Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower

    PubMed Central

    Whiley, Harriet; Giglio, Steven; Bentham, Richard

    2015-01-01

    Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the “unhooking” showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation. PMID:26213977

  16. Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

    PubMed

    Konjeti, Venkata Rajesh; Paluri, Sravanthi

    2014-01-01

    Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death. PMID:25672059

  17. Infection of Eurasian badgers (Meles meles) with Mycobacterium bovis and Mycobacterium avium complex in Spain.

    PubMed

    Balseiro, Ana; Rodríguez, Oscar; González-Quirós, Pablo; Merediz, Isabel; Sevilla, Iker A; Davé, Dipesh; Dalley, Deanna J; Lesellier, Sandrine; Chambers, Mark A; Bezos, Javier; Muñoz, Marta; Delahay, Richard J; Gortázar, Christian; Prieto, José M

    2011-11-01

    The prevalence, distribution and pathology related to infection with Mycobacterium bovis and other mycobacteria were determined in trapped (n=36) and road-killed (n=121) badgers in Spain from 2006 to 2010. The prevalence of M. bovis based on bacteriological culture from road-killed badgers was 8/121 (6.6%) and from trapped badgers was 0/36 (0%). Tuberculosis/M. bovis infection was evident in 15/121 (12.4%) road-killed badgers when bacteriology and histopathology were combined. Mycobacterium avium complex was isolated by culture from the tracheal aspirate of 1/36 (2.8%) trapped badgers and from tissue pools from 8/121 (6.6%) road-killed badgers.

  18. Detection of mycobacteria, Mycobacterium avium subspecies, and Mycobacterium tuberculosis complex by a novel tetraplex real-time PCR assay.

    PubMed

    Sevilla, Iker A; Molina, Elena; Elguezabal, Natalia; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A

    2015-03-01

    Mycobacterium tuberculosis complex, Mycobacterium avium, and many other nontuberculous mycobacteria are worldwide distributed microorganisms of major medical and veterinary importance. Considering the growing epidemiologic significance of wildlife-livestock-human interrelation, developing rapid detection tools of high specificity and sensitivity is vital to assess their presence and accelerate the process of diagnosing mycobacteriosis. Here we describe the development and evaluation of a novel tetraplex real-time PCR for simultaneous detection of Mycobacterium genus, M. avium subspecies, and M. tuberculosis complex in an internally monitored single assay. The method was evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28) strains, tissues spiked with different CFU amounts of three mycobacterial species (n = 57), archival clinical samples (n = 233), and strains isolated from various hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M. bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked samples were analyzed, the method consistently detected as few as 100 to 1,000 mycobacterial CFU per gram. The sensitivity and specificity values for the panel of clinical samples were 97.5 and 100% using a verified culture-based method as the reference method. The assays performed on clinical isolates confirmed these results. This PCR was able to identify M. avium and M. tuberculosis complex in the same sample in one reaction. In conclusion, the tetraplex real-time PCR we designed represents a highly specific and sensitive tool for the detection and identification of mycobacteria in routine laboratory diagnosis with potential additional uses.

  19. Detection of Mycobacteria, Mycobacterium avium Subspecies, and Mycobacterium tuberculosis Complex by a Novel Tetraplex Real-Time PCR Assay

    PubMed Central

    Molina, Elena; Elguezabal, Natalia; Pérez, Valentín; Garrido, Joseba M.

    2015-01-01

    Mycobacterium tuberculosis complex, Mycobacterium avium, and many other nontuberculous mycobacteria are worldwide distributed microorganisms of major medical and veterinary importance. Considering the growing epidemiologic significance of wildlife-livestock-human interrelation, developing rapid detection tools of high specificity and sensitivity is vital to assess their presence and accelerate the process of diagnosing mycobacteriosis. Here we describe the development and evaluation of a novel tetraplex real-time PCR for simultaneous detection of Mycobacterium genus, M. avium subspecies, and M. tuberculosis complex in an internally monitored single assay. The method was evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28) strains, tissues spiked with different CFU amounts of three mycobacterial species (n = 57), archival clinical samples (n = 233), and strains isolated from various hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M. bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked samples were analyzed, the method consistently detected as few as 100 to 1,000 mycobacterial CFU per gram. The sensitivity and specificity values for the panel of clinical samples were 97.5 and 100% using a verified culture-based method as the reference method. The assays performed on clinical isolates confirmed these results. This PCR was able to identify M. avium and M. tuberculosis complex in the same sample in one reaction. In conclusion, the tetraplex real-time PCR we designed represents a highly specific and sensitive tool for the detection and identification of mycobacteria in routine laboratory diagnosis with potential additional uses. PMID:25588660

  20. Use of Specific rRNA Oligonucleotide Probes for Microscopic Detection of Mycobacterium avium Complex Organisms in Tissue

    PubMed Central

    Amand, Allison L. St.; Frank, Daniel N.; De Groote, Mary Ann; Pace, Norman R.

    2005-01-01

    Members of the Mycobacterium avium complex (MAC) are important environmental pathogens that are implicated in several chronic, idiopathic diseases. Diagnosis of MAC-based diseases is compromised by the need to cultivate these fastidious and slowly growing organisms in order to identify which mycobacterial species are present. Detection is particularly difficult when MAC is intracellular or embedded within mammalian tissues. We report on the development of culture-independent, in situ hybridization (ISH) assays for the detection of MAC in culture, sputum, and tissue. This assay includes a highly reliable technique for the permeabilization of mycobacterial cells within culture and tissues. We describe a set of rRNA-based oligonucleotide probes that specifically detect either M. intracellulare, the two M. avium subspecies associated with human disease, or all members of MAC. The results call into question the validity of ISH results derived by the use of other gene loci, such as IS900. PMID:15814959

  1. Mycobacterium avium complex--the role of potable water in disease transmission.

    PubMed

    Whiley, H; Keegan, A; Giglio, S; Bentham, R

    2012-08-01

    Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major public health concern. It is responsible for a wide spectrum of disease dependent on subspecies, route of infection and patients pre-existing conditions. Presently, there is limited research on the incidence of MAC infection that considers both pulmonary and other clinical manifestations. MAC has been isolated from various terrestrial and aquatic environments including natural waters, engineered water systems and soils. Identifying the specific environmental sources responsible for human infection is essential in minimizing disease prevalence. This paper reviews current literature and case studies regarding the wide spectrum of disease caused by MAC and the role of potable water in disease transmission. Potable water was recognized as a putative pathway for MAC infection. Contaminated potable water sources associated with human infection included warm water distribution systems, showers, faucets, household drinking water, swimming pools and hot tub spas. MAC can maintain long-term contamination of potable water sources through its high resistance to disinfectants, association with biofilms and intracellular parasitism of free-living protozoa. Further research is required to investigate the efficiency of water treatment processes against MAC and into construction and maintenance of warm water distribution systems and the role they play in MAC proliferation.

  2. Rapid susceptibility testing of mycobacterium avium complex and mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1993-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of the Human Immunodeficiency Virus (HIV) infection will continue to rise more rapidly worldwide than predicted earlier. The Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to diseases called opportunistic infections of which tuberculosis and M. avium Complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, Maryland, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. Therefore, we proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis. The work was initiated in June 1992. In the last report, we described our efforts in developing ATP assay method using MAC. Studies were continued further, and during the period of this report, we established the relationship between colony forming units and ATP levels of these organisms during the growth cycle. Also, we evaluated the effects of standard antimycobacterial drugs using ATP assay technique and compared the results with those obtained with conventional tube dilution proportional method.

  3. Isolation of Mycobacterium avium complex from bone marrow aspirates of AIDS patients in Brazil.

    PubMed

    Barreto, J A; Palaci, M; Ferrazoli, L; Martins, M C; Suleiman, J; Lorenço, R; Ferreira, O C; Riley, L W; Johnson, W D; Galvão, P A

    1993-09-01

    Mycobacterium avium complex (MAC) infection has not been reported as a major opportunistic infection among patients with AIDS in Latin America or Africa. In this study, 125 AIDS patients who had persistent fever, anemia, and leukopenia were examined among 2628 AIDS patients admitted to Instituto de Infectologia Emilio Ribas between May 1990 and April 1992. From the bone marrow aspirates of the 125 patients, MAC was isolated from 23 (18.4%) and Mycobacterium tuberculosis was isolated from 9 (7.2%). Between 1985 and 1990, only 11 MAC isolations among 60,000 cultures obtained from human immunodeficiency virus-seronegative patients were documented in São Paulo. Hence, the minimal estimated rate of MAC infection in AIDS patients in this city was 23/2628, or 0.88%. These findings suggest that MAC infection is an important opportunistic infection, especially among a subset of patients with AIDS in Brazil who have clinical characteristics and risk activities similar to those associated with MAC infections in North America and Europe.

  4. The Significance of Mycobacterium abscessus Subspecies abscessus Isolation During Mycobacterium avium Complex Lung Disease Therapy

    PubMed Central

    Philley, Julie V.; Brown-Elliott, Barbara A.; Benwill, Jeana L.; Shepherd, Sara; York, Deanna; Wallace, Richard J.

    2015-01-01

    BACKGROUND: Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical significance of the MAA isolates. METHODS: We identified 53 of 180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those without (group 1) and those with (group 2) MAA lung disease. RESULTS: There were no significant demographic differences between patients with and without MAA isolation or between groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (P = .7; 95% CI, −13.4 to 8.6) and length of follow-up (P = .8; 95% CI, −21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA (mean±SD, 15.0 ± 11.1 vs 1.2 ± 0.4; P < .0001; 95% CI, −17.7 to −9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (P > .0001), and were significantly more likely to meet all three American Thoracic Society diagnostic criteria for nontuberculous mycobacterial disease (21 of 21 [100%] vs 0 of 32 [0%]; P < .0001) compared with group 1 patients. Group 1 patients were significantly more likely to have single, positive MAA cultures than group 2 patients (25 of 31 vs 0 of 21; P < .0001). CONCLUSIONS: Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant. PMID:25357074

  5. Modulation of Innate Host Factors by Mycobacterium avium Complex in Human Macrophages Includes Interleukin 17

    PubMed Central

    Vázquez, Nancy; Rekka, Sofia; Gliozzi, Maria; Feng, Carl G.; Amarnath, Shoba; Orenstein, Jan M.; Wahl, Sharon M.

    2012-01-01

    Background. Although opportunistic infections due to Mycobacterium avium complex (MAC) have been less common since the introduction of highly active antiretroviral therapy, globally, human immunodeficiency virus-1 (HIV-1)–positive patients remain predisposed to these infections. Absence of a properly functioning acquired immune response allows MAC persistence within macrophages localized in lymph nodes coinfected with HIV and MAC. Although a deficiency in interferon γ appears to play a part in the ability of MAC to deflect the macrophage-associated antimicrobial attack, questions about this process remain. Our study examines the ability of MAC to regulate interleukin 17 (IL-17), a proinflammatory cytokine involved in host cell recruitment. Methods. Coinfected lymph nodes were examined for IL-17 by immunohistochemical analysis. In vitro, macrophages exposed to mycobacteria were evaluated for transcription activities, proteins, and signaling pathways responsible for IL-17 expression. Infected macrophages were also analyzed for expression of interleukin 21 (IL-21) and negative regulators of immune responses. Results. Infection of macrophages triggered synthesis of IL-17, correlating with IL-17 expression by macrophages in coinfected lymph nodes. Infected macrophages exposed to exogenous IL-17 expressed CXCL10, which favors recruitment of new macrophages as targets for infection. Blockade of nuclear factor κ-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways suppressed mycobacteria-induced IL-17 expression. MAC triggered expression of IL-21, IRF4, and STAT3 genes related to IL-17 regulation, as well as expression of the negative immunoregulators CD274(PD-L1) and suppressors of cytokine signaling. Conclusions. MAC-infected macrophages can provide an alternative source for IL-17 that favors accumulation of new targets for perpetuating bacterial and viral infection while suppressing host antimicrobial immune responses. PMID

  6. Macrolide/Azalide Therapy for Nodular/Bronchiectatic Mycobacterium avium Complex Lung Disease

    PubMed Central

    Wallace, Richard J.; Brown-Elliott, Barbara A.; McNulty, Steven; Philley, Julie V.; Killingley, Jessica; Wilson, Rebecca W.; York, Deanna S.; Shepherd, Sara

    2014-01-01

    BACKGROUND: There is no large study validating the appropriateness of current treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is a retrospective single-center review evaluating the efficacy of macrolide/azalide-containing regimens for nodular/bronchiectatic (NB) MAC lung disease. METHODS: Patients were treated according to contemporary guidelines with evaluation of microbiologic responses. Macrolide susceptibility of MAC isolates was done at initiation of therapy, 6 to 12 months during therapy, and on the first microbiologic recurrence isolate. Microbiologic recurrence isolates also underwent genotyping for comparison with the original isolates. RESULTS: One hundred eighty patients completed > 12 months of macrolide/azalide multidrug therapy. Sputum conversion to culture negative occurred in 154 of 180 patients (86%). There were no differences in response between clarithromycin or azithromycin regimens. Treatment regimen modification occurred more frequently with daily (24 of 30 [80%]) vs intermittent (2 of 180 [1%]) therapy (P = .0001). No patient developed macrolide resistance during treatment. Microbiologic recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC isolates, 27% with true relapse isolates (P = .03). Overall, treatment success (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after completion of therapy: 75% reinfection isolates, 25% true relapse isolates. CONCLUSIONS: Current guidelines for macrolide/azalide-based therapies for NB MAC lung disease result in favorable microbiologic outcomes for most patients without promotion of macrolide resistance. Intermittent therapy is effective and significantly better tolerated than daily therapy. Microbiologic recurrences during or after therapy are common and most often due to reinfection MAC genotypes. PMID:24457542

  7. Relationship Between Lung Cancer and Mycobacterium Avium Complex Isolated Using Bronchoscopy

    PubMed Central

    Tamura, Atsuhisa; Hebisawa, Akira; Kusaka, Kei; Hirose, Takashi; Suzuki, Junko; Yamane, Akira; Nagai, Hideaki; Fukami, Takeshi; Ohta, Ken; Takahashi, Fumiaki

    2016-01-01

    Introduction: The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. Materials and Methods: The medical records of 1382 untreated lung cancer patients between 2003 and 2011 were collected using our hospital database. Of them, records for 1258 that had undergone bronchoscopy together with sampling for mycobacterial culture were reviewed. Patient characteristics were compared between those with MAC-positive/other nontuberculous mycobacteria (NTM)-negative bronchial washings and those with MAC-negative/other NTM-negative bronchial washings. Patients with MAC-positive lung cancer were cross-sectionally divided into MACLD and non-MACLD groups, and their features were assessed. Follow-up data for patients with lung cancer but without MACLD were reviewed for subsequent development of MACLD. Results: Of the 1258 patients with lung cancer, 25 (2.0%) had MAC-positive/other NTM-negative bronchial washings. The proportion of women (52% vs 30%; P = 0.0274) and patient age (72 years vs 69 years; P = 0.0380) were significantly higher in the MAC-positive/other NTM-negative lung cancer group (n = 25) than in the MAC-negative/other NTM-negative lung cancer group (n = 1223). There were 10 patients with lung cancer and MACLD and 15 without MACLD; significant differences in patient characteristics were not found between the two groups, and none of the 15 patients without MACLD subsequently developed MACLD. Conclusion: MAC culture-positive bronchial washing is positively associated with lung cancer. Female sex and advanced age, but not lung cancer characteristics, were found to be associated with MAC infection in patients with lung cancer. PMID:27335625

  8. THE EFFECT OF TEMPERATURE ON THE GROWTH OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS

    EPA Science Inventory

    MAC organisms are able to grow, persist, and colonize in water distribution systems and may amplify in hospital hot water systems. This study examined the response of MAC organisms (M. avium, M. intracellulare, and MX) to a range of temperatures commonly associated with drinking...

  9. [Strategies for Mycobacterium avium complex infection control in Japan: how do they improve the present situation?].

    PubMed

    Ogawa, Kenji; Sano, Chiaki

    2013-03-01

    Mycobacterium avium complex (MAC) were the most frequently isolated (about 80%) and most common cause of lung nontuberculosis. Its rate of infection is globally increasing, especially in Japan. In this situation, it is urgently needed to provide scientific evidences and develop therapeutic interventions in MAC infections. Recently, more and more patients are elderly women with no history of smoking, and they have reticulonodular infiltrates and patchy bilateral bronchiectasis. However the prognostic and intractable factors of MAC infections are poorly known. In this symposium, we address five novel strategies for MAC infection, concerning the more accurate incidence and prevalence rates compared with other countries, host defense associated with Th1/Th17 balance, route of MAC infection related soil exposure, MAC IgA antibody as a diagnosis maker, and improved chemotherapy including aminoglycoside or new quinolone. Appropriate clinical intervention may help to reduce the prolongation of MAC infection or enhance the activity of chemotherapy for the improved control of MAC. Below are the abstracts for each of the five speakers. 1. Review of current epidemiological study of pulmonary nontuberculous mycobacterial disease in Japan and the rest of the world: Kozo MORIMOTO (Respiratory Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association) The studies on pulmonary nontuberculous mycobacterial (NTM) disease prevalence were started in early 1970s in Japan by the Mycobacteriosis Research Group of National Chest Hospitals. They were followed by a questionnaire survey in 1990s, by the National Tuberculosis and NTM Survey in late 1990s, and recently by the questionnaire surveys conducted by the NTM Disease Research Committee. The latest data in Japan (from 2007) indicated a morbidity rate of 5.7 per 100,000 population. Deaths from NTM disease were reported for the first time in 1970 and showed a marked, steady increase until 2007, with 912 deaths in that year. We

  10. Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Moon, Seong Mi; Kim, Su-Young; Lee, Soo-Youn; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-10-01

    Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.). PMID:27480854

  11. Paradigm redux--Mycobacterium avium subspecies paratuberculosis-macrophage interactions show clear variations between bovine and human physiological body temperatures.

    PubMed

    Lamont, Elise A; Sreevatsan, Srinand

    2010-05-01

    The physiological conditions encountered by pathogenic mycobacteria inside their hosts significantly influence their adaptation, virulence, and gene expression. Current in vitro models investigating host-pathogen interactions of Mycobacterium avium subsp. paratuberculosis use 37 degrees C, the normal body temperatures of mice and humans. However since the physiological temperature of MAP's natural host is 39 degrees C, we hypothesized that host and pathogen behavior to vary considerably in comparison to 37 degrees C. Our MAP-macrophage interaction studies show striking differences in regards to velocity of cell invasion of MAP as well as bacterial and host gene regulation at 39 degrees C compared with 37 degrees C. Upregulation of host genes (nod2, tlr2, mapkp38 and il-10) follow a similar trend at 37 degrees C and 39 degrees C; however, there is over a five-fold increase as early as 0.5 and 2 h in 39 degrees C treatments. While host signaling is completed by 48 h p.i. at 39 degrees C in MDMs cultures due to early cell death, signaling and infection is sustained at 37 degrees C. Surprisingly, transcription of MAP genes did not show a set pattern and were upregulated at different time points for both temperatures. Interestingly, MAP genes encoding a lipase (lipN) and an oxidoreductase (MAP3464) are staggered at 39 degrees C, while they increase steadily at 37 degrees C. In conclusion, infection and culture at a physiologically relevant temperature influences host-pathogen interaction, which may have far reaching ramifications including for currently used animal models, in vitro culture methods, bacterial pathogenesis and host responses, and vaccine candidate design and screening.

  12. Isolation and identification of Mycobacterium avium complex and other nontuberculosis mycobacteria from drinking-water in Basra governorate, Iraq.

    PubMed

    Al-Sulami, A A; Al-Taee, A M R; Wida'a, Q H

    2012-03-01

    This study aimed to determine the occurrence of Mycobacterium avium complex and other nontuberculous mycobacteria in drinking-water in Basra governorate, Iraq and their susceptibility to several antibiotics and the effect of 0.5 mg/L of chlorine on their survival. A total of 404 samples of drinking-water were collected from 33 different districts of the governorate from November 2006 to August 2007. Filtered samples were incubated for 7 days or less in a monophasic-biphasic culture setup of tuberculosis broth and Lowenstein-Jensen agar. The 252 isolates were identified as M. avium complex (21), M. marinum (15), M. kansasii (30), M. simiae (20), M. szulgai (19), M. xenopi (16), M. malmoense (11), M. fortuitum (37), M. chelonae (50) and M. abscessus (33). Isolates were tested for antibiotic susceptibility as well as their ability to tolerate chlorine at a concentration of 0.5 mg/L. The presence of these pathogenic bacteria in drinking-water renders the water unfit for human consumption.

  13. [Identification of Mycobacterium avium-intracellulare complex by PCR of AIDS and disseminated mycobacteriosis].

    PubMed

    García-Elorriaga, Guadalupe; Degollado-Estrada, Edgar; Villagómez-Ruiz, Alfredo; Cortés-Torres, Nancy; Arreguín-Reséndiz, Lilián; Del Rey-Pineda, Guillermo; González-Bonilla, César

    2016-01-01

    Introducción: el objetivo de este artículo es Identificar y diferenciar el complejo MAC por PCR en pacientes con SIDA y micobacteriosis diseminada. Métodos: se llevó a cabo un estudio transversal para identificar MAC por biología molecular. Se sintetizaron dos conjuntos de iniciadores: MAV y MIN, para M. avium y M. intracellulare, respectivamente. El ADN total de células obtenidas de 29 aislados clínicos y muestras de suero de otros 24 pacientes con SIDA e infección micobacteriana diseminada fue extraído y se amplificó por PCR con los iniciadores MAV y MIN. Cada uno de los iniciadores MAV y MIN amplificó un segmento altamente específico de 1.3 kb del ADN homólogo, respectivamente. Resultados: veintinueve ADN de los aislados clínicos de MAC identificadas por Gen-Probe AccuProbes se amplificaron con los iniciadores MAV (M. avium). De las 24 muestras clínicas, 3 fueron positivas para M. avium y 6 para M. tuberculosis. Conclusiones: nuestros resultados demostraron que la técnica de PCR se puede aplicar para la diferenciación de M. avium y M. intracellulare por iniciadores específicos 16S rRNA. En pacientes con estadio avanzado de SIDA y en quienes se sospecha micobacteriosis diseminada, la presencia de anemia (incluso con cultivos negativos) fosfatasa alcalina elevada y una mediana de CD4 de 15.9/ml, se debe considerar seriamente el diagnóstico de infección por MAC; sugerimos que, de acuerdo con nuestros resultados, se justifica una estratificación más precisa de los pacientes en términos de sus recuentos de células T CD4.

  14. Preliminary Evaluation of a Sitafloxacin-Containing Regimen for Relapsed or Refractory Pulmonary Mycobacterium avium Complex Disease

    PubMed Central

    Fujita, Kohei; Fujita, Masaki; Ito, Yutaka; Hirai, Toyohiro; Mio, Tadashi; Watanabe, Kentaro; Mishima, Michiaki

    2016-01-01

    Although sitafloxacin (STFX) is known to have a favorable minimum inhibitory concentration for Mycobacterium avium, few studies have evaluated the clinical efficacy of an STFX-containing regimen for pulmonary M avium complex (MAC) disease. To evaluate the clinical efficacy of STFX-containing regimens for relapsed or refractory pulmonary MAC disease, we retrospectively reviewed 18 patients with pulmonary MAC disease who received STFX for at least 4 weeks for pulmonary MAC disease between January 2008 and February 2016. Of 18 patients, 10 (55.6%) showed improved radiological characteristics and 8 (44.4%) showed negative sputum cultures at 6 months. Regarding the clinical symptoms, improvements were observed in decreasing order in sputum production (77.8%), cough (72.2%), and malaise (55.6%). Common adverse events included nausea or vomiting (38.9%), followed by loose stool or diarrhea (27.8%) and sleepiness (11.1%). Although this study contained a small number of subjects, we describe a STFX-containing regimen that was effective in achieving sputum culture negative conversions and had an acceptable adverse events profile.

  15. Genetic relatedness of Mycobacterium avium-intracellulare complex isolates from patients with pulmonary MAC disease and their residential soils.

    PubMed

    Fujita, K; Ito, Y; Hirai, T; Maekawa, K; Imai, S; Tatsumi, S; Niimi, A; Iinuma, Y; Ichiyama, S; Mishima, M

    2013-06-01

    Mycobacterium avium-intracellulare complex (MAC) strains were recovered from 48.9% of residential soil samples (agricultural farms (n = 7), residential yards (n = 79), and planting pots (n = 49)) of 100 pulmonary MAC patients and 35 non-infected control patients. The frequency of MAC recovery did not differ among soil types or among patients regardless of the presence of pulmonary MAC disease, infecting MAC species or period of soil exposure. Variable numbers of tandem repeats (VNTR) analysis for MAC clinical and soil isolates revealed 78 different patterns in 47 M. avium clinical isolates and 41 soil isolates, and 53 different patterns in 18 M. intracellulare clinical isolates and 37 soil isolates. Six clinical and corresponding soil isolate pairs with an identical VNTR genotype were from case patients with high soil exposure (≥2 h per week, 37.5% (6/16) with high exposure compared with 0.0% (0/19) with low or no exposure, p <0.01), suggesting that residential soils are a likely source of pulmonary MAC infection.

  16. Broncho-Pleural Fistula with Hydropneumothorax at CT: Diagnostic Implications in Mycobacterium avium Complex Lung Disease with Pleural Involvement

    PubMed Central

    Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Kim, Jung Soo; Park, Hye Yun

    2016-01-01

    Objective To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. Materials and Methods We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. Results The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410–100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. Conclusion In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion. PMID:26957917

  17. Complex Engineered Systems: A New Paradigm

    NASA Astrophysics Data System (ADS)

    Mina, Ali A.; Braha, Dan; Bar-Yam, Yaneer

    Human history is often seen as an inexorable march towards greater complexity — in ideas, artifacts, social, political and economic systems, technology, and in the structure of life itself. While we do not have detailed knowledge of ancient times, it is reasonable to conclude that the average resident of New York City today faces a world of much greater complexity than the average denizen of Carthage or Tikal. A careful consideration of this change, however, suggests that most of it has occurred recently, and has been driven primarily by the emergence of technology as a force in human life. In the 4000 years separating the Indus Valley Civilization from 18th century Europe, human transportation evolved from the bullock cart to the hansom, and the methods of communication used by George Washington did not differ significantly from those used by Alexander or Rameses. The world has moved radically towards greater complexity in the last two centuries. We have moved from buggies and letter couriers to airplanes and the Internet — an increase in capacity, and through its diversity also in complexity, orders of magnitude greater than that accumulated through the rest of human history. In addition to creating iconic artifacts — the airplane, the car, the computer, the television, etc. — this change has had a profound effect on the scope of experience by creating massive, connected and multiultra- level systems — traffic networks, power grids, markets, multinational corporations — that defy analytical understanding and seem to have a life of their own. This is where complexity truly enters our lives.

  18. Isolation of the Mycobacterium avium-M. intracellulare-M. scrofulaceum complex from tank water in Queensland, Australia.

    PubMed

    Tuffley, R E; Holbeche, J D

    1980-01-01

    Disease-associated serotypes of Mycobacterium intracellulare and M. avium have been isolated from 32 of 141 rainwater tanks situated in the basin of the Fitzroy River and its tributaries in central Queensland, 7 of 32 tanks situated in the hinterland of the coastal city of Rockhampton, and 2 of 32 tanks sampled repetitively in the southeastern Queensland city of Toowoomba. M. gordonae was also isolated from 23 of the river basin tanks, from 9 in the Rockhampton hinterland, and from 5 in the city of Toowoomba. One half of these isolates came from tanks which also yielded M. intracellulare. Mycobacteria of the M. terrae-M. triviale-M. nonchromogenicum complex were found in 7 tanks, usually in conjunction with M. intracellulare. The humans who consume the contaminated tank water are free of symptoms but have not been medically examined. It is suggested that mycobacteria adhering to dust particles disturbed by mechanical cultivation may be the source of contamination.

  19. Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection.

    PubMed

    Asano, Shuichi; Mizuno, Shige; Okachi, Shotaro; Aso, Hiromichi; Wakahara, Keiko; Hashimoto, Naozumi; Ito, Satoru; Kozaki, Yohei; Katsuno, Takayuki; Maruyama, Shoichi; Hasegawa, Yoshinori

    2016-01-01

    A 73-year-old woman was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection and received no treatment. Disease progression was evident one year later with the development of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) titers and systemic symptoms of a fever, polyarthritis, purpura, and rapidly progressive glomerulonephritis. Her symptoms did not improve with antibiotic treatment. A renal biopsy revealed crescentic glomerulonephritis with immunodeposition. According to these findings, she was diagnosed with ANCA-associated vasculitis (AAV) superimposed on infection-related glomerulonephritis (IRGN). Although there was a risk of aggravating an underlying infection, the combination therapy of corticosteroid and antibiotics improved AAV, IRGN, and even the lung radiological findings. To the best of our knowledge, this is the first case of AAV and IRGN secondary to pulmonary MAC infection. PMID:27580547

  20. The presence of opportunistic pathogens, Legionella spp., L. pneumophila and Mycobacterium avium complex, in South Australian reuse water distribution pipelines.

    PubMed

    Whiley, H; Keegan, A; Fallowfield, H; Bentham, R

    2015-06-01

    Water reuse has become increasingly important for sustainable water management. Currently, its application is primarily constrained by the potential health risks. Presently there is limited knowledge regarding the presence and fate of opportunistic pathogens along reuse water distribution pipelines. In this study opportunistic human pathogens Legionella spp., L. pneumophila and Mycobacterium avium complex were detected using real-time polymerase chain reaction along two South Australian reuse water distribution pipelines at maximum concentrations of 10⁵, 10³ and 10⁵ copies/mL, respectively. During the summer period of sampling the concentration of all three organisms significantly increased (P < 0.05) along the pipeline, suggesting multiplication and hence viability. No seasonality in the decrease in chlorine residual along the pipelines was observed. This suggests that the combination of reduced chlorine residual and increased water temperature promoted the presence of these opportunistic pathogens. PMID:26042986

  1. Commentary: is the paradigm for humiliation sufficiently complex?

    PubMed

    Altshul, Victor A

    2010-01-01

    The authors Torres and Bergner present a simple, elegant paradigm for understanding the phenomenon of humiliation. They suggest it may have universal applicability and may be of heuristic value for clinicians and policy-makers involved in forensic and social arenas. They offer case examples to illustrate its utility. It is open to question, however, whether the paradigm is sufficiently complex to encompass all the variables in actual situations. In real life, the evolution of humiliation is a highly complicated, often messy process that takes place over time and often results in intense feelings of humiliation in more than one person, often affecting several persons. The authors' examples are reexamined from alternate assumptions about what may have happened in each case. An additional case example illustrates a high degree of interpersonal complexity, suggesting that actual situations may be too unwieldy to allow for simple analysis by the paradigm. PMID:20542940

  2. Validation of a Multiplex Real-Time PCR Assay for Detection of Mycobacterium spp., Mycobacterium tuberculosis Complex, and Mycobacterium avium Complex Directly from Clinical Samples by Use of the BD Max Open System.

    PubMed

    Rocchetti, Talita T; Silbert, Suzane; Gostnell, Alicia; Kubasek, Carly; Widen, Raymond

    2016-06-01

    A multiplex real-time PCR was validated on the BD Max open system to detect different Mycobacterium tuberculosis complex, Mycobacterium avium complex, and Mycobacterium spp. directly from clinical samples. The PCR results were compared to those with traditional cultures. The multiplex PCR assay was found to be a specific and sensitive method for the rapid detection of mycobacteria directly from clinical specimens.

  3. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease.

    PubMed

    Wallace, Richard J; Iakhiaeva, Elena; Williams, Myra D; Brown-Elliott, Barbara A; Vasireddy, Sruthi; Vasireddy, Ravikiran; Lande, Leah; Peterson, Donald D; Sawicki, Janet; Kwait, Rebecca; Tichenor, Wellington S; Turenne, Christine; Falkinham, Joseph O

    2013-06-01

    Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.

  4. [The dimension of the paradigm of complexity in health systems].

    PubMed

    Fajardo-Ortiz, Guillermo; Fernández-Ortega, Miguel Ángel; Ortiz-Montalvo, Armando; Olivares-Santos, Roberto Antonio

    2015-01-01

    This article presents elements to better understand health systems from the complety paradigm, innovative perspective that offers other ways in the conception of the scientific knowledge prevalent away from linear, characterized by the arise of emerging dissociative and behaviors, based on the intra and trans-disciplinarity concepts such knowledges explain and understand in a different way what happens in the health systems with a view to efficiency and effectiveness. The complexity paradigm means another way of conceptualizing the knowledge, is different from the prevalent epistemology, is still under construction does not separate, not isolated, is not reductionist, or fixed, does not solve the problems, but gives other bases to know them and study them, is a different strategy, a perspective that has basis in the systems theory, informatics and cybernetics beyond traditional knowledge, the positive logics, the newtonian physics and symmetric mathematics, in which everything is centered and balanced, joint the "soft sciences and hard sciences", it has present the Social Determinants of Health and organizational culture. Under the complexity paradigm the health systems are identified with the following concepts: entropy, neguentropy, the thermodynamic second law, attractors, chaos theory, fractals, selfmanagement and self-organization, emerging behaviors, percolation, uncertainty, networks and robusteness; such expressions open new possibilities to improve the management and better understanding of the health systems, giving rise to consider health systems as complex adaptive systems. PMID:25982615

  5. [The dimension of the paradigm of complexity in health systems].

    PubMed

    Fajardo-Ortiz, Guillermo; Fernández-Ortega, Miguel Ángel; Ortiz-Montalvo, Armando; Olivares-Santos, Roberto Antonio

    2015-01-01

    This article presents elements to better understand health systems from the complety paradigm, innovative perspective that offers other ways in the conception of the scientific knowledge prevalent away from linear, characterized by the arise of emerging dissociative and behaviors, based on the intra and trans-disciplinarity concepts such knowledges explain and understand in a different way what happens in the health systems with a view to efficiency and effectiveness. The complexity paradigm means another way of conceptualizing the knowledge, is different from the prevalent epistemology, is still under construction does not separate, not isolated, is not reductionist, or fixed, does not solve the problems, but gives other bases to know them and study them, is a different strategy, a perspective that has basis in the systems theory, informatics and cybernetics beyond traditional knowledge, the positive logics, the newtonian physics and symmetric mathematics, in which everything is centered and balanced, joint the "soft sciences and hard sciences", it has present the Social Determinants of Health and organizational culture. Under the complexity paradigm the health systems are identified with the following concepts: entropy, neguentropy, the thermodynamic second law, attractors, chaos theory, fractals, selfmanagement and self-organization, emerging behaviors, percolation, uncertainty, networks and robusteness; such expressions open new possibilities to improve the management and better understanding of the health systems, giving rise to consider health systems as complex adaptive systems.

  6. Mycobacterium avium complex olecranon bursitis resolves without antimicrobials or surgical intervention: A case report and review of the literature

    PubMed Central

    Working, Selene; Tyser, Andrew; Levy, Dana

    2015-01-01

    Introduction Nontuberculous mycobacteria are an uncommon cause of septic olecranon bursitis, though cases have increasingly been described in both immunocompromised and immunocompetent hosts. Guidelines recommend a combination of surgical resection and antimicrobials for treatment. This case is the first reported case of nontuberculous mycobacterial olecranon bursitis that resolved without medical or surgical intervention. Case presentation A 67-year-old female developed a painless, fluctuant swelling of the olecranon bursa following blunt trauma to the elbow. Due to persistent bursal swelling, she underwent three separate therapeutic bursal aspirations, two involving intrabursal steroid injection. After the third aspiration, the bursa became erythematous and severely swollen, and bursal fluid grew Mycobacterium avium complex. Triple-drug antimycobacterial therapy was initiated, but discontinued abruptly due to a rash. Surgery was not performed. The patient was observed off antimicrobials, and gradually clinically improved with a compressive dressing. By 14 months after initial presentation, clinical exam revealed complete resolution of the previously erythematous bursal mass. Discussion This is the first reported case of nontuberculous mycobacterial olecranon bursitis managed successfully without surgery or antimicrobials. Musculoskeletal nontuberculous mycobacterial infections are challenging given the lack of clinical data about optimal duration and choice of antimicrobials or the role of surgery. Additionally, the potential toxicity and drug interactions of antimycobacterials are not insignificant and warrant close monitoring if treatment is pursued. Conclusion This case raises an important clinical question of whether close observation off antimicrobials is appropriate in select cases of immunocompetent patients with localized atypical mycobacterial disease of soft tissue and skeletal structures. PMID:26793457

  7. Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

    PubMed Central

    González-Pérez, Mónica; Mariño-Ramírez, Leonardo; Parra-López, Carlos Alberto; Murcia, Martha Isabel; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Míguez, Yadira; Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara

    2013-01-01

    The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue. PMID:23959717

  8. Mycobacterium avium-Intracellulare Complex (MAC) Producing a Periportal Pseudotumor in a Patient With HIV and a Normal CD4 Count

    PubMed Central

    Johnson, Jessica; Driscoll, Meghan; Cohen, Michael

    2016-01-01

    Mycobacterium avium-intracellulare complex (MAC) is an opportunistic infection typically associated with profound immunosuppression, such as AIDS. The presentation of disseminated MAC can be subtle and mimic systemic symptoms associated with lymphoma; abdominal pseudotumor is an exceptionally rare presentation. In the era of highly active anti-retroviral therapy (HAART), opportunistic infections are increasingly rare, and secondary prophylaxis for MAC may be discontinued after adequate therapy and immune reconstitution. Recurrence of disseminated MAC after adequate therapy may be due to macrolide resistance, but with an adequate CD4 T-cell count and undetectable HIV viral load, recurrence raises questions of more subtle immune dysregulation. PMID:27807554

  9. Non-Major Histocompatibility Complex Control of Antibody Isotype and Th1 versus Th2 Cytokines during Experimental Infection of Mice with Mycobacterium avium

    PubMed Central

    Nagabhushanam, Vijaya; Cheers, Christina

    2001-01-01

    Infection of different strains of mice with Mycobacterium avium has revealed genetic control of the immunoglobulin isotype induced and of the balance between Th1 and Th2 cytokines. Female BALB/c or C57BL/10 mice were infected intranasally with 105 M. avium organisms. The antibody response was measured over 18 weeks by enzyme-linked immunosorbent assay and Western blotting, while numbers of cytokine-producing cells were assessed at 12 to 15 weeks by ELISPOT assay. Upon infection, C57BL/10 mice produced a clear Th1 response with strong gamma interferon (IFN-γ) production, no interleukin-4 (IL-4), and almost entirely immunoglobulin G2a (IgG2a) antibody. In contrast, BALB/c mice developed T cells producing IL-4, as well as those producing IFN-γ, while the antibody response was a mixture of IgG1 and IgG2a. Antibodies from BALB/c mice were also able to recognize a greater range of antigens than were C56BL/10 mice. B10D2 mice, which carry the BALB/c major histocompatibility complex haplotype on a C57BL/10 background, followed the C57BL/10 cytokine pattern. Mice infected with Listeria monocytogenes did not show a similar response dichotomy. PMID:11179347

  10. Mycobacterium Avium Complex (MAC)

    MedlinePlus

    ... MAC? The symptoms of MAC can include high fevers, chills, diarrhea , weight loss, stomach aches, fatigue, and anemia ( ... anemia. Many drug interactions. Rifampin (Rifampicin, Rifadin, Rimactane): fever, chills, muscle or bone pain; can turn urine, sweat, ...

  11. [Disseminated Mycobacterium avium complex infections in AIDS. Apropos of 100 cases. Groupe d'Epidémiologie clinique du SIDA en Aquitaine].

    PubMed

    Lasseur, C; Maugein, J; Pellegrin, J L; Dupon, M; Ragnaud, J M; Morlat, P; Pellegrin, I; Constans, J; Monlun, E; Chene, G

    1995-01-01

    The improvement of survival of AIDS patients allowed the emergence of disseminated Mycobacterium avium Complex infections (D.MAC). Here we report the experience of the group of "Epidémiologie clinique du sida en Aquitaine (GECSA)" about 100 patients. There were no differences according to sex, age and route of acquisition of HIV. Clinical and biological characteristics of the infections were not specific. The mean TCD4+ lymphocytes count was 18/mm3. The diagnostic was generally established by systematic blood culture on Septi-Chek in patients with TCD4+ lymphocytes count below 75/mm3. The recommendations on therapy for D.MAC are to use regimen containing azithromycin or clarithromycin, ethambutol and one of the following drugs, rifabutin, clofazimine, amikacin, or ciprofloxacin. Rifabutin is recommended for prophylaxis in patients with lymphocytes TCD4+ count below 100/mm3.

  12. Complexity, Training Paradigm Design, and the Contribution of Memory Subsystems to Grammar Learning.

    PubMed

    Antoniou, Mark; Ettlinger, Marc; Wong, Patrick C M

    2016-01-01

    Although there is variability in nonnative grammar learning outcomes, the contributions of training paradigm design and memory subsystems are not well understood. To examine this, we presented learners with an artificial grammar that formed words via simple and complex morphophonological rules. Across three experiments, we manipulated training paradigm design and measured subjects' declarative, procedural, and working memory subsystems. Experiment 1 demonstrated that passive, exposure-based training boosted learning of both simple and complex grammatical rules, relative to no training. Additionally, procedural memory correlated with simple rule learning, whereas declarative memory correlated with complex rule learning. Experiment 2 showed that presenting corrective feedback during the test phase did not improve learning. Experiment 3 revealed that structuring the order of training so that subjects are first exposed to the simple rule and then the complex improved learning. The cumulative findings shed light on the contributions of grammatical complexity, training paradigm design, and domain-general memory subsystems in determining grammar learning success. PMID:27391085

  13. Complexity, Training Paradigm Design, and the Contribution of Memory Subsystems to Grammar Learning

    PubMed Central

    Ettlinger, Marc; Wong, Patrick C. M.

    2016-01-01

    Although there is variability in nonnative grammar learning outcomes, the contributions of training paradigm design and memory subsystems are not well understood. To examine this, we presented learners with an artificial grammar that formed words via simple and complex morphophonological rules. Across three experiments, we manipulated training paradigm design and measured subjects' declarative, procedural, and working memory subsystems. Experiment 1 demonstrated that passive, exposure-based training boosted learning of both simple and complex grammatical rules, relative to no training. Additionally, procedural memory correlated with simple rule learning, whereas declarative memory correlated with complex rule learning. Experiment 2 showed that presenting corrective feedback during the test phase did not improve learning. Experiment 3 revealed that structuring the order of training so that subjects are first exposed to the simple rule and then the complex improved learning. The cumulative findings shed light on the contributions of grammatical complexity, training paradigm design, and domain-general memory subsystems in determining grammar learning success. PMID:27391085

  14. Complexity, Training Paradigm Design, and the Contribution of Memory Subsystems to Grammar Learning.

    PubMed

    Antoniou, Mark; Ettlinger, Marc; Wong, Patrick C M

    2016-01-01

    Although there is variability in nonnative grammar learning outcomes, the contributions of training paradigm design and memory subsystems are not well understood. To examine this, we presented learners with an artificial grammar that formed words via simple and complex morphophonological rules. Across three experiments, we manipulated training paradigm design and measured subjects' declarative, procedural, and working memory subsystems. Experiment 1 demonstrated that passive, exposure-based training boosted learning of both simple and complex grammatical rules, relative to no training. Additionally, procedural memory correlated with simple rule learning, whereas declarative memory correlated with complex rule learning. Experiment 2 showed that presenting corrective feedback during the test phase did not improve learning. Experiment 3 revealed that structuring the order of training so that subjects are first exposed to the simple rule and then the complex improved learning. The cumulative findings shed light on the contributions of grammatical complexity, training paradigm design, and domain-general memory subsystems in determining grammar learning success.

  15. Complexity and human health: the case for a transdisciplinary paradigm.

    PubMed

    Albrecht, G; Freeman, S; Higginbotham, N

    1998-03-01

    Transdisciplinary thinking is an emerging philosophy underpinning health social science. We advance a definition of transdisciplinary thinking and link it with complexity theory. Complexity theory's concern with non-linear relationships, interactive causality and emergent properties of systems compels researchers to adopt a transdisciplinary perspective. We construct a generic framework for analyzing health processes from diverse disciplines and apply it to coronary heart disease in the Australian Coalfields. Insights from this analysis support our argument that transdisciplinary thinking maximizes understanding of the complexity of human health.

  16. Behavioral tests of hippocampal function: simple paradigms complex problems.

    PubMed

    Gerlai, R

    2001-11-01

    Behavioral tests have become important tools for the analysis of functional effects of induced mutations in transgenic mice. However, depending on the type of mutation and several experimental parameters, false positive or negative findings may be obtained. Given the fact that molecular neurobiologists now make increasing use of behavioral paradigms in their research, it is imperative to revisit such problems. In this review three tests, T-maze spontaneous alternation task (T-CAT), Context dependent fear conditioning (CDFC), and Morris water maze (MWM) sensitive to hippocampal function, serve as illustrative examples for the potential problems. Spontaneous alternation tests are sometimes flawed because the handling procedure makes the test dependent on fear rather than exploratory behavior leading to altered alternation rates independent of hippocampal function. CDFC can provide misleading results because the context test, assumed to be a configural task dependent on the hippocampus, may have a significant elemental, i.e. cued, component. MWM may pose problems if its visible platform task is disproportionately easier for the subjects to solve than the hidden platform task, if the order of administration of visible and hidden platform tasks is not counterbalanced, or if inappropriate parameters are measured. Without attempting to be exhaustive, this review discusses such experimental problems and gives examples on how to avoid them.

  17. Descriptive analysis of the prevalence and the molecular epidemiology of Mycobacterium avium complex-infected pigs that were slaughtered on the main island of Okinawa.

    PubMed

    Hibiya, K; Kazumi, Y; Nishiuchi, Y; Sugawara, I; Miyagi, K; Oda, Y; Oda, E; Fujita, J

    2010-09-01

    Recent genetic studies have revealed that several epidemiological factors affect Mycobacterium avium complex (MAC) infection in pig populations. However, mechanisms underlying the spread of MAC infection among hog farms have not been clarified. In consideration of this situation, we cross-sectionally investigated the mechanisms underlying the spread of MAC on the island of Okinawa. Pigs slaughtered (n=706,763) and 331 hog farms on Okinawa were surveyed during the years 2002-2004. Two outbreaks of MAC infection were occurred in several farms during survey period. Bacteria were isolated from randomly selected pigs and genotype of isolates was determined by using genetic finger printing methods with the insertion sequence (IS) 1245 restriction fragment length polymorphism (RFLP). Most isolates had large numbers of IS1245 copies, while strains with low copy numbers of IS1245 and isolates without IS1245 were seen in few farms. MACs strains were repeatedly isolated from pigs of the affected farms during the survey period. Those farms with an identical pig rearing systems showed synchronic changes in the prevalence of MAC infection. An industrial farm without an outbreak had an independent pig flow, but maintained distinct MAC strains. Multivariate analysis did not reveal independent factors for the prevalence of the MAC infection. These findings suggest that there were three clusters distinguished genetically in the main island of Okinawa, which were potentially spread by common pig flow. However, the outbreaks occurred because of unspecified conditions on each farm environment.

  18. [Clinical features of the patients with "secondary infection" of Mycobacterium avium complex--Radiographic pattern of progressions in the patients with and without underlying pulmonary conditions].

    PubMed

    Tanaka, E; Amitani, R; Kuze, F

    1993-01-01

    We reviewed the radiographic features of 42 patients with Mycobacterium avium complex (MAC) infection. Six cases were definite "primary", 20 were "secondary", and 15 were indeterminate (probably "primary"). In the definite and probable "primary" cases, and some of the "secondary" cases, pulmonary lesions slowly progressed following a common and characteristic sequence from a cluster of small nodules or fibro-productive nodules to those with subpleural thickening, or with thickening of the draining bronchi, or with both subpleural and bronchial thickening, and to cystic bronchiectatic changes associated with collapse of the segment or the lobe, in the final stage. Cases of airspace pneumonia appeared rarely. In these cases, neither apical-subapical region prevalence, pleural effusion, nor mediastinal lymphadenopathy were found. On the contrary, in five cases of "secondary" infection, MAC lesions located at the same place with the predisposing lung disease and did not progress during more than five years of observation. In the progressive cases of "secondary" infection, however, the appearance of new lesions and the progressions thereafter showed the same pattern as in "primary" infection. These features would suggest that MAC infection would occur and progress slowly among patients who had unknown pathogenetical factor, whether they had underlying predisposing lung conditions or not.

  19. Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

    PubMed

    Goh, Wilson Wen Bin; Wong, Limsoon

    2016-09-01

    Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts.

  20. Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

    PubMed

    Goh, Wilson Wen Bin; Wong, Limsoon

    2016-09-01

    Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts. PMID:27454466

  1. Toward a Complexity Paradigm for Understanding Gender Role Conflict

    ERIC Educational Resources Information Center

    Enns, Carolyn Zerbe

    2008-01-01

    The well-developed body of theory and research on men's gender role conflict provides an excellent foundation for developing increasingly complex models of men's gender-related concerns. Theorists and researchers are encouraged to incorporate themes related to social structural aspects of gender as well as to examine the ways in which men's…

  2. Challenging the Limits of Critique in Education through Morin's Paradigm of Complexity

    ERIC Educational Resources Information Center

    Alhadeff-Jones, Michel

    2010-01-01

    The position adopted in this paper is inspired by Edgar Morin's paradigm of complexity and his critique of scientific and philosophical forms of reductionism. This paper is based on research focusing on the diversity of conceptions of critique developed in academic discourses. It aims to challenge the fragmentation and the reduction framing the…

  3. Complexity aided design. The FuturICT technological innovation paradigm

    NASA Astrophysics Data System (ADS)

    Carbone, A.; Ajmone-Marsan, M.; Axhausen, K. W.; Batty, M.; Masera, M.; Rome, E.

    2012-11-01

    "In the next century, planet earth will don an electronic skin. It will use the Internet as a scaffold to support and transmit its sensations. This skin is already being stitched together. It consists of millions of embedded electronic measuring devices: thermostats, pressure gauges, pollution detectors, cameras, microphones, glucose sensors, EKGs, electroencephalographs. These will probe and monitor cities and endangered species, the atmosphere, our ships, highways and fleets of trucks, our conversations, our bodies-even our dreams ....What will the earth's new skin permit us to feel? How will we use its surges of sensation? For several years-maybe for a decade-there will be no central nervous system to manage this vast signaling network. Certainly there will be no central intelligence...some qualities of self-awareness will emerge once the Net is sensually enhanced. Sensuality is only one force pushing the Net toward intelligence". These statements are quoted by an interview by Cherry Murray, Dean of the Harvard School of Engineering and Applied Sciences and Professor of Physics. It is interesting to outline the timeliness and highly predicting power of these statements. In particular, we would like to point to the relevance of the question "What will the earth's new skin permit us to feel?" to the work we are going to discuss in this paper. There are many additional compelling questions, as for example: "How can the electronic earth's skin be made more resilient?"; "How can the earth's electronic skin be improved to better satisfy the need of our society?";"What can the science of complex systems contribute to this endeavour?"

  4. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis

    PubMed Central

    Shibata, Yuji; Horita, Nobuyuki; Yamamoto, Masaki; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Narita, Atsuya; Kanai, Akinori; Sato, Takashi; Kaneko, Takeshi

    2016-01-01

    Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6–52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837–0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621–0.761) and 0.906 (95% CI 0.836–0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1–13.8) and 0.34 (95% CI 0.26–0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value. PMID:27373718

  5. An eye-tracking paradigm for analyzing the processing time of sentences with different linguistic complexities.

    PubMed

    Wendt, Dorothea; Brand, Thomas; Kollmeier, Birger

    2014-01-01

    An eye-tracking paradigm was developed for use in audiology in order to enable online analysis of the speech comprehension process. This paradigm should be useful in assessing impediments in speech processing. In this paradigm, two scenes, a target picture and a competitor picture, were presented simultaneously with an aurally presented sentence that corresponded to the target picture. At the same time, eye fixations were recorded using an eye-tracking device. The effect of linguistic complexity on language processing time was assessed from eye fixation information by systematically varying linguistic complexity. This was achieved with a sentence corpus containing seven German sentence structures. A novel data analysis method computed the average tendency to fixate the target picture as a function of time during sentence processing. This allowed identification of the point in time at which the participant understood the sentence, referred to as the decision moment. Systematic differences in processing time were observed as a function of linguistic complexity. These differences in processing time may be used to assess the efficiency of cognitive processes involved in resolving linguistic complexity. Thus, the proposed method enables a temporal analysis of the speech comprehension process and has potential applications in speech audiology and psychoacoustics.

  6. Characterization of clinical and environmental Mycobacterium avium spp. isolates and their interaction with human macrophages

    EPA Science Inventory

    Members of the Mycobacterium avium complex (MAC) are naturally occurring bacteria in the environment. A link has been suggested between M. avium strains in drinking water and clinical isolates from infected individuals. There is a need to develop new screening methodologies tha...

  7. Perils of paradigm: Complexity, policy design, and the Endocrine Disruptor Screening Program

    PubMed Central

    Vogel, Jason M

    2005-01-01

    The Endocrine Disruptor Screening Program (EDSP), mandated by the United States Congress in the Food Quality Protection Act of 1996, attempts to protect public health from adverse endocrine effects of synthetic chemical compounds by establishing a new testing regime. But the complexities and uncertainties of endocrine disruption and its broader regulatory and social context all but ensure the failure of this policy. This article addresses the issues facing EDSP comprehensively and in detail, in order to move beyond the current regulatory paradigm and foster discourse on a positive role for scientists in support of EDSP's end goal: to protect public health. PMID:15701170

  8. Viewing Complex, Dynamic Scenes "Through the Eyes" of Another Person: The Gaze-Replay Paradigm.

    PubMed

    Bush, Jennifer Choe; Pantelis, Peter Christopher; Morin Duchesne, Xavier; Kagemann, Sebastian Alexander; Kennedy, Daniel Patrick

    2015-01-01

    We present a novel "Gaze-Replay" paradigm that allows the experimenter to directly test how particular patterns of visual input-generated from people's actual gaze patterns-influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze "donor." This was intended to simulate the donor's visual selection, such that a participant could effectively view scenes "through the eyes" of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition. PMID:26252493

  9. Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex▿ †

    PubMed Central

    Mackenzie, Nick; Alexander, David C.; Turenne, Christine Y.; Behr, Marcel A.; De Buck, Jeroen M.

    2009-01-01

    The Mycobacterium avium complex (MAC) comprises genomically similar but phenotypically divergent bacteria that inhabit diverse environments and that cause disease in different hosts. In this study, a whole-genome approach was used to examine the polymorphic PE (Pro-Glu) and PPE (Pro-Pro-Glu) gene families, implicated in immunostimulation and virulence. The four major groups of MAC organisms were examined, including the newly sequenced type strains of M. intracellulare and M. avium subsp. avium, plus M. avium subsp. paratuberculosis and M. avium subsp. hominissuis, for the purpose of finding genetic differences that could be exploited to design diagnostic tests specific to these groups and that could help explain their divergence in pathogenesis and host specificity. Unique and missing PPE genes were found in all MAC members except M. avium subsp. avium. Only M. intracellulare had a unique PE gene. Apart from this, most PE and PPE sequences were conserved, with average nucleotide sequence identities of 99.1 and 98.1%, respectively, among the M. avium subspecies, but only 82.9 and 79.7% identities with the PE and PPE sequences of M. intracellulare, respectively. A detailed analysis of the amino acid sequences was performed between M. avium subsp. paratuberculosis and M. avium subsp. hominissuis. Most differences were detected in the PPE proteins, with amino acid substitutions and frame shifts leading to unique amino acid sequences. In conclusion, several unique PPE proteins were identified in MAC organisms next to numerous polymorphisms in both the PE and PPE gene families. These substantial differences could help explain the divergence in phenotypes within the MAC and could lead to diagnostic tests with better discriminatory abilities. PMID:19144814

  10. Genomic and Transcriptomic Studies in Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microarray technology is an important tool in functional genomic research. It has enabled a deeper analysis of genomic diversity among bacteria belonging to the Mycobacterium avium Complex (MAC). In addition, the expression of thousands of genes can be studied simultaneously in a single experiment...

  11. Urinary mycobacterium avium presenting as sterile pyuria

    PubMed Central

    Yang, Kai; Samplaski, Mary; Mazzulli, Tony; Lo, Kirk; Grober, Ethan; Jarvi, Keith Allen

    2016-01-01

    A 65-year-old healthy woman presented with persistent, asymptomatic sterile pyuria detected by her family physician. While she did not have symptoms, the patient recounts that she has had cloudy urine for years. Cultures of the urine for bacteria showed no growth and no fungi were identified. First-morning urine samples were sent for both tuberculosis and nontuberculosis mycobacterium species testing. The culture grew genotypically identified Mycobaterium avium complex (MAC). Mantoux skin testing was positive. No urological abnormalities were detected by ultrasound and computed tomography (CT) imaging of the urinary tract.

  12. Using Common Graphics Paradigms Implemented in a Java Applet to Represent Complex Scheduling Requirements

    NASA Technical Reports Server (NTRS)

    Jaap, John; Meyer, Patrick; Davis, Elizabeth

    1997-01-01

    The experiments planned for the International Space Station promise to be complex, lengthy and diverse. The scarcity of the space station resources will cause significant competition for resources between experiments. The scheduling job facing the Space Station mission planning software requires a concise and comprehensive description of the experiments' requirements (to ensure a valid schedule) and a good description of the experiments' flexibility (to effectively utilize available resources). In addition, the continuous operation of the station, the wide geographic dispersion of station users, and the budgetary pressure to reduce operations manpower make a low-cost solution mandatory. A graphical representation of the scheduling requirements for station payloads implemented via an Internet-based application promises to be an elegant solution that addresses all of these issues. The graphical representation of experiment requirements permits a station user to describe his experiment by defining "activities" and "sequences of activities". Activities define the resource requirements (with alternatives) and other quantitative constraints of tasks to be performed. Activities definitions use an "outline" graphics paradigm. Sequences define the time relationships between activities. Sequences may also define time relationships with activities of other payloads or space station systems. Sequences of activities are described by a "network" graphics paradigm. The bulk of this paper will describe the graphical approach to representing requirements and provide examples that show the ease and clarity with which complex requirements can be represented. A Java applet, to run in a web browser, is being developed to support the graphical representation of payload scheduling requirements. Implementing the entry and editing of requirements via the web solves the problems introduced by the geographic dispersion of users. Reducing manpower is accomplished by developing a concise

  13. Inflammation, Genetics, Dysbiosis, and the Environment: New Paradigms for Diagnosis in Complex Chronic Gut Syndromes.

    PubMed

    Walker, Marjorie M

    2016-10-01

    Chronic and complex gut syndromes are complex to diagnose and manage, but good clinicopathologic correlation, recognition of new entities, understanding (and understanding the limits) of genetic susceptibility and the importance of the microbiome, dysbiosis and influence of the environmental allows development of new models for diagnosis. An awareness of overlap in chronic gut syndromes has been clarified by the realization that inflammatory pathways involved in chronic gut disease can arise through variable gene expression that is influenced by the environment in susceptible individuals. Recent advances in diagnosis of inflammatory bowel disease and diverticular disease may be aided by genetic tests but at present, pathology and some simple biomarkers such as C-reactive protein and fecal calprotectin are still mainstream investigative measures. When made aware of the importance of these recent developments in chronic gut disease, histopathologists can easily recognize colonic spirochetosis and microscopic colitis. The role of the microbiome alongside interaction with the environment, are now recognized as key players in complex diseases. Integration of appropriate and cost-effective tests into new paradigms will surely advance patients' well-being and allow development of curative-targeted therapies rather than current treatments which, in many cases, merely alleviate symptoms. PMID:27622361

  14. Inflammation, Genetics, Dysbiosis, and the Environment: New Paradigms for Diagnosis in Complex Chronic Gut Syndromes.

    PubMed

    Walker, Marjorie M

    2016-10-01

    Chronic and complex gut syndromes are complex to diagnose and manage, but good clinicopathologic correlation, recognition of new entities, understanding (and understanding the limits) of genetic susceptibility and the importance of the microbiome, dysbiosis and influence of the environmental allows development of new models for diagnosis. An awareness of overlap in chronic gut syndromes has been clarified by the realization that inflammatory pathways involved in chronic gut disease can arise through variable gene expression that is influenced by the environment in susceptible individuals. Recent advances in diagnosis of inflammatory bowel disease and diverticular disease may be aided by genetic tests but at present, pathology and some simple biomarkers such as C-reactive protein and fecal calprotectin are still mainstream investigative measures. When made aware of the importance of these recent developments in chronic gut disease, histopathologists can easily recognize colonic spirochetosis and microscopic colitis. The role of the microbiome alongside interaction with the environment, are now recognized as key players in complex diseases. Integration of appropriate and cost-effective tests into new paradigms will surely advance patients' well-being and allow development of curative-targeted therapies rather than current treatments which, in many cases, merely alleviate symptoms.

  15. Characterization of a Mycobacterium avium subsp. avium Operon Associated with Virulence and Drug Detoxification

    PubMed Central

    Viale, Mariana Noelia; Imperiale, Belén; Gioffre, Andrea Karina; Colombatti Olivieri, María Alejandra; Moyano, Roberto Damián; Morcillo, Nora; Santangelo, María de la Paz; Davis, William; Romano, María Isabel

    2014-01-01

    The lprG-p55 operon of Mycobacterium tuberculosis and Mycobacterium bovis is involved in the transport of toxic compounds. P55 is an efflux pump that provides resistance to several drugs, while LprG is a lipoprotein that modulates the host's immune response against mycobacteria. The knockout mutation of this operon severely reduces the replication of both mycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in the Mycobacterium avium complex, in this study, we assayed the effect of the deletion of lprG gene in the D4ER strain of Mycobacterium avium subsp. avium. The replacement of lprG gene with a hygromycin cassette caused a polar effect on the expression of p55. Also, a twofold decrease in ethidium bromide susceptibility was observed and the resistance to the antibiotics rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant strain. In addition, the mutation decreased the virulence of the bacteria in macrophages in vitro and in a mice model in vivo. These findings clearly indicate that functional LprG and P55 are necessary for the correct transport of toxic compounds and for the survival of MAA in vitro and in vivo. PMID:24967408

  16. "To Give an Example Is a Complex Act": Agamben's Pedagogy of the Paradigm

    ERIC Educational Resources Information Center

    Meskin, Jacob; Shapiro, Harvey

    2014-01-01

    Agamben's notion of the "paradigm" has far-reaching implications for educational thinking, curriculum design and pedagogical conduct. In his approach, examples--or paradigms--deeply engage our powers of analogy, enabling us to discern previously unseen affinities among singular objects by stepping outside established systems of…

  17. Genotyping of Mycobacterium avium subsp. avium isolates from naturally infected lofts of domestic pigeons in Ahvaz by IS901 RFLP

    PubMed Central

    Parvandar-Asadollahi, Kaveh; Mosavari, Nader; Mayahi, Mansoor

    2015-01-01

    Background and Objectives: Avian tuberculosis is one of the most important infections affecting most species of birds. Mycobacterium avium can not only infect all species of birds, but also infect some domesticated mammals. The most crucial aspect of control and eradication scheme is identification of infection sources and transmission routs. Molecular techniques such as restriction fragment length polymorphism and pulse field gel electrophoresis have been shown to be much more discriminatory and suitable for use in the epidemiological study. Materials and Methods: Eighty suspected pigeons to avian tuberculosis based on their clinical signs, were subjected to the study. Forty Mycobacterium avium subsp. avium isolates out of a total of 51 identified isolates were subjected to the test. Results: IS901-RFLP using Pvu II was successfully conducted and produced 7 patterns. The majority of isolates (60%) were RFLP type PI.1. This type was the most similar type to standard strain. However, all the patterns obtained in this study were different from the standard strain. Conclusion: The result of this study indicate that these isolates probably are limited to Khuzestan region. We recommend DNA fingerprinting differentiation of non tuberculous Mycobacteria particularly Mycobacterium avium complex isolated from infected birds and human to possibly find source of infections. PMID:26719782

  18. Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine.

    PubMed

    Bonnet, F; Dequae-Merchadou, L; Taupin, J L; Sire, S; Dupon, M; Ragnaud, J M; Lacoste, D; Texier-Maugein, J; Romagné, F; Dabis, F; Pellegrin, J L; Moreau, J F

    1999-08-01

    In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.

  19. Reducing human exposure to Mycobacterium avium.

    PubMed

    Falkinham, Joseph O

    2013-08-01

    In light of the increasing prevalence of Mycobacterium avium pulmonary disease and the challenges of treating patients with M. avium infection, consideration of measures to reduce exposure is warranted. Because M. avium inhabits water and soil, humans are surrounded by that opportunistic pathogen. Because infection has been linked to the presence of M. avium in household plumbing, increasing hot water temperature, reducing aerosol (mist) exposures in bathrooms and showers, and installing filters that prevent the passage of mycobacteria will likely reduce M. avium exposure. Granular activated carbon (charcoal) filters support the growth of M. avium and should be avoided. When gardening, avoid the inhalation of soil dusts by using a mask or wetting the soil because peat-rich potting soils have high numbers of mycobacteria.

  20. Paradigms lost?

    PubMed

    Fleener, M Jayne; Merritt, Michael L

    2007-01-01

    Thomas Kuhn (1957, 1962) explored the issues of paradigm shifts, scientific revolutions, and the relationship between them. Written before the techniques and practices of the complexity sciences were developed, Kuhn described what he termed the Copernican Revolution as the last scientific revolution signifying a paradigmatic shift in society. We will explore whether New Science approaches in nonlinear dynamics and complexity research signify postmodern science perspectives, and examine the role of New Science in what may be the on-going evolution of the next paradigm shift. PMID:17173727

  1. Isolation of Mycobacterium avium from waterfowl with polycystic livers.

    USGS Publications Warehouse

    Roffe, Thomas J.

    1989-01-01

    An unusual gross appearance of avian tuberculosis, where fluid-filled thin-walled cysts are produced and grossly apparent in preference to granulomas, is presented. Histopathology confirmed the granulomatous nature of the lesions and the presence of intracellular acid-fast organisms. Mycobacterium avium complex was cultured from affected organs. The unusual gross presentation in these cases indicates the need to consider tuberculosis in the differential of cystic diseases of avian livers.

  2. Tuberculosis in swine co-infected with Mycobacterium avium subsp. hominissuis and Mycobacterium bovis in a cluster from Argentina.

    PubMed

    Barandiaran, S; Pérez, A M; Gioffré, A K; Martínez Vivot, M; Cataldi, A A; Zumárraga, M J

    2015-04-01

    SUMMARY In Argentina little is known about the epidemiology of tuberculosis (TB) infection in swine. We characterized the epidemiological dynamics of Mycobacterium avium complex (MAC) infection in a swine population of Argentina using molecular tools and spatial analysis techniques. Isolates (n = 196) obtained from TB-like lesions (n = 200) were characterized by polymerase chain reaction. The isolates were positive to either M. bovis (IS6110) (n = 160) or M. avium (IS1245) (n = 16) while the remaining 20 (10.2%) isolates were positive to both M. bovis and M. avium. The detection of both bacteria together suggests co-infection at the animal level. In addition, MAC-positive isolates (n = 36) were classified as M. avium subsp. avium (MAA) (n = 30) and M. avium subsp. hominissuis (MAH) (n = 6), which resulted in five genotypes when they were typed using mycobacterial interspersed repetitive unit, variable number of tandem repeats (MIRU-VNTR). One significant (P = 0.017) spatial clustering of genotypes was detected, in which the proportion of MAH isolates was larger than expected under the null hypothesis of even distribution of genotypes. These results show that in Argentina the proportion of TB cases in pigs caused by M. avium is larger than that reported in earlier studies. The proportion of M. bovis-MAC co-infections was also higher than in previous reports. These results provide valuable information on the epidemiology of MAC infection in swine in Argentina.

  3. Mycobacterium avium MAV_2941 mimics Phosphoinositol-3-Kinase to interfere with macrophage phagosome maturation

    PubMed Central

    Danelishvili, Lia; Bermudez, Luiz E.

    2015-01-01

    Mycobacterium avium subsp hominissuis (M. avium) is a pathogen that infects and survives in macrophages. Previously, we have identified the M. avium MAV_2941 gene encoding a 73 amino acid protein exported by the oligopeptide transporter OppA to the macrophage cytoplasm. Mutations in MAV_2941 were associated with significant impairment of M. avium growth in THP-1 macrophages. In this study, we investigated the molecular mechanism of MAV_2941 action and demonstrated that MAV_2941 interacts with the vesicle trafficking proteins syntaxin-8 (STX8), adaptor-related protein complex 3 (AP-3) complex subunit beta-1 (AP3B1) and Archain 1 (ARCN1) in mononuclear phagocytic cells. Sequencing analysis revealed that the binding site of MAV_2941 is structurally homologous to the human phosphatidylinositol 3-kinase (PI3K) chiefly in the region recognized by vesicle trafficking proteins. The β3A subunit of AP-3, encoded by AP3B1, is essential for trafficking cargo proteins, including lysosomal-associated membrane protein 1 (LAMP-1), to the phagosome and lysosome-related organelles. Here, we show that while the heat-killed M. avium when ingested by macrophages co-localizes with LAMP-1 protein, transfection of MAV_2941 in macrophages results in significant decrease of LAMP-1 co-localization with the heat-killed M. avium phagosomes. Mutated MAV_2941, where the amino acids homologous to the binding region of PI3K were changed, failed to interact with trafficking proteins. Inactivation of the AP3B1 gene led to alteration in the trafficking of LAMP-1. These results suggest that M. avium MAV_2941 interferes with the protein trafficking within macrophages altering the maturation of phagosome. PMID:26043821

  4. Iron Acquisition in Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Wang, Joyce; Moolji, Jalal; Dufort, Alex; Staffa, Alfredo; Domenech, Pilar; Reed, Michael B.

    2015-01-01

    ABSTRACT Mycobacterium avium subsp. paratuberculosis is a host-adapted pathogen that evolved from the environmental bacterium M. avium subsp. hominissuis through gene loss and gene acquisition. Growth of M. avium subsp. paratuberculosis in the laboratory is enhanced by supplementation of the media with the iron-binding siderophore mycobactin J. Here we examined the production of mycobactins by related organisms and searched for an alternative iron uptake system in M. avium subsp. paratuberculosis. Through thin-layer chromatography and radiolabeled iron-uptake studies, we showed that M. avium subsp. paratuberculosis is impaired for both mycobactin synthesis and iron acquisition. Consistent with these observations, we identified several mutations, including deletions, in M. avium subsp. paratuberculosis genes coding for mycobactin synthesis. Using a transposon-mediated mutagenesis screen conditional on growth without myobactin, we identified a potential mycobactin-independent iron uptake system on a M. avium subsp. paratuberculosis-specific genomic island, LSPP15. We obtained a transposon (Tn) mutant with a disruption in the LSPP15 gene MAP3776c for targeted study. The mutant manifests increased iron uptake as well as intracellular iron content, with genes downstream of the transposon insertion (MAP3775c to MAP3772c [MAP3775-2c]) upregulated as the result of a polar effect. As an independent confirmation, we observed the same iron uptake phenotypes by overexpressing MAP3775-2c in wild-type M. avium subsp. paratuberculosis. These data indicate that the horizontally acquired LSPP15 genes contribute to iron acquisition by M. avium subsp. paratuberculosis, potentially allowing the subsequent loss of siderophore production by this pathogen. IMPORTANCE Many microbes are able to scavenge iron from their surroundings by producing iron-chelating siderophores. One exception is Mycobacterium avium subsp. paratuberculosis, a fastidious, slow-growing animal pathogen whose growth

  5. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice

    PubMed Central

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M.; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  6. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice.

    PubMed

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  7. Exercise hemorheology: Moving from old simplistic paradigms to a more complex picture.

    PubMed

    Brun, Jean-Frédéric; Varlet-Marie, Emmanuelle; Romain, Ahmed-Jérôme; Guiraudou, M; Raynaud de Mauverger, Eric

    2013-01-01

    Classic studies on exercise hemorheology evidenced that blood fluidity is impaired during exercise (short term exercise-induced hyperviscosity) and is improved as a result of regular exercise practice (hemorheologic fitness). Extensive description of these events led to the concepts of "the triphasic effects of exercise", "the paradox of hematocrit", and "the hemorheological paradox of lactate". However, some results obtained in training studies do not fit with this classical picture and cannot be explained by a simplistic paradigm based on the Hagen-Poiseuille law. Taking into account the non-linearity of the effects of viscosity factors on blood flow and oxygen delivery helps to elaborate another picture. For example, moderately high values of hematocrit and erythrocyte rigidity induced by high intensity exercise are likely to trigger a physiological vasodilation improving circulatory adaptation (rather than limiting performance as was previously assumed). This may apply to the acute rise in red cell rigidity observed during strenuous exercise, and also to the paradoxical rise in hematocrit or red cell rigidity observed after some training protocols and that did not fit with the previous (simplistic) paradigms. The "healthy primitive lifestyle" hypothesis assumes that evolution has selected genetic polymorphisms leading to insulin resistance as an adaptative strategy to cope with continuous low intensity physical activity and a special alimentation based on lean meat and wild herbs (i.e., moderately high in protein, rich in low glycemic index carbohydrates, and poor in saturated fat). We propose here that this model may help to explain on an evolutionary perspective these apparently inconsistent findings. The pivotal explanation is that the true physiological picture would be that of an individual whose exercise and nutritional habits are close from this lifestyle, both sedentary subjects and trained athletes representing situations on the edge of this model.

  8. The role of tumour necrosis factor-alpha in combination with interferon-gamma or interleukin-1 in the induction of immunosuppressive macrophages because of Mycobacterium avium complex infection.

    PubMed Central

    Tomioka, H; Maw, W W; Sato, K; Saito, H

    1996-01-01

    The role of some cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6) in the generation of immunosuppressive macrophages (M phi s) in host spleen cells of Mycobacterium avium complex (MAC)-infected mice was studied. M phi populations with potent suppressor activity against concanavalin A (Con A)-induced mitogenesis of splenocytes (SPCs) were elicited not only in euthymic but also in athymic nude mice during MAC infection. The suppressor M phi s are, therefore, inducible not only through a T-cell-dependent mechanism but also through T-cell-independent mechanism. However, MAC-induced M phi s of athymic mice displayed about four times lower suppressor activity than those of euthymic mice, indicating that mature T cells are important for M phi activation to the highly immunosuppressive state. Anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies (Abs) but not anti-IL-6 Ab inhibited in vivo generation of MAC-induced immunosuppressive M phi s, and the neutralizing efficacy was in the order of anti-IFN-gamma Ab > anti-TNF Ab > anti-TGF-beta Ab. The effects of TNF-alpha, IL-1 alpha, IL-6, and IFN-gamma alone or combinations of them upon the acquisition of the suppressor activity by cultured splenic M phi s were studied. When normal splenic M phi s were treated with each cytokine for 3 days, TNF-alpha, IFN-gamma, and IL-1 alpha alone caused a slight elevation of their suppressive activity. Treatment of the normal M phi s with the combination of either TNF-alpha+IL-1 alpha or TNF-alpha+IFN-gamma yielded a marked increase in the suppressor activity, followed by IL-1 alpha+IFN-gamma. These findings indicate the important roles of TNF-alpha, IFN-gamma, and IL-1 alpha in the generation of MAC-induced suppressor M phi s. PMID:8707352

  9. Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

    PubMed Central

    Mozdarani, Hossein

    2012-01-01

    Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity). It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation therapy, all these

  10. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

    PubMed Central

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  11. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

    PubMed

    Tieri, Paolo; Grignolio, Andrea; Zaikin, Alexey; Mishto, Michele; Remondini, Daniel; Castellani, Gastone C; Franceschi, Claudio

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information.

  12. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

    PubMed

    Tieri, Paolo; Grignolio, Andrea; Zaikin, Alexey; Mishto, Michele; Remondini, Daniel; Castellani, Gastone C; Franceschi, Claudio

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  13. MYCOBACTERIUM AVIUM AND DRINKING WATER WHAT ARE THE CONNECTIONS?

    EPA Science Inventory

    Background: Human Mycobacterium avium infections are only known to be acquired from environmental sources such as water and soil. We compared M. avium isolates from clinical and drinking water sources using molecular tools. Methods: M. avium was isolated from water samples colle...

  14. Dynamic self-organization phenomena in complex ionized gas systems: new paradigms and technological aspects

    NASA Astrophysics Data System (ADS)

    Vladimirov, S. V.; Ostrikov, K.

    2004-04-01

    An overview of dynamic self-organization phenomena in complex ionized gas systems, associated physical phenomena, and industrial applications is presented. The most recent experimental, theoretical, and modeling efforts to understand the growth mechanisms and dynamics of nano- and micron-sized particles, as well as the unique properties of the plasma-particle systems (colloidal, or complex plasmas) and the associated physical phenomena are reviewed and the major technological applications of micro- and nanoparticles are discussed. Until recently, such particles were considered mostly as a potential hazard for the microelectronic manufacturing and significant efforts were applied to remove them from the processing volume or suppress the gas-phase coagulation. Nowadays, fine clusters and particulates find numerous challenging applications in fundamental science as well as in nanotechnology and other leading high-tech industries.

  15. Fenestrated stent grafts for the treatment of complex aortic aneurysm disease: A mature treatment paradigm.

    PubMed

    Georgiadis, George S; van Herwaarden, Joost A; Antoniou, George A; Giannoukas, Athanasios D; Lazarides, Miltos K; Moll, Frans L

    2016-06-01

    The introduction of fenestrated stent grafts (SGs) to treat abdominal aortic aneurysms (AAAs) with short proximal necks began in 1999. Nowadays, the whole visceral aorta can be treated totally by endovascular means. The established use of fenestrated devices to treat complex AAAs as a first-line management option has been previously reported. An up-to-date evaluation of the literature was performed including all types of publications regarding the use of fenestrated technology to repair complex AAAs. Fenestrated repair is now an established alternative to hybrid/chimney/snorkel repairs. However, specific criteria and prerequisites are required for the use and improvement of this method. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. This modular strategy connects different devices (bridging covered stents and bifurcated SGs) with the aortic main body, thus excluding the aneurysm from the circulation. Precise deployment of the fenestrated SG is mandatory for successful visceral vessel revascularization. Accurate SG sizing and customization, a high level of technical skill, and facilities with modern imaging techniques including 3D road mapping and dedicated hybrid rooms are required. Most experience has been with the custom-made Zenith Cook platform, although off-the-shelf devices have been recently implanted. More complex repairs have been performed over the last few years, but device complexity has also increased. Perioperative, mid-term, and a few recently reported long-term results are encouraging. Secondary interventions remain the main problem, similar to that observed after traditional endovascular abdominal aortic aneurysm repair (EVAR). PMID:27013644

  16. Fenestrated stent grafts for the treatment of complex aortic aneurysm disease: A mature treatment paradigm.

    PubMed

    Georgiadis, George S; van Herwaarden, Joost A; Antoniou, George A; Giannoukas, Athanasios D; Lazarides, Miltos K; Moll, Frans L

    2016-06-01

    The introduction of fenestrated stent grafts (SGs) to treat abdominal aortic aneurysms (AAAs) with short proximal necks began in 1999. Nowadays, the whole visceral aorta can be treated totally by endovascular means. The established use of fenestrated devices to treat complex AAAs as a first-line management option has been previously reported. An up-to-date evaluation of the literature was performed including all types of publications regarding the use of fenestrated technology to repair complex AAAs. Fenestrated repair is now an established alternative to hybrid/chimney/snorkel repairs. However, specific criteria and prerequisites are required for the use and improvement of this method. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. This modular strategy connects different devices (bridging covered stents and bifurcated SGs) with the aortic main body, thus excluding the aneurysm from the circulation. Precise deployment of the fenestrated SG is mandatory for successful visceral vessel revascularization. Accurate SG sizing and customization, a high level of technical skill, and facilities with modern imaging techniques including 3D road mapping and dedicated hybrid rooms are required. Most experience has been with the custom-made Zenith Cook platform, although off-the-shelf devices have been recently implanted. More complex repairs have been performed over the last few years, but device complexity has also increased. Perioperative, mid-term, and a few recently reported long-term results are encouraging. Secondary interventions remain the main problem, similar to that observed after traditional endovascular abdominal aortic aneurysm repair (EVAR).

  17. GHOST Protocol: Greatest Healing Opportunity for Soft Tissue, a Treatment Paradigm for Complex Sarcoma Reconstruction.

    PubMed

    Kobraei, Edward M; Eberlin, Kyle R; Ricci, Joseph A; Reish, Richard G; Winograd, Jonathan M; Cetrulo, Curtis L

    2015-06-01

    Modern sarcoma treatment has created new challenges for plastic surgeons. This study was designed to review the recent experience and practice patterns following complex sarcoma resection at a large sarcoma center. All cases from October 2013 to October 2014 involving rare nonepithelial tumors, a multidisciplinary surgical team, radiation and/or chemotherapy treatments, and plastic surgical reconstruction were included in the analysis. In addition to evaluating clinical outcomes, cases were reviewed to identify factors associated with excellent or poor patient care. Review of these cases formed the basis of the greatest healing opportunity for soft tissue (GHOST) protocol. Our patient population included seven males (64%) and four females (36%). All except one patient was exposed to radiotherapy, chemotherapy, or some combination. Diverse procedures were used for reconstruction. Early complications occurred in two patients (18%), and late complications in four patients (36%). Sarcoma resection was found to be highly morbid in our series. Patients with poor preoperative nutritional status were more likely to experience complications postoperatively. The decision to stage a reconstruction was complex and influenced by several factors. Multimodal sarcoma treatments may involve highly morbid procedures and create complex wounds. The GHOST protocol is a useful reference for plastic surgeons.

  18. Nanobiology of the primary cilium--paradigm of a multifunctional nanomachine complex.

    PubMed

    Wheatley, Denys N

    2008-01-01

    Of all the organelles in the eukaryotic cells, it is argued that the primary cilium is a paradigm in terms of nanomachinery found in the living cell. The components that are brought together in this single structure endow it with an extraordinary range of receptor and signaling functions. This organelle is based on the centriole, which is itself a minute compact structure that has been conserved throughout evolution for well over a billion years. After more than a century of interest in the presence and structural features of the primary cilium, it became clear from the advent of the electron microscope that they were much more ubiquitous and had many more functions in situations other than the most obvious of cases, that is, the retinal rods and cones. However, these other functional activities were considered to be largely speculative by nonspecialists, until more recently. In the last decade, more has been learned about their molecular biology and function than in all the preceding years of research. The impetus came from a better understanding of the process of ciliogenesis at the macromolecular level, the discovery of wide range of receptors localized in the ciliary membrane, and the appropriate signaling mechanisms to relay messages to the cell internum. These are the three central themes of current investigations. The reason for the recent flurry of activity stemmed from work in the mid-1990s emphasizing the fact that the failure of cells to develop primary cilia in certain tissues and organs was directly correlated with some drastic pathological consequences, just as failure to develop the primary cilia that form the basis of retinal cells, observed now over a half a century ago by Sjöstrand, F. S. (Sjöstrand, F. S. (1953). The ultrastructure of the inner segments of the retinal rods of the guinea pig eye as revealed by electron microscopy long ago, so blatantly causes blindness. The medical implications did in due course prove to be of such magnitude

  19. Laser chimeras as a paradigm for multistable patterns in complex systems

    NASA Astrophysics Data System (ADS)

    Larger, Laurent; Penkovsky, Bogdan; Maistrenko, Yuri

    2015-07-01

    A chimera state is a rich and fascinating class of self-organized solutions developed in high-dimensional networks. Necessary features of the network for the emergence of such complex but structured motions are non-local and symmetry breaking coupling. An accurate understanding of chimera states is expected to bring important insights on deterministic mechanism occurring in many structurally similar high-dimensional dynamics such as living systems, brain operation principles and even turbulence in hydrodynamics. Here we report on a powerful and highly controllable experiment based on an optoelectronic delayed feedback applied to a wavelength tuneable semiconductor laser, with which a wide variety of chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher-order chimeras as a pattern transition from N to N+1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how chimera state is gradually destroyed on the way to apparent turbulence-like system behaviour.

  20. Laser chimeras as a paradigm for multistable patterns in complex systems

    PubMed Central

    Larger, Laurent; Penkovsky, Bogdan; Maistrenko, Yuri

    2015-01-01

    A chimera state is a rich and fascinating class of self-organized solutions developed in high-dimensional networks. Necessary features of the network for the emergence of such complex but structured motions are non-local and symmetry breaking coupling. An accurate understanding of chimera states is expected to bring important insights on deterministic mechanism occurring in many structurally similar high-dimensional dynamics such as living systems, brain operation principles and even turbulence in hydrodynamics. Here we report on a powerful and highly controllable experiment based on an optoelectronic delayed feedback applied to a wavelength tuneable semiconductor laser, with which a wide variety of chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher-order chimeras as a pattern transition from N to N+1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how chimera state is gradually destroyed on the way to apparent turbulence-like system behaviour. PMID:26169585

  1. Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm.

    PubMed

    Azé, Jérôme; Sola, Christophe; Zhang, Jian; Lafosse-Marin, Florian; Yasmin, Memona; Siddiqui, Rubina; Kremer, Kristin; van Soolingen, Dick; Refrégier, Guislaine

    2015-01-01

    Infra-species taxonomy is a prerequisite to compare features such as virulence in different pathogen lineages. Mycobacterium tuberculosis complex taxonomy has rapidly evolved in the last 20 years through intensive clinical isolation, advances in sequencing and in the description of fast-evolving loci (CRISPR and MIRU-VNTR). On-line tools to describe new isolates have been set up based on known diversity either on CRISPRs (also known as spoligotypes) or on MIRU-VNTR profiles. The underlying taxonomies are largely concordant but use different names and offer different depths. The objectives of this study were 1) to explicit the consensus that exists between the alternative taxonomies, and 2) to provide an on-line tool to ease classification of new isolates. Genotyping (24-VNTR, 43-spacers spoligotypes, IS6110-RFLP) was undertaken for 3,454 clinical isolates from the Netherlands (2004-2008). The resulting database was enlarged with African isolates to include most human tuberculosis diversity. Assignations were obtained using TB-Lineage, MIRU-VNTRPlus, SITVITWEB and an algorithm from Borile et al. By identifying the recurrent concordances between the alternative taxonomies, we proposed a consensus including 22 sublineages. Original and consensus assignations of the all isolates from the database were subsequently implemented into an ensemble learning approach based on Machine Learning tool Weka to derive a classification scheme. All assignations were reproduced with very good sensibilities and specificities. When applied to independent datasets, it was able to suggest new sublineages such as pseudo-Beijing. This Lineage Prediction tool, efficient on 15-MIRU, 24-VNTR and spoligotype data is available on the web interface "TBminer." Another section of this website helps summarizing key molecular epidemiological data, easing tuberculosis surveillance. Altogether, we successfully used Machine Learning on a large dataset to set up and make available the first consensual

  2. Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm

    PubMed Central

    Azé, Jérôme; Sola, Christophe; Zhang, Jian; Lafosse-Marin, Florian; Yasmin, Memona; Siddiqui, Rubina; Kremer, Kristin; van Soolingen, Dick; Refrégier, Guislaine

    2015-01-01

    Infra-species taxonomy is a prerequisite to compare features such as virulence in different pathogen lineages. Mycobacterium tuberculosis complex taxonomy has rapidly evolved in the last 20 years through intensive clinical isolation, advances in sequencing and in the description of fast-evolving loci (CRISPR and MIRU-VNTR). On-line tools to describe new isolates have been set up based on known diversity either on CRISPRs (also known as spoligotypes) or on MIRU-VNTR profiles. The underlying taxonomies are largely concordant but use different names and offer different depths. The objectives of this study were 1) to explicit the consensus that exists between the alternative taxonomies, and 2) to provide an on-line tool to ease classification of new isolates. Genotyping (24-VNTR, 43-spacers spoligotypes, IS6110-RFLP) was undertaken for 3,454 clinical isolates from the Netherlands (2004-2008). The resulting database was enlarged with African isolates to include most human tuberculosis diversity. Assignations were obtained using TB-Lineage, MIRU-VNTRPlus, SITVITWEB and an algorithm from Borile et al. By identifying the recurrent concordances between the alternative taxonomies, we proposed a consensus including 22 sublineages. Original and consensus assignations of the all isolates from the database were subsequently implemented into an ensemble learning approach based on Machine Learning tool Weka to derive a classification scheme. All assignations were reproduced with very good sensibilities and specificities. When applied to independent datasets, it was able to suggest new sublineages such as pseudo-Beijing. This Lineage Prediction tool, efficient on 15-MIRU, 24-VNTR and spoligotype data is available on the web interface “TBminer.” Another section of this website helps summarizing key molecular epidemiological data, easing tuberculosis surveillance. Altogether, we successfully used Machine Learning on a large dataset to set up and make available the first

  3. THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX AS A PARADIGM IN GENOMICS RESEARCH

    PubMed Central

    Vandiedonck, Claire; Knight, Julian C

    2010-01-01

    Since its discovery more than 50 years ago, the human Major Histocompatibility Complex (MHC) on chromosome 6p21.3 has been at the forefront of human genetic research. Here, we review from a historical perspective the major advances in our understanding of the nature and consequences of genetic variation which have involved the MHC, as well as highlighting likely future directions. As a consequence of its particular genomic structure, its remarkable polymorphism and its early implication in numerous diseases, the MHC has been considered as a model region for genomics, being the first substantial region to be sequenced and establishing fundamental concepts of linkage disequilibrium, haplotypic structure and meiotic recombination. Recently, the MHC became the first genomic region to be entirely re-sequenced for common haplotypes, while studies mapping gene expression phenotypes across the genome have strongly implicated variation in the MHC. This review shows how the MHC continues to provide new insights and remains in the vanguard of contemporary research in human genomics. PMID:19468039

  4. Deciphering the Complexities of Atopic Dermatitis: Shifting Paradigms in Treatment Approaches

    PubMed Central

    Leung, Donald Y. M.; Guttman-Yassky, Emma

    2014-01-01

    Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus (HSV). Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental and immunologic factors. These factors likely account for the heterogeneity of AD onset, severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved by early interventions protecting the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention may improve long term outcomes for AD and reduce the systemic allergen sensitization leading to associated allergic diseases in the gastrointestinal and respiratory tract. PMID:25282559

  5. Detection of Mycobacterium avium in pet birds

    PubMed Central

    Godoy, Silvia Neri; Sakamoto, Sidnei Miyoshi; de Paula, Cátia Dejuste; Catão-Dias, José Luiz; Matushima, Eliana Reiko

    2009-01-01

    The present study is a report on the presence of Mycobacterium avium in four birds of the psittaciform order kept as pets. Anatomopathological diagnosis showed lesions suggestive of the agent and presence of alcohol-acid resistant bacilli (AARB) shown by the Ziehl-Neelsen staining. The identification of Mycobacterium avium was performed by means of PRA (PCR Restriction Analysis). DNA was directly extracted from tissue of the lesions and blocked in paraffin. The role of this agent in pet bird infection is discussed, as well as its zoonotic potential. PMID:24031356

  6. Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections

    PubMed Central

    Khare, Sangeeta; Drake, Kenneth L.; Lawhon, Sara D.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris. A.; Adams, Leslie Garry

    2016-01-01

    It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer’s patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

  7. Experimental inoculation of BFDV-positive budgerigars (Melopsittacus undulatus) with two Mycobacterium avium subsp. avium isolates.

    PubMed

    Ledwoń, Aleksandra; Sapierzyński, Rafał; Augustynowicz-Kopeć, Ewa; Szeleszczuk, Piotr; Kozak, Marcin

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group. PMID:24738057

  8. Mycobacterium avium subsp. avium found in raptors exposed to infected domestic fowl.

    PubMed

    Kriz, Petr; Kaevska, Marija; Bartejsova, Iva; Pavlik, Ivo

    2013-09-01

    We report a case of a falcon breeding facility, where raptors (both diurnal and nocturnal) were raised in contact with domestic fowl (Gallus gallus f. domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental samples from 20 raptors and four common ravens (Corvus corax) were collected. Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the flock of domestic fowl and one of the infected raptors had the same origin (zoological collection), they might have had a common source of colonization/infection. However, the detection of M. a. avium in feces of three other raptors may point at transmission of the agent between the birds in the facility. Contact of raptors with domestic fowl infected by M. a. avium may pose a risk for transmission of the infection for them; however, raptors from the falcon breeding facility seemed to be relatively resistant to the infection.

  9. Experimental inoculation of BFDV-positive budgerigars (Melopsittacus undulatus) with two Mycobacterium avium subsp. avium isolates.

    PubMed

    Ledwoń, Aleksandra; Sapierzyński, Rafał; Augustynowicz-Kopeć, Ewa; Szeleszczuk, Piotr; Kozak, Marcin

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group.

  10. Experimental Inoculation of BFDV-Positive Budgerigars (Melopsittacus undulatus) with Two Mycobacterium avium subsp. avium Isolates

    PubMed Central

    Sapierzyński, Rafał; Szeleszczuk, Piotr

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group. PMID:24738057

  11. Mycobacterium avium subsp. avium found in raptors exposed to infected domestic fowl.

    PubMed

    Kriz, Petr; Kaevska, Marija; Bartejsova, Iva; Pavlik, Ivo

    2013-09-01

    We report a case of a falcon breeding facility, where raptors (both diurnal and nocturnal) were raised in contact with domestic fowl (Gallus gallus f. domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental samples from 20 raptors and four common ravens (Corvus corax) were collected. Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the flock of domestic fowl and one of the infected raptors had the same origin (zoological collection), they might have had a common source of colonization/infection. However, the detection of M. a. avium in feces of three other raptors may point at transmission of the agent between the birds in the facility. Contact of raptors with domestic fowl infected by M. a. avium may pose a risk for transmission of the infection for them; however, raptors from the falcon breeding facility seemed to be relatively resistant to the infection. PMID:24283140

  12. Mycobacterium avium infection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens.

    PubMed Central

    Denis, M; Ghadirian, E

    1994-01-01

    The complex interaction between HIV-1 infection and Mycobacterium avium was studied. Viral burden was assessed, as well as immune response to HIV-1 in the context of Myco. avium infections. We also examined serum cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectable serum levels of IL-1, tumour necrosis factor-alpha (TNF-alpha) and IL-6 were found in normal controls and in groups I, II and III of HIV-1-infected subjects. Moderate levels of TNF-alpha, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided into subjects with and without Myco. avium infections, subjects with Myco, avium infections were shown to have higher serum levels of TNF-alpha, IL-1 beta and IL-6 than those with other infections. Blood mononuclear cells from controls and HIV subjects were stimulated with bacterial lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-alpha and IL-6, and lower levels of IL-1 beta; group III subjects released higher levels of IL-6. Patients in group IV had blood cells that released elevated levels of IL-6 and TNF-alpha, and lower levels of IL-1 beta. Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-alpha, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infected subjects revealed that Myco. avium-infected subjects had a higher level of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in HIV-1-infected subjects hasten the progression of viral disease, enhance cytokine release and contribute to the anergy to viral antigens. PMID:8033423

  13. Mycobacterium avium infection in mice is associated with time-related expression of Th1 and Th2 CD4+ T-lymphocyte response.

    PubMed Central

    Azouaou, N; Petrofsky, M; Young, L S; Bermudez, L E

    1997-01-01

    Disseminated infection caused by organisms of Mycobacterium avium complex is common in acquired immune deficiency syndrome (AIDS) patients. M. avium is an intracellular bacterium that multiplies within macrophages. We examined the effect of M. avium infection on the T-helper cell response in C57/BL/6 black mice. At weekly intervals, CD4+ T-cells were isolated from spleens and lines were created. T-cell lines were exposed to sonicated M. avium in the presence of feeder cells and macrophages and the supernatant were collected to measure the concentrations of interferon-gamma (IFN-gamma and interleukin-10 (IL-10). Production of IFN-gamma in CD4+ T-cells obtained from uninfected mice did not vary significantly during the 5 weeks. Levels of IFN-gamma produced by T-cell lines of infected mice were similar to the control mice during the first 2 weeks but significantly reduced (approximately 30 ng/ml) thereafter. In contrast, production of IL-10 by T-cell lines of infected mice was in a range of 190 to 342 pg/ml in weeks 1, 2 and 3, but increased to an average of 1300 pg/ml at weeks 4 and 5. Pre-immunized mice, when infected with M. avium strain 101, showed a different profile of T-cell cytokines, with high IFN-gamma and low IL-10 production. Proteins purified from a number of disease-associated (D-A) and non-D-A strains of M. avium were tested for the ability to induce IL-10. 65,000 MW and 60,000 MW proteins of M. avium induced significantly more IL-10 than 45,000 MW, 33,000 MW and 27,000 MW proteins. These results showed that M. avium predominantly stimulates either Th1 or Th2 T-helper cells according to the phase of the infection. PMID:9301531

  14. Endobronchial avium mycobacteria infection in an immunocompetent child.

    PubMed

    Perisson, Caroline; Nathan, Nadia; Thierry, Briac; Corvol, Harriet

    2013-01-01

    A 12-month-old boy, with no medical history, was admitted for dyspnoea with no cough or fever. Chest auscultation revealed an expiratory wheezing with decreased right-sided breath sounds. Chest imaging revealed subcarinal adenopathy and a nodule in the right principal bronchus (RB). Bronchoscopy showed a major obstruction of the RB by a granuloma, and a smaller granuloma in the left principal bronchus. The granulation tissue was removed by laser section. Histological examination revealed a necrotising granulomatous inflammation, culture showed a Mycobacterium avium complex (MAC). Tests to rule out tuberculosis and immunodeficiency were negative. The diagnosis of an MAC endobronchial granuloma was ascertained and a multidrug therapy associating clarithromycin, rifampin and ethambutol was started. The clinical outcome was good after 3 months of treatment and the bronchoscopy normalised after 1 year. Although rare, the frequency of MAC respiratory infections in immunocompetent children can increase. Reporting these cases should help to optimise diagnosis and treatment. PMID:24252838

  15. Pulmonary Mycobacterium avium infection demonstrating unusual lobar caseous pneumonia.

    PubMed

    Okuzumi, Shinichi; Minematsu, Naoto; Sasaki, Mamoru; Ohsawa, Kazuma; Murakami, Marohito

    2016-09-01

    Mycobacterium avium complex (MAC) infection is a major medical concern in Japan because of its increased prevalence and associated mortality. A common radiological feature in pulmonary MAC infection is a mixture of two basic patterns: fibrocavitary and nodular bronchiectatic; however, lobar consolidation is rare. We report an 83-year-old man with lobar caseous pneumonia caused by pulmonary MAC infection. Radiological findings were predominantly composed of dense lobar consolidation and ground-glass opacity. A diagnosis was made in accordance with the clinical and microbiological criteria set by the American Thoracic Society. A histological examination of lung specimens obtained by using a bronchoscope revealed a caseous granulomatous inflammation with an appearance of Langhans cells. The patient was treated using combined mycobacterium chemotherapy with an initial positive response for 6 months; however, the disease progressed later. We suggest that an awareness of lobar pneumonic consolidation as a rare radiological finding in pulmonary MAC infection is important. PMID:27516892

  16. Effects of Stop-Signal Probability in the Stop-Signal Paradigm: The N2/p3 Complex Further Validated

    ERIC Educational Resources Information Center

    Ramautar, J.R.; Kok, A.; Ridderinkhof, K.R.

    2004-01-01

    The aim of this study was to examine the effects of frequency of occurrence of stop signals in the stop-signal paradigm. Presenting stop signals less frequently resulted in faster reaction times to the go stimulus and a lower probability of inhibition. Also, go stimuli elicited larger and somewhat earlier P3 responses when stop signals occurred…

  17. Loci of Mycobacterium avium ser2 gene cluster and their functions.

    PubMed Central

    Mills, J A; McNeil, M R; Belisle, J T; Jacobs, W R; Brennan, P J

    1994-01-01

    The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit. PMID:8050992

  18. Loci of Mycobacterium avium ser2 gene cluster and their functions.

    PubMed

    Mills, J A; McNeil, M R; Belisle, J T; Jacobs, W R; Brennan, P J

    1994-08-01

    The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit. PMID:8050992

  19. Genetic IS901 RFLP diversity among Mycobacterium avium subsp. avium isolates from four pheasant flocks.

    PubMed

    Moravkova, Monika; Lamka, Jiri; Slany, Michal; Pavlik, Ivo

    2013-01-01

    IS901 RFLP analysis of 36 Mycobacterium avium subsp. avium (MAA) isolates from 15 pheasants (Phasianus colchicus) and two goshawks (Accipiter gentilis) from four pheasant farms was performed. Using this method, six different IS901 RFLP types (E, F, G, M, Q, and V) were identified. The distribution of IS901 RFLP profiles was tightly linked to individual flocks. Matching IS901 RFLP profiles observed in the present study indicate MAA transmission between pheasants and goshawks in the same locality. In two flocks, different pheasants within a flock as well as in various organs of five individual pheasants were found to have two distinct IS901 RFLP profiles.

  20. Mycobacterium avium subspecies impair dendritic cell maturation.

    PubMed

    Basler, Tina; Brumshagen, Christina; Beineke, Andreas; Goethe, Ralph; Bäumer, Wolfgang

    2013-10-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, a chronic, granulomatous enteritis of ruminants. Dendritic cells (DC) of the gut are ideally placed to combat invading mycobacteria; however, little is known about their interaction with MAP. Here, we investigated the interaction of MAP and the closely related M. avium ssp. avium (MAA) with murine DC and the effect of infected macrophages on DC maturation. The infection of DC with MAP or MAA induced DC maturation, which differed to that of LPS as maturation was accompanied by higher production of IL-10 and lower production of IL-12. Treatment of maturing DC with supernatants from mycobacteria-infected macrophages resulted in impaired DC maturation, leading to a semi-mature, tolerogenic DC phenotype expressing low levels of MHCII, CD86 and TNF-α after LPS stimulation. Though the cells were not completely differentiated they responded with an increased IL-10 and a decreased IL-12 production. Using recombinant cytokines we provide evidence that the semi-mature DC phenotype results from a combination of secreted cytokines and released antigenic mycobacterial components of the infected macrophage. Our results indicate that MAP and MAA are able to subvert DC function directly by infecting and indirectly via the milieu created by infected macrophages.

  1. Identification of Mycobacterium avium subsp. hominissuis Isolated From Drinking Water

    EPA Science Inventory

    Mycobacterium avium (MA) is divided into four subspecies based primarily on host-range and consists of MA subsp. avium (birds), MA subsp. silvaticum (wood pigeons), MA subsp. paratuberculosis (broad, poorly-defined host range), and the recently described MA subsp. hominissuis (hu...

  2. Avian mycobacteriosis caused by Mycobacterium avium subspecies avium in four ornamental birds and in vitro drug sensitivity testing of isolates.

    PubMed

    Stepień-Pyśniak, Dagmara; Puk, Krzysztof; Guz, Leszek; Wawrzyniak, Agata; Marek, Agnieszka; Kosikowska, Urszula

    2016-01-01

    Avian tuberculosis, one of the most important diseases affecting various species of birds, is most often caused by Mycobacterium (M.) avium. This report describes cases of M. avium subsp. avium (MAA) infection in a white-crested Holland dwarf rooster, a male and a female golden pheasant and a male peacock. We also investigated the prevalence of mycobacteria in 60 other birds and 40 alpacas. Tissue samples of necropsied birds were cultured for mycobacteria. From non-necropsied 60 other birds and alpacas only faecal samples were collected. Clinical signs in the affected white-crested Holland cock included gradual loss of body weight and hoarse attempts at crowing during its last 3 weeks, with a dramatic loss of body condition and depression over the final week. Only slight weakening was observed in the peacock just before its death, and the golden pheasants died suddenly. Diagnosis was confirmed by microbiological, molecular and pathological results. Mycobacterium avium subsp. avium strains were isolated from the internal organs of the affected birds. Only one faecal sample from 60 other birds was culture- and PCR-positive for M. avium subsp. avium, while another one was only PCR-positive for M. chelonae. We did not isolate any Mycobacterium spp. from faecal samples of alpacas and all of them were PCR-negative. All 18 isolated M. avium strains were resistant to rifampicin, isoniazid, ethambutol, ethionamide, capreomycin and ofloxacin, and susceptible to cycloserine and streptomycin.

  3. Avian mycobacteriosis caused by Mycobacterium avium subspecies avium in four ornamental birds and in vitro drug sensitivity testing of isolates.

    PubMed

    Stepień-Pyśniak, Dagmara; Puk, Krzysztof; Guz, Leszek; Wawrzyniak, Agata; Marek, Agnieszka; Kosikowska, Urszula

    2016-01-01

    Avian tuberculosis, one of the most important diseases affecting various species of birds, is most often caused by Mycobacterium (M.) avium. This report describes cases of M. avium subsp. avium (MAA) infection in a white-crested Holland dwarf rooster, a male and a female golden pheasant and a male peacock. We also investigated the prevalence of mycobacteria in 60 other birds and 40 alpacas. Tissue samples of necropsied birds were cultured for mycobacteria. From non-necropsied 60 other birds and alpacas only faecal samples were collected. Clinical signs in the affected white-crested Holland cock included gradual loss of body weight and hoarse attempts at crowing during its last 3 weeks, with a dramatic loss of body condition and depression over the final week. Only slight weakening was observed in the peacock just before its death, and the golden pheasants died suddenly. Diagnosis was confirmed by microbiological, molecular and pathological results. Mycobacterium avium subsp. avium strains were isolated from the internal organs of the affected birds. Only one faecal sample from 60 other birds was culture- and PCR-positive for M. avium subsp. avium, while another one was only PCR-positive for M. chelonae. We did not isolate any Mycobacterium spp. from faecal samples of alpacas and all of them were PCR-negative. All 18 isolated M. avium strains were resistant to rifampicin, isoniazid, ethambutol, ethionamide, capreomycin and ofloxacin, and susceptible to cycloserine and streptomycin. PMID:26904899

  4. Real-time quantitative PCR detection of Mycobacterium avium subspecies in meat products.

    PubMed

    Klanicova, B; Slana, I; Vondruskova, H; Kaevska, M; Pavlik, I

    2011-04-01

    The aim of this work was to examine various purchased meat products and to find out if any traces of Mycobacterium avium subsp. avium, M. avium subsp. hominissuis, and M. avium subsp. paratuberculosis could be detected in these samples. Analysis of the meat products (raw, cooked, and fermented) was performed using a real-time quantitative PCR (qPCR) method for the detection of specific insertion sequences: duplex qPCR for the detection of IS900 specific for M. avium subsp. paratuberculosis, and triplex qPCR for the detection of IS901 specific for Mycobacterium avium subsp. avium and IS 1245 specific for M. avium subsp. hominissuis. Of the 77 analyzed meat samples, 17 (22%) were found to contain M. avium subsp. paratuberculosis DNA, 4 (5%) samples contained Mycobacterium avium subsp. avium DNA, and in 12 (16%) samples M. avium subsp. hominissuis DNA was detected. The concentration of M. avium subsp. paratuberculosis and M. avium subsp. hominissuis DNA in some meat products exceeded 10(4) genomes per g. Culture examination of these mycobacterial subspecies was negative. By analyzing a range of meat products, we have provided evidence to support the hypothesis that M. avium is present in everyday commodities sold to the general public.

  5. Apa antigen of Mycobacterium avium subsp. paratuberculosis as a target for species-specific immunodetection of the bacteria in infected tissues of cattle with paratuberculosis.

    PubMed

    Souza, Giliane S; Rodrigues, Ana Bárbara F; Gioffré, Andrea; Romano, Maria I; Carvalho, Eulógio C Q; Ventura, Thatiana L B; Lasunskaia, Elena B

    2011-09-15

    Comparative genomics of Mycobacterium spp. have revealed conservative genes and respective proteins differently expressed in mycobacteria that could be used as targets for the species-specific immunodiagnostics. The alanine and proline-rich antigen Apa is a mycobacterial protein that present significant variability in primary sequence length and composition between members of M. avium and M. tuberculosis complexes. In this study, the recombinant Apa protein encoded by the MAP1569/ModD gene of M. avium subsp. paratuberculosis (Map) was used to generate a panel of monoclonal antibodies which were shown to recognize the most important veterinary pathogens of the M. avium complex, specifically Map and M. avium subsp. hominissuis, and which did not cross-react with M. bovis or M. tuberculosis. The produced antibodies were demonstrated to be a useful tool for the species-specific immunofluorescence or immunohistochemical detection of Map in experimentally infected cell cultures or intestinal tissues from cattle with bovine paratuberculosis and, additionally, they may be employed for the discrimination of pathogenic M. avium subspecies via Western blotting.

  6. Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice.

    PubMed Central

    Klemens, S P; Cynamon, M H

    1994-01-01

    The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection. PMID:7986001

  7. Characterization of a Novel Plasmid, pMAH135, from Mycobacterium avium Subsp. hominissuis

    PubMed Central

    Uchiya, Kei-ichi; Takahashi, Hiroyasu; Nakagawa, Taku; Yagi, Tetsuya; Moriyama, Makoto; Inagaki, Takayuki; Ichikawa, Kazuya; Nikai, Toshiaki; Ogawa, Kenji

    2015-01-01

    Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium’s pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection. PMID:25671431

  8. Interaction of Mycobacterium avium with environmental amoebae enhances virulence.

    PubMed Central

    Cirillo, J D; Falkow, S; Tompkins, L S; Bermudez, L E

    1997-01-01

    Environmental mycobacteria are a common cause of human infections. Recently, contaminated domestic water supplies have been suggested as a potential environmental source of several mycobacterial diseases. Since many of these mycobacterial species replicate best intracellularly, environmental hosts have been sought. In the present study, we examined the interaction of Mycobacterium avium with a potential protozoan host, the water-borne amoeba Acanthamoeba castellanii. We found that M. avium enters and replicates in A. castellanii. In addition, similar to that shown for mycobacteria within macrophages, M. avium inhibits lysosomal fusion and replicates in vacuoles that are tightly juxtaposed to the bacterial surfaces within amoebae. In order to determine whether growth of M. avium in amoebae plays a role in human infections, we tested the effects of this growth condition on virulence. We found that growth of M. avium in amoebae enhances both entry and intracellular replication compared to growth of bacteria in broth. Furthermore, amoeba-grown M. avium was also more virulent in the beige mouse model of infection. These data suggest a role for protozoa present in water environments as hosts for pathogenic mycobacteria, particularly M. avium. PMID:9284149

  9. Multidrug therapy of Mycobacterium avium subsp. avium infection in experimentally inoculated budgerigars (Melopsittacus undulatus).

    PubMed

    Ledwoń, A; Dolka, I; Dolka, B; Cegiełkowska, M; Czopowicz, M; Szeleszczuk, P

    2015-01-01

    The aim of the study was to determine whether the four-month experimental therapy of mycobacteriosis in budgerigars may cause a complete recovery. A group of nine budgerigars was infected with a Mycobacterium avium subsp. avium isolate with proven pathogenicity for budgerigars. Five weeks post-inoculation, multidrug therapy was started. Another group comprising six birds received the same treatment but no infection, and the third group also comprising six birds was kept without infection or treatment as a control. The adopted antibiotic regimen included clarithromycin 61 mg/kg b.w., moxifloxacin 25 mg/kg b.w. and ethambutol 60 mg/kg b.w. administered by crop gavage every 12 h for 18 weeks. Despite a significant improvement in the condition of the infected, treated birds, the four-month therapy was not sufficient for the complete recovery of all. PMID:26364975

  10. Cryptosporidium avium n. sp. (Apicomplexa: Cryptosporidiidae) in birds.

    PubMed

    Holubová, Nikola; Sak, Bohumil; Horčičková, Michaela; Hlásková, Lenka; Květoňová, Dana; Menchaca, Sarah; McEvoy, John; Kváč, Martin

    2016-06-01

    The morphological, biological, and molecular characteristics of Cryptosporidium avian genotype V are described, and the species name Cryptosporidium avium is proposed to reflect its specificity for birds under natural and experimental conditions. Oocysts of C. avium measured 5.30-6.90 μm (mean = 6.26 μm) × 4.30-5.50 μm (mean = 4.86 μm) with a length to width ratio of 1.29 (1.14-1.47). Oocysts of C. avium obtained from four naturally infected red-crowned parakeets (Cyanoramphus novaezealandiae) were infectious for 6-month-old budgerigars (Melopsittacus undulatus) and hens (Gallus gallus f. domestica). The prepatent periods in both susceptible bird species was 11 days postinfection (DPI). The infection intensity of C. avium in budgerigars and hens was low, with a maximum intensity of 5000 oocysts per gram of feces. Oocysts of C. avium were microscopically detected at only 12-16 DPI in hens and 12 DPI in budgerigars, while PCR analyses revealed the presence of specific DNA in fecal samples from 11 to 30 DPI (the conclusion of the experiment). Cryptosporidium avium was not infectious for 8-week-old SCID and BALB/c mice (Mus musculus). Naturally or experimentally infected birds showed no clinical signs of cryptosporidiosis, and no pathology was detected. Developmental stages of C. avium were detected in the ileum and cecum using scanning electron microscopy. Phylogenetic analyses based on small subunit rRNA, actin, and heat shock protein 70 gene sequences revealed that C. avium is genetically distinct from previously described Cryptosporidium species. PMID:26905074

  11. Evaluation of quantitative polymerase chain reaction assays targeting Mycobacterium avium, M. intracellulare, and M. avium subspecies paratuberculosis in drinking water biofilms.

    PubMed

    Chern, Eunice C; King, Dawn; Haugland, Richard; Pfaller, Stacy

    2015-03-01

    Mycobacterium avium (MA), Mycobacterium intracellulare (MI), and Mycobacterium avium subsp. paratuberculosis (MAP) are difficult to culture due to their slow growing nature. A quantitative polymerase chain reaction (qPCR) method for the rapid detection of MA, MI, and MAP can be used to provide data supporting drinking water biofilms as potential sources of human exposure. The aim of this study was to characterize two qPCR assays targeting partial 16S rRNA gene sequences of MA and MI and use these assays, along with two previously reported MAP qPCR assays (IS900 and Target 251), to investigate Mycobacterium occurrence in kitchen faucet biofilms. MA and MI qPCR assays demonstrated 100% specificity and sensitivity when evaluated against 18 non-MA complex, 76 MA, and 17 MI isolates. Both assays detected approximately 1,000 cells from a diluted cell stock inoculated on a sampling swab 100% of the time. DNA analysis by qPCR indicated that 35.3, 56.9 and 11.8% of the 51 kitchen faucet biofilm samples collected contained MA, MI, and MAP, respectively. This study introduces novel qPCR assays designed to specifically detect MA and MI in biofilm. Results support the use of qPCR as an alternative to culture for detection and enumeration of MA, MI, and MAP in microbiologically complex samples.

  12. An unusual presentation of Mycobacterium avium spp. paratuberculosis infection in a captive tundra reindeer (Rangifer tarandus tarandus).

    PubMed

    Del-Pozo, J; Girling, S; McLuckie, J; Abbondati, E; Stevenson, K

    2013-07-01

    This report describes an unusual presentation of paratuberculosis in a captive, 4-year-old female tundra reindeer (Rangifer tarandus tarandus). The gross and histological presentation was consistent with clinical paratuberculosis as previously reported for other ruminants, with poor body condition, subcutaneous oedema, granulomatous ileitis (multibacillary), mesenteric lymphadenitis and hepatitis. However, this animal also presented with unusual lung lesions, with necrosis and mineralization similar to that reported for Mycobacterium bovis in other wild and domestic ruminants. The presence of DNA of Mycobacterium avium subsp. paratuberculosis was confirmed by polymerase chain reaction (PCR) in intestine and lung tissue (IS900, Hsp65) and PCR tests for the detection of Mycobacterium tuberculosis complex and other members of the M. avium complex were negative.

  13. Apoptosis of human monocytes and macrophages by Mycobacterium avium sonicate.

    PubMed Central

    Hayashi, T; Catanzaro, A; Rao, S P

    1997-01-01

    Mycobacterium avium is an intracellular organism which multiplies predominantly within human macrophages. This organism has previously been shown to induce apoptosis in human macrophages. With a view to identifying M. avium components that induce cell death in infected host cells, sonicated extracts of M. avium as well as individual components isolated from the M. avium sonicate were tested in various assays with a human monocytic cell line (THP-1). THP-1 cells incubated with M. avium sonicate showed significantly reduced viability after a 2-day exposure compared to control cells incubated with media alone. This effect was dose dependent, with only 6.6% +/- 5.2% and 48.8% +/- 10.3% of the cells being viable by trypan blue exclusion at 600 and 300 microg/ml, respectively. Control cells, on the other hand, exhibited a viability of 98.8% +/- 1.0%. In addition, an 80% ammonium sulfate fraction of the M. avium sonicate and the previously characterized 68-kDa protein were found to have similar effects on THP-1 cells. In both cases, the reduction in viability was due to apoptosis characterized by chromatin condensation, DNA fragmentation by agarose gel electrophoresis, or terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL) and release of nuclear matrix protein (NMP) into the culture medium. M. avium sonicate-induced apoptosis of THP-1 cells was completely inhibited by the commonly used antioxidants pyrrolidinedithiocarbamate (PDTC) and butylated hydroxyanisole (BHA), indicating that the generation of free oxygen radicals may be responsible for inducing cell death. M. avium sonicate was found to induce apoptosis of monocyte-derived macrophages (MDMs) as well. This effect was not reversed in the presence of PDTC and was not accompanied with DNA fragmentation when determined by agarose gel electrophoresis, as seen in the case of THP-1 cells. However, these MDMs were found to contain fragmented DNA by TUNEL. These findings suggest that the mechanism

  14. Rethinking the longitudinal stream temperature paradigm: region-wide comparison of thermal infrared imagery reveals unexpected complexity of river temperatures

    USGS Publications Warehouse

    Fullerton, Aimee H.; Torgersen, Christian; Lawler, Joshua J.; Faux, Russell N.; Steel, E. Ashley; Beechie, Timothy J.; Ebersole, Joseph L.; Leibowitz, Scott J.

    2015-01-01

    Prevailing theory suggests that stream temperature warms asymptotically in a downstream direction, beginning at the temperature of the source in the headwaters and leveling off downstream as it converges to match meteorological conditions. However, there have been few empirical examples of longitudinal patterns of temperature in large rivers due to a paucity of data. We constructed longitudinal thermal profiles (temperature versus distance) for 53 rivers in the Pacific Northwest (USA) using an extensive dataset of remotely sensed summertime river temperatures and classified each profile into one of five patterns of downstream warming: asymptotic (increasing then flattening), linear (increasing steadily), uniform (not changing), parabolic (increasing then decreasing), or complex (not fitting other classes). We evaluated (1) how frequently profiles warmed asymptotically downstream as expected, and (2) whether relationships between river temperature and common hydroclimatic variables differed by profile class. We found considerable diversity in profile shape, with 47% of rivers warming asymptotically, and 53% having alternative profile shapes. Water temperature did not warm substantially over the course of the river for coastal parabolic and uniform profiles, and for some linear and complex profiles. Profile classes showed no clear geographical trends. The degree of correlation between river temperature and hydroclimatic variables differed among profile classes, but there was overlap among classes. Water temperature in rivers with asymptotic or parabolic profiles was positively correlated with August air temperature, tributary temperature and velocity, and negatively correlated with elevation, August precipitation, gradient, and distance upstream. Conversely, associations were less apparent in rivers with linear, uniform, or complex profiles. Factors contributing to the unique shape of parabolic profiles differed for coastal and inland rivers, where downstream cooling

  15. A Gene Specific to Mycobacterium avium subsp. paratuberculosis, But Only at the Transcription-translation Level

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is no known antibody that detects M. avium subsp paratuberculosis and does not cross react with other M. avium subspecies. In the present study, a monoclonal antibody was identified from mice immunized with a cell membrane fraction of M. avium subsp paratuberculosis strain K-10. This antibod...

  16. Characterization of biofilm formation by clinical isolates of Mycobacterium avium.

    PubMed

    Carter, George; Wu, Martin; Drummond, Daryl C; Bermudez, Luiz E

    2003-09-01

    Mycobacterium avium is an environmental organism encountered in natural and urban water sources as well as soil. M. avium biofilm has recently been identified on sauna walls and in city water pipes and might have a role in the survival of virulent strains in the environment and in the host. To characterize the M. avium biofilm, an in vitro model was adapted wherein biofilm develops on a PVC surface. Biofilm was detected by staining with crystal violet and visualization by optical microscopy and quantified by A(570). M. avium strains MAC 101, MAC 100, MAC 104, MAC 109, MAC A5 and MAC 5501 (all isolated from the blood of AIDS patients) were used in the assays. Biofilm formation was dependent on the presence of Ca(2+), Mg(2+) or Zn(2+) ions in the water, with the maximal effect seen at a concentration of 1 micro M. The presence of 2 % glucose and peptone as sources of carbon increased the formation of biofilm, while this was partially inhibited by humic acid. Since sliding motility has been associated with the amount of glycopeptidolipid (GPL), TLC was used to determine the presence of GPL. The supernatant of a biofilm-forming culture induced formation of a stable biofilm and amikacin blocked the establishment of biofilm by M. avium strains at subinhibitory concentrations. Bacteria in the biofilm were more resistant to chlorine as well as to exposure to potassium monopersulfate and chloroheximide acetate than were planktonic bacteria. Identification of M. avium genes involved in biofilm formation and further studies of the effect of antimicrobials on the establishment of biofilm may identify approaches for inhibiting M. avium biofilm formation and colonization.

  17. TGF-β-Mediated Sustained ERK1/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates

    PubMed Central

    L'Abbate, Carolina; Cipriano, Ivone; Pérez-Hurtado, Elizabeth Cristina; Leão, Sylvia Cardoso; Carneiro, Célia Regina Whitaker; Machado, Joel

    2011-01-01

    Transforming growth factor beta (TGF-β) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-β production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-β and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-β produced by ECs are sufficient to induce a self-sustaining autocrine TGF-β signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-β to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-β receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-β produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-β receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-β production. In summary, our findings indicate that the amplitude of TGF-β signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth. PMID:21731758

  18. Control of information in working memory: Encoding and removal of distractors in the complex-span paradigm.

    PubMed

    Oberauer, Klaus; Lewandowsky, Stephan

    2016-11-01

    The article reports four experiments with complex-span tasks in which encoding of memory items alternates with processing of distractors. The experiments test two assumptions of a computational model of complex span, SOB-CS: (1) distractor processing impairs memory because distractors are encoded into working memory, thereby interfering with memoranda; and (2) free time following distractors is used to remove them from working memory by unbinding their representations from list context. Experiment 1 shows that distractors are erroneously chosen for recall more often than not-presented stimuli, demonstrating that distractors are encoded into memory. Distractor intrusions declined with longer free time, as predicted by distractor removal. Experiment 2 shows these effects even when distractors precede the memory list, ruling out an account based on selective rehearsal of memoranda during free time. Experiments 3 and 4 test the notion that distractors decay over time. Both experiments show that, contrary to the notion of distractor decay, the chance of a distractor intruding at test does not decline with increasing time since encoding of that distractor. Experiment 4 provides additional evidence against the prediction from distractor decay that distractor intrusions decline over an unfilled retention interval. Taken together, the results support SOB-CS and rule out alternative explanations. Data and simulation code are available on Open Science Framework: osf.io/3ewh7.

  19. Hyper-longevity, a late-modern paradigm for understanding longevity, ageing and their complexities in Western developed globalised countries.

    PubMed

    Alzetta, Roberto; Cesario, Alfredo; Fini, Massimo

    2014-01-01

    If longevity is a biological and demographic indicator to determine human lifetime extension, hyper-longevity notion can represent a heuristic tool to better disentangle the complex bio-psycho-social implications of ageing and elderly in Western developed globalised countries. Departing from the assumption of a holistic approach to human condition understanding, it is possible to reveal the grounds and patterns of a multilayered and multidimensional structuring of longevity and ageing in our societies that would lead to a form of hyper-longevity. Socio-cultural processes, underlying hyper-longevity notion, rise the question of transition from modern/ latemodern societies to post-modern ones and it offers room for a cultural analysis of concepts, such as space time compression, digital capitalism, knowledge and mass information society. These are relevant ideas that can contribute to reshape and rethink the boundaries and traits of ageing experience in 21(st) century societies. To better catch the point emerging social category of Baby Boomers is presented and used to provide a concrete context related example on how hyper-longevity can better explain complex social evidences in many cultural respects and social domains. As a conclusive step some preliminary reflections, largely centered on the relation between Baby Boomers, hyper-longevity and bio-medical sciences are presented and discussed to provide a starting point for further future analyses within a trans and inter-disciplinary framework. PMID:24641235

  20. Control of information in working memory: Encoding and removal of distractors in the complex-span paradigm.

    PubMed

    Oberauer, Klaus; Lewandowsky, Stephan

    2016-11-01

    The article reports four experiments with complex-span tasks in which encoding of memory items alternates with processing of distractors. The experiments test two assumptions of a computational model of complex span, SOB-CS: (1) distractor processing impairs memory because distractors are encoded into working memory, thereby interfering with memoranda; and (2) free time following distractors is used to remove them from working memory by unbinding their representations from list context. Experiment 1 shows that distractors are erroneously chosen for recall more often than not-presented stimuli, demonstrating that distractors are encoded into memory. Distractor intrusions declined with longer free time, as predicted by distractor removal. Experiment 2 shows these effects even when distractors precede the memory list, ruling out an account based on selective rehearsal of memoranda during free time. Experiments 3 and 4 test the notion that distractors decay over time. Both experiments show that, contrary to the notion of distractor decay, the chance of a distractor intruding at test does not decline with increasing time since encoding of that distractor. Experiment 4 provides additional evidence against the prediction from distractor decay that distractor intrusions decline over an unfilled retention interval. Taken together, the results support SOB-CS and rule out alternative explanations. Data and simulation code are available on Open Science Framework: osf.io/3ewh7. PMID:27552059

  1. Induction of Mycobacterium avium proteins upon infection of human macrophages.

    PubMed

    Brunori, Lara; Giannoni, Federico; Bini, Luca; Liberatori, Sabrina; Frota, Cristiane; Jenner, Peter; Thoresen, Ove Fredrik; Orefici, Graziella; Fattorini, Lanfranco

    2004-10-01

    Induction of Mycobacterium avium proteins labelled with [35S]methionine and mRNAs upon infection of the human macrophage cell line THP-1 was investigated by two-dimensional gel electrophoresis-mass spectrometry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. M. avium overexpressed proteins within the macrophages that are involved in fatty acids metabolism (FadE2, FixA), cell wall synthesis (KasA), and protein synthesis (EF-tu). The correlation of differential protein and mRNA expression varied between good and no correlation. Overall, these four proteins may be involved in the adaptation and survival of M. avium within human macrophages. PMID:15378697

  2. Experimental infection of Eurasian wild boar with Mycobacterium avium subsp. avium.

    PubMed

    Garrido, J M; Vicente, J; Carrasco-García, R; Galindo, R C; Minguijón, E; Ballesteros, C; Aranaz, A; Romero, B; Sevilla, I; Juste, R; de la Fuente, J; Gortazar, C

    2010-07-29

    The Eurasian wild boar (Sus scrofa) is increasingly relevant as a host for several pathogenic mycobacteria. We aimed to characterize the first experimental Mycobacterium avium subsp. avium (MAA) infection in wild boar in order to describe the lesions and the immune response as compared to uninfected controls. Twelve 1-4-month-old wild boar piglets were housed in class III bio-containment facilities. Four concentrations of MAA suspension were used: 10, 10(2) and 10(4) mycobacteria (2 animals each, oropharyngeal route) and 2.5 x 10(6) mycobacteria (2 animals each by the oropharyngeal and nasal routes). No clinical signs were observed and pathology evidenced a low pathogenicity of this MAA strain for this particular host. Bacteriological and pathological evidence of successful infection after experimental inoculation was found for the group challenged with 2.5 x 10(6) mycobacteria. These four wild boar showed a positive IFN-gamma response to the avian PPD and the real-time RT-PCR data revealed that three genes, complement component C3, IFN-gamma and RANTES, were significantly down regulated in infected animals. These results were similar to those found in naturally and experimentally M. bovis-infected wild boar and may constitute biomarkers of mycobacterial infection in this species.

  3. Cavitary pulmonary infection with Mycobacterium avium observed by bronchoscopy.

    PubMed

    Uruga, Hironori; Suzuki, Aika; Hanada, Shigeo; Takaya, Hisashi; Miyamoto, Atsushi; Morokawa, Nasa; Fujii, Takeshi; Kurosaki, Atsuko; Kishi, Kazuma

    2012-10-01

    A 58-year-old man was admitted to our hospital because of fever and loss of appetite. He had undergone surgery for esophageal cancer. A chest radiography 12 years after the surgery revealed cavitary lesions in the right upper lobe of the lung. The patient was then diagnosed as having Mycobacterium avium infection. The cavitary lesions worsened 2 years after clarithromycin monotherapy. Bronchoscopy was performed to observe the interior of the cavity. Gray debris adhering to the cavitary wall decreased after intensive treatment with Streptomycin, rifabutin, levofloxacin, and ethambutol. This is a rare case in which treatment efficacy of M. avium infection was directly observed by serial bronchoscopy. PMID:23207537

  4. Oral traditions: a contextual framework for complex science concepts—laying the foundation for a paradigm of promise in rural science education

    NASA Astrophysics Data System (ADS)

    Avery, Leanne M.; Hains, Bryan J.

    2016-08-01

    The overarching goal of this paper is to bring a diverse educational context—rural sayings and oral traditions situated in ecological habitats—to light and emphasize that they need to be taken into consideration regarding twenty-first century science education. The rural sayings or tenets presented here are also considered alternative ways of learning and knowing that rural people (elders and children) acquire outside of school in rural places of home and habitat. Throughout this paper we explore the complex nature of rural sayings or tenets that have been shared by community elders and examine their historic scientific roots. In so doing, we uncover a wealth of information regarding the diverse rural sociocultural and ecological connections and the situated macro and micro-contexts from which these tenets arise. We argue for a preservation and educational revitalization of these tenets for current and future generations. We show how this knowledge both augments and differs from traditional western science and science curricula by illuminating the ways in which oral traditions are embedded in place, people, memory and culture. We close by presenting an alternative paradigm for science education that incorporates pluralism as a means to enrich current place-based pedagogies and practices. We suggest that in order to tackle the complex problems in this new age of the Anthropocene, revitalizing elders' wisdom as well as valuing rural children's diverse knowledge and the inherent connectivity to their habitats needs be cultivated and not expunged by the current trends that standardize learning. As stated in the call for this special issue, "rurality has a real positionality" and much can be learned from individual and unique rural contexts.

  5. High-Density Lipoprotein Binds to Mycobacterium avium and Affects the Infection of THP-1 Macrophages

    PubMed Central

    Ichimura, Naoya; Sato, Megumi; Yoshimoto, Akira; Yano, Kouji; Ohkawa, Ryunosuke; Kasama, Takeshi

    2016-01-01

    High-density lipoprotein (HDL) is involved in innate immunity toward various infectious diseases. Concerning bacteria, HDL is known to bind to lipopolysaccharide (LPS) and to neutralize its physiological activity. On the other hand, cholesterol is known to play an important role in mycobacterial entry into host cells and in survival in the intracellular environment. However, the pathogenicity of Mycobacterium avium (M. avium) infection, which tends to increase worldwide, remains poorly studied. Here we report that HDL indicated a stronger interaction with M. avium than that with other Gram-negative bacteria containing abundant LPS. A binding of apolipoprotein (apo) A-I, the main protein component of HDL, with a specific lipid of M. avium might participate in this interaction. HDL did not have a direct bactericidal activity toward M. avium but attenuated the engulfment of M. avium by THP-1 macrophages. HDL also did not affect bacterial killing after ingestion of live M. avium by THP-1 macrophage. Furthermore, HDL strongly promoted the formation of lipid droplets in M. avium-infected THP-1 macrophages. These observations provide new insights into the relationship between M. avium infection and host lipoproteins, especially HDL. Thus, HDL may help M. avium to escape from host innate immunity. PMID:27516907

  6. Co-infection by Cryptococcus neoformans and Mycobacterium avium intracellulare in AIDS.

    PubMed

    Arastéh, K; Cordes, C; Futh, U; Grosse, G; Dietz, E; Staib, F

    In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20 microl. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an odds ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.

  7. Co-infection by Cryptococcus neoformans and Mycobacterium avium intracellulare in AIDS. Clinical and epidemiological aspects.

    PubMed

    Arastéh, K; Cordes, C; Futh, U; Grosse, G; Dietz, E; Staib, F

    In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20/microliters. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an ods ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.

  8. Fibronectin Attachment Protein Homologue Mediates Fibronectin Binding by Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Secott, T. E.; Lin, T. L.; Wu, C. C.

    2001-01-01

    Attachment of Mycobacterium avium subsp. paratuberculosis to host tissue and penetration of mucosal surfaces are pivotal events in the pathogenesis of Johne's disease. Fibronectin (FN) binding is required for attachment and internalization of several mycobacteria by epithelial cells in vitro. The objective of this study was to further characterize the FN binding activity of M. avium subsp. paratuberculosis. Although the bacteria bound FN poorly at pH above 7, brief acid pretreatment greatly enhanced FN binding within the pH range (3 to 10) studied. A 4.6-kbp fragment from an M. avium subsp. paratuberculosis genomic library was found to contain a 1,107-bp open reading frame that shows very high nucleotide sequence identity with that of the FN attachment protein (FAP) gene of M. avium subsp. avium. Pretreatment of FN with an FN-binding peptide from M. avium subsp. avium FAP abolished FN binding, indicating that M. avium subsp. paratuberculosis binds FN in a FAP-dependent manner. Pretreatment of M. avium subsp. paratuberculosis with anti-FAP immunoglobulin G did not abrogate FN binding; blocking occurred only when anti-FAP was added together with FN. FAP was detected by immunofluorescence only in lipid-extracted M. avium subsp. paratuberculosis. Western blotting and immunoelectron microscopy revealed that FAP is located near the interior of the cell envelope of M. avium subsp. paratuberculosis. The results indicate that a FAP homologue mediates the attachment of FN to M. avium subsp. paratuberculosis. Further, given the subcellular location of FAP, it is considered that this protein operates at the terminus of a coordinated FN binding system in the cell envelope of M. avium subsp. paratuberculosis. PMID:11254560

  9. Cellular Interactions in Mycobacterium avium subsp. paratuberculosis Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Noted as one of the more fastidious mycobacteria, infection with MAP is often chara...

  10. Tuberculosis in Birds: Insights into the Mycobacterium avium Infections

    PubMed Central

    Dhama, Kuldeep; Mahendran, Mahesh; Tiwari, Ruchi; Dayal Singh, Shambhu; Kumar, Deepak; Singh, Shoorvir; Sawant, Pradeep Mahadev

    2011-01-01

    Tuberculosis, a List B disease of World Organization for Animal Health, caused by M. avium or M. genavense predominantly affects poultry and pet or captive birds. Clinical manifestations in birds include emaciation, depression and diarrhea along with marked atrophy of breast muscle. Unlike tuberculosis in animals and man, lesions in lungs are rare. Tubercular nodules can be seen in liver, spleen, intestine and bone marrow. Granulomatous lesion without calcification is a prominent feature. The disease is a rarity in organized poultry sector due to improved farm practices, but occurs in zoo aviaries. Molecular techniques like polymerase chain reaction combined with restriction fragment length polymorphism and gene probes aid in rapid identification and characterization of mycobacteria subspecies, and overcome disadvantages of conventional methods which are slow, labour intensive and may at times fail to produce precise results. M. avium subsp. avium with genotype IS901+ and IS1245+ causes infections in animals and human beings too. The bacterium causes sensitivity in cattle to the tuberculin test. The paper discusses in brief the M. avium infection in birds, its importance in a zoonotic perspective, and outlines conventional and novel strategies for its diagnosis, prevention and eradication in domestic/pet birds and humans alike. PMID:21776352

  11. Methylation of GPLs in Mycobacterium smegmatis and Mycobacterium avium

    PubMed Central

    Jeevarajah, Dharshini; Patterson, John H.; Taig, Ellen; Sargeant, Tobias; McConville, Malcolm J.; Billman-Jacobe, Helen

    2004-01-01

    Several species of mycobacteria express abundant glycopeptidolipids (GPLs) on the surfaces of their cells. The GPLs are glycolipids that contain modified sugars including acetylated 6-deoxy-talose and methylated rhamnose. Four methyltransferases have been implicated in the synthesis of the GPLs of Mycobacterium smegmatis and Mycobacterium avium. A rhamnosyl 3-O-methytransferase and a fatty acid methyltransferase of M. smegmatis have been previously characterized. In this paper, we characterize the methyltransferases that are responsible for modifying the hydroxyl groups at positions 2 and 4 of rhamnose and propose the biosynthetic sequence of GPL trimethylrhamnose formation. The analysis of M. avium genes through the creation of specific mutants is technically difficult; therefore, an alternative approach to determine the function of putative methyltransferases of M. avium was undertaken. Complementation of M. smegmatis methyltransferase mutants with M. avium genes revealed that MtfC and MtfB of the latter species have 4-O-methyltransferase activity and that MtfD is a 3-O-methyltransferase which can modify rhamnose of GPLs in M. smegmatis. PMID:15466031

  12. Mycobacterium avium subsp. paratuberculosis infection, immunology and pathology of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) infection in ruminants leads to a chronic and progressive enteric disease (Johne’s disease) that results in loss of intestinal function, poor body condition, and eventual death. Transmission is primarily through a fecal-oral route in neonates but con...

  13. Skin Test Reactivity and Cellular Immune Responses to Mycobacterium avium Sensitin in AIDS Patients at Risk for Disseminated M. avium Infection

    PubMed Central

    von Reyn, C. Fordham; Williams, Paige L.; Lederman, Howard M.; McCutchan, J. Allen; Koletar, Susan L.; Murphy, Robert L.; Cohn, Susan E.; Evans, Thomas; Heald, Alison E.; Colquhoun, Dodi; Bassily, Ehab L.; Currier, Judith S.

    2001-01-01

    Skin tests and lymphocyte proliferation assays (LPA) were performed with Mycobacterium avium sensitin on patients with AIDS. Among 139 subjects, 13% had positive skin test results and 32% had positive LPA results. The LPA may be a more sensitive indicator of prior M. avium infection in this population. PMID:11687476

  14. Mannosylated lipoarabinomannans from Mycobacterium avium subsp. paratuberculosis alters the inflammatory response by bovine macrophages and suppresses killing of Mycobacterium avium subsp. avium organisms.

    PubMed

    Souza, Cleverson; Davis, William C; Eckstein, Torsten M; Sreevatsan, Srinand; Weiss, Douglas J

    2013-01-01

    Analysis of the mechanisms through which pathogenic mycobacteria interfere with macrophage activation and phagosome maturation have shown that engagement of specific membrane receptors with bacterial ligands is the initiating event. Mannosylated lipoarabinomannan (Man-LAM) has been identified as one of the ligands that modulates macrophage function. We evaluated the effects of Man-LAM derived from Mycobacterium avium subsp. paratuberculosis (MAP) on bovine macrophages. Man-LAM induced a rapid and prolonged expression of IL-10 message as well as transient expression of TNF-α. Preincubation with Man-LAM for up to 16 h did not suppress expression of IL-12 in response to interferon-γ. Evaluation of the effect of Man-LAM on phagosome acidification, phagosome maturation, and killing of Mycobacterium avium subsp. avium (MAA) showed that preincubation of macrophages with Man-LAM before addition of MAA inhibited phagosome acidification, phagolysosome fusion, and reduced killing. Analysis of signaling pathways provided indirect evidence that inhibition of killing was associated with activation of the MAPK-p38 signaling pathway but not the pathway involved in regulation of expression of IL-10. These results support the hypothesis that MAP Man-LAM is one of the virulence factors facilitating survival of MAP in macrophages.

  15. Thermal Inactivation of Mycobacterium avium subsp. paratuberculosis in Artificially Contaminated Milk by Direct Steam Injection

    PubMed Central

    Butot, Sophie; Jagadeesan, Balamurugan; Bakker, Douwe; Donaghy, John

    2016-01-01

    ABSTRACT The efficiency of direct steam injection (DSI) at 105°C for 3 s to inactivate Mycobacterium avium subsp. paratuberculosis in milk at a pilot-plant scale was investigated. Milk samples were artificially contaminated with M. avium subsp. paratuberculosis and also with cow fecal material naturally infected with M. avium subsp. paratuberculosis. We also tested milk artificially contaminated with Mycobacterium smegmatis as a candidate surrogate to compare thermal inactivation between M. smegmatis and M. avium subsp. paratuberculosis. Following the DSI process, no viable M. avium subsp. paratuberculosis or M. smegmatis was recovered using culture methods for both strains. For pure M. avium subsp. paratuberculosis cultures, a minimum reduction of 5.6 log10 was achieved with DSI, and a minimum reduction of 5.7 log10 was found with M. smegmatis. The minimum log10 reduction for wild-type M. avium subsp. paratuberculosis naturally present in feces was 3.3. In addition, 44 dairy and nondairy powdered infant formula (PIF) ingredients used during the manufacturing process of PIF were tested for an alternate source for M. avium subsp. paratuberculosis and were found to be negative by quantitative PCR (qPCR). In conclusion, the results obtained from this study indicate that a >7-fold-log10 reduction of M. avium subsp. paratuberculosis in milk can be achieved with the applied DSI process. IMPORTANCE M. avium subsp. paratuberculosis is widespread in dairy herds in many countries. M. avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle, and infected animals can directly or indirectly (i.e., fecal contamination) contaminate milk. Despite much research and debate, there is no conclusive evidence that M. avium subsp. paratuberculosis is a zoonotic bacterium, i.e., one that causes disease in humans. The presence of M. avium subsp. paratuberculosis or its DNA has been reported in dairy products, including pasteurized milk, cheese, and infant formula

  16. Indices of onchocerciasis transmission by different members of the Simulium damnosum complex conflict with the paradigm of forest and savanna parasite strains.

    PubMed

    Cheke, Robert A; Garms, Rolf

    2013-01-01

    Onchocerciasis in savanna zones is generally more severe than in the forest and pathologies also differ geographically, differences often ascribed to the existence of two or more strains and incompatibilities between vectors and strains. However, flies in the forest transmit more infective larvae than their savanna counterparts, even in sympatry, contradicting expectations based on the forest and savanna strains paradigm. We analysed data on the numbers of Onchocerca volvulus larvae of different stages found in 10 different taxonomic categories of the Simulium damnosum complex derived from more than 48,800 dissections of flies from Sierra Leone in the west of Africa to Uganda in the east. The samples were collected before widespread ivermectin distribution and thus provide a baseline for evaluating control measures. Savanna species contained fewer larvae per infected or per infective fly than the forest species, even when biting and parous rates were accounted for. The highest transmission indices were found in the forest-dwelling Pra form of Simulium sanctipauli (616 L3/1000 parous flies) and the lowest in the savanna-inhabiting species S. damnosum/S. sirbanum (135) and S. kilibanum (65). Frequency distributions of numbers of L1-2 and L3 larvae found in parous S. damnosum/S. sirbanum, S. kilibanum, S. squamosum, S. yahense, S. sanctipauli, S. leonense and S. soubrense all conformed to the negative binomial distribution, with the mainly savanna-dwelling species (S. damnosum/S. sirbanum) having less overdispersed distributions than the mainly forest-dwelling species. These infection patterns were maintained even when forest and savanna forms were sympatric and biting the same human population. Furthermore, for the first time, levels of blindness were positively correlated with infection intensities of the forest vector S. yahense, consistent with relations previously reported for savanna zones. Another novel result was that conversion rates of L1-2 larvae to L3s

  17. Indices of onchocerciasis transmission by different members of the Simulium damnosum complex conflict with the paradigm of forest and savanna parasite strains.

    PubMed

    Cheke, Robert A; Garms, Rolf

    2013-01-01

    Onchocerciasis in savanna zones is generally more severe than in the forest and pathologies also differ geographically, differences often ascribed to the existence of two or more strains and incompatibilities between vectors and strains. However, flies in the forest transmit more infective larvae than their savanna counterparts, even in sympatry, contradicting expectations based on the forest and savanna strains paradigm. We analysed data on the numbers of Onchocerca volvulus larvae of different stages found in 10 different taxonomic categories of the Simulium damnosum complex derived from more than 48,800 dissections of flies from Sierra Leone in the west of Africa to Uganda in the east. The samples were collected before widespread ivermectin distribution and thus provide a baseline for evaluating control measures. Savanna species contained fewer larvae per infected or per infective fly than the forest species, even when biting and parous rates were accounted for. The highest transmission indices were found in the forest-dwelling Pra form of Simulium sanctipauli (616 L3/1000 parous flies) and the lowest in the savanna-inhabiting species S. damnosum/S. sirbanum (135) and S. kilibanum (65). Frequency distributions of numbers of L1-2 and L3 larvae found in parous S. damnosum/S. sirbanum, S. kilibanum, S. squamosum, S. yahense, S. sanctipauli, S. leonense and S. soubrense all conformed to the negative binomial distribution, with the mainly savanna-dwelling species (S. damnosum/S. sirbanum) having less overdispersed distributions than the mainly forest-dwelling species. These infection patterns were maintained even when forest and savanna forms were sympatric and biting the same human population. Furthermore, for the first time, levels of blindness were positively correlated with infection intensities of the forest vector S. yahense, consistent with relations previously reported for savanna zones. Another novel result was that conversion rates of L1-2 larvae to L3s

  18. Utilization of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) to Identify environmental Strains of Mycobacterium Complex

    EPA Science Inventory

    Species within the Mycobacterium avium Complex (MAC) group are found to be both prevalent and persistent in drinking water distribution systems. The MAC is composed of two predominant species: M. avium and M. intracellulare. These species have the ability to survive drinking ...

  19. Serologic tests for detecting antibodies against Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis in Eurasian wild boar (Sus scrofa scrofa).

    PubMed

    Boadella, Mariana; Lyashchenko, Konstantin; Greenwald, Reena; Esfandiari, Javan; Jaroso, Raquel; Carta, Tania; Garrido, Joseba M; Vicente, Joaquín; de la Fuente, José; Gortázar, Christian

    2011-01-01

    New tools to detect exposure of free-range Eurasian wild boar (Sus scrofa scrofa) to pathogenic mycobacteria would be valuable for improved disease surveillance and wildlife management. Two hundred sera from wild boar of known Mycobacterium bovis infection status were used to evaluate test suitability for the detection of antibodies against M. bovis and Mycobacterium avium subsp. paratuberculosis (or cross-reacting members of the M. avium complex). Two traditional enzyme-linked immunosorbent assays were evaluated using M. bovis purified protein derivative (bPPD) and paratuberculosis protoplasmatic antigen 3 (PPA3) as antigens, respectively, and a new point-of-care test format for bovine tuberculosis (bTB) that uses the innovative dual-path platform (DPP TB) test. The effect of individual factors (sex, age, lesions) on the diagnostic performance of the serologic tests was also determined. Although the DPP had a sensitivity of 89.6% and a specificity of 90.4%, for bPPD, the sensitivity was 79.2% and the specificity 100%. Both tests had a kappa agreement of 0.80. Sixty-five of 68 (95.6%) wild boar sera with antibodies against the PPA3 antigen corresponded to known M. bovis-infected wild boar. Significant differences were not observed in the bPPD and DPP readings among lesion categories or between age classes. A slight sex-related difference in sensitivity toward males in the DPP was found, but it was not detected in the bPPD enzyme-linked immunosorbent assay. The results support the use of antibody-based diagnostic tests for both large-scale and individual bTB testing of Eurasian wild boar and suggest that wild boar cannot be used as sentinels for infections caused by M. avium complex members.

  20. Molecular identification of Mycobacterium avium subsp. silvaticum by duplex high-resolution melt analysis and subspecies-specific real-time PCR.

    PubMed

    Rónai, Zsuzsanna; Csivincsik, Ágnes; Dán, Ádám

    2015-05-01

    Accurate identification of mycobacterial species and subspecies is essential to evaluate their significance and to perform epidemiological studies. The subspecies of Mycobacterium avium have different attributes but coincide in their zoonotic potential. Our knowledge about M. avium subsp. silvaticum is limited, since its identification is uncertain. Mycobacterium avium subsp. avium and M. avium subsp. silvaticum can be discriminated from each other based only on phenotypic characteristics, as they have almost identical genome sequences. Here we describe the development of a diagnostic method which enables the molecular identification of M. avium subsp. silvaticum and discrimination from M. avium subsp. avium based on genomic differences in a duplex high-resolution melt and M. avium subsp. silvaticum-specific mismatch real-time PCR. The developed assay was tested on reference strains and 199 field isolates, which were analyzed by phenotypic methods previously. This assay not only identified all 63 M. avium subsp. silvaticum and 138 M. avium subsp. avium strains correctly but also enabled the detection of mixed M. avium subsp. avium-M. avium subsp. silvaticum cultures. This is the first time that such a large panel of strains has been analyzed, and we also report the first isolation of M. avium subsp. silvaticum from red fox, red deer, wild boar, cattle, and badger. This assay is reliable, rapid, simple, inexpensive, and robust. It eliminates the long-existing problem of ambiguous phenotypic identification and opens up the possibility for detailed and comprehensive strain studies.

  1. Roles for Cell Wall Glycopeptidolipid in Surface Adherence and Planktonic Dispersal of Mycobacterium avium

    EPA Science Inventory

    The opportunistic pathogen Mycobacterium avium is a significant inhabitant of biofilms in drinking water distribution systems. M. avium expresses on its cell surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the core GPL in biofilm formation by M. aviu...

  2. Antigenic Profiles of Recombinant Proteins from Mycobacterium avium subsp paratuberculosis in Sheep with Johne's Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods to improve the ELISA test to detect Mycobacterium avium subsp paratuberculosis have been explored over several years. Previously, selected recombinant proteins of M. avium subspecies paratuberculosis were found to be immunogenic in cattle with Johne’s disease. In the present study, antibo...

  3. Complete genome sequence of Mycobacterium avium subsp. paratuberculosis, isolated from human breast milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp paratuberculosis is the etiologic agent of Johne’s disease. We report the draft genome sequences of six M. avium subsp paratuberculosis isolates obtained from diverse hosts including bison, cattle and sheep. These sequences will deepen our understanding of host association ...

  4. Development and Characterization of Monoclonal Antibodies and Aptamers Against Major Antigens of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Specific antibodies, available in unlimited quantities, have not been produced against Mycobacterium avium subsp. paratuberculosis, the bacterium that causes Johne’s disease (JD). To fill this gap in JD research, monoclonal antibodies (mAbs) against M. avium subsp. paratuberculosis were produced fr...

  5. Paradigms for Abstracting Systems.

    ERIC Educational Resources Information Center

    Pinto, Maria; Galvez, Carmen

    1999-01-01

    Discussion of abstracting systems focuses on the paradigm concept and identifies and explains four paradigms: communicational, or information theory; physical, including information retrieval; cognitive, including information processing and artificial intelligence; and systemic, including quality management. Emphasizes multidimensionality and…

  6. Beyond desertification: New paradigms for dryland landscapes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dryland desertification paradigm focuses on losses of ecosystem services accompanying transitions from grasslands to systems dominated by bare ground or woody plants unpalatable for domestic livestock. However, recent studies reveal complex transitions across a range of environmental conditions ...

  7. A biosensor assay for the detection of Mycobacterium avium subsp. paratuberculosis in fecal samples.

    PubMed

    Kumanan, Vijayarani; Nugen, Sam R; Baeumner, Antje J; Chang, Yung-Fu

    2009-03-01

    A simple, membrane-strip-based lateral-flow (LF) biosensor assay and a high-throughput microtiter plate assay have been combined with a reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of a small number (ten) of viable Mycobacterium (M.) avium subsp. paratuberculosis (MAP) cells in fecal samples. The assays are based on the identification of the RNA of the IS900 element of MAP. For the assay, RNA was extracted from fecal samples spiked with a known quantity of (10(1) to 10(6)) MAP cells and amplified using RT-PCR and identified by the LF biosensor and the microtiter plate assay. While the LF biosensor assay requires only 30 min of assay time, the overall process took 10 h for the detection of 10 viable cells. The assays are based on an oligonucleotide sandwich hybridization assay format and use either a membrane flow through system with an immobilized DNA probe that hybridizes with the target sequence or a microtiter plate well. Signal amplification is provided when the target sequence hybridizes to a second DNA probe that has been coupled to liposomes encapsulating the dye, sulforhodamine B. The dye in the liposomes provides a signal that can be read visually, quantified with a hand-held reflectometer, or with a fluorescence reader. Specificity analysis of the assays revealed no cross reactivity with other mycobacteria, such as M. avium complex, M. ulcerans, M. marium, M. kansasii, M. abscessus, M. asiaticum, M. phlei, M. fortutitum, M. scrofalaceum, M. intracellular, M. smegmatis, and M. bovis. The overall assay for the detection of live MAP organisms is comparatively less expensive and quick, especially in comparison to standard MAP detection using a culture method requiring 6-8 weeks of incubation time, and is significantly less expensive than real-time PCR. PMID:19255522

  8. Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease

    PubMed Central

    Deshpande, Devyani; Pasipanodya, Jotam G.

    2016-01-01

    Mycobacterium avium complex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonary M. avium disease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. PMID:26810646

  9. Paradigms of polyamory.

    PubMed

    Zambrano, M

    1999-01-01

    SUMMARY The paradigm theory of Thomas Kuhn is used as a framework to discuss alternative ways of intimacy. The author discusses the implications of structuring actual lesbian relationships by a paradigm of monogamy among Latin-American women. The author proposes that creating alternative paradigms of multiple relationships would be useful for many lesbians as models for alternative life patterns.

  10. Mycobacterium avium subspecies induce differential expression of pro-inflammatory mediators in a murine macrophage model: evidence for enhanced pathogenicity of Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Basler, Tina; Geffers, Robert; Weiss, Siegfried; Valentin-Weigand, Peter; Goethe, Ralph

    2008-01-01

    Mycobacterium avium subspecies (ssp.) paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic, non-treatable granulomatous enteritis of ruminants. MAP is the only mycobacterium affecting the intestinal tract, which is of interest since it is presently the most favoured pathogen linked to Crohn's disease (CD) in humans due to its frequent detection in CD tissues. MAP is genetically closely related to other M. avium ssp. such as M. avium ssp. avium (MAA) and M. avium ssp. hominissuis (MAH) which can cause mycobacteriosis in animals and immunocompromised humans. We have recently shown that murine macrophage cell lines represent suitable systems to analyse M. avium ssp. patho-mechanisms and could show that MAP, but not MAA, specifically inhibited the antigen-specific stimulatory capacity for CD4(+) T-cells. In the present study, we compared gene expression profiles of murine RAW264.7 macrophages in response to infections with MAP or MAA using murine high-density oligonucleotide Affymetrix microarrays. A comparison of MAP and MAA infection revealed 17 differentially expressed genes. They were expressed at a much lower level in MAP-infected macrophages than in MAA-infected macrophages. Among these were the genes for IL-1beta, IL-1alpha, CXCL2, PTGS2 (COX2), lipocalin (LCN2) and TNF, which are important pro-inflammatory factors. The microarray data were confirmed for selected genes by quantitative real-time reverse transcription PCR and, by protein array analyses and ELISA. Similar to MAA, infection with MAH also showed robust induction of IL-1beta, CXCL2, COX2, LCN2 and TNF. Taken together, our results from M. avium ssp.-infected murine macrophages provide evidence that MAP in contrast to MAA and MAH specifically suppresses the pro-inflammatory defence mechanisms of infected macrophages.

  11. A new paradigm and computational framework to estimate stop-signal reaction time distributions from the inhibition of complex motor sequences

    PubMed Central

    Teichert, Tobias; Ferrera, Vincent P.

    2015-01-01

    Inhibitory control is an important component of executive function that allows organisms to abort emerging behavioral plans or ongoing actions on the fly as new sensory information becomes available. Current models treat inhibitory control as a race between a Go- and a Stop process that may be mediated by partially distinct neural substrates, i.e., the direct and the hyper-direct pathway of the basal ganglia. The fact that finishing times of the Stop process (Stop-Signal Reaction Time, SSRT) cannot be observed directly has precluded a precise comparison of the functional properties that govern the initiation (GoRT) and inhibition (SSRT) of a motor response. To solve this problem, we modified an existing inhibitory paradigm and developed a non-parametric framework to measure the trial-by-trial variability of SSRT. A series of simulations verified that the non-parametric approach is on par with a parametric approach and yields accurate estimates of the entire SSRT distribution from as few as ~750 trials. Our results show that in identical settings, the distribution of SSRT is very similar to the distribution of GoRT albeit somewhat shorter, wider and significantly less right-skewed. The ability to measure the precise shapes of SSRT distributions opens new avenues for research into the functional properties of the hyper-direct pathway that is believed to mediate inhibitory control. PMID:26236226

  12. Clinical outbreak of Bordetella avium infection in two turkey breeder flocks.

    PubMed

    Kelly, B J; Ghazikhanian, G Y; Mayeda, B

    1986-01-01

    An acute upper respiratory disease was observed in two broad-breasted white (BBW) turkey primary breeder flocks. Associated clinical signs included sneezing, depression, and a deep dry cough originating from large conducting airways. Morbidity reached approximately 15-20% of the hens in an affected house. None of the turkeys died, and total feed consumption was not affected. A minimal effect upon egg production was noticed. Sera from an acutely affected flock exhibited a marked rise in titer to Bordetella avium compared with preinfection sera samples. In Case 1, B. avium was isolated in pure culture from affected birds. In Case 2, B. avium was diagnosed by serological results and clinical signs; bacteriological examination was not attempted. The findings presented here are consistent with an acute clinical outbreak of B. avium-induced turkey rhinotracheitis (turkey coryza) in BBW turkey breeder hens. PMID:3729868

  13. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    EPA Science Inventory

    BACKGROUND: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexis...

  14. Trypanosoma avium incidence, pathogenicity and response to melarsomine in falcons from Kuwait.

    PubMed

    Tarello, W

    2005-03-01

    Epidemiological and clinical studies on Trypanosoma avium are lacking in the Middle East. The aims of this study were to determine the T. avium incidence in falcons from Kuwait, report clinical signs and find an effective therapy. Blood smears from 921 diseased and 56 healthy falcons were examined between May 2003 and April 2004. 12 birds 11.3%) were found infected by T. avium and ten of these were treated with melarsomine (Cymelarsan) at a dosage of 0.25 mg/kg intramuscularly for four days. All affected birds presented clinical signs, including incapacity of flying high, poor appetite, lethargy, loosing weight, weakness, dyspnoea and death. Signs disappeared within 1-7 days after administration of melarsomine. Trypomastigotes were not detected in blood smears made 1-7 days after the end of therapy. This study suggests that T. avium induces disease in falcons and that melarsomine can be an effective therapy eliminating both clinical signs and circulating trypomastigotes.

  15. Clinical outbreak of Bordetella avium infection in two turkey breeder flocks.

    PubMed

    Kelly, B J; Ghazikhanian, G Y; Mayeda, B

    1986-01-01

    An acute upper respiratory disease was observed in two broad-breasted white (BBW) turkey primary breeder flocks. Associated clinical signs included sneezing, depression, and a deep dry cough originating from large conducting airways. Morbidity reached approximately 15-20% of the hens in an affected house. None of the turkeys died, and total feed consumption was not affected. A minimal effect upon egg production was noticed. Sera from an acutely affected flock exhibited a marked rise in titer to Bordetella avium compared with preinfection sera samples. In Case 1, B. avium was isolated in pure culture from affected birds. In Case 2, B. avium was diagnosed by serological results and clinical signs; bacteriological examination was not attempted. The findings presented here are consistent with an acute clinical outbreak of B. avium-induced turkey rhinotracheitis (turkey coryza) in BBW turkey breeder hens.

  16. Composition and potency characterization of Mycobacterium avium subsp. paratuberculosis purified protein derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) purified protein derivatives (PPDs) are immunologic reagents prepared from cultured filtrates of the type strain ATCC 19698. Traditional production consists of floating culture incubation at 37oC, organism inactivation by autoclaving, coarse filtrat...

  17. An Integrative Paradigm

    ERIC Educational Resources Information Center

    Hammack, Phillip L.

    2005-01-01

    Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

  18. The Investment Paradigm

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2005-01-01

    Is marketing an expense or an investment? Most accountants will claim that marketing is an expense, and clearly that seems true when cutting the checks to fund these efforts. When it is done properly, marketing is the best investment. A key principle to Smart Marketing is the Investment Paradigm. The Investment Paradigm is understanding that every…

  19. Organizational Paradigm Shifts.

    ERIC Educational Resources Information Center

    National Association of College and University Business Officers, Washington, DC.

    This collection of essays explores a new paradigm of higher education. The first essay, "Beyond Re-engineering: Changing the Organizational Paradigm" (L. Edwin Coate), suggests a model of quality process management and a structure for managing organizational change. "Thinking About Consortia" (Mary Jo Maydew) discusses cooperative effort and…

  20. Flow Cytometric Detection of Mycobacterium avium subsp. paratuberculosis-Specific Antibodies in Experimentally Infected and Naturally Exposed Calves

    PubMed Central

    Bridger, P. S.; Bulun, H.; Fischer, M.; Akineden, Ö.; Seeger, T.; Barth, S.; Henrich, M.; Doll, K.; Bülte, M.; Menge, C.; Bauerfeind, R.

    2013-01-01

    A desirable test to diagnose infections with Mycobacterium avium subsp. paratuberculosis facilitates identification of infected cattle prior to the state of M. avium subsp. paratuberculosis shedding. This study aimed at adjusting a flow cytometry (FC)-based assay, using intact M. avium subsp. paratuberculosis bacteria as the antigen, for diagnosis of M. avium subsp. paratuberculosis infections in calves. Serum samples were collected from experimentally infected (n = 12) and naturally exposed (n = 32) calves. Samples from five calves from positive dams were analyzed to determine the dynamics of maternal antibodies. Samples from adult cattle with defined infection status served as the standard (18 M. avium subsp. paratuberculosis shedders, 22 M. avium subsp. paratuberculosis free). After preadsorption with Mycobacterium phlei, sera were incubated with M. avium subsp. paratuberculosis and M. avium subsp. avium bacterial suspensions, respectively, followed by the separate detection of bovine IgG, IgG1, IgG2, and IgM attached to the bacterial surface. M. avium subsp. paratuberculosis-specific sample/positive (S/P) ratios were compared to enzyme-linked immunosorbent assay (ELISA) S/P ratios. In adult cattle, the FC assay for IgG1 had a sensitivity of 78% at a specificity of 100%. Maternally acquired antibodies could be detected in calves up to 121 days of life. While all but two sera taken at day 100 ± 10 postnatum from naturally exposed calves tested negative, elevated S/P ratios (IgG and IgG1) became detectable from 44 and 46 weeks postinoculation onwards in two calves infected experimentally. Even with the optimized FC assay, M. avium subsp. paratuberculosis-specific antibodies can only occasionally be detected in infected calves less than 12 months of age. The failure to detect such antibodies apparently reflects the distinct immunobiology of M. avium subsp. paratuberculosis infections rather than methodological constraints. PMID:23885032

  1. Expression library immunization confers protection against Mycobacterium avium subsp. paratuberculosis infection.

    PubMed

    Huntley, J F; Stabel, J R; Paustian, M L; Reinhardt, T A; Bannantine, J P

    2005-10-01

    Currently, paratuberculosis vaccines are comprised of crude whole-cell preparations of Mycobacterium avium subsp. paratuberculosis. Although effective in reducing clinical disease and fecal shedding, these vaccines have severe disadvantages as well, including seroconversion of vaccinated animals and granulomatous lesions at the site of vaccination. DNA vaccines can offer an alternative approach that may be safer and elicit more protective responses. In an effort to identify protective M. avium subsp. paratuberculosis sequences, a genomic DNA expression library was generated and subdivided into pools of clones (approximately 1,500 clones/pool). The clone pools were evaluated to determine DNA vaccine efficacy by immunizing mice via gene gun delivery and challenging them with live, virulent M. avium subsp. paratuberculosis. Four clone pools resulted in a significant reduction in the amount of M. avium subsp. paratuberculosis recovered from mouse tissues compared to mice immunized with other clone pools and nonvaccinated, infected control mice. One of the protective clone pools was further partitioned into 10 clone arrays of 108 clones each, and four clone arrays provided significant protection from both spleen and mesenteric lymph node colonization by M. avium subsp. paratuberculosis. The nucleotide sequence of each clone present in the protective pools was determined, and coding region functions were predicted by computer analysis. Comparison of the protective clone array sequences implicated 26 antigens that may be responsible for protection in mice. This study is the first study to demonstrate protection against M. avium subsp. paratuberculosis infection with expression library immunization. PMID:16177367

  2. Mycobacterium avium serovars 2 and 8 infections elicit unique activation of the host macrophage immune responses.

    PubMed

    Cebula, B R; Rocco, J M; Maslow, J N; Irani, V R

    2012-12-01

    Mycobacterium avium is an opportunistic pathogen whose pathogenesis is attributed to its serovar-specific glycopeptidolipid (ssGPL), which varies among its 31 serovars. To determine if the presence and type of ssGPLs contribute to M. avium pathogenesis, we infected murine macrophages (mφs) with two M. avium wild type (wt) serovars (2 and 8) and their serovar-null strains. We examined the influence of ssGPL (presence and type) on cytokine production in non-activated (-IFN-γ) and activated (+IFN-γ) mφs, and the bacterial intra-mφ survival over a 6-day infection process. Serovar-2 infections activated TNF-α production that increased over the 6 day period and was capable of controlling the intra-mφ serovar-2 null strain. In contrast, the serovar-8 infection stimulated a strong pro-inflammatory response, but was incapable of removing the invading pathogen, maybe through IL-10 production. It was clear that the intracellular growth of serovar-null in contrast to the wt M. avium strains was easily controlled. Based on our findings and the undisputed fact that M. avium ssGPL is key to its pathogenesis, we conclude that it is not appropriate to dissect the pathogenesis of one M. avium serovar and apply those findings to other serovars. PMID:22991047

  3. Mycobacterium avium subspecies paratuberculosis, Crohn's disease and the Doomsday scenario.

    PubMed

    Hermon-Taylor, John

    2009-01-01

    Johne's disease is chronic inflammation of the intestine caused by Mycobacterium avium subspecies paratuberculosis. Infection and disease are mainly in domestic livestock but can affect many species including primates. Johne's is a new disease which emerged at the turn of the 19th and 20th centuries and principally involved Europe and North America. It has since spread to former low incidence regions to become a global problem. Crohn's disease is a chronic inflammation of the intestine in humans which emerged in Europe and North America mid 20th century and increased to become a major healthcare problem. It has now spread to former low incidence regions. Infected animals shed Mycobacterium avium subspecies paratuberculosis in milk and into the environment. Human populations are widely exposed. Outcomes maybe influenced by microbial phenotype. Exposure to extracellular forms of these pathogens may confer some natural protection; exposure to intracellular forms which have passaged through milk macrophages or environmental protists may pose a greater threat to humans particularly individuals with an inherited or acquired susceptibility. Hot spots of human disease such as in Winnipeg which sits on rock at the junction of two rivers may result from local exposure to high levels of waterborne pathogens brought down from farmland. When appropriate methods are used most people with Crohn's disease are found to be infected. There are no data which demonstrate that these pathogens are harmless to humans. An overwhelming balance of probability and Public health risk favours the conclusion that Mycobacterium avium subspecies paratuberculosis is also pathogenic for people. A two tier co-operative pathogenic mechanism is proposed in Crohn's disease. Intracellular infection with the primary pathogen widely distributed throughout the gut causes an immune dysregulation and a specific chronic enteric neuropathy with loss of mucosal integrity. Segments of gross inflammatory disease

  4. Communication Policy at the Chalk Face in Scotland and Jamaica: Complexity as a New Paradigm for Understanding Language Policy Interpretation and Implementation.

    ERIC Educational Resources Information Center

    Cross, Beth

    2003-01-01

    Examples from upper primary classrooms in Scotland and Jamaica demonstrate the subtle ways in which teachers support or restrict the classroom use of community languages (Scots and Patwa) through their broad or narrow implementation of language policy. The metaphor of fractals, derived from complexity theory, can form a sensitive and appropriate…

  5. Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm.

    PubMed

    Podlech, Jürgen; Reddehase, Matthias J; Adler, Barbara; Lemmermann, Niels A W

    2015-06-01

    Initial virus entry into cells of host organs and subsequent spread of viral progeny between tissue cells are events fundamental to viral pathogenesis. Glycoprotein complexes inserted in the virion envelope are critically involved in the cell entry process. Here we review and discuss recent work that has shed light on the in vivo role of the trimeric glycoprotein complex gH/gL/gO of murine cytomegalovirus (mCMV) as a model to propose the role of the corresponding complex of human CMV, for which experimental studies in vivo are not feasible due to the host species specificity of CMVs and evident ethical constraints. A novel approach combining gO transcomplementation of a genetically gO-deficient virus and a mathematical log-linear regression analysis of the viral multiplication kinetics in host tissues revealed a critical role of mCMV gH/gL/gO only in first target cell entry of virions arriving with the circulation, whereas intra-tissue spread proceeded unaffected also in the absence of gH/gL/gO. These findings predict that targeting gO for an antiviral intervention may be of prophylactic value in preventing the seeding of virus to organs, but will likely fail to interfere with an established primary organ infection or with recurrent infection after virus reactivation from latency within tissue cells. The demonstration in the murine model of alternative gH/gL complexes gH/gL/gO and gH/gL/MCK-2, substituting one another in a redundant fashion for securing viral spread in tissues, has the medically interesting bearing that targeting the gH/gL core complex directly may be a promising approach to preventing primary, established, and recurrent CMV infections.

  6. Paradigms for machine learning

    NASA Technical Reports Server (NTRS)

    Schlimmer, Jeffrey C.; Langley, Pat

    1991-01-01

    Five paradigms are described for machine learning: connectionist (neural network) methods, genetic algorithms and classifier systems, empirical methods for inducing rules and decision trees, analytic learning methods, and case-based approaches. Some dimensions are considered along with these paradigms vary in their approach to learning, and the basic methods are reviewed that are used within each framework, together with open research issues. It is argued that the similarities among the paradigms are more important than their differences, and that future work should attempt to bridge the existing boundaries. Finally, some recent developments in the field of machine learning are discussed, and their impact on both research and applications is examined.

  7. Influence of cultivar and processing on cherry (Prunus avium) allergenicity.

    PubMed

    Primavesi, L; Brenna, O V; Pompei, C; Pravettoni, V; Farioli, L; Pastorello, E A

    2006-12-27

    Oral allergy syndrome is an immediate food allergic event that affects lips, mouth, and pharynx, is often triggered by fruits and vegetables, and may be associated with pollinosis. Here, we report on the allergenic pattern of different varieties of cherry (Prunus avium) and results obtained by applying several technological processes to the selected varieties. Whole cherries were submitted to chemical peeling, thermal treatment, and syruping processes, and the relative protein extracts were analyzed by in vitro (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis) and in vivo tests (skin prick test). Electrophoretic analyses demonstrated that there was no marked difference among cherry cultivars. Chemical peeling successfully removed Pru av 3, a lipid transfer protein (LTP) responsible for oral allergy syndrome in patients without pollinosis, leading to the industrial production of cherry hypoallergenic derivatives. Furthermore, the syruping process removed almost all allergenic proteins to whom patients with pollinosis are responsive. In vivo tests confirmed electrophoretic results.

  8. Emphysematous pyometra secondary to Enterococcus avium infection in a dog.

    PubMed

    Chang, An-Chi; Cheng, Ching-Chang; Wang, Hsien-Chi; Lee, Wei-Ming; Shyu, Ching-Lin; Lin, Cheng-Chung; Chen, Kuan-Sheng

    2016-06-16

    A 5-year-old female intact Mastiff dog was presented with a history of vaginal discharge for 1 day. Physical examination revealed a sanguineo-purulent vaginal discharge and systemic inflammatory response syndrome. Abdominal radiographs showed several dilated and gas- filled tubular loops. The differential diagnoses included emphysematous pyometra or small intestinal mechanical ileus. Surgical exploration of the abdomen demonstrated a severely dilated and gas-filled uterus, and emphysematous pyometra was confirmed. The patient's clinical signs resolved after ovariohysterectomy. Histopathology revealed mild endometrial cystic hyperplasia with infiltration of inflammatory cells in the superficial endometrial epithelia. Enterococcus avium, an α-hemolytic gram-positive coccus, was isolated from the uterus. This paper highlights the radiographic features of emphysematous pyometra and a pathogen that has never been reported to be associated with canine pyometra previously. PMID:27111397

  9. Binding of Mycobacterium avium-Mycobacterium intracellulare to human leukocytes.

    PubMed Central

    Catanzaro, A; Wright, S D

    1990-01-01

    We examined nonopsonic binding of Mycobacterium avium-Mycobacterium intracellulare (MAI) by human leukocytes. Macrophages (M phi) avidly bound fluorescently labeled MAI in the absence of serum proteins. Binding appeared to be mediated by a lineage-specific, proteinaceous receptor on M phi, since (i) binding of labeled bacteria could be competitively inhibited by unlabeled MAI, (ii) treatment of M phi with trypsin ablated the ability of M phi to bind MAI, and (iii) the capacity to bind MAI was observed on monocytes, M phi, and stimulated polymorphonuclear cells but not on lymphocytes or unstimulated polymorphonuclear cells. The receptor for MAI appeared mobile in the plane of the membrane, since spreading of M phi on a carpet of immobilized, unlabeled MAI down modulated binding of labeled MAI added in suspension. The receptor required neither calcium nor magnesium for activity and appeared different from other known receptors for intracellular pathogens. Images PMID:2387629

  10. The fictionalist paradigm.

    PubMed

    Paley, John

    2011-01-01

    The fictionalist paradigm is introduced, and differentiated from other paradigms, using the Lincoln & Guba template. Following an initial overview, the axioms of fictionalism are delineated by reference to standard metaphysical categories: the nature of reality, the relationship between knower and known, the possibility of generalization, the possibility of causal linkages, and the role of values in inquiry. Although a paradigm's 'basic beliefs' are arbitrary and can be assumed for any reason, in this paper the fictionalist axioms are supported with philosophical considerations, and the key differences between fictionalism, positivism, and constructivism are briefly explained. Paradigm characteristics are then derived, focusing particularly on the methodological consequences. Towards the end of the paper, various objections and misunderstandings are discussed.

  11. LAMP technology: Rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Trangoni, Marcos D.; Gioffré, Andrea K.; Cerón Cucchi, María E.; Caimi, Karina C.; Ruybal, Paula; Zumárraga, Martín J.; Cravero, Silvio L.

    2015-01-01

    In this study, we developed new sets of primers to detect Brucella spp. and M. avium subsp. paratuberculosis (MAP) through isothermal amplification. We selected a previously well-characterized target gene, bscp31, specific for Brucella spp. and IS900 for MAP. The limits of detection using the loop-mediated isothermal amplification (LAMP) protocols described herein were similar to those of conventional PCR targeting the same sequences. Hydroxynaphtol blue and SYBR GreenTM allowed direct naked-eye detection with identical sensitivity as agarose gel electrophoresis. We included the LAMP-based protocol in a rapid identification scheme of the respective pathogens, and all tested isolates were correctly identified within 2 to 3 h. In addition, both protocols were suitable for specifically identifying the respective pathogens; in the case of Brucella, it also allowed the identification of all the biovars tested. We conclude that LAMP is a suitable rapid molecular typing tool that could help to shorten the time required to identify insidious bacteria in low-complexity laboratories, mainly in developing countries. PMID:26273282

  12. Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium

    PubMed Central

    Matsuyama, Masashi; Ishii, Yukio; Sakurai, Hirofumi; Ano, Satoshi; Morishima, Yuko; Yoh, Keigyou; Takahashi, Satoru; Ogawa, Kenji; Hizawa, Nobuyuki

    2016-01-01

    Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection. PMID:26784959

  13. Paradigm Change in Political Science.

    ERIC Educational Resources Information Center

    Rodman, John

    1980-01-01

    Traces the shift of paradigms in the political science profession from the 1960s to 1980, examines the classical paradigm, compares it with modern paradigms, and reviews contemporary efforts to articulate a new paradigm which takes the ecological crisis into account. (Author/DB)

  14. [Paradigm errors in the old biomedical science].

    PubMed

    Skurvydas, Albertas

    2008-01-01

    The aim of this article was to review the basic drawbacks of the deterministic and reductionistic thinking in biomedical science and to provide ways for dealing with them. The present paradigm of research in biomedical science has not got rid of the errors of the old science yet, i.e. the errors of absolute determinism and reductionism. These errors restrict the view and thinking of scholars engaged in the studies of complex and dynamic phenomena and mechanisms. Recently, discussions on science paradigm aimed at spreading the new science paradigm that of complex dynamic systems as well as chaos theory are in progress all over the world. It is for the nearest future to show which of the two, the old or the new science, will be the winner. We have come to the main conclusion that deterministic and reductionistic thinking applied in improper way can cause substantial damage rather than prove benefits for biomedicine science. PMID:18541951

  15. ISOLATION OF THE GENOME SEQUENCE STRAIN MYCOBACTERIUM AVIUM 104 FROM MULTIPLE PATIENTS OVER A 17-YEAR PERIOD

    EPA Science Inventory

    The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated form an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genoty...

  16. Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

    PubMed

    de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

    2011-03-01

    We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.

  17. The persistence of Mycobacterium avium in a drinking water system, what is the risk to human health?

    EPA Science Inventory

    Drinking water is believed to be a major source of human exposure to nontuberculous mycobacteria (NTM) such as Mycobacterium avium. We monitored the prevalence of M. avium in a drinking water system during the addition of filtration treatment. Our goal was to determine if the pre...

  18. Survival of Mycobacterium avium in drinking water biofilms as affected by water flow velocity, availability of phosphorus, and temperature.

    PubMed

    Torvinen, Eila; Lehtola, Markku J; Martikainen, Pertti J; Miettinen, Ilkka T

    2007-10-01

    Mycobacterium avium is a potential pathogen occurring in drinking water systems. It is a slowly growing bacterium producing a thick cell wall containing mycolic acids, and it is known to resist chlorine better than many other microbes. Several studies have shown that pathogenic bacteria survive better in biofilms than in water. By using Propella biofilm reactors, we studied how factors generally influencing the growth of biofilms (flow rate, phosphorus concentration, and temperature) influence the survival of M. avium in drinking water biofilms. The growth of biofilms was followed by culture and DAPI (4',6'-diamidino-2-phenylindole) staining, and concentrations of M. avium were determined by culture and fluorescence in situ hybridization methods. The spiked M. avium survived in biofilms for the 4-week study period without a dramatic decline in concentration. The addition of phosphorus (10 microg/liter) increased the number of heterotrophic bacteria in biofilms but decreased the culturability of M. avium. The reason for this result is probably that phosphorus increased competition with other microbes. An increase in flow velocity had no effect on the survival of M. avium, although it increased the growth of biofilms. A higher temperature (20 degrees C versus 7 degrees C) increased both the number of heterotrophic bacteria and the survival of M. avium in biofilms. In conclusion, the results show that in terms of affecting the survival of slowly growing M. avium in biofilms, temperature is a more important factor than the availability of nutrients like phosphorus.

  19. The mechanism of cytoskeleton protein β-actin and cofilin-1 of macrophages infected by Mycobacterium avium

    PubMed Central

    Wang, Jianjun; Yao, Yongliang; Wu, Jianhong; Deng, Zhiyong; Gu, Tao; Tang, Xin; Cheng, Yang; Li, Guangxin

    2016-01-01

    Cytoskeleton proteins and their regulation proteins could be influenced seriously in Mycobacterium tuberculosis infection host cells leading to the apoptosis of host cells. Macrophages infected by Mycobacterium avium were detected from cell morphology and genome levels to analyze changes of the cytoskeleton of M. avium infection macrophages. Then the expression of β-actin, cofilin-1 proteins in M. avium infected macrophages were analyzed by western blotting, and the apoptosis of M. avium infection macrophages were tested by flow cytometry. Results indicated that the morphology and genomic DNA of M. avium infection macrophages were not damaged significantly. Meanwhile, β-actin gene and its proteins in M. avium infection macrophages were both decreased, but its regulatory protein cofilin-1 was expressed conversely. Furthermore, macrophages could be induced to apoptosis due to M. avium infection by cytoskeleton changes. These findings contributed us to understand that macrophages infected by M. avium could be lead to apoptosis by regulating cytoskeleton protein β-actin or its regulatory protein cofilin-1. PMID:27158391

  20. Characterization of the fibronectin-attachment protein of Mycobacterium avium reveals a fibronectin-binding motif conserved among mycobacteria.

    PubMed

    Schorey, J S; Holsti, M A; Ratliff, T L; Allen, P M; Brown, E J

    1996-07-01

    Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that the initial portal of infection by M. avium is often the gastrointestinal tract. However, the mechanism by which the M. avium crosses the epithelial barrier is unclear. A possible mechanism is suggested by the ability of M. avium to bind fibronectin, an extracellular matrix protein that is a virulence factor for several extracellular pathogenic bacteria which bind to mucosal surfaces. To further characterize fibronectin binding by M. avium, we have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non-continuous regions in FAP-A bind fibronectin. Peptides from these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have no homology to eukaryotic fibronectin-binding proteins and are only distantly related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless, these fibronectin-binding regions are highly conserved among the mycobacterial FAPs, suggesting an essential function for this interaction in mycobacteria infection of their metazoan hosts.

  1. Estimation of Mycobacterium avium subsp. paratuberculosis Growth Parameters: Strain Characterization and Comparison of Methods▿

    PubMed Central

    Elguezabal, Natalia; Bastida, Felix; Sevilla, Iker A.; González, Nuria; Molina, Elena; Garrido, Joseba M.; Juste, Ramón A.

    2011-01-01

    The growth rate of Mycobacterium avium subsp. paratuberculosis was assessed by different methods in 7H9 medium supplemented with OADC (oleic acid, albumin, dextrose, catalase), Tween 80, and mycobactin J. Generation times and maximum specific growth rates were determined by wet weight, turbidometric measurement, viable count, and quantitative PCR (ParaTB-Kuanti; F57 gene) for 8 M. avium subsp. paratuberculosis strains (K10, 2E, 316F, 81, 445, 764, 22G, and OVICAP 49). Strain-to-strain differences were observed in growth curves and calculated parameters. The quantification methods gave different results for each strain at specific time points. Generation times ranged from an average of 1.4 days for viable count and qPCR to approximately 10 days for wet weight and turbidometry. The wet-weight, turbidometry, and ParaTB-Kuanti qPCR methods correlated best with each other. Generally, viability has been assessed by viable count as a reference method; however, due to M. avium subsp. paratuberculosis clumping problems and the presence of noncultivable M. avium subsp. paratuberculosis cells, we conclude that qPCR of a single-copy gene may be used reliably for rapid estimation of M. avium subsp. paratuberculosis bacterial numbers in a sample. PMID:22003015

  2. Adhesion of Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET) used for bottled waters.

    PubMed

    Tatchou-Nyamsi-König, Josiane-Aurore; Dague, Etienne; Mullet, Martine; Duval, Jérôme F L; Gaboriaud, Fabien; Block, Jean-Claude

    2008-12-01

    Adhesion of the bacteria Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET), a polymer widely used within the bottled water industry was measured in two different groundwater solutions. From this, it was found that whilst the percentage cell adhesion for a given strain did not change between groundwater types, substantial variation was obtained between the two bacterial species tested: M. avium (10-30% adhered cells) and C. jejuni (1-2%) and no major variations were measured as a function of groundwater composition for a given strain. To explain this, the interfacial electro-hydrodynamic properties of the bacteria were investigated by microelectrophoresis, with the resultant data analysed on the basis of electrokinetic theory for soft biocolloidal particles. The results obtained showed that M. avium carries a significant volume charge density and that its peripheral layer exhibits limited hydrodynamic flow permeation compared to that of C. jejuni. It was also demonstrated that steric hindrance to flow penetration and the degree of hydrophobicity within/of the outer bacterial interface are larger for M. avium cells. In line with this, the larger amount of M. avium cells deposited onto PET substrates as compared to that of C. jejuni can be explained by hydrophobic attraction and chemical binding between hydrophobic PET and outer soft surface layer of the bacteria. Hydrophobicity of PET was addressed by combining contact angle analyses and force spectroscopy using CH(3)-terminated AFM tip. PMID:18929388

  3. Fate of Mycobacterium avium subsp. paratuberculosis in Swiss hard and semihard cheese manufactured from raw milk.

    PubMed

    Spahr, U; Schafroth, K

    2001-09-01

    Raw milk was artificially contaminated with declumped cells of Mycobacterium avium subsp. paratuberculosis at a concentration of 10(4) to 10(5) CFU/ml and was used to manufacture model hard (Swiss Emmentaler) and semihard (Swiss Tisliter) cheese. Two different strains of M. avium subsp. paratuberculosis were tested, and for each strain, two model hard and semihard cheeses were produced. The survival of M. avium subsp. paratuberculosis cells was monitored over a ripening period of 120 days by plating out homogenized cheese samples onto 7H10-PANTA agar. In both the hard and the semihard cheeses, counts decreased steadily but slowly during cheese ripening. Nevertheless, viable cells could still be detected in 120-day cheese. D values were calculated at 27.8 days for hard and 45.5 days for semihard cheese. The most important factors responsible for the death of M. avium subsp. paratuberculosis in cheese were the temperatures applied during cheese manufacture and the low pH at the early stages of cheese ripening. Since the ripening period for these raw milk cheeses lasts at least 90 to 120 days, the D values found indicate that 10(3) to 10(4) cells of M. avium subsp. paratuberculosis per g will be inactivated.

  4. Fate of Mycobacterium avium subsp. paratuberculosis in Swiss Hard and Semihard Cheese Manufactured from Raw Milk

    PubMed Central

    Spahr, U.; Schafroth, K.

    2001-01-01

    Raw milk was artificially contaminated with declumped cells of Mycobacterium avium subsp. paratuberculosis at a concentration of 104 to 105 CFU/ml and was used to manufacture model hard (Swiss Emmentaler) and semihard (Swiss Tisliter) cheese. Two different strains of M. avium subsp. paratuberculosis were tested, and for each strain, two model hard and semihard cheeses were produced. The survival of M. avium subsp. paratuberculosis cells was monitored over a ripening period of 120 days by plating out homogenized cheese samples onto 7H10-PANTA agar. In both the hard and the semihard cheeses, counts decreased steadily but slowly during cheese ripening. Nevertheless, viable cells could still be detected in 120-day cheese. D values were calculated at 27.8 days for hard and 45.5 days for semihard cheese. The most important factors responsible for the death of M. avium subsp. paratuberculosis in cheese were the temperatures applied during cheese manufacture and the low pH at the early stages of cheese ripening. Since the ripening period for these raw milk cheeses lasts at least 90 to 120 days, the D values found indicate that 103 to 104 cells of M. avium subsp. paratuberculosis per g will be inactivated. PMID:11526024

  5. Changing the Paradigm of Air Pollution Monitoring

    EPA Science Inventory

    Historically, approaches for monitoring air pollution generally use expensive, complex, stationary equipment,1,2 which limits who collects data, why data are collected, and how data are accessed. This paradigm is changing with the materialization of lower-cost, easy-to...

  6. Disseminated mycobacteriosis due to Mycobacterium avium in captive Bengal tiger (Panthera tigris).

    PubMed

    Cho, Ho-Seong; Kim, Yong-Hwan; Park, Nam-Yong

    2006-05-01

    A 2-year-old captive female Bengal Tiger (Panthera tigris) died after prolonged anorexia in the Gwangju Uchi Park Zoo, Gwangju, Republic of Korea. Necropsy revealed multiple nodules of varying sizes in the lung, liver, kidney, and spleen. Histopathologic examination revealed a typical granuloma composed of caseous necrotic areas surrounded by lymphocytes with a few giant cells and foamy macrophages. Periodic acid-Schiff stain and Gomori methenamine silver stain did not reveal any fungal bodies. The Ziehl-Neelsen acid-fast stain revealed few acid-fast organisms in the lung, liver, kidney, and spleen. A polymerase chain reaction assay of the lung, liver, kidney, and spleen yielded a positive result for Mycobacterium avium subsp. avium. This is an unusual case of disseminated infection of a wild mammal with avian mycobacteriosis, and is believed to be most likely associated with the feeding of tigers with culled chickens infected with M. avium.

  7. Disseminated mycobacteriosis due to Mycobacterium avium in captive Bengal tiger (Panthera tigris).

    PubMed

    Cho, Ho-Seong; Kim, Yong-Hwan; Park, Nam-Yong

    2006-05-01

    A 2-year-old captive female Bengal Tiger (Panthera tigris) died after prolonged anorexia in the Gwangju Uchi Park Zoo, Gwangju, Republic of Korea. Necropsy revealed multiple nodules of varying sizes in the lung, liver, kidney, and spleen. Histopathologic examination revealed a typical granuloma composed of caseous necrotic areas surrounded by lymphocytes with a few giant cells and foamy macrophages. Periodic acid-Schiff stain and Gomori methenamine silver stain did not reveal any fungal bodies. The Ziehl-Neelsen acid-fast stain revealed few acid-fast organisms in the lung, liver, kidney, and spleen. A polymerase chain reaction assay of the lung, liver, kidney, and spleen yielded a positive result for Mycobacterium avium subsp. avium. This is an unusual case of disseminated infection of a wild mammal with avian mycobacteriosis, and is believed to be most likely associated with the feeding of tigers with culled chickens infected with M. avium. PMID:16789727

  8. Deconstructing Research: Paradigms Lost

    ERIC Educational Resources Information Center

    Trifonas, Peter Pericles

    2009-01-01

    In recent decades, proponents of naturalistic and/or critical modes of inquiry advocating the use of ethnographic techniques for the narrative-based study of phenomena within pedagogical contexts have challenged the central methodological paradigm of educational research: that is, the tendency among its practitioners to adhere to quantitative…

  9. Alternative Evaluation Research Paradigm.

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    This monograph is one of a continuing series initiated to provide materials for teachers, parents, school administrators, and governmental decision-makers that might encourage reexamination of a range of evaluation issues and perspectives about schools and schooling. This monograph is a description and analysis of two contrasting paradigms: one…

  10. Paradigms of School Change

    ERIC Educational Resources Information Center

    Wrigley, Terry

    2011-01-01

    This short paper points to some paradigm issues in the field of school development (leadership, effectiveness, improvement) and their relationship to social justice. It contextualises the dominant School Effectiveness and School Improvement models within neo-liberal marketisation, paying attention to their transformation through a "marriage of…

  11. Description of a Novel Adhesin of Mycobacterium avium Subsp. paratuberculosis

    PubMed Central

    Viale, Mariana Noelia; Echeverria-Valencia, Gabriela; Romasanta, Pablo; Mon, María Laura; Fernandez, Marisa; Malchiodi, Emilio; Romano, María Isabel; Gioffré, Andrea Karina; Santangelo, María de la Paz

    2014-01-01

    The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by host cells are fibronectin (FN) dependent. In several species of mycobacteria, a specific family of proteins allows the attachment and internalization of these bacteria by epithelial cells through interaction with FN. Thus, the identification of adhesion molecules is essential to understand the pathogenesis of MAP. The aim of this study was to identify and characterize FN binding cell wall proteins of MAP. We searched for conserved adhesins within a large panel of surface immunogenic proteins of MAP and investigated a possible interaction with FN. For this purpose, a cell wall protein fraction was obtained and resolved by 2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and a homology search was performed. We selected elongation factor Tu (EF-Tu) as candidate for further studies. We demonstrated the FN-binding capability of EF-Tu using a ligand blot assay and also confirmed the interaction with FN in a dose-dependent manner by ELISA. The dissociation constant of EF-Tu was determined by surface plasmon resonance and displayed values within the μM range. These data support the hypothesis that this protein could be involved in the interaction of MAP with epithelial cells through FN binding. PMID:25136616

  12. Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection

    PubMed Central

    2016-01-01

    Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized. PMID:27489800

  13. Description of a novel adhesin of Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Viale, Mariana Noelia; Echeverria-Valencia, Gabriela; Romasanta, Pablo; Mon, María Laura; Fernandez, Marisa; Malchiodi, Emilio; Romano, María Isabel; Gioffré, Andrea Karina; Santangelo, María de la Paz

    2014-01-01

    The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by host cells are fibronectin (FN) dependent. In several species of mycobacteria, a specific family of proteins allows the attachment and internalization of these bacteria by epithelial cells through interaction with FN. Thus, the identification of adhesion molecules is essential to understand the pathogenesis of MAP. The aim of this study was to identify and characterize FN binding cell wall proteins of MAP. We searched for conserved adhesins within a large panel of surface immunogenic proteins of MAP and investigated a possible interaction with FN. For this purpose, a cell wall protein fraction was obtained and resolved by 2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and a homology search was performed. We selected elongation factor Tu (EF-Tu) as candidate for further studies. We demonstrated the FN-binding capability of EF-Tu using a ligand blot assay and also confirmed the interaction with FN in a dose-dependent manner by ELISA. The dissociation constant of EF-Tu was determined by surface plasmon resonance and displayed values within the μM range. These data support the hypothesis that this protein could be involved in the interaction of MAP with epithelial cells through FN binding. PMID:25136616

  14. Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection.

    PubMed

    Park, Hong-Tae; Yoo, Han Sang

    2016-07-01

    Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized. PMID:27489800

  15. Mycobacterium avium subsp. paratuberculosis: pathogen, pathogenesis and diagnosis.

    PubMed

    Manning, E J; Collins, M T

    2001-04-01

    Johne's disease, or paratuberculosis, is a chronic intestinal infection caused by Mycobacterium avium subsp. paratuberculosis. The usually fatal disease is characterised by cachexia, and in some species diarrhoea, after a long pre-clinical phase. Treatment is ineffective and economically impracticable. The infection primarily affects domestic and free-ranging ruminants, but has also been reported in primates, rabbits, stoats and foxes. Since paratuberculosis is often subclinical, under-reporting is suspected, even though the disease is notifiable in numerous countries. Herd prevalence of bovine paratuberculosis in Europe ranges from 7% to 55%. In the United States of America, herd prevalence is strongly associated with herd size; 40% of herds of more than 300 head were found to be infected. In Australia, reported dairy herd infection rates range between 9% and 22%. Paratuberculosis in domestic livestock entails significant economic losses due to several factors (e.g. reduced production, premature culling and increased veterinary costs). Free-ranging and captive wildlife are also at risk from paratuberculosis.

  16. Complex networks: Patterns of complexity

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2010-07-01

    The Turing mechanism provides a paradigm for the spontaneous generation of patterns in reaction-diffusion systems. A framework that describes Turing-pattern formation in the context of complex networks should provide a new basis for studying the phenomenon.

  17. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome.

  18. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome. PMID:27629965

  19. PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response.

    PubMed

    Mendoza-Coronel, Elizabeth; Camacho-Sandoval, Rosa; Bonifaz, Laura C; López-Vidal, Yolanda

    2011-01-01

    The exposure to certain species of Nontuberculous Mycobacteria (NTM) can modulate the immune response induced by Mycobacterium bovis BCG. Mycobacterium avium has been postulated as a weak inducer of dendritic cell (DC) maturation. However, how the DC exposure to M. avium could contribute to the modulation of a BCG-specific CD4+ T cell response and the molecules involved remain unknown. Here, we exposed bone marrow-derived DCs (BMDCs) to M. avium either prior to exposure to BCG or as a unique stimulus. We found that M. avium induces high expression of PD-L2 (B7-DC) in BMDCs. This was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway. Exposure to M. avium prior to BCG results in BMDCs that do not express co-stimulatory molecules and pro-inflammatory cytokines, while the expression of PD-L2 and IL-10 was maintained. BMDCs exposed to M. avium impaired the activation of BCG-specific T cells through the PD-1: PD-L interaction. This suggests that a M. avium-induced phenotype in DCs might be implicated in the induction of mechanisms of tolerance that could impact the T cell response induced by BCG vaccination.

  20. In Vivo Volatile Organic Compound Signatures of Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Bergmann, Andreas; Trefz, Phillip; Fischer, Sina; Klepik, Klaus; Walter, Gudrun; Steffens, Markus; Ziller, Mario; Schubert, Jochen K.; Reinhold, Petra; Köhler, Heike; Miekisch, Wolfram

    2015-01-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of a chronic enteric disease of ruminants. Available diagnostic tests are complex and slow. In vitro, volatile organic compound (VOC) patterns emitted from MAP cultures mirrored bacterial growth and enabled distinction of different strains. This study was intended to determine VOCs in vivo in the controlled setting of an animal model. VOCs were pre-concentrated from breath and feces of 42 goats (16 controls and 26 MAP-inoculated animals) by means of needle trap microextraction (breath) and solid phase microextraction (feces) and analyzed by gas chromatography/ mass spectrometry. Analyses were performed 18, 29, 33, 41 and 48 weeks after inoculation. MAP-specific antibodies and MAP-specific interferon-γ-response were determined from blood. Identities of all marker-VOCs were confirmed through analysis of pure reference substances. Based on detection limits in the high pptV and linear ranges of two orders of magnitude more than 100 VOCs could be detected in breath and in headspace over feces. Twenty eight substances differed between inoculated and non-inoculated animals. Although patterns of most prominent substances such as furans, oxygenated substances and hydrocarbons changed in the course of infection, differences between inoculated and non-inoculated animals remained detectable at any time for 16 substances in feces and 3 VOCs in breath. Differences of VOC concentrations over feces reflected presence of MAP bacteria. Differences in VOC profiles from breath were linked to the host response in terms of interferon-γ-response. In a perspective in vivo analysis of VOCs may help to overcome limitations of established tests. PMID:25915653

  1. Association of ISMav6 with the Pattern of Antibiotic Resistance in Korean Mycobacterium avium Clinical Isolates but No Relevance between Their Genotypes and Clinical Features

    PubMed Central

    Kim, Su-Young; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Han, Seung Jung; Shin, Sung Jae; Koh, Won-Jung

    2016-01-01

    The aim of this study was to genetically characterize clinical isolates from patients diagnosed with Mycobacterium avium lung disease and to investigate the clinical significance. Multi-locus sequencing analysis (MLSA) and pattern of insertion sequence analysis of M. avium isolates from 92 Korean patients revealed that all isolates were M. avium subspecies hominissuis. In hsp65 sequevar analysis, codes 2, 15, and 16 were most frequently found (88/92) with similar proportions among cases additionally two isolates belonging to code N2 and an unreported code were identified, respectively. In insertion element analysis, all isolates were IS1311 positive and IS900 negative. Four of the M. avium subsp. hominissuis isolates did not harbor IS1245 and 1 of the M. avium isolates intriguingly harbored DT1, which is thought to be a M. intracellulare-specific element. M. avium subsp. hominissuis harboring ISMav6 is prevalent in Korea. No significant association between clinical manifestation and treatment response has been found in patients with the hsp65 code type and ISMav6, indicating that no specific strain/genotype among M. avium subsp. hominissuis organisms was a major source of M. avium lung disease. Interestingly, the presence of ISMav6 was correlated with greater resistance to moxifloxacin. Conclusively, the genotype of Korean M. avium subsp. hominissuis isolates is not a disease determinant responsible for lung disease and specific virulent factors of M. avium subsp. hominissuis need to be investigated further. PMID:26859598

  2. A synchronous paradigm for modeling stable reactive systems

    SciTech Connect

    Winter, V.L.

    1998-12-01

    This paper describes a modeling technique for single-agent reactive systems, that is influenced by the modeling paradigm of Parnas as well as by the synchronous paradigms of LUSTRE and ESTEREL. In this paradigm, single-agent reactive systems are modeled in a universe having a discrete clock. This discretization of time greatly reduces the temporal complexity of the model. He believes that the advantage of this reduction in temporal complexity is that the resulting model is in many ways better suited to automated software construction and analysis techniques (e.g., deductive synthesis, transformation, and verification) than models that are based on continuous representations of time.

  3. Transcriptional profiling of ileocecal valve of holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advan...

  4. Detection of Mycobacterium avium subsp. paratuberculosis in Drinking Water and Biofilms Using Quantitative PCR

    EPA Science Inventory

    Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease in domestic animals and has been implicated in Crohn’s disease in humans. Cows infected with Johne’s disease shed large quantities of MAP into soil. Further, MAP has been isolated from surface water, is resi...

  5. Unraveling the Host Response to Mycobacterium avium subsp. paratuberculosis: One Thread at a Time

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...

  6. Detection of Mycobacterium avium subspecies paratuberculosis in Drinking Water and Biofilms Using Quantitative PCR

    EPA Science Inventory

    Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s disease in domestic animals and has been implicated in Crohn’s disease in humans. This bacterium is a slow growing, gram-positive, acid-fast organism which can be difficult to culture from the environment. For ...

  7. Lymphoproliferative and gamma interferon responses to stress-regulated Mycobacterium avium subsp. paratuberculosis recombinant proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. Economic losses associated with Johne’s disease arise due to premature culling, reduced production of milk and wool and mortalities. The disease is characterised by a long inc...

  8. Genome sequencing of ovine isolates of Mycobacterium avium subspecies paratuberculosis offer insights into host association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genome of Mycobacterium avium subspecies paratuberculosis (MAP) is remarkably homogeneous among the genomes of bovine, human and wildlife isolates. However previous work in our laboratories with the bovine K-10 strain has revealed substantial differences compared to sheep isolates. To systemat...

  9. Immunlogic responses to Mycobacterium avium subsp. paratuberculosis protein cocktail vaccines in a mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a chronic granulomatous enteritis characterized by severe diarrhea, wasting, and a decline in milk production caused by the bacterium Mycobacterium avium subsp. paratuberculosis (MAP). The vaccine currently on the market has some limitations including a severe injection site react...

  10. Synthesis and release of sulfolipid by Mycobacterium avium during growth andcell division.

    PubMed Central

    McCarthy, C

    1976-01-01

    Mycobacterium avium exhibits a life cycle wherein small cells elongate to form filaments. The life cycle is unique in that elongated cells will undergo rapid division by fragmentation only if fatty acid is present. The utilization of [14C]palmitic acid and [3H]oleic acid by M. avium during the life cycle was assessed. Four glycolipids, identifiable by elution patterns from hydroxylapatite columns, were associated with postfission cells and contained isotope from the precursor fatty acid. The incorporation of 3H from oleic acid into the cellular glycolipids was maximal during cell division, but as much as 73% of the radioactivity was lost to the lipids from cells in the postfission status. Three of the glycolipids were sulfatides into which 36S was incorporated by M. avium. The [35]sulfatides were synthesized by cells undergoing fragmentation and were recovered from the medium at the termination of cell fission. These results demonstrated that the isotope was not lost to the cells because of turnover, but rather that the labeled compounds were released, intact, from the cells after fission. Because of the facile release of the sulfolipids, it was suggested that they were part of the cell envelope of M. avium cells during the division process. Images PMID:977128

  11. From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease (JD) is a chronic enteric infection of cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP). The high economic cost and potential zoonotic threat of JD have driven efforts to develop tools and approaches to effectively manage this disease within livestock herds. Efforts...

  12. Shared Mycobacterium avium genotypes observed among unlinked clinical and environmental isolates*

    EPA Science Inventory

    Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this a...

  13. COMPARISON OF MYCOBACTERIUM AVIUM ISOLATES FROM DRINKING WATER AND FROM THE POPULATION SERVED BY THE SYSTEM

    EPA Science Inventory

    Background: Current evidence suggests that drinking water, soil, and produce are potential sources of Mycobacterium avium infections, a pathogen not known to be transmitted person-to-person.

    Methods: We sampled water during 2000 - 2002 from a large municipal drinking wate...

  14. Optimization of hexadecylpyridinium chloride decontamination for culture of Mycobacterium avium subsp. paratuberculosis from milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cows in advanced stages of Johne’s disease shed Mycobacterium avium subsp. paratuberculosis (MAP) into both their milk and feces, allowing for transmission of the bacteria between animals. The objective of this study was to formulate an optimized protocol for the isolation of MAP from milk and colos...

  15. Characteristics of an Extensive Mycobacterium avium subspecies paratuberculosis Recombinant Protein Set

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the first step of a comprehensive large-scale antigen discovery project, 651 Mycobacterium avium subspecies paratuberculosis proteins were produced in Escherichia coli. All of these were purified by affinity chromatography, dialyzed in phosphate buffered saline, and analyzed on SDS-PAGE gels. C...

  16. Shared Mycobacterium avium genotypes observed among unlinked clinical and environmental isolates

    EPA Science Inventory

    Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this, ...

  17. Environmental contamination with Mycobacterium avium subsp. paratuberculosis in endemically infected dairy herds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental contamination with Mycobacterium avium subsp. paratuberculosis (MAP) is thought to be the primary source of infection for dairy cattle. The exact link between fecal shedding of MAP by individual cows and environmental contamination levels at the herd level was explored with a cross-se...

  18. Mycobacterium avium subspecies paratuberculosis recombinant proteins modulate antimycobacterial functions of bovine macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been shown that Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) activates the Mitogen Activated Protein Kinase (MAPK) p38 pathway, yet it is unclear which components of M. paratuberculosis are involved in the process. Therefore, a set of 42 M. paratuberculosis recombinan...

  19. Novel Single Nucleotide Polymorphism-Based Assay for Genotyping Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Goldstone, Robert J.; McLuckie, Joyce; Smith, David G. E.

    2015-01-01

    Typing of Mycobacterium avium subspecies paratuberculosis strains presents a challenge, since they are genetically monomorphic and traditional molecular techniques have limited discriminatory power. The recent advances and availability of whole-genome sequencing have extended possibilities for the characterization of Mycobacterium avium subspecies paratuberculosis, and whole-genome sequencing can provide a phylogenetic context to facilitate global epidemiology studies. In this study, we developed a single nucleotide polymorphism (SNP) assay based on PCR and restriction enzyme digestion or sequencing of the amplified product. The SNP analysis was performed using genome sequence data from 133 Mycobacterium avium subspecies paratuberculosis isolates with different genotypes from 8 different host species and 17 distinct geographic regions around the world. A total of 28,402 SNPs were identified among all of the isolates. The minimum number of SNPs required to distinguish between all of the 133 genomes was 93 and between only the type C isolates was 41. To reduce the number of SNPs and PCRs required, we adopted an approach based on sequential detection of SNPs and a decision tree. By the analysis of 14 SNPs Mycobacterium avium subspecies paratuberculosis isolates can be characterized within 14 phylogenetic groups with a higher discriminatory power than mycobacterial interspersed repetitive unit–variable number tandem repeat assay and other typing methods. Continuous updating of genome sequences is needed in order to better characterize new phylogenetic groups and SNP profiles. The novel SNP assay is a discriminative, simple, reproducible method and requires only basic laboratory equipment for the large-scale global typing of Mycobacterium avium subspecies paratuberculosis isolates. PMID:26677250

  20. Novel Single Nucleotide Polymorphism-Based Assay for Genotyping Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Leão, Célia; Goldstone, Robert J; Bryant, Josephine; McLuckie, Joyce; Inácio, João; Smith, David G E; Stevenson, Karen

    2016-03-01

    Typing of Mycobacterium avium subspecies paratuberculosis strains presents a challenge, since they are genetically monomorphic and traditional molecular techniques have limited discriminatory power. The recent advances and availability of whole-genome sequencing have extended possibilities for the characterization of Mycobacterium avium subspecies paratuberculosis, and whole-genome sequencing can provide a phylogenetic context to facilitate global epidemiology studies. In this study, we developed a single nucleotide polymorphism (SNP) assay based on PCR and restriction enzyme digestion or sequencing of the amplified product. The SNP analysis was performed using genome sequence data from 133 Mycobacterium avium subspecies paratuberculosis isolates with different genotypes from 8 different host species and 17 distinct geographic regions around the world. A total of 28,402 SNPs were identified among all of the isolates. The minimum number of SNPs required to distinguish between all of the 133 genomes was 93 and between only the type C isolates was 41. To reduce the number of SNPs and PCRs required, we adopted an approach based on sequential detection of SNPs and a decision tree. By the analysis of 14 SNPs Mycobacterium avium subspecies paratuberculosis isolates can be characterized within 14 phylogenetic groups with a higher discriminatory power than mycobacterial interspersed repetitive unit-variable number tandem repeat assay and other typing methods. Continuous updating of genome sequences is needed in order to better characterize new phylogenetic groups and SNP profiles. The novel SNP assay is a discriminative, simple, reproducible method and requires only basic laboratory equipment for the large-scale global typing of Mycobacterium avium subspecies paratuberculosis isolates.

  1. Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

    PubMed Central

    Begg, Douglas J.; Purdie, Auriol C.; Bannantine, John P.; Whittington, Richard J.

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be expressed in vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp. paratuberculosis fusion proteins were evaluated using serum samples from sheep infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced. PMID:24132604

  2. The stroke rehabilitation paradigm.

    PubMed

    Kelly, Brian M; Pangilinan, Percival H; Rodriguez, Gianna M

    2007-11-01

    The matrix of stroke rehabilitation is evolving as we look outside the box of traditional therapy type, timing, and intensity of rehabilitation techniques. For inpatient wards, the goal of medical stability and prompt resolution of complications to maximize participation in therapy remains paramount. In the current medical model, we focus on teaching compensatory strategies and rarely on restorative approaches because of time and financial limitations. Researchers aim to identify new technologic and molecular approaches to improve functional outcomes and more accurately predict disability. This article examines different concepts surrounding the comprehensive rehabilitation paradigm of stroke survivors.

  3. Extracellular ATP is cytotoxic to mononuclear phagocytes but does not induce killing of intracellular Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Woo, Seng-Ryong; Barletta, Raúl G; Czuprynski, Charles J

    2007-09-01

    Mycobacterium avium subsp. paratuberculosis is the etiologic agent of Johne's disease, a chronic granulomatous enteritis in ruminants. ATP has been reported to induce cell death of macrophages and killing of Mycobacterium species in human and murine macrophages. In this study we investigated the short-term effect of ATP on the viability of M. avium subsp. paratuberculosis-infected bovine mononuclear phagocytes and the bacilli within them. Addition of 5 mM ATP to M. avium subsp. paratuberculosis-infected bovine monocytes resulted in 50% cytotoxicity of bovine monocytes at 24 h. Addition of 2'(3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt (Bz-ATP), which is a longer-lived ATP homologue and purinergic receptor agonist, significantly increased the uptake of YO-PRO, which is a marker for membrane pore activation by P2X receptors. Addition of Bz-ATP also stimulated lactate dehydrogenase release and caspase-3 activity in infected bovine monocytes. Neither ATP nor Bz-ATP reduced the survival of M. avium subsp. paratuberculosis in bovine mononuclear phagocytes. Likewise, addition of ATP or Bz-ATP was cytotoxic to murine macrophage cell lines (RAW 264.7 and J774A.1 cells) but did not affect the intracellular survival of M. avium subsp. paratuberculosis, nor were the numbers of viable Mycobacterium avium subsp. avium or Mycobacterium bovis BCG cells altered in bovine mononuclear phagocytes or J774A.1 cells following ATP or Bz-ATP treatment. These data suggest that extracellular ATP does not induce the killing of intracellular M. avium subsp. paratuberculosis in bovine mononuclear phagocytes.

  4. Contrasting results of culture-dependent and molecular analyses of Mycobacterium avium subsp. paratuberculosis from wood bison.

    PubMed

    Forde, Taya; De Buck, Jeroen; Elkin, Brett; Kutz, Susan; van der Meer, Frank; Orsel, Karin

    2013-07-01

    Reduced to near extinction in the late 1800s, a number of wood bison populations (Bison bison athabascae) have been re-established through reintroduction initiatives. Although an invaluable tool for conservation, translocation of animals can spread infectious agents to new areas or expose animals to pathogens in their new environment. Mycobacterium avium subsp. paratuberculosis, a bacterium that causes chronic enteritis in ruminants, is among the pathogens of potential concern for wood bison management and conservation. In order to inform translocation decisions, our objectives were to determine the M. avium subsp. paratuberculosis infection status of wood bison herds in Canada and to culture and genetically characterize the infective strain(s). We tested fecal samples from bison (n = 267) in nine herds using direct PCR for three M. avium subsp. paratuberculosis-specific genetic targets with different copy numbers within the M. avium subsp. paratuberculosis genome. Restriction enzyme analysis (REA) and sequencing of IS1311 were performed on seven samples from five different herds. We also evaluated a panel of different culture conditions for their ability to support M. avium subsp. paratuberculosis growth from feces and tissues of direct-PCR-positive animals. Eighty-one fecal samples (30%) tested positive using direct IS900 PCR, with positive samples from all nine herds; of these, 75% and 21% were also positive using ISMAP02 and F57, respectively. None of the culture conditions supported the growth of M. avium subsp. paratuberculosis from PCR-positive samples. IS1311 REA and sequencing indicate that at least two different M. avium subsp. paratuberculosis strain types exist in Canadian wood bison. The presence of different M. avium subsp. paratuberculosis strains among wood bison herds should be considered in the planning of translocations.

  5. Single nucleotide polymorphisms in the IS900 sequence of Mycobacterium avium subsp. paratuberculosis are strain type specific.

    PubMed

    Castellanos, Elena; Aranaz, Alicia; de Juan, Lucia; Alvarez, Julio; Rodríguez, Sabrina; Romero, Beatriz; Bezos, Javier; Stevenson, Karen; Mateos, Ana; Domínguez, Lucas

    2009-07-01

    Insertion sequence IS900 is used as a target for the identification of Mycobacterium avium subsp. paratuberculosis. Previous reports have revealed single nucleotide polymorphisms within IS900. This study, which analyzed the IS900 sequences of a panel of isolates representing M. avium subsp. paratuberculosis strain types I, II, and III, revealed conserved type-specific polymorphisms that could be utilized as a tool for diagnostic and epidemiological purposes.

  6. Immune-Enhancing Effects of Taishan Pinus massoniana Pollen Polysaccharides on DNA Vaccine Expressing Bordetella avium ompA

    PubMed Central

    Zhu, Fujie; Liu, Xiao; Sun, Zhenhong; Yu, Cuilian; Liu, Liping; Yang, Shifa; Li, Bing; Wei, Kai; Zhu, Ruiliang

    2016-01-01

    Bordetella avium is the causative agent of bordetellosis, which remains to be the cause of severe losses in the turkey industry. Given the lack of vaccines that can provide good protection, developing a novel vaccine against B. avium infection is crucial. In this study, we constructed a eukaryotic expression plasmid, which expressed the outer membrane protein A (ompA) of B. avium, to prepare a B. avium recombinant ompA-DNA vaccine. Three concentrations (low, middle, and high) of Taishan Pinus massoniana pollen polysaccharides (TPPPS), a known immunomodulator, were used as adjuvants, and their immune conditioning effects on the developed DNA vaccine were examined. The pure ompA-DNA vaccine, Freund’s incomplete adjuvant ompA-DNA vaccine, and the empty plasmid served as the controls. The chickens in each group were separately inoculated with these vaccines three times at 1, 7, and 14 days old. Dynamic changes in antibody production, cytokine secretion, and lymphocyte count were then determined from 7 to 49 days after the first inoculation. Protective rates of the vaccines were also determined after the third inoculation. Results showed that the pure DNA vaccine obviously induced the production of antibodies, the secretion of cytokines, and the increase in CD4+ and CD8+ T lymphocyte counts in peripheral blood, as well as provided a protective rate of 50% to the B. avium-challenged chickens. The chickens inoculated with the TPPPS adjuvant ompA-DNA vaccine and Freund’s adjuvant ompA-DNA vaccine demonstrated higher levels of immune responses than those inoculated with pure ompA-DNA vaccine, whereas only the ompA-DNA vaccine with 200 mg/mL TPPPS completely protected the chickens against B. avium infection. These findings indicate that the B. avium ompA-DNA vaccine combined with TPPPS is a potentially effective B. avium vaccine. PMID:26870023

  7. Paradigms for parasite conservation.

    PubMed

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  8. Paradigms for parasite conservation.

    PubMed

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  9. MIRU-VNTR genotype diversity and indications of homoplasy in M. avium strains isolated from humans and slaughter pigs in Latvia.

    PubMed

    Kalvisa, Adrija; Tsirogiannis, Constantinos; Silamikelis, Ivars; Skenders, Girts; Broka, Lonija; Zirnitis, Agris; Jansone, Inta; Ranka, Renate

    2016-09-01

    Diseases which are caused by non-tuberculous mycobacteria (NTM) are an increasing problem in the developed countries. In Latvia, one of the most clinically important members of NTM is Mycobacterium avium (M. avium), an opportunistic pathogen which has been isolated from several lung disease patients and tissue samples of slaughter pigs. This study was designed to characterize the genetic diversity of the M. avium isolates in Latvia and to compare the distribution of genotypic patterns among humans and pigs. Eleven (Hall and Salipante, 2010) clinical M. avium samples, isolated from patients of Center of Tuberculosis and Lung Diseases (years 2003-2010), and 32 isolates from pig necrotic mesenterial lymph nodes in different regions (years 2003-2007) were analyzed. The majority (42 of 43) of samples were identified as M. avium subsp. hominissuis; one porcine isolate belonged to M. avium subsp. avium. MIRU-VNTR genotyping revealed 13 distinct genotypes, among which nine genotype patterns, including M. avium subsp. avium isolate, were newly identified. IS1245 RFLP fingerprinting of 25 M. avium subsp. hominissuis samples yielded 17 different IS1245 RFLP patterns, allowing an efficient discrimination of isolates. Clusters of identical RFLP profiles were observed within host species, geographical locations and time frame of several years. Additional in silico analysis on simulated MIRU-VNTR genotype population datasets showed that the MIRU-VNTR pattern similarity could partly arise due to probabilistic increase of acquiring homoplasy among subpopulations, thus the similar MIRU-VNTR profiles of M. avium strains even in close geographical proximity should be interpreted with caution. PMID:27178993

  10. Effect of soil slope on the appearance of Mycobacterium avium subsp. paratuberculosis in water running off grassland soil after application of contaminated slurry.

    PubMed

    Salgado, M; Alfaro, M; Salazar, F; Troncoso, E; Mitchell, R M; Ramirez, L; Naguil, A; Zamorano, P; Collins, M T

    2013-06-01

    The study assessed the effect of soil slope on Mycobacterium avium subsp. paratuberculosis transport into rainwater runoff from agricultural soil after application of M. avium subsp. paratuberculosis-contaminated slurry. Under field conditions, 24 plots of undisturbed loamy soil 1 by 2 m(2) were placed on platforms. Twelve plots were used for water runoff: 6 plots at a 3% slope and 6 plots at a 15% slope. Half of the plots of each slope were treated with M. avium subsp. paratuberculosis-contaminated slurry, and half were not treated. Using the same experimental design, 12 plots were established for soil sampling on a monthly basis using the same spiked slurry application and soil slopes. Runoff following natural rainfall was collected and analyzed for M. avium subsp. paratuberculosis, coliforms, and turbidity. M. avium subsp. paratuberculosis was detected in runoff from all plots treated with contaminated slurry and one control plot. A higher slope (15%) increased the likelihood of M. avium subsp. paratuberculosis detection but did not affect the likelihood of finding coliforms. Daily rainfall increased the likelihood that runoff would have coliforms and the coliform concentration, but it decreased the M. avium subsp. paratuberculosis concentration in the runoff. When there was no runoff, rain was associated with increased M. avium subsp. paratuberculosis concentrations. Coliform counts in runoff were related to runoff turbidity. M. avium subsp. paratuberculosis presence/absence, however, was related to turbidity. Study duration decreased bacterial detection and concentration. These findings demonstrate the high likelihood that M. avium subsp. paratuberculosis in slurry spread on pastures will contaminate water runoff, particularly during seasons with high rainfall. M. avium subsp. paratuberculosis contamination of water has potential consequences for both animal and human health.

  11. Disseminated Mycobacterium avium subsp. paratuberculosis infection in two wild Eurasian otters (Lutra lutra L.) from Portugal.

    PubMed

    Matos, Ana Cristina; Figueira, Luis; Martins, Maria Helena; Matos, Manuela; Alvares, Sofia; Pinto, Maria Lurdes; Coelho, Ana Cláudia

    2013-03-01

    Disseminated Mycobacterium avium subsp. paratuberculosis (MAP) infections were found in two Eurasian otters (Lutra lutra, L. 1758) killed by vehicular trauma in February and March 2010 in Castelo Branco, Portugal. At postmortem examination, the organs showed no significant gross alterations; however, microscopically, both animals had diffuse lymphadenitis with macrophage infiltration and deposition of hyaline material in the center of the lymphoid follicles. Acid-fast organisms were isolated from gastrointestinal tissue samples via bacteriologic culture. These organisms were identified as M. avium subsp. paratuberculosis by IS900 polymerase chain reaction (PCR). Additionally, direct IS900 PCR-positive results were obtained for multiple organs of both animals. This is the first report of MAP infection of otters in Portugal.

  12. Disseminated mycobacteriosis manifesting as paraplegia in two Parma wallabies (Macropus parma) naturally exposed to Mycobacterium avium.

    PubMed

    Robveille, Cynthia; Albaric, Olivier; Gaide, Nicolas; Abadie, Jérome

    2015-11-01

    Two captive female Parma wallabies (Macropus parma) died after a history of flaccid paraplegia. On postmortem examination, granulomatous and suppurative osteomyelitis involving the left ischium and the lumbosacral region, with meningeal extension at the cauda equina, and caseonecrotic mastitis were the most significant changes. Multiple small nodules in the liver and spleen, and an enlargement of some lymph nodes with central caseous necrosis were also observed. Microscopically, a disseminated granulomatous inflammation with numerous multinucleate giant cells was seen. Numerous acid-fast bacilli were detected in macrophages, in multinucleated giant cells, and free in the central necrosis and suppurative exudate. After culture, polymerase chain reaction assays were carried out to detect the 65-kDa heat shock protein (Hsp65) and insertion sequences (IS)1245 and IS900. The causative agent was identified as Mycobacterium avium subsp. avium. PMID:26450834

  13. Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18

    PubMed Central

    Kim, S H; Cho, D; Kim, T S

    2001-01-01

    Interferon-gamma (IFN-γ) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-γ production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with κ leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-γ throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria. PMID:11260329

  14. Mycobacterium avium-intracellulare pulmonary infection complicated by cutaneous leukocytoclastic vasculitis in a woman with anorexia nervosa.

    PubMed

    Walsh, T L; Baca, V; Stalling, S S; Natalie, A A; Veldkamp, P J

    2014-06-01

    A 53-year-old Caucasian woman with a history of anorexia nervosa developed a bilateral lower extremity rash comprised of palpable red to violaceous, sub-centimeter papular lesions that increased in quantity rapidly. She also noted a 2-month history of non-productive cough. Imaging modalities revealed a thin-walled cavitary lesion in the right lung apex and scattered nodular opacities. Acid fast bacilli (AFB) were found in sputum and subsequently identified by culture as Mycobacterium avium-intracellulare (MAI). Punch biopsies of her skin lesions yielded a histological diagnosis of small-to-medium vessel vasculitis. Stains and cultures for organisms were negative. Her skin lesions resolved quickly after the initiation of antimicrobial therapy for MAI. Hypersensitivity vasculitis associated with an atypical mycobacterial infection is unusual. The postulated underlying mechanism is the deposit of immune complexes and not the bacillus itself. While cutaneous leukocytoclastic vasculitis (CLV) due to MAI is certainly a rare entity, it should be entertained in patients with vasculitic skin lesions and a concomitant pulmonary disease. PMID:24363210

  15. A Paradigm of Environmental Action.

    ERIC Educational Resources Information Center

    Hungerford, Harold R.; Peyton, R. Ben

    A paradigm is proposed that would permit curriculum developers and others to specifically plan for training in environmental action as an integral and substantial component in this field. The three-part paradigm identifies and defines specific categories of action. It then identifies and illustrates the levels at which these actions can be taken.…

  16. Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.

    PubMed

    Nepal, Rajeev M; Mampe, Stephanie; Shaffer, Brian; Erickson, Ann H; Bryant, Paula

    2006-06-01

    Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or Cat S activity. In contrast, the activity of Cat L was altered in infected cells. Specifically, whereas the 24-kDa two-chain mature form of active Cat L predominated in uninfected cells, we observed an increase in the steady-state activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa two-chain form was impaired in infected macrophages, and that maturation into the 24-kDa two-chain form did not occur. Consistent with these data, M. avium infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by macrophages. Viable bacilli were not required to disrupt Cat L maturation, suggesting that a constitutively expressed mycobacterial component was responsible. The absence of the major active form of lysosomal Cat L in M. avium- and M. tuberculosis-infected macrophages may influence the types of T cell epitopes generated in these antigen-presenting cells, and/or the rate of class II MHC peptide loading. PMID:16636015

  17. Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease

    PubMed Central

    2012-01-01

    Background Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations

  18. Human Nature and Research Paradigms: Theory Meets Physical Therapy Practice

    ERIC Educational Resources Information Center

    Plack, Margaret M.

    2005-01-01

    Human nature is a very complex phenomenon. In physical therapy this complexity is enhanced by the need to understand the intersection between the art and science of human behavior and patient care. A paradigm is a set of basic beliefs that represent a worldview, defines the nature of the world and the individual's place in it, and helps to…

  19. A new paradigm for geosciences information management

    SciTech Connect

    Bolivar, Stephen L.; Nasser, K.; Dorries, A. M.; Canepa, Julie Ann

    2002-01-01

    Over the past two decades, geoscientists have been increasingly engaged in providing answers to complex environmental problems with significant societal, political, and economic consequences. Today, these scientists have to perform under increasingly greater visibility to stakeholders and the general public. Their activities are much more scrutinized with regards to economic pressure, litigation support and regulatory compliance than in the past. Their current work is built on decades of past work and in many cases will continue for decades to come. Stakeholders are increasingly evaluating raw data rather than just examining summaries in final reports. They also need assurance that proper data control and data quality procedures were followed. Geoscientists are now faced with a new paradigm, i.e. with the challenge of cost effectively collecting, managing, analyzing, and synthesizing enormous volumes of multidisciplinary and complex information. In addition, these data must be processed and disseminated in a way that allows the public to make informed and rational assessments on decisions that are proposed or have been made. The new paradigm is clear - client and stakeholder needs must be better met, and the systems used to store and generate data must meet these needs. This paper addresses the challenges and the implications of this new paradigm on geosciences information management in the 21st Century. It concludes with a case study for a successful implementation of the new paradigm in an environmental restoration project at the Los Alamos National Laboratory (LANL) that is operated by the Department of Energy (DOE). LANL is upgrading and reengineering its data and business processes to better address client, user and stakeholder issues regarding data accessibility, control and quality.

  20. Radioprotection of Swiss albino mice by Prunus avium with special reference to hematopoietic system.

    PubMed

    Sisodia, Rashmi; Singh, Smita; Mundotiya, Chaturbhuj; Meghnani, Ekta; Srivastava, Preeti

    2011-01-01

    Prunus avium (family Rosaceae) has been used ethnomedicinally for the treatment of many diseases,but its radioprotective efficacy has hardly been explored. Presence of high anthocyanin content and phenolic compound with good antioxidative capacity has been reported by researchers. Its radioprotective effect against 5, 7, 10, and 12 Gygamma radiation was evaluated by 30 day survival assay. Regression analysis yielded LD(50/30) 5.81 and 9.43Gy for irradiated only and (P. avium fruit extract) PAE + radiation groups, respectively. The dose reduction factor was computed as 1.62. For biochemical and hematological studies, Swiss albino mice were divided into four groups: (i) control (vehicle treated), (ii) PAE treated (450 mg kg/day for 15 consequetive days), (iii) irradiated (5 Gy), and (4) PAE + irradiated. The irradiation of animals resulted in a significant elevation of lipid peroxidation and depletion in glutathione and protein levels in blood serum and spleen, which could be significantly checked by administration of PAE. Radiation-induced deficit in blood sugar, cholesterol, and hematological constituents could also be modulated by supplementation of PAE before and after irradiation. The possible prophylactic and therapeutic action noted by P. avium against radiation induced metabolic disorders may be due to synergistic action of various antioxidants, minerals, vitamins, etc., present in the fruit. Further mechanistic studies aimed at identifying the role of major ingredients in the extract are needed. PMID:21609316

  1. Genetic relationships between diploid and allotetraploid cherry species (Prunus avium, Prunus x gondouinii and Prunus cerasus).

    PubMed

    Tavaud, M; Zanetto, A; David, J L; Laigret, F; Dirlewanger, E

    2004-12-01

    Prunus avium L. (diploid, AA, 2n=2x=16), Prunus cerasus L. (allotetraploid, AAFF, 2n=4x=32) species, and their hybrid Prunus x gondouinii Rehd., constitute the most widely cultivated cherry tree species. P. cerasus is supposed to be an hybrid species produced by the union of unreduced P. avium gametes and normal P. fruticosa gametes. A continuum of morphological traits between these three species makes their assignation difficult. The aim of this paper is to study the genetic relationships between tetraploid and diploid cherry species. In all, 114 genotypes belonging to these species were analyzed using 75 AFLP markers. The coordinates of these genotypes on the first axis of a correspondence analysis allowed us to clearly distinguish each species, to identify misclassifications and to assign unknown genotypes to one species. We showed that there are specific alleles in P. cerasus, which are not present in the A genome of P. avium and which probably come from the F genome of P. cerasus. The frequencies of each marker in the A and the F genomes were estimated in order to identify A and F specific markers. We discuss the utility of these specific markers for finding the origin of the A and F genomes in the allopolyploid species. PMID:15354194

  2. Prunus avium: nuclear DNA study in wild populations and sweet cherry cultivars.

    PubMed

    Guarino, Carmine; Santoro, Simona; De Simone, Luciana; Cipriani, Guido

    2009-04-01

    The PCR-SSR technique was used to detect nuclear DNA diversity in five wild populations of Prunus avium from deciduous forests in Italy, Slovenia, and Croatia and 87 sweet cherry accessions from different geographical areas that have been maintained in the sweet cherry collection in Italy. This sweet cherry collection includes local accessions from the Campania Region as well as accessions from different countries. Twenty-eight microsatellites, previously developed in this species, generated polymorphic amplification products. Between 2 and 14 alleles were revealed for the polymorphic loci studied, with the expected heterozygosity ranging from 0.045 to 0.831. The total probability of identity was 56.94 x 10-18. A model-based Bayesian clustering analysis identified nine distinct gene pools in cultivated P. avium. The probability that wild populations were assigned to cultivated gene pools indicated that three gene pools accounted for the genomic origin of 53% of P. avium sampled. A dendrogram was generated using UPGMA (unweighted pair group method with arithmetic averages) based on Nei genetic distance analysis. This dendrogram classified most of the genotypes into one major group with an additional group of five accessions. The results indicate that this set of SSRs is highly informative, and they are discussed in terms of the implications for sweet cherry characterization.

  3. Mycobacterium avium subsp. paratuberculosis Antibody Response, Fecal Shedding, and Antibody Cross-Reactivity to Mycobacterium bovis in M. avium subsp. paratuberculosis-Infected Cattle Herds Vaccinated against Johne's Disease

    PubMed Central

    Hovingh, Ernest; Linscott, Rick; Martel, Edmond; Lawrence, John; Wolfgang, David; Griswold, David

    2014-01-01

    Vaccination for Johne's disease with killed inactivated vaccine in cattle herds has shown variable success. The vaccine delays the onset of disease but does not afford complete protection. Johne's disease vaccination has also been reported to interfere with measurements of cell-mediated immune responses for the detection of bovine tuberculosis. Temporal antibody responses and fecal shedding of Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease, were measured in 2 dairy cattle herds using Johne's disease vaccine (Mycopar) over a period of 7 years. Vaccination against Johne's disease resulted in positive serum M. avium subsp. paratuberculosis antibody responses in both herds, and the responses persisted in vaccinated cattle up to 7 years of age. Some vaccinated animals (29.4% in herd A and 36.2% in herd B) showed no serological reactivity to M. avium subsp. paratuberculosis. M. avium subsp. paratuberculosis-specific antibody responses were also detected in milk from Johne's disease-vaccinated animals, but fewer animals (39.3% in herd A and 49.4% in herd B) had positive results with milk than with serum samples. With vaccination against M. avium subsp. paratuberculosis, fecal shedding in both dairy herds was reduced significantly (P < 0.001). In addition, when selected Johne's disease-vaccinated and -infected animals were investigated for serological cross-reactivity to Mycobacterium bovis, no cross-reactivity was observed. PMID:24623626

  4. Complete Genome Sequence of Mycobacterium avium, Isolated from Commercial Domestic Pekin Ducks (Anas platyrhynchos domestica), Determined Using PacBio Single-Molecule Real-Time Technology.

    PubMed

    Song, Xiao-Heng; Chen, Hong-Xi; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue; Zhu, De-Kang

    2016-01-01

    Mycobacterium avium is an important pathogenic bacterium in birds and has never, to our knowledge, reported to be isolated from domestic ducks. We present here the complete genome sequence of a virulent strain of Mycobacterium avium, isolated from domestic Pekin ducks for the first time, which was determined by PacBio single-molecule real-time technology. PMID:27587804

  5. Highly Specific and Quick Detection of Mycobacterium avium subsp. paratuberculosis in Feces and Gut Tissue of Cattle and Humans by Multiple Real-Time PCR Assays▿

    PubMed Central

    Imirzalioglu, Can; Dahmen, Heinrich; Hain, Torsten; Billion, Andre; Kuenne, Carsten; Chakraborty, Trinad; Domann, Eugen

    2011-01-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle and may be associated with Crohn's disease (CD) in humans. It is the slowest growing of the cultivable mycobacteria, and culture from clinical, veterinary, food, or environmental specimens can take 4 months or even longer. Currently, the insertion element IS900 is used to detect M. avium subsp. paratuberculosis DNA. However, closely related IS900 elements are also present in other mycobacteria, thus limiting its specificity as a target. Here we describe the use of novel primer sets derived from the sequences of two highly specific single copy genes, MAP2765c and MAP0865, for the quantitative detection of M. avium subsp. paratuberculosis within 6 h by using real-time PCR. Specificity of the target was established using 40 M. avium subsp. paratuberculosis isolates, 67 different bacterial species, and two intestinal parasites. Using the probes and methods described, we detected 27 (2.09%) M. avium subsp. paratuberculosis-positive stool specimens from 1,293 individual stool samples by the use of either IS900 or probes deriving from the MAP2765c and MAP0865 genes described here. In general, bacterial load due to M. avium subsp. paratuberculosis was uniformly low in these samples and we estimated 500 to 5,000 M. avium subsp. paratuberculosis bacteria per gram of stool in assay-positive samples. Thus, the methods described here are useful for rapid and specific detection of M. avium subsp. paratuberculosis in clinical samples. PMID:21430100

  6. Complete Genome Sequence of Mycobacterium avium, Isolated from Commercial Domestic Pekin Ducks (Anas platyrhynchos domestica), Determined Using PacBio Single-Molecule Real-Time Technology

    PubMed Central

    Song, Xiao-Heng; Chen, Hong-Xi; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue

    2016-01-01

    Mycobacterium avium is an important pathogenic bacterium in birds and has never, to our knowledge, reported to be isolated from domestic ducks. We present here the complete genome sequence of a virulent strain of Mycobacterium avium, isolated from domestic Pekin ducks for the first time, which was determined by PacBio single-molecule real-time technology. PMID:27587804

  7. Boosting Effect of 2-Phenylquinoline Efflux Inhibitors in Combination with Macrolides against Mycobacterium smegmatis and Mycobacterium avium.

    PubMed

    Machado, Diana; Cannalire, Rolando; Santos Costa, Sofia; Manfroni, Giuseppe; Tabarrini, Oriana; Cecchetti, Violetta; Couto, Isabel; Viveiros, Miguel; Sabatini, Stefano

    2015-12-11

    The identification of efflux inhibitors to be used as adjuvants alongside existing drug regimens could have a tremendous value in the treatment of any mycobacterial infection. Here, we investigated the ability of four 2-(4'-propoxyphenyl)quinoline Staphylococcus aureus NorA efflux inhibitors (1-4) to reduce the efflux activity in Mycobacterium smegmatis and Mycobacterium avium strains. All four compounds were able to inhibit efflux pumps in both mycobacterial species; in particular, O-ethylpiperazinyl derivative 2 showed an efflux inhibitory activity comparable to that of verapamil, the most potent mycobacterial efflux inhibitor reported to date, and was able to significantly reduce the MIC values of macrolides against different M. avium strains. The contribution of the M. avium efflux pumps MAV_1406 and MAV_1695 to clarithromycin resistance was proved because they were found to be overexpressed in two M. avium 104 isogenic strains showing high-level clarithromycin resistance. These results indicated a correlation between increased expression of efflux pumps, increased efflux, macrolide resistance, and reduction of resistance by efflux pump inhibitors such as compound 2. Additionally, compound 2 showed synergistic activity with clarithromycin, at a concentration below the cytotoxicity threshold, in an ex vivo experiment against M. avium 104-infected macrophages. In summary, the 2-(4'-propoxyphenyl)quinoline scaffold is suitable to obtain compounds endowed with good efflux pump inhibitory activity against both S. aureus and nontuberculous mycobacteria. PMID:27623057

  8. Life behind cell walls: paradigm lost, paradigm regained.

    PubMed

    Lamport, D T

    2001-09-01

    This review of the living cell wall and its protein components is in two parts. The first is anecdotal. A personal account spanning over 40 years research may perhaps be an antidote to one stereotypical view of scientists as detached and humorless. The second part deals with the meaning of function, particularly as it applies to hydroxyproline-rich glycoproteins. Function is a difficult word to define objectively. However, with help from such luminaries as Humpty Dumpty: "A word means what I want it to mean, neither more nor less," and Wittgenstein: "Giving examples of usage ... is the only way to talk about meaning," it is possible to construct a ziggurat representing increasingly complex levels of organization from molecular structure to ecology. Forty years ago I suggested that hydroxyproline-rich structural proteins played a key role in cell wall functioning. But because the bulk of the wall is carbohydrate, there has been an understandable resistance to paradigm change. Expansins, paradoxically, contribute greatly to this resistance because their modus operandi as cell-wall-loosening proteins is based on the idea that they break hydrogen bonds between polysaccharide chains allowing slippage. However, this view is not consistent with the recent discovery [Grobe et al. (1999) Eur. J. Biochem 263: 33-40] that beta-expansins may be proteases, as it implies that the extensin network is not a straightjacket but a substrate for expansin in muro. Such a direct role for extensins in both negative and positive regulation of cell expansion and elongation may constitute a major morphogenetic mechanism operating at all levels of plant growth and development.

  9. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    PubMed Central

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  10. Biological robustness: paradigms, mechanisms, and systems principles.

    PubMed

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  11. Effects of gamma interferon, interleukin-10, and transforming growth factor beta on the survival of Mycobacterium avium subsp. paratuberculosis in monocyte-derived macrophages from naturally infected cattle.

    PubMed

    Khalifeh, M S; Stabel, J R

    2004-04-01

    Gamma interferon (IFN-gamma) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-gamma, IL-10, and TGF-beta by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-gamma, IL-10, and TGF-beta on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-beta in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-beta, but after stimulation with live M. avium subsp. paratuberculosis, TGF-beta levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-beta to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-beta during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

  12. Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

    PubMed Central

    Khare, Sangeeta; Lawhon, Sara D.; Drake, Kenneth L.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris A.; Galindo, Cristi L.; Garner, Harold R.; Adams, Leslie Garry

    2012-01-01

    Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways

  13. Mycobacterium avium-induced SOCS contributes to resistance to IFN-gamma-mediated mycobactericidal activity in human macrophages.

    PubMed

    Vázquez, Nancy; Greenwell-Wild, Teresa; Rekka, Sofia; Orenstein, Jan M; Wahl, Sharon M

    2006-11-01

    Mycobacterium avium is an opportunistic pathogen that commonly infects individuals colonized with HIV-1, although it is less frequent in the post-HAART era. These microorganisms invade macrophages after interacting with TLR2 and/or CD14 co-receptors, but signaling pathways promoting survival in macrophages are not well defined. Although IFN-gamma plays an important role in protective immunity against bacterial infections, IFN-gamma responses are compromised in AIDS patients and evidence suggests that exogenous IFN-gamma is inadequate to clear the mycobacteria. To determine the mechanism by which M. avium survives intracellularly, even in the presence of IFN-gamma, we studied the effect of mycobacteria infection in macrophages during early IFN-gamma signaling events. M. avium infected cells exhibited a reduced response to IFN-gamma, with suppressed phosphorylation of STAT-1 compared with uninfected cells. Interaction of M. avium with macrophage receptors increased gene expression of the suppressors of cytokine signaling (SOCS) to diminish IFN responsiveness. Specifically, we observed an increase in mRNA for both SOCS-3 and SOCS-1, which correlates with elevated levels of SOCS protein and positive immunostaining in M. avium/HIV-1 co-infected tissues. We also linked the p38 MAPK signaling pathway to mycobacterial-induced SOCS gene transcription. The induction of SOCS may be part of the strategy that allows the invader to render the macrophages unresponsive to IFN-gamma, which otherwise promotes clearance of the infection. Our data provide new insights into the manipulation of the host response by this opportunistic pathogen and the potential for modulating SOCS to influence the outcome of M. avium infection in immunocompromised hosts.

  14. Replication and long-term persistence of bovine and human strains of Mycobacterium avium subsp. paratuberculosis within Acanthamoeba polyphaga.

    PubMed

    Mura, Manuela; Bull, Tim J; Evans, Hugh; Sidi-Boumedine, Karim; McMinn, Liz; Rhodes, Glenn; Pickup, Roger; Hermon-Taylor, John

    2006-01-01

    Free-living protists are ubiquitous in the environment and form a potential reservoir for the persistence of animal and human pathogens. Mycobacterium avium subsp. paratuberculosis is the cause of Johne's disease, a systemic infection accompanied by chronic inflammation of the intestine that affects many animals, including primates. Most humans with Crohn's disease are infected with this chronic enteric pathogen. Subclinical infection with M. avium subsp. paratuberculosis is widespread in domestic livestock. Infected animals excrete large numbers of robust organisms into the environment, but little is known about their ability to replicate and persist in protists. In the present study we fed laboratory cultures of Acanthamoeba polyphaga with bovine and human strains of M. avium subsp. paratuberculosis. Real-time PCR showed that the numbers of the pathogens fell over the first 4 to 8 days and recovered by 12 to 16 days. Encystment of the amoebic cultures after 4 weeks resulted in a 2-log reduction in the level of M. avium subsp. paratuberculosis, which returned to the original level by 24 weeks. Extracts of resection samples of human gut from 39 patients undergoing abdominal surgery were fed to cultures of A. polyphaga. M. avium subsp. paratuberculosis detected by nested IS900 PCR with amplicon sequencing and visualized by IS900 in situ hybridization and auramine-rhodamine staining was found in cultures derived from 13 of the patients and was still present in the cultures after almost 4 years of incubation. Control cultures were negative. M. avium subsp. paratuberculosis has the potential for long-term persistence in environmental protists.

  15. High-Throughput Direct Fecal PCR Assay for Detection of Mycobacterium avium subsp. paratuberculosis in Sheep and Cattle

    PubMed Central

    Waldron, Anna M.; Galea, Francesca; Whittington, Ann-Michele; Saunders, Vanessa F.; Begg, Douglas J.; de Silva, Kumudika; Purdie, Auriol C.; Whittington, Richard J.

    2014-01-01

    Johne's disease (JD) is a chronic enteric disease caused by Mycobacterium avium subsp. paratuberculosis that affects ruminants. Transmission occurs by the fecal-oral route. A commonly used antemortem diagnostic test for the detection of M. avium subsp. paratuberculosis in feces is liquid culture; however, a major constraint is the 2- to 3-month incubation period needed for this method. Rapid methods for the detection of M. avium subsp. paratuberculosis based on PCR have been reported, but comprehensive validation data are lacking. We describe here a new test, the high-throughput-Johnes (HT-J), to detect M. avium subsp. paratuberculosis in feces. Its diagnostic accuracy was compared with that of liquid radiometric (Bactec) fecal culture using samples from cattle (1,330 samples from 23 herds) and sheep (596 samples from 16 flocks). The multistage protocol involves the recovery of M. avium subsp. paratuberculosis cells from a fecal suspension, cell rupture by bead beating, extraction of DNA using magnetic beads, and IS900 quantitative PCR. The limit of detection of the assay was 0.0005 pg, and the limit of quantification was 0.005 pg M. avium subsp. paratuberculosis genomic DNA. Only M. avium subsp. paratuberculosis was detected from a panel of 51 mycobacterial isolates, including 10 with IS900-like sequences. Of the 549 culture-negative fecal samples from unexposed herds and flocks, 99% were negative in the HT-J test, while 60% of the bovine- and 84% of the ovine-culture-positive samples were positive in the HT-J test. As similar total numbers of samples from M. avium subsp. paratuberculosis-exposed animals were positive in culture and HT-J tests in both species, and as the results of a McNemar's test were not significant, these methods probably have similar sensitivities, but the true diagnostic sensitivities of these tests are unknown. These validation data meet the consensus-based reporting standards for diagnostic test accuracy studies for paratuberculosis and

  16. Health Inequities: Evaluation of Two Paradigms

    ERIC Educational Resources Information Center

    Ashcroft, Rachelle

    2010-01-01

    Social work practice in health is shaped by underlying paradigms. To effectively target health inequities, practitioners need to consider appropriate paradigms. In this exploration of how six health paradigms shape theory and practice, the two health paradigms that most attended to health inequalities are social determinants of health and…

  17. PRESENCE OF MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS IN ALPACAS (LAMA PACOS) INHABITING THE CHILEAN ALTIPLANO.

    PubMed

    Salgado, Miguel; Sevilla, Iker; Rios, Carolina; Crossley, Jorge; Tejeda, Carlos; Manning, Elizabeth

    2016-03-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis. The organism causes disease in both domestically managed and wild ruminant species. South American camelids have a long, shared history with indigenous people in the Andes. Over the last few decades, increasing numbers of alpacas were exported to numerous countries outside South America. No paratuberculosis surveillance has been reported for these source herds. In this study, individual fecal samples from 85 adult alpacas were collected from six separate herds in the Chilean Altiplano. A ParaTB mycobacterial growth indicator tube (MGIT) liquid culture of each individual fecal sample, followed by real-time polymerase chain reaction (PCR) protocol was used for confirmation. DNA extracts from a subset of confirmed MAP isolates were subjected to mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing. Fifteen alpaca were fecal culture test-positive. Five false-positive culture samples were negative on PCR analysis for Mycobacterium avium subsp. avium (MAA), Mycobacterium bovis (M. bovis), and the 16 S rDNA gene. Three MAP isolates subset-tested belonged to the same MIRU-VNTR type, showing four repeats for TR292 (locus 1) in contrast to the three repeats typical of the MAP reference strain K10. The number of repeats found in the remaining loci was identical to that of the K10 strain. It is not known how nor when MAP was introduced into the alpaca population in the Chilean Altiplano. The most plausible hypothesis to explain the presence of MAP in these indigenous populations is transmission by contact with infected domestic small ruminant species that may on occasion share pastures or range with alpacas. Isolation of this mycobacterial pathogen from such a remote region suggests that MAP has found its way beyond the confines of intensively managed domestic agriculture premises.

  18. The two paradigms of persistence.

    PubMed

    Pittenger, David J

    2002-08-01

    Persistence refers to the extent to which an individual pursues reinforcement that is no longer available. The most common generalization regarding persistence is the partial reinforcement extinction effect, which states that partial, rather than continuous, reinforcement creates the greatest level of persistence. Although the partial reinforcement effect is the most common effect in humans, exceptions exist, namely the generalized and the reversed partial reinforcement effect. Since the 1930s, psychologists have used 2 general paradigms for studying persistence in humans: the experimental paradigm and the cognitive/individual differences paradigm. For the experimental paradigm, the primary independent variable is the schedule of reinforcement used to establish the behavior prior to the removal of reinforcement. Explanations of persistence from the experimental perspective depend on associative principles derived from various theories of learning. By contrast, the cognitive/individual differences paradigm treats persistence as a function of trait variables, including locus of control and self-esteem, or general cognitive processes, such as cognitive dissonance or social cognition. In this article, the author reviews the status of the current literature on persistence and recommends directions for future research.

  19. Fluorescent acid-fast microscopy for measuring phagocytosis of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum by Tetrahymena pyriformis and their intracellular growth.

    PubMed

    Strahl, E D; Gillaspy, G E; Falkinham, J O

    2001-10-01

    Fluorescent acid-fast microscopy (FAM) was used to enumerate intracellular Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum in the ciliated phagocytic protozoan Tetrahymena pyriformis. There was a linear relationship between FAM and colony counts of M. avium cells both from cultures and within protozoa. The Ziehl-Neelsen acid-fast stain could not be used to enumerate intracellular mycobacteria because uninfected protozoa contained acid-fast, bacterium-like particles. Starved, 7-day-old cultures of T. pyriformis transferred into fresh medium readily phagocytized M. avium, M. intracellulare, and M. scrofulaceum. Phagocytosis was rapid and reached a maximum in 30 min. M. avium, M. intracellulare, and M. scrofulaceum grew within T. pyriformis, increasing by factors of 4- to 40-fold after 5 days at 30 degrees C. Intracellular M. avium numbers remained constant over a 25-day period of growth (by transfer) of T. pyriformis. Intracellular M. avium cells also survived protozoan encystment and germination. The growth and viability of T. pyriformis were not affected by mycobacterial infection. The results suggest that free-living phagocytic protozoa may be natural hosts and reservoirs for M. avium, M. intracellulare, and M. scrofulaceum.

  20. Molecular identification of Mycobacterium avium subspecies paratuberculosis in oral biopsies of Crohn's disease patients.

    PubMed

    Molicotti, Paola; Scanu, Antonio M; Lumbau, Aurea; Cannas, Sara; Bua, Alessandra; Lugliè, Pietrina; Zanetti, Stefania

    2013-07-10

    Oral lesions may be found in patients with Crohn's disease (CD), in a percentage up to 20%. The aim of this study was to investigate a possible relationship between Mycobacterium avium subsp. paratuberculosis (MAP) and oral lesions in CD patients. 23 oral biopsies were examined performing IS900 Nested PCR; 9 of them were positive: 8 from CD patients and 1 from a control. Our purpose is to go on with this study, amplifying the number of subjects examined and testing subjects with oral lesions related to diseases other than CD to verify the specific association between MAP and oral lesions in CD patients.

  1. Facts, myths and hypotheses on the zoonotic nature of Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Atreya, Raja; Bülte, Michael; Gerlach, Gerald-F; Goethe, Ralph; Hornef, Mathias W; Köhler, Heike; Meens, Jochen; Möbius, Petra; Roeb, Elke; Weiss, Siegfried

    2014-10-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of paratuberculosis (Johne's disease [JD]), a chronic granulomatous enteritis in ruminants. JD is one of the most widespread bacterial diseases of domestic animals with significant economic impact. The histopathological picture of JD resembles that of Crohn's disease (CD), a human chronic inflammatory bowel disease of still unresolved aetiology. An aetiological relevance of MAP for CD has been proposed. This and the ambiguity of other published epidemiological findings raise the question whether MAP represents a zoonotic agent. In this review, we will discuss evidence that MAP has zoonotic capacity.

  2. Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult.

    PubMed

    Kwon, Yong Soo; Han, Joungho; Jung, Ki Hwan; Kim, Je Hyeong; Koh, Won-Jung

    2013-01-01

    We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin. PMID:23346002

  3. Cutaneous gallium uptake in patients with AIDS with mycobacterium avium-intracellulare septicemia

    SciTech Connect

    Allwright, S.J.; Chapman, P.R.; Antico, V.F.; Gruenewald, S.M.

    1988-07-01

    Gallium imaging is increasingly being used for the early detection of complications in patients with AIDS. A 26-year-old homosexual man who was HIV antibody positive underwent gallium imaging for investigation of possible Pneumocystis carinii pneumonia. Widespread cutaneous focal uptake was seen, which was subsequently shown to be due to mycobacterium avium-intracellulare (MAI) septicemia. This case demonstrates the importance of whole body imaging rather than imaging target areas only, the utility of gallium imaging in aiding the early detection of clinically unsuspected disease, and shows a new pattern of gallium uptake in disseminated MAI infection.

  4. Identification and comparative analysis of a genomic island in Mycobacterium avium subsp. hominissuis.

    PubMed

    Lahiri, Annesha; Sanchini, Andrea; Semmler, Torsten; Schäfer, Hubert; Lewin, Astrid

    2014-11-01

    Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacterium causing opportunistic infections. The objective of this study was to identify flexible genome regions in MAH isolated from different sources. By comparing five complete and draft MAH genomes we identified a genomic island conferring additional flexibility to the MAH genomes. The island was absent in one of the five strains and had sizes between 16.37 and 84.85kb in the four other strains. The genes present in the islands differed among strains and included phage- and plasmid-derived genes, integrase genes, hypothetical genes, and virulence-associated genes like mmpL or mce genes.

  5. Detection of Legionella, L. pneumophila and Mycobacterium Avium Complex (MAC) along Potable Water Distribution Pipelines

    PubMed Central

    Whiley, Harriet; Keegan, Alexandra; Fallowfield, Howard; Bentham, Richard

    2014-01-01

    Inhalation of potable water presents a potential route of exposure to opportunistic pathogens and hence warrants significant public health concern. This study used qPCR to detect opportunistic pathogens Legionella spp., L. pneumophila and MAC at multiple points along two potable water distribution pipelines. One used chlorine disinfection and the other chloramine disinfection. Samples were collected four times over the year to provide seasonal variation and the chlorine or chloramine residual was measured during collection. Legionella spp., L. pneumophila and MAC were detected in both distribution systems throughout the year and were all detected at a maximum concentration of 103 copies/mL in the chlorine disinfected system and 106, 103 and 104 copies/mL respectively in the chloramine disinfected system. The concentrations of these opportunistic pathogens were primarily controlled throughout the distribution network through the maintenance of disinfection residuals. At a dead-end and when the disinfection residual was not maintained significant (p < 0.05) increases in concentration were observed when compared to the concentration measured closest to the processing plant in the same pipeline and sampling period. Total coliforms were not present in any water sample collected. This study demonstrates the ability of Legionella spp., L. pneumophila and MAC to survive the potable water disinfection process and highlights the need for greater measures to control these organisms along the distribution pipeline and at point of use. PMID:25046636

  6. Detection of Legionella, L. pneumophila and Mycobacterium avium complex (MAC) along potable water distribution pipelines.

    PubMed

    Whiley, Harriet; Keegan, Alexandra; Fallowfield, Howard; Bentham, Richard

    2014-07-18

    Inhalation of potable water presents a potential route of exposure to opportunistic pathogens and hence warrants significant public health concern. This study used qPCR to detect opportunistic pathogens Legionella spp., L. pneumophila and MAC at multiple points along two potable water distribution pipelines. One used chlorine disinfection and the other chloramine disinfection. Samples were collected four times over the year to provide seasonal variation and the chlorine or chloramine residual was measured during collection. Legionella spp., L. pneumophila and MAC were detected in both distribution systems throughout the year and were all detected at a maximum concentration of 103 copies/mL in the chlorine disinfected system and 106, 103 and 104 copies/mL respectively in the chloramine disinfected system. The concentrations of these opportunistic pathogens were primarily controlled throughout the distribution network through the maintenance of disinfection residuals. At a dead-end and when the disinfection residual was not maintained significant (p < 0.05) increases in concentration were observed when compared to the concentration measured closest to the processing plant in the same pipeline and sampling period. Total coliforms were not present in any water sample collected. This study demonstrates the ability of Legionella spp., L. pneumophila and MAC to survive the potable water disinfection process and highlights the need for greater measures to control these organisms along the distribution pipeline and at point of use.

  7. Chemical decontamination with N-acetyl-L-cysteine-sodium hydroxide improves recovery of viable Mycobacterium avium subsp. paratuberculosis organisms from cultured milk.

    PubMed

    Bradner, L; Robbe-Austerman, S; Beitz, D C; Stabel, J R

    2013-07-01

    Mycobacterium avium subsp. paratuberculosis is shed into the milk and feces of cows with advanced Johne's disease, allowing the transmission of M. avium subsp. paratuberculosis between animals. The objective of this study was to formulate an optimized protocol for the isolation of M. avium subsp. paratuberculosis in milk. The parameters investigated included chemical decontamination with N-acetyl-l-cysteine-sodium hydroxide (NALC-NaOH), alone and in combination with antibiotics (vancomycin, amphotericin B, and nalidixic acid), and the efficacy of solid (Herrold's egg yolk medium [HEY]) and liquid (Bactec 12B and para-JEM) culture media. For each experiment, raw milk samples from a known noninfected cow were inoculated with 10(2) to 10(8) CFU/ml of live M. avium subsp. paratuberculosis organisms. The results indicate that an increased length of exposure to NALC-NaOH from 5 to 30 min and an increased concentration of NaOH from 0.5 to 2.0% did not affect the viability of M. avium subsp. paratuberculosis. Additional treatment of milk samples with the antibiotics following NALC-NaOH treatment decreased the recovery of viable M. avium subsp. paratuberculosis cells more than treatment with NALC-NaOH alone. The Bactec 12B medium was the superior medium of the three evaluated for the isolation of M. avium subsp. paratuberculosis from milk, as it achieved the lowest threshold of detection. The optimal conditions for NALC-NaOH decontamination were determined to be exposure to 1.50% NaOH for 15 min followed by culture in Bactec 12B medium. This study demonstrates that chemical decontamination with NALC-NaOH resulted in a greater recovery of viable M. avium subsp. paratuberculosis cells from milk than from samples treated with hexadecylpyridinium chloride (HPC). Therefore, it is important to optimize milk decontamination protocols to ensure that low concentrations of M. avium subsp. paratuberculosis can be detected.

  8. Chemical Decontamination with N-Acetyl-l-Cysteine–Sodium Hydroxide Improves Recovery of Viable Mycobacterium avium subsp. paratuberculosis Organisms from Cultured Milk

    PubMed Central

    Bradner, L.; Robbe-Austerman, S.; Beitz, D. C.

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis is shed into the milk and feces of cows with advanced Johne's disease, allowing the transmission of M. avium subsp. paratuberculosis between animals. The objective of this study was to formulate an optimized protocol for the isolation of M. avium subsp. paratuberculosis in milk. The parameters investigated included chemical decontamination with N-acetyl-l-cysteine–sodium hydroxide (NALC-NaOH), alone and in combination with antibiotics (vancomycin, amphotericin B, and nalidixic acid), and the efficacy of solid (Herrold's egg yolk medium [HEY]) and liquid (Bactec 12B and para-JEM) culture media. For each experiment, raw milk samples from a known noninfected cow were inoculated with 102 to 108 CFU/ml of live M. avium subsp. paratuberculosis organisms. The results indicate that an increased length of exposure to NALC-NaOH from 5 to 30 min and an increased concentration of NaOH from 0.5 to 2.0% did not affect the viability of M. avium subsp. paratuberculosis. Additional treatment of milk samples with the antibiotics following NALC-NaOH treatment decreased the recovery of viable M. avium subsp. paratuberculosis cells more than treatment with NALC-NaOH alone. The Bactec 12B medium was the superior medium of the three evaluated for the isolation of M. avium subsp. paratuberculosis from milk, as it achieved the lowest threshold of detection. The optimal conditions for NALC-NaOH decontamination were determined to be exposure to 1.50% NaOH for 15 min followed by culture in Bactec 12B medium. This study demonstrates that chemical decontamination with NALC-NaOH resulted in a greater recovery of viable M. avium subsp. paratuberculosis cells from milk than from samples treated with hexadecylpyridinium chloride (HPC). Therefore, it is important to optimize milk decontamination protocols to ensure that low concentrations of M. avium subsp. paratuberculosis can be detected. PMID:23637290

  9. The Synthesis Paradigm in Genetics

    PubMed Central

    Rice, William R.

    2014-01-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics—and other fields of biology—are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous “-omics” data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time. PMID:24496401

  10. The synthesis paradigm in genetics.

    PubMed

    Rice, William R

    2014-02-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

  11. Emergence of life: Physical chemistry changes the paradigm.

    PubMed

    Spitzer, Jan; Pielak, Gary J; Poolman, Bert

    2015-06-10

    Origin of life research has been slow to advance not only because of its complex evolutionary nature (Franklin Harold: In Search of Cell History, 2014) but also because of the lack of agreement on fundamental concepts, including the question of 'what is life?'. To re-energize the research and define a new experimental paradigm, we advance four premises to better understand the physicochemical complexities of life's emergence: (1) Chemical and Darwinian (biological) evolutions are distinct, but become continuous with the appearance of heredity. (2) Earth's chemical evolution is driven by energies of cycling (diurnal) disequilibria and by energies of hydrothermal vents. (3) Earth's overall chemical complexity must be high at the origin of life for a subset of (complex) chemicals to phase separate and evolve into living states. (4) Macromolecular crowding in aqueous electrolytes under confined conditions enables evolution of molecular recognition and cellular self-organization. We discuss these premises in relation to current 'constructive' (non-evolutionary) paradigm of origins research - the process of complexification of chemical matter 'from the simple to the complex'. This paradigm artificially avoids planetary chemical complexity and the natural tendency of molecular compositions toward maximum disorder embodied in the second law of thermodynamics. Our four premises suggest an empirical program of experiments involving complex chemical compositions under cycling gradients of temperature, water activity and electromagnetic radiation.

  12. Integrating Essential Components of Quality Improvement into a New Paradigm for Continuing Education

    ERIC Educational Resources Information Center

    Van Hoof, Thomas J.; Meehan, Thomas P.

    2011-01-01

    Continuing education (CE) that strives to improve patient care in a complex health care system requires a different paradigm than CE that seeks to improve clinician knowledge and competence in an educational setting. A new paradigm for CE is necessary in order to change clinician behavior and to improve patient outcomes in an increasingly…

  13. Multi-World Paradigm in Mathematical Learning (1): An Analysis of Mathematics Classes.

    ERIC Educational Resources Information Center

    Nakahara, Tadao; Sasaki, Tetsuro; Koyama, Masataka; Yamaguchi, Takeshi

    2000-01-01

    Illustrates two analyses of mathematical learning based on the multi-word paradigm and considers it theoretically. The multi-world paradigm suggests the very important forward direction for research in teaching and learning mathematics because educational phenomena are often complex and can not be reduced to a single theory. (Contains 28…

  14. The Development of the Foundations of Modern Pedagogy: Paradigmal and Methodological Aspects of Research

    ERIC Educational Resources Information Center

    Dmitrenko, ?amara ?.; Lavryk, Tatjana V.; Yaresko, Ekaterina V.

    2015-01-01

    Changes in the various fields of knowledge influenced the pedagogical science. The article explains the structure of the foundations of modern pedagogy through paradigmal and methodological aspects. Bases of modern pedagogy include complex of paradigms, object and subject of science, general and specific principles, methods and technologies.…

  15. Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully under...

  16. Analysis of Mycobacterium avium subsp. paratuberculosis mutant libraries reveals loci-dependent transcription biases and strategies to novel mutant discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease in ruminants and it has been implicated as a cause of Crohn’s disease in humans. The generation of comprehensive random mutant banks by transposon mutagenesis is a fundamental wide genomic technology utilized...

  17. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  18. Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live va...

  19. COMPARISON OF MYCOBACTERIUM AVIUM ISOLATES FROM A DRINKING WATER DISTRIBUTION SYSTEM AND FROM THE POPULATION SERVED BY THE SYSTEM

    EPA Science Inventory

    Background: Current evidence suggests that drinking water, soil, and produce are potential sources of Mycobacterium avium infections, a pathogen not known to be transmitted person-to-person.

    Methods: We sampled water during 2000-2002 from a large municipal drinking water ...

  20. Development and Evaluation of a Variable-number Tandem Repeat (VNTR) Method for Subtyping of Mycobacterium avium subspecies paratuberculosis Isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (Map) is the causative agent of Johne’s disease in cattle and other ruminants. Because of the apparent ease by which Map can spread to susceptible animals within a dairy herd, a better understanding of the epidemiology of Map infections is required. In thi...

  1. Evaluation of survival of Mycobacterium avium subsp. paratuberculosis (Map) in ciliates isolated from Johne’s positive cow.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Persistence of Mycobacterium avium subsp. paratuberculosis (Map) in farm environments is not well understood. Previously we examined the ability of amoebae from a cow’s watering trough to sequester and enhance growth of Map and found that one amoeba species released vesicles containin...

  2. A Novel Cell Wall Lipopeptide Is Important for Biofilm Formation and Pathogenicity of Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biofilm formation by pathogenic bacteria plays a key role in their pathogenesis. Previously, the pstA gene was shown to be involved in the virulence of Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne's disease in cattle and a potential risk factor for Crohn's d...

  3. Isolation of Mycobacterium avium subspecies paratuberculosis Reactive T-cells from Intestinal Biopsies of Crohn's Disease Patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crohn’s disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is still unknown. One hypothesis is that CD is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) in genetically predisposed individuals. MAP causes a similar disease in ruminants,...

  4. CD4 T Cells From Intestinal Biopsies of Crohn's Disease Patients React to Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn’s disease (CD) remains controversial. One issue that has been raised is the lack of data showing a cellular immune response to MAP. Earlier studies have mostly focused on responses in peripheral blood which have several limit...

  5. Mediation of host immune responses after immunization of neonatal calves with a heat-killed Mycobacterium avium subsp. paratuberculosis vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major drawback of current whole-cell vaccines for Mycobacterium avium subsp. paratuberculosis(MAP) is the interference with diagnostic tests for bovine tuberculosis and paratuberculosis. The current study was designed to explore effects of immunization with a heat-killed whole cell vaccine (Mycop...

  6. ZAP-70, CTLA-4 and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Paratuberculosis is a chronic intestinal disease of ruminant animals caused by Mycobacterium avium subsp. paratuberculosis (MAP). A hallmark of paratuberculosis is a transition from a cell-mediated Th1 type response to a humoral Th2 response with the progression of disease from a subclinical to clin...

  7. Analysis of Mycobacterium avium subspecies paratuberculosis mutant libraries reveals loci-dependent transposition biases and strategies to novel mutant discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease, is one of the most important bacterial pathogens in ruminants. The lack of efficacious control measures demands a thorough understanding of MAP pathogenesis to develop new vaccines and diagnostic tests. The ge...

  8. NlpC/P60 domain-containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While intense research is being conducted to develop faster and more reliable methods for diagnosis of Johne’s disease, there are still significant knowledge gaps concerning the molecular function of Mycobacterium avium subspecies paratuberculosis proteins. Therefore, we describe atomic resolution ...

  9. Genome Sequence of Mycobacterium avium subspecies paratuberculosis Sheep Isolate 397 Reveals Striking Differences Among a Genetically Homogeneous Subspecies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genome of Mycobacterium avium subspecies paratuberculosis is remarkably homogeneous among the bovine, human and wildlife isolates. However previous work in our labs using genomic DNA hybridizations with the bovine K-10 DNA microarray has revealed substantial differences in sheep isolates. A dr...

  10. Optimization of methods for the detection of Mycobacterium avium subsp. paratuberculosis in milk and colostrum of naturally infected dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two decontamination chemicals, hexadecylpyridinium choride (HPC) and N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH), were compared for their efficacy of reducing the growth of non-specific microorganisms in milk while minimally affecting the recovery of Mycobacterium avium subsp. paratuberculosis ...

  11. Evaluation of Control Points in Youngstock and Adult Dairy Cow Management to Control Transmission of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Goal Complete a series of controlled on-farm trials to critically evaluate the efficacy and cost-benefit of commonly recommended management practices for reducing the transmission of Mycobacterium avium subsp. paratuberculosis (Map) in infected herds. Objective 1. Evaluate the effect of maternity...

  12. Shedding of Mycobacterium avium subsp. paratuberculosis into milk and colostrum of naturally infected dairy cows over complete lactation cycles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary mode of transmission of Mycobacterium avium subsp. paratuberculosis (MAP) is fecal-oral. However, MAP is also shed into the milk and colostrum of infected cows. The objective of this study was to identify if an association exists between stage of MAP infection and days in lactation with ...

  13. Longitudinal data collection of Mycobacterium avium subspecies Paratuberculosis infections in dairy herds. Collection and use of observational data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longitudinal infection data on Mycobacterium avium subspecies paratuberculosis (MAP) was collected on three dairy farms in Northeastern United States during approximately 10 years. Precise data on animal characteristics and animal location within farm were collected on these farms. Cows were followe...

  14. Characterization of the inflammatory phenotype of Mycobacterium avium subspecies paratuberculosis using a novel cell culture passage model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the pathogenic mechanisms and host responses to Johne’s disease, a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), is complicated by the multifaceted disease progression, late-onset host reaction, and the lack of ex vivo infection models ...

  15. ZAP-70, CTLA-4, and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Paratuberculosis is a chronic intestinal disease of ruminant animals caused by Mycobacterium avium subsp. paratuberculosis (MAP). A hallmark of paratuberculosis is a transition from a cell-mediated Th1 type response to a humoral Th2 response with the progression of disease from a subclinical to clin...

  16. The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longitudinal data from three commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Johne’s disease status and path on milk production. Disease status, as indicated by Mycobacterium avium subsp. paratuberculosis test results, was ...

  17. Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large-scale meta-analysis of both natural and experimental infections. Large difference...

  18. Relatedness of Mycobacterium avium subspecies hominissuis clinical isolates of human and porcine origins assessed by MLVA.

    PubMed

    Leão, Célia; Canto, Ana; Machado, Diana; Sanches, Ilda Santos; Couto, Isabel; Viveiros, Miguel; Inácio, João; Botelho, Ana

    2014-09-17

    Mycobacterium avium subsp. hominissuis (MAH) is an important opportunistic pathogen, infecting humans and animals, notably pigs. Several methods have been used to characterize MAH strains. RFLP and PFGE typing techniques have been used as standard methods but are technically demanding. In contrast, the analysis of VNTR loci is a simpler, affordable and highly reliable PCR-based technique, allowing a numerical and reproductive digitalization of typing data. In this study, the analysis of Mycobacterium avium tandem repeats (MATRs) loci was adapted to evaluate the genetic diversity of epidemiological unrelated MAH clinical strains of human (n=28) and porcine (n=69) origins, collected from diverse geographical regions across mainland Portugal. These MAH isolates were found to be genetically diverse and genotypes are randomly distributed across the country. Some of the human strains shared identical VNTR profiles with porcine isolates. Our study shows that the VNTR genotyping using selected MATR loci is a useful analysis technique for assessing the genetic diversity of MAH isolates from Portugal. This typing method could be successfully applied in other countries toward the implementation of a worldwide open-access database of MATR-VNTR profiles of MAH isolates, allowing a better assessment of the global epidemiology traits of this important pathogenic species.

  19. Short communication: Recovery of viable Mycobacterium avium subspecies paratuberculosis from retail pasteurized whole milk in Brazil.

    PubMed

    Carvalho, I A; Pietralonga, P A G; Schwarz, D G G; Faria, A C S; Moreira, M A S

    2012-12-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic granulomatous enteritis that affects all ruminants worldwide. Some researchers have indicated a possible role of MAP in Crohn's disease. Despite extensive research and large and important advances in the past few decades, the etiology of Crohn's disease remains indefinite. The most probable transmission route of MAP from animals to humans is milk and dairy products. Mycobacterium avium ssp. paratuberculosis has already been detected in milk samples worldwide, and some studies have reported that MAP is resistant to pasteurization. In Brazil, MAP has been reported in raw milk samples; however, Brazilian retail pasteurized milk has not yet been tested for viable MAP. The aim of this study was to investigate MAP in pasteurized milk in the region of Viçosa (Minas Gerais, Brazil). Thirty-seven samples were collected and processed for culture of MAP. One colony similar to MAP was observed and confirmed by IS900-nested PCR and sequencing. Analysis revealed 97 to 99% identity with the MAP K-10 strain. This study is the first report of the presence of MAP in retail pasteurized whole milk in Brazil.

  20. Mycobacterium avium subsp. hominissuis infection in swine associated with peat used for bedding.

    PubMed

    Johansen, Tone Bjordal; Agdestein, Angelika; Lium, Bjørn; Jørgensen, Anne; Djønne, Berit

    2014-01-01

    Mycobacterium avium subsp. hominissuis is an environmental bacterium causing opportunistic infections in swine, resulting in economic losses. Additionally, the zoonotic aspect of such infections is of concern. In the southeastern region of Norway in 2009 and 2010, an increase in condemnation of pig carcasses with tuberculous lesions was seen at the meat inspection. The use of peat as bedding in the herds was suspected to be a common factor, and a project examining pigs and environmental samples from the herds was initiated. Lesions detected at meat inspection in pigs originating from 15 herds were sampled. Environmental samples including peat from six of the herds and from three peat production facilities were additionally collected. Samples were analysed by culture and isolates genotyped by MLVA analysis. Mycobacterium avium subsp. hominissuis was detected in 35 out of 46 pigs, in 16 out of 20 samples of peat, and in one sample of sawdust. MLVA analysis demonstrated identical isolates from peat and pigs within the same farms. Polyclonal infection was demonstrated by analysis of multiple isolates from the same pig. To conclude, the increase in condemnation of porcine carcasses at slaughter due to mycobacteriosis seemed to be related to untreated peat used as bedding.

  1. Shared Mycobacterium avium Genotypes Observed among Unlinked Clinical and Environmental Isolates

    PubMed Central

    Weigel, Kris M.; Yakrus, Mitchell A.; Becker, Annie L.; Chen, Hui-Ling; Fridley, Gina; Sikora, Arthur; Speake, Cate; Hilborn, Elizabeth D.; Pfaller, Stacy

    2013-01-01

    Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this assumption, a high-resolution PCR-based genotyping approach, large-sequence polymorphism (LSP)-mycobacterial interspersed repetitive unit–variable-number tandem repeat (MIRU-VNTR), was selected and used to analyze clinical and environmental isolates of M. avium from geographically diverse sources. Among 127 clinical isolates from seven locations in North America, South America, and Europe, 42 genotypes were observed. Among 12 of these genotypes, matches were seen in isolates from apparently unlinked patients in two or more geographic locations. Six of the 12 were also observed in environmental isolates. A subset of these isolates was further analyzed by alternative strain genotyping methods, pulsed-field gel electrophoresis and MIRU-VNTR, which confirmed the existence of geographically dispersed strain genotypes. These results suggest that caution should be exercised in interpreting high-resolution genotypic matches as evidence for an acquisition event. PMID:23851084

  2. Environmental survival of Mycobacterium avium subsp. paratuberculosis in different climatic zones of eastern Australia.

    PubMed

    Eppleston, Jeffrey; Begg, Douglas J; Dhand, Navneet K; Watt, Bruce; Whittington, Richard J

    2014-04-01

    The duration of survival of both the S and C strains of Mycobacterium avium subsp. paratuberculosis in feces was quantified in contrasting climatic zones of New South Wales, Australia, and detailed environmental temperature data were collected. Known concentrations of S and C strains in feces placed on soil in polystyrene boxes were exposed to the environment with or without the provision of shade (70%) at Bathurst, Armidale, Condobolin, and Broken Hill, and subsamples taken every 2 weeks were cultured for the presence of M. avium subsp. paratuberculosis. The duration of survival ranged from a minimum of 1 week to a maximum of 16 weeks, and the provision of 70% shade was the most important factor in extending the survival time. The hazard of death for exposed compared to shaded samples was 20 and 9 times higher for the S and C strains, respectively. Site did not affect the survival of the C strain, but for the S strain, the hazard of death was 2.3 times higher at the two arid zone sites (Broken Hill and Condobolin) than at the two temperate zone sites (Bathurst and Armidale). Temperature measurements revealed maximum temperatures exceeding 60°C and large daily temperature ranges at the soil surface, particularly in exposed boxes.

  3. Environmental Survival of Mycobacterium avium subsp. paratuberculosis in Different Climatic Zones of Eastern Australia

    PubMed Central

    Begg, Douglas J.; Dhand, Navneet K.; Watt, Bruce; Whittington, Richard J.

    2014-01-01

    The duration of survival of both the S and C strains of Mycobacterium avium subsp. paratuberculosis in feces was quantified in contrasting climatic zones of New South Wales, Australia, and detailed environmental temperature data were collected. Known concentrations of S and C strains in feces placed on soil in polystyrene boxes were exposed to the environment with or without the provision of shade (70%) at Bathurst, Armidale, Condobolin, and Broken Hill, and subsamples taken every 2 weeks were cultured for the presence of M. avium subsp. paratuberculosis. The duration of survival ranged from a minimum of 1 week to a maximum of 16 weeks, and the provision of 70% shade was the most important factor in extending the survival time. The hazard of death for exposed compared to shaded samples was 20 and 9 times higher for the S and C strains, respectively. Site did not affect the survival of the C strain, but for the S strain, the hazard of death was 2.3 times higher at the two arid zone sites (Broken Hill and Condobolin) than at the two temperate zone sites (Bathurst and Armidale). Temperature measurements revealed maximum temperatures exceeding 60°C and large daily temperature ranges at the soil surface, particularly in exposed boxes. PMID:24463974

  4. Survival of Mycobacterium avium and Mycobacterium tuberculosis in Acidified Vacuoles of Murine Macrophages

    PubMed Central

    Gomes, Maria Salomé; Paul, Simon; Moreira, Andre L.; Appelberg, Rui; Rabinovitch, Michel; Kaplan, Gilla

    1999-01-01

    Despite the antimicrobial mechanisms of vertebrate phagocytes, mycobacteria can survive within the phagosomes of these cells. These organisms use various strategies to evade destruction, including inhibition of acidification of the phagosome and inhibition of phagosome-lysosome fusion. In contrast to mycobacteria, Coxiella burnetii, the etiologic agent of Q fever, inhabits a spacious acidified intracellular vacuole which is prone to fusion with other vacuoles of the host cell, including phagosomes containing mycobacteria. The Coxiella-infected cell thus provides a unique model for investigating the survival of mycobacteria in an acidified phagosome-like compartment. In the present study, murine bone marrow-derived macrophages were infected with either Mycobacterium avium or Mycobacterium tuberculosis and then coinfected with C. burnetii. We observed that the majority of phagocytosed mycobacteria colocalized to the C. burnetii-containing vacuole, which maintained its acidic properties. In coinfected macrophages, the growth of M. avium was not impaired following fusion with the acidified vacuole. In contrast, the growth rate of M. tuberculosis was reduced in acidified vacuoles. These results suggest that although both species of mycobacteria inhibit phagosome-lysosome fusion, they may be differentially susceptible to the toxic effects of the acidic environment in the mature phagolysosome. PMID:10377091

  5. Coexistent Pseudogout and Mycobacterium avium-intracellulare Septic Arthritis in a Patient with HIV and ESRD

    PubMed Central

    Wali, Omer M.; Cervellione, Kelly L.; Singh, Bhupinder B.; Bagheri, Farshad

    2016-01-01

    Pseudogout is a crystal-induced arthropathy characterized by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluid, menisci, or articular cartilage. Although not very common, this entity can be seen in patients with chronic kidney disease (CKD). Septic arthritis due to Mycobacterium avium-intracellulare (MAI) is a rare entity that can affect immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or those who are on immunosuppressive drugs. Here, we describe a 51-year-old female who presented with fever, right knee pain, swelling, warmth, and decreased range of motion for several days. The initial assessment was consistent with pseudogout, with negative bacterial and fungal cultures. However, due to high white blood cell (WBC) count in the synovial fluid analysis, she was empirically started on intravenous (IV) vancomycin and piperacillin-tazobactam and discharged on IV vancomycin and cefepime, while acid-fast bacilli (AFB) culture was still in process. Seventeen days later, AFB culture grew Mycobacterium avium-intracellulare (MAI), and she was readmitted for relevant management. This case illustrates that septic arthritis due to MAI should be considered in the differential diagnosis of septic arthritis in immunocompromised patients. PMID:27803833

  6. Detection of Mycobacterium avium subsp. paratuberculosis in Infected Tissues by New Species-Specific Immunohistological Procedures

    PubMed Central

    Coetsier, Christophe; Havaux, Xavier; Mattelard, Francois; Sadatte, Sanaa; Cormont, Francoise; Buergelt, Klaus; Limbourg, Bernard; Latinne, Dominique; Bazin, Herve; Denef, Jean-Francois; Cocito, Carlo

    1998-01-01

    We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne’s disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930–4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947–954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne’s disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity. PMID:9665946

  7. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

    PubMed

    Klopman, G; Li, J Y; Wang, S; Pearson, A J; Chang, K; Jacobs, M R; Bajaksouzian, S; Ellner, J J

    1994-08-01

    The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

  8. Paradigms of Justice and Love.

    ERIC Educational Resources Information Center

    Byrne, Patick H.

    This paper examines the philosophy behind the Pulse Program of Boston College and its attempt at integrating theory and practice and transforming student's paradigms of justice and love. The basic idea of the program, begun in the fall of 1969, is that students receive academic credit for participation in off-campus field projects which have a…

  9. Paradigms, Exemplars and Social Change

    ERIC Educational Resources Information Center

    Lawson, Hal A.

    2009-01-01

    Researchers' social-cultural organization influences the scope, quality, quantity, coherence, dissemination, utilization and impact of research-based, theoretically sound knowledge. Five concepts--paradigm, exemplar, segment, network and gatekeeper--are salient to research on researchers' organization. Autobiographical reflections signal these…

  10. [The female paradigm in psychoanalysis].

    PubMed

    Rohde-Dachser, C

    1990-01-01

    According to the author, the necessary change to a new psychoanalytic paradigm of femininity can only take place if the patriarchal discourse of psychoanalytic metatheory is systematically deconstructed. Only then can a reconstruction of this discourse occur with a view toward the emancipation of both genders. PMID:2406796

  11. Alternative Paradigms of Teacher Education.

    ERIC Educational Resources Information Center

    Zeichner, Kenneth M.

    1983-01-01

    Four paradigms have dominated the debate on teacher education in recent years: (1) the "behavioristic" orientation; (2) the "personalistic" mode; (3) the "traditional-craft" approach; and (4) the "inquiry" orientation. A heuristic device for organizing discussion about desirable teacher education practices is presented, which permits consideration…

  12. Staff Development: A Gestalt Paradigm.

    ERIC Educational Resources Information Center

    Parsons, Michael H.

    Hagerstown Junior College, Maryland, has had a staff development program for the past five years. The major components have been evaluated, revised, and integrated into a gestalt paradigm--a total institutional thrust designed to insure that the goals of the college meet the challenges presented by the service area. Each component exists to foster…

  13. THE RETURN OF THE PARADIGM.

    ERIC Educational Resources Information Center

    BREND, RUTH M.

    TWO SIGNIFICANT ASPECTS OF LANGUAGE LEARNING, THE VERTICAL ORGANIZATION OF THE PARADIGM AND THE STUDENT'S ANALYTICAL ABILITY, HAVE BEEN OVERLOOKED IN FAVOR OF DEVELOPING CONVERSATIONAL SKILLS BY A HORIZONTAL APPROACH IN WHICH, FOR EXAMPLE, THE MATERIAL PRESENTS THE ACCUSATIVE CASE ONE DAY AND THE FIRST PERSON PRESENT OF ALL VERBS ON ANOTHER.…

  14. Multimission Software Reuse in an Environment of Large Paradigm Shifts

    NASA Technical Reports Server (NTRS)

    Wilson, Robert K.

    1996-01-01

    The ground data systems provided for NASA space mission support are discussed. As space missions expand, the ground systems requirements become more complex. Current ground data systems provide for telemetry, command, and uplink and downlink processing capabilities. The new millennium project (NMP) technology testbed for 21st century NASA missions is discussed. The program demonstrates spacecraft and ground system technologies. The paradigm shift from detailed ground sequencing to a goal oriented planning approach is considered. The work carried out to meet this paradigm for the Deep Space-1 (DS-1) mission is outlined.

  15. Achieving Operability via the Mission System Paradigm

    NASA Technical Reports Server (NTRS)

    Hammer, Fred J.; Kahr, Joseph R.

    2006-01-01

    In the past, flight and ground systems have been developed largely-independently, with the flight system taking the lead, and dominating the development process. Operability issues have been addressed poorly in planning, requirements, design, I&T, and system-contracting activities. In many cases, as documented in lessons-learned, this has resulted in significant avoidable increases in cost and risk. With complex missions and systems, operability is being recognized as an important end-to-end design issue. Never-the-less, lessons-learned and operability concepts remain, in many cases, poorly understood and sporadically applied. A key to effective application of operability concepts is adopting a 'mission system' paradigm. In this paradigm, flight and ground systems are treated, from an engineering and management perspective, as inter-related elements of a larger mission system. The mission system consists of flight hardware, flight software, telecom services, ground data system, testbeds, flight teams, science teams, flight operations processes, procedures, and facilities. The system is designed in functional layers, which span flight and ground. It is designed in response to project-level requirements, mission design and an operations concept, and is developed incrementally, with early and frequent integration of flight and ground components.

  16. Bacteremia with an iliopsoas abscess and osteomyelitis of the femoral head caused by Enterococcus avium in a patient with end-stage kidney disease.

    PubMed

    Okada, Akira; Hangai, Mika; Oda, Toshimi

    2015-01-01

    A 70-year-old man on hemodialysis for end-stage kidney disease due to polycystic kidney disease presented with hip pain on extension and a high C-reactive protein level. Further examinations revealed an iliopsoas abscess and femoral head osteomyelitis caused by Enterococcus avium (E. avium) detected in blood and pus cultures. Complete resolution of the infection with ampicillin-resistant E. avium required six months of vancomycin therapy and two surgical drainage procedures. There have been no previous case reports in which both blood and abscess cultures confirmed E. avium infection. Careful attention should be paid to the detection of non-specific symptoms in patients on hemodialysis, with blood cultures being essential in such cases.

  17. Treatment with antibiotics is detrimental to the recovery of viable Mycobacterium avium subsp. paratuberculosis cultured from milk and colostrum of dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic cocktails are frequently used as secondary decontaminants prior to the culture of Mycobacterium avium subsp. paratuberculosis (MAP). This study investigated whether secondary incubation with an antibiotic cocktail containing vancomycin, nalidixic acid, and amphotericin B after primary exp...

  18. Efficacy of various pasteurization time-temperature conditions in combination with homogenization on inactivation of Mycobacterium avium subsp. paratuberculosis in milk.

    PubMed

    Grant, Irene R; Williams, Alan G; Rowe, Michael T; Muir, D Donald

    2005-06-01

    The effect of various pasteurization time-temperature conditions with and without homogenization on the viability of Mycobacterium avium subsp. paratuberculosis was investigated using a pilot-scale commercial high-temperature, short-time (HTST) pasteurizer and raw milk spiked with 10(1) to 10(5) M. avium subsp. paratuberculosis cells/ml. Viable M. avium subsp. paratuberculosis was cultured from 27 (3.3%) of 816 pasteurized milk samples overall, 5 on Herrold's egg yolk medium and 22 by BACTEC culture. Therefore, in 96.7% of samples, M. avium subsp. paratuberculosis had been completely inactivated by HTST pasteurization, alone or in combination with homogenization. Heat treatments incorporating homogenization at 2,500 lb/in2, applied upstream (as a separate process) or in hold (at the start of a holding section), resulted in significantly fewer culture-positive samples than pasteurization treatments without homogenization (P < 0.001 for those in hold and P < 0.05 for those upstream). Where colony counts were obtained, the number of surviving M. avium subsp. paratuberculosis cells was estimated to be 10 to 20 CFU/150 ml, and the reduction in numbers achieved by HTST pasteurization with or without homogenization was estimated to be 4.0 to 5.2 log10. The impact of homogenization on clump size distribution in M. avium subsp. paratuberculosis broth suspensions was subsequently assessed using a Mastersizer X spectrometer. These experiments demonstrated that large clumps of M. avium subsp. paratuberculosis cells were reduced to single-cell or "miniclump" status by homogenization at 2,500 lb/in2. Consequently, when HTST pasteurization was being applied to homogenized milk, the M. avium subsp. paratuberculosis cells would have been present as predominantly declumped cells, which may possibly explain the greater inactivation achieved by the combination of pasteurization and homogenization.

  19. Key Role for the Alternative Sigma Factor, SigH, in the Intracellular Life of Mycobacterium avium subsp. paratuberculosis during Macrophage Stress

    PubMed Central

    Ghosh, Pallab; Wu, Chia-wei

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease, an enteric infection in cattle and other ruminants, greatly afflicting the dairy industry worldwide. Once inside the cell, M. avium subsp. paratuberculosis is known to survive harsh microenvironments, especially those inside activated macrophages. To improve our understanding of M. avium subsp. paratuberculosis pathogenesis, we examined phagosome maturation associated with transcriptional responses of M. avium subsp. paratuberculosis during macrophage infection. Monitoring cellular markers, only live M. avium subsp. paratuberculosis bacilli were able to prevent phagosome maturation and reduce its acidification. On the transcriptional level, over 300 M. avium subsp. paratuberculosis genes were significantly and differentially regulated in both naive and IFN-γ-activated macrophages. These genes include the sigma factor H (sigH) that was shown to be important for M. avium subsp. paratuberculosis survival inside gamma interferon (IFN-γ)-activated bovine macrophages. Interestingly, an sigH-knockout mutant showed increased sensitivity to a sustained level of thiol-specific oxidative stress. Large-scale RNA sequence analysis revealed that a large number of genes belong to the sigH regulon, especially following diamide stress. Genes involved in oxidative stress and virulence were among the induced genes in the sigH regulon with a putative consensus sequence for SigH binding that was recognized in a subset of these genes (n = 30), suggesting direct regulation by SigH. Finally, mice infections showed a significant attenuation of the ΔsigH mutant compared to its parental strain, suggesting a role for sigH in M. avium subsp. paratuberculosis virulence. Such analysis could identify potential targets for further testing as vaccine candidates against Johne's disease. PMID:23569115

  20. Connecting traditional sciences with the OLAP and data mining paradigms

    NASA Astrophysics Data System (ADS)

    Guergachi, Aziz A.

    2003-03-01

    The paradigms of OLAP, multidimensional modeling and data mining have first emerged in the areas of market analysis and finance to address various needs of people working in these areas. Does this mean that they are useful and applicable in these areas only? Or, can they also be applicable in the other more traditional areas of science and engineering? What characterize the systems for which these paradigms are suitable? What are the goals of these paradigms? How do they relate to the traditional body of knowledge that has been developed throughout the centuries in the areas of mathematics, statistics, systems science and engineering? Where, how and to what extent can we leverage the conventional wisdom that has been accumulated in the aforementioned disciplines to develop a foundational basis for the above paradigms? The goal of this paper is to address these questions at the foundational level. We argue that the paradigms of OLAP, multidimensional modeling and data mining can also be applied successfully to complex engineering systems, such as membrane-based water/wastewater treatment plants, for example. We develop mathematically-based axiomatic definition of the concepts of 'dimension,' 'dimension level,' 'dimension hierarchy' and 'measure' using set theory and equivalence relations.

  1. e-Science Paradigm for Astroparticle Physics at KISTI

    NASA Astrophysics Data System (ADS)

    Cho, Kihyeon

    2016-03-01

    The Korea Institute of Science and Technology Information (KISTI) has been studying the e-Science paradigm. With its successful application to particle physics, we consider the application of the paradigm to astroparticle physics. The Standard Model of particle physics is still not considered perfect even though the Higgs boson has recently been discovered. Astrophysical evidence shows that dark matter exists in the universe, hinting at new physics beyond the Standard Model. Therefore, there are efforts to search for dark matter candidates using direct detection, indirect detection, and collider detection. There are also efforts to build theoretical models for dark matter. Current astroparticle physics involves big investments in theories and computing along with experiments. The complexity of such an area of research is explained within the framework of the e-Science paradigm. The idea of the e-Science paradigm is to unify experiment, theory, and computing. The purpose is to study astroparticle physics anytime and anywhere. In this paper, an example of the application of the paradigm to astrophysics is presented.

  2. Intracellular fate of Mycobacterium avium subspecies paratuberculosis in monocytes from normal and infected, interferon-responsive cows as determined by a radiometric method.

    PubMed

    Zhao, B Y; Czuprynski, C J; Collins, M T

    1999-01-01

    The ability of Mycobacterium avium subsp. paratuberculosis to survive in bovine monocytes was studied using radiometric (BACTEC) culture, standard plate counting and microscopic counting of acid-fast stained monocyte monolayers. Results of microscopic counts sharply contrasted with results of viable counts determined both by plate counting and radiometric counting. We observed an early phase (the first 6 d after in vitro infection) of intracellular bacillary growth, followed by a later phase of mycobacteriostasis or killing (up to 12 d after in vitro infection) in monocytes from non-infected cows. The data suggest that multiplication and death of M. avium subsp. paratuberculosis occur simultaneously in bovine monocytes infected in vitro. Using the BACTEC method, we compared the ability of bovine monocytes from normal cows and cows infected with M. avium subsp. paratuberculosis and showing evidence of a strong Thl-like cellular immune response to ingest and inhibit the intracellular growth of M. avium subsp. paratuberculosis. There was a trend toward greater phagocytosis and faster killing of Mycobacterium avium subsp. paratuberculosis by monocytes from the infected, immune responder cows. However, the observed numbers of viable M. avium subsp. paratuberculosis at each time after monocyte infection were not significantly different between normal and infected cows.

  3. Employee discipline: a changing paradigm.

    PubMed

    Raper, J L; Myaya, S N

    1993-12-01

    To increase the receptiveness of health care supervisors to a broader meaning of discipline and to simulate investigation of nontraditional methods of encouragement to employees who fail to meet minimum standards of conduct and thereby negatively affect the quality of patient care, a subjectively realistic view of the implications of the traditional punitive disciplinary paradigm is presented. Through the use of a case study, the authors present, explain, and apply the contemporary concept of discipline without punishment as first described by J. Huberman.

  4. The Afrocentric Paradigm: Contours and Definitions.

    ERIC Educational Resources Information Center

    Mazama, Ama

    2001-01-01

    Defines and describes Afrocentricity, suggesting that Afrocentricity within the academic context is best understood as a paradigm. Explains how Afrocentricity meets the definition of a paradigm, examining the affective, cognitive, and conative aspects of the Afrocentric paradigm (metaphysical and sociological) and looking at the structural and…

  5. A Proposal for a New Communication Paradigm.

    ERIC Educational Resources Information Center

    Gardiner, Peter C.

    This paper discusses the inadequacies of existing communication paradigms and proposes a new paradigm which integrates general semantics and general system theory in an application to communication theory. The paper includes an historical overview of traditional communication models as well as a discussion of the implications of the paradigm for…

  6. The Learner-Centered Paradigm of Education

    ERIC Educational Resources Information Center

    Watson, Sunnie Lee; Reigeluth, Charles M.

    2008-01-01

    This article, the third in a series of four installments, begins by discussing the need for paradigm change in education and for a critical systems approach to paradigm change, and examines current progress toward paradigm change. Then it explores what a learner-centered, Information-Age educational system should be like, including the APA…

  7. Poverty eradication: a new paradigm.

    PubMed

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation.

  8. Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

    PubMed Central

    Ferro, Beatriz E.; Meletiadis, Joseph; Wattenberg, Melanie; de Jong, Arjan; van Soolingen, Dick; Mouton, Johan W.

    2015-01-01

    Multidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment. Mycobacterium abscessus and Mycobacterium avium type strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25× to 2× MIC. Pharmacodynamic interactions were assessed by response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA), calculating the percentage of statistically significant Bliss interactions and interaction indices (I), respectively. Monte Carlo simulations with predicted human lung concentrations were used to calculate target attainment rates for combination and monotherapy regimens. Clofazimine alone was bacteriostatic for both NTM. Clofazimine-amikacin was synergistic against M. abscessus (I = 0.41; 95% confidence interval [CI], 0.29 to 0.55) and M. avium (I = 0.027; 95% CI, 0.007 to 0.048). Based on RSBI analysis, synergistic interactions of 28.4 to 29.0% and 23.2 to 56.7% were observed at 1× to 2× MIC and 0.25× to 2× MIC for M. abscessus and M. avium, respectively. Clofazimine-clarithromycin was also synergistic against M. abscessus (I = 0.53; 95% CI, 0.35 to 0.72) and M. avium (I = 0.16; 95% CI, 0.04 to 0.35), RSBI analysis showed 23.5% and 23.3 to 53.3% at 2× MIC and 0.25× to 0.5× MIC for M. abscessus and M. avium, respectively. Clofazimine prevented the regrowth observed with amikacin or clarithromycin alone. Target attainment rates of combination regimens were >60% higher than those of monotherapy regimens for M. abscessus and M. avium. The combination of clofazimine with amikacin or clarithromycin was synergistic in vitro. This suggests a potential role for clofazimine in treatment regimens that warrants further

  9. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    PubMed

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  10. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    PubMed

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  11. Detection of Mycobacterium avium subsp. paratuberculosis by a Direct In Situ PCR Method

    PubMed Central

    Delgado, Fernando; Aguilar, Diana; Garbaccio, Sergio; Francinelli, Gladys; Hernández-Pando, R.; Romano, María Isabel

    2011-01-01

    In situ detection of Mycobacterium avium subsp. paratuberculosis is useful for diagnosis and research of paratuberculosis. The aim of this paper was to detect this agent in formalin-fixed, paraffin-embedded tissue samples by a direct in situ PCR. The technique was performed on ileum or ileocaecal lymph node samples from 8 naturally infected cattle and 1 healthy calf, by using p89 and p92 primers for amplification of IS900 sequence. Moderate positive signal was detected in all positive samples and not in negative control, but tissues resulted were affected in many cases due to the enzymatic treatment and the high temperature exposition. Although the technique was useful for Map detection, the signal was lower than immunohistochemistry probably because of the fixation process. In one case, signal was higher, which might be due to the detection of spheroplasts. Thus, the described method should be recommended when others resulted negative or for spheroplasts detection. PMID:21772965

  12. Characterisation of an ELISA detecting immunoglobulin G to Mycobacterium avium subsp. paratuberculosis in bovine colostrum.

    PubMed

    Zervens, Lisa Marie-Louise; Nielsen, Søren Saxmose; Jungersen, Gregers

    2013-09-01

    Although colostrum has been used to detect specific immunoglobulin (Ig) G to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle, confounding, non-specific reactions can be a problem. The objectives of this study were to determine the proportion of non-specific ELISA reactions in samples of colostrum taken between 0 and 4 days-in-milk (DIM), and to assess the probability of an animal testing positive for MAP specific IgG over this time-period. Non-specific reactions were found in 3/365 (0.8%) of samples. The odds of an animal testing positive on day of calving were 130 times higher than at 4 DIM. The findings suggest colostral samples may have enhanced diagnostic potential over milk samples in determining if cattle have been exposed to or infected with MAP. PMID:23611487

  13. Association between cattle herd Mycobacterium avium subsp. paratuberculosis (MAP) infection and infection of a hare population.

    PubMed

    Salgado, Miguel; Monti, Gustavo; Sevilla, Iker; Manning, Elizabeth

    2014-10-01

    Paratuberculosis has long been considered a disease of domestic and wild ruminants only. The known host range of Mycobacterium avium subsp. paratuberculosis (MAP) was recently extended to include non-ruminant wildlife species believed to be exposed to spillover of MAP from infected domestic cattle herds. The aim of the present study was to assess the association between cattle herd MAP infection pressure level and the infection level of a hare population in two dairy farms of southern Chile. Fifty hares from a herd A and 42 hares from herd B were captured and sampled for MAP culture. The results showed a statistically significant association between the cattle herds' infection prevalence and the hare infection prevalence.

  14. Genetic diversity in wild sweet cherries (Prunus avium) in Turkey revealed by SSR markers.

    PubMed

    Ercisli, S; Agar, G; Yildirim, N; Duralija, B; Vokurka, A; Karlidag, H

    2011-06-21

    Wild sweet cherry (Prunus avium) trees are abundant in the northern part of Turkey, including the Coruh Valley. We analyzed 18 wild sweet cherry genotypes collected from diverse environments in the upper Coruh Valley in Turkey to determine genetic variation, using 10 SSR primers. These SSR primers generated 46 alleles; the number of alleles per primer ranged from 3 to 7, with a mean of 4.6. The primer PS12A02 gave the highest number of polymorphic bands (N = 7), while CPSCT010, UDAp-401 and UDAp-404 gave the lowest number (N = 3). Seven groups were separated in the dendrogram, although most of the genotypes did not cluster according to phenological and morphological traits. This level of genetic diversity in these wild sweet cherry genotypes is very high and therefore these trees would be useful as breeders for crosses between cultivated sweet cherry and wild genotypes.

  15. Mycobacterium avium-related epizootic in free-ranging lesser flamingos in Kenya.

    PubMed

    Kock, N D; Kock, R A; Wambua, J; Kamau, G J; Mohan, K

    1999-04-01

    An epizootic in free-ranging lesser flamingos (Phoeniconaias minor) in Kenya resulted in more than 18,500 deaths from August through mid-November 1993. Disease was concentrated along the shores of Rift Valley Lakes Bogoria and Nakuru (Kenya) and did not involve any of the other avian or mammalian species frequenting the lakes. Coincidental to the outbreak was a bloom of algae on Lake Bogoria, toxins from which were first suspected to be causative. Discrete necrotic and granulomatous lesions were often noted in spleen and liver, and Mycobacterium avium serovar I was isolated from both organs. Escherichia coli and Pseudomonas aeruginosa also were often recovered in pure culture from liver. Gross and histopathological evaluation of the cases disclosed signs of acute sepsis and also chronic, potentially life-threatening lesions of mycobacteriosis, primarily involving the spleen and liver. Lesions typical for algae toxicosis were not seen in any birds. Deaths were attributed to septicemia complicated in those affected, by mycobacteriosis.

  16. Prevalence of Mycobacterium avium subspecies paratuberculosis in Swiss raw milk cheeses collected at the retail level.

    PubMed

    Stephan, R; Schumacher, S; Tasara, T; Grant, I R

    2007-08-01

    A total of 143 raw milk cheese samples (soft cheese, n = 9; semihard cheese, n = 133; hard cheese, n = 1), collected at the retail level throughout Switzerland, were tested for Mycobacterium avium ssp. paratuberculosis (MAP) by immunomagnetic capture plus culture on 7H10-PANTA medium and in supplemented BAC-TEC 12B medium, as well as by an F57-based real-time PCR system. Furthermore, pH and water activity values were determined for each sample. Although no viable MAP cells could be cultured, 4.2% of the raw milk cheese samples tested positive with the F57-based real-time PCR system, providing evidence for the presence of MAP in the raw material. As long as the link between MAP and Crohn's disease in humans remains unclear, measures designed to minimize public exposure should also include a focus on milk products.

  17. Interferon gamma response to Mycobacterium avium subsp. paratuberculosis specific lipopentapeptide antigen L5P in cattle.

    PubMed

    Holbert, Sébastien; Branger, Maxime; Souriau, Armel; Lamoureux, Bérénice; Ganneau, Christelle; Richard, Gaëlle; Cochard, Thierry; Tholoniat, Christophe; Bay, Sylvie; Winter, Nathalie; Moyen, Jean Louis; Biet, Franck

    2015-10-01

    After Mycobacterium avium subsp. paratuberculosis (Map) infection the cell-mediated immune (CMI) response indicative of early Th1 activation may be detected using interferon-gamma release assay (IGRA). Currently, the purified protein derivatives (PPDs), i.e., the total extract of mycobacteria antigens are used to recall CMI responses against Map. This study aimed to assess the ability of the chemically synthesized Map specific cell wall lipopentapeptide L5P to induce CMI response in cows infected by Map compared to PPD. L5P and PPD elicited an IFN-γ response in 12 and 35 animals from two Map infected herds respectively, but IFN-γ was not detected in the 13 cows recruited from a non-infected herd. Levels of IFN-γ detected were higher with PPD than with L5P. There was no correlation between the IFN-γ response and the humoral response to Map or faecal culture.

  18. Interferon gamma response to Mycobacterium avium subsp. paratuberculosis specific lipopentapeptide antigen L5P in cattle.

    PubMed

    Holbert, Sébastien; Branger, Maxime; Souriau, Armel; Lamoureux, Bérénice; Ganneau, Christelle; Richard, Gaëlle; Cochard, Thierry; Tholoniat, Christophe; Bay, Sylvie; Winter, Nathalie; Moyen, Jean Louis; Biet, Franck

    2015-10-01

    After Mycobacterium avium subsp. paratuberculosis (Map) infection the cell-mediated immune (CMI) response indicative of early Th1 activation may be detected using interferon-gamma release assay (IGRA). Currently, the purified protein derivatives (PPDs), i.e., the total extract of mycobacteria antigens are used to recall CMI responses against Map. This study aimed to assess the ability of the chemically synthesized Map specific cell wall lipopentapeptide L5P to induce CMI response in cows infected by Map compared to PPD. L5P and PPD elicited an IFN-γ response in 12 and 35 animals from two Map infected herds respectively, but IFN-γ was not detected in the 13 cows recruited from a non-infected herd. Levels of IFN-γ detected were higher with PPD than with L5P. There was no correlation between the IFN-γ response and the humoral response to Map or faecal culture. PMID:26412530

  19. Induction of murine macrophage TNF-alpha synthesis by Mycobacterium avium is modulated through complement-dependent interaction via complement receptors 3 and 4 in relation to M. avium glycopeptidolipid.

    PubMed

    Irani, Vida R; Maslow, Joel N

    2005-05-15

    We studied whether complement receptor (CR) mediated Mycobacterium avium interaction modulated macrophage TNF-alpha expression. Compared to control conditions, infections performed with C3-depletion yielded significantly higher TNF-alpha levels. Blockage of the CR4 iC3b site yielded increases in TNF-alpha for all morphotypic variants of a virulent serovar-8 strain (smooth transparent (SmT), smooth opaque (SmO), serovar-specific glycopeptidolipid (ssGPL) deficient knockout mutant) whereas CR3 blockage increased TNF-alpha only for SmT and ssGPL-deficient strains. Thus, complement-mediated binding of M. avium to CR3 and CR4 was shown to modulate TNF-alpha expression. The differential activation of morphotypic and isogenic variants of a single strain provides an excellent model system to delineate signaling pathways. PMID:15899409

  20. Mycobacterium avium Possesses Extracellular DNA that Contributes to Biofilm Formation, Structural Integrity, and Tolerance to Antibiotics

    PubMed Central

    Rose, Sasha J.; Babrak, Lmar M.; Bermudez, Luiz E.

    2015-01-01

    Mycobacterium avium subsp. hominissuis is an opportunistic pathogen that is associated with biofilm-related infections of the respiratory tract and is difficult to treat. In recent years, extracellular DNA (eDNA) has been found to be a major component of bacterial biofilms, including many pathogens involved in biofilm-associated infections. To date, eDNA has not been described as a component of mycobacterial biofilms. In this study, we identified and characterized eDNA in a high biofilm-producing strain of Mycobacterium avium subsp. hominissuis (MAH). In addition, we surveyed for presence of eDNA in various MAH strains and other nontuberculous mycobacteria. Biofilms of MAH A5 (high biofilm-producing strain) and MAH 104 (reference strain) were established at 22°C and 37°C on abiotic surfaces. Acellular biofilm matrix and supernatant from MAH A5 7 day-old biofilms both possess abundant eDNA, however very little eDNA was found in MAH 104 biofilms. A survey of MAH clinical isolates and other clinically relevant nontuberculous mycobacterial species revealed many species and strains that also produce eDNA. RAPD analysis demonstrated that eDNA resembles genomic DNA. Treatment with DNase I reduced the biomass of MAH A5 biofilms when added upon biofilm formation or to an already established biofilm both on abiotic surfaces and on top of human pharyngeal epithelial cells. Furthermore, co-treatment of an established biofilm with DNase 1 and either moxifloxacin or clarithromycin significantly increased the susceptibility of the bacteria within the biofilm to these clinically used antimicrobials. Collectively, our results describe an additional matrix component of mycobacterial biofilms and a potential new target to help treat biofilm-associated nontuberculous mycobacterial infections. PMID:26010725

  1. Mycobacterium avium Possesses Extracellular DNA that Contributes to Biofilm Formation, Structural Integrity, and Tolerance to Antibiotics.

    PubMed

    Rose, Sasha J; Babrak, Lmar M; Bermudez, Luiz E

    2015-01-01

    Mycobacterium avium subsp. hominissuis is an opportunistic pathogen that is associated with biofilm-related infections of the respiratory tract and is difficult to treat. In recent years, extracellular DNA (eDNA) has been found to be a major component of bacterial biofilms, including many pathogens involved in biofilm-associated infections. To date, eDNA has not been described as a component of mycobacterial biofilms. In this study, we identified and characterized eDNA in a high biofilm-producing strain of Mycobacterium avium subsp. hominissuis (MAH). In addition, we surveyed for presence of eDNA in various MAH strains and other nontuberculous mycobacteria. Biofilms of MAH A5 (high biofilm-producing strain) and MAH 104 (reference strain) were established at 22°C and 37°C on abiotic surfaces. Acellular biofilm matrix and supernatant from MAH A5 7 day-old biofilms both possess abundant eDNA, however very little eDNA was found in MAH 104 biofilms. A survey of MAH clinical isolates and other clinically relevant nontuberculous mycobacterial species revealed many species and strains that also produce eDNA. RAPD analysis demonstrated that eDNA resembles genomic DNA. Treatment with DNase I reduced the biomass of MAH A5 biofilms when added upon biofilm formation or to an already established biofilm both on abiotic surfaces and on top of human pharyngeal epithelial cells. Furthermore, co-treatment of an established biofilm with DNase 1 and either moxifloxacin or clarithromycin significantly increased the susceptibility of the bacteria within the biofilm to these clinically used antimicrobials. Collectively, our results describe an additional matrix component of mycobacterial biofilms and a potential new target to help treat biofilm-associated nontuberculous mycobacterial infections.

  2. GENETIC DIVERSITY OF SOME IRANIAN SWEET CHERRY (PRUNUS AVIUM) CULTIVARS USING MICROSATELLITE MARKERS AND MORPHOLOGICAL TRAITS.

    PubMed

    Farsad, A; Esna-Ashari, M

    2016-01-01

    The aim of this study was to characterize 23 important Iranian sweet cherry (Prunus avium) cultivars collected from different provinces of Iran and 1 foreign cultivar, which was used as control, considered for breeding programs by using 21 microsatellite markers and 27 morphological traits. In sweet cherry (Prunus avium) accessions, leaf, fruit, and stone morphological characters were evaluated during two consecutive years. The study revealed a high variability in the set of evaluated sweet cherry accessions. The majority of important correlations were determined among variables representing fruit and leaf size and variables related to color. Cluster analysis distinguished sweet cherry accessions into two distinct groups. Principal component analysis (PCA) of qualitative and quantitative morphological parameters explained over 86.59% of total variability in the first seven axes. In PCA, leaf traits such as leaf length and width, and fruit traits such as length, width, and weight, and fruit flesh and juice color were predominant in the first two components, indicating that they were useful for the assessment of sweet cherry germplasm characterization. Out of 21 SSR markers, 16 were polymorphic, producing 177 alleles that varied from 4 to 16 alleles (9.35 on average) with a mean heterozygosity value of 0.82 that produced successful amplifications and revealed DNA polymorphisms. Allele size varied from 95 to 290 bp. Cluster analyses showed that the studied sweet cherry genotypes were classified intofive main groups based mainly on their species characteristics and SSR data. In general, our results did not show a clear structuring of genetic variability within the Iranian diffusion area of sweet cherry, so it was not possible to draw any indications on regions of provenance delimitation. The results of this study contribute to a better understanding of sweet cherry genetic variations in Iran, thus making for more efficient programs aimed at preserving biodiversity and

  3. Host responses to the pathogen Mycobacterium avium subsp. paratuberculosis and beneficial microbes exhibit host sex specificity.

    PubMed

    Karunasena, Enusha; McMahon, K Wyatt; Chang, David; Brashears, Mindy M

    2014-08-01

    Differences between microbial pathogenesis in male and female hosts are well characterized in disease conditions connected to sexual transmission. However, limited biological insight is available on variances attributed to sex specificity in host-microbe interactions, and it is most often a minimized variable outside these transmission events. In this work, we studied two gut microbes-a pathogen, Mycobacterium avium subsp. paratuberculosis, and a probiotic, Lactobacillus animalis NP-51-and the interaction between each agent and the male and female gastrointestinal systems. This trial was conducted in BALB/c mice (n=5 per experimental group and per sex at a given time point), with analysis at four time points over 180 days. Host responses to M.avium subsp. paratuberculosis and L. animalis were sensitive to sex. Cytokines that were significantly different (P ≤ 0.05) betweenthe sexes included interleukin-1α/β (IL-1α/β), IL-17, IL-6, IL-10, IL-12, and gamma interferon (IFN-) and were dependent on experimental conditions. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and IL-13/23 showed no sex specificity. A metabolomics study indicated a 0.5- to 2.0-fold (log2 scale) increase in short-chain fatty acids (butyrate and acetate) in males and greater increases in o-phosphocholine or histidine from female colon tissues; variances distinct to each sex were observed with age or long-term probiotic consumption. Two genera, Staphylococcus and Roseburia, were consistently overrepresented in females compared to males; other species were specific to one sex but fluctuated depending on experimental conditions. The differences observed suggest that male and female gut tissues and microbiota respond to newly introduced microorganisms differently and that gut-associated microorganisms with host immune system responses and metabolic activity are supported by biology distinct to the host sex.

  4. GENETIC DIVERSITY OF SOME IRANIAN SWEET CHERRY (PRUNUS AVIUM) CULTIVARS USING MICROSATELLITE MARKERS AND MORPHOLOGICAL TRAITS.

    PubMed

    Farsad, A; Esna-Ashari, M

    2016-01-01

    The aim of this study was to characterize 23 important Iranian sweet cherry (Prunus avium) cultivars collected from different provinces of Iran and 1 foreign cultivar, which was used as control, considered for breeding programs by using 21 microsatellite markers and 27 morphological traits. In sweet cherry (Prunus avium) accessions, leaf, fruit, and stone morphological characters were evaluated during two consecutive years. The study revealed a high variability in the set of evaluated sweet cherry accessions. The majority of important correlations were determined among variables representing fruit and leaf size and variables related to color. Cluster analysis distinguished sweet cherry accessions into two distinct groups. Principal component analysis (PCA) of qualitative and quantitative morphological parameters explained over 86.59% of total variability in the first seven axes. In PCA, leaf traits such as leaf length and width, and fruit traits such as length, width, and weight, and fruit flesh and juice color were predominant in the first two components, indicating that they were useful for the assessment of sweet cherry germplasm characterization. Out of 21 SSR markers, 16 were polymorphic, producing 177 alleles that varied from 4 to 16 alleles (9.35 on average) with a mean heterozygosity value of 0.82 that produced successful amplifications and revealed DNA polymorphisms. Allele size varied from 95 to 290 bp. Cluster analyses showed that the studied sweet cherry genotypes were classified intofive main groups based mainly on their species characteristics and SSR data. In general, our results did not show a clear structuring of genetic variability within the Iranian diffusion area of sweet cherry, so it was not possible to draw any indications on regions of provenance delimitation. The results of this study contribute to a better understanding of sweet cherry genetic variations in Iran, thus making for more efficient programs aimed at preserving biodiversity and

  5. Host Responses to the Pathogen Mycobacterium avium subsp. paratuberculosis and Beneficial Microbes Exhibit Host Sex Specificity

    PubMed Central

    McMahon, K. Wyatt; Chang, David; Brashears, Mindy M.

    2014-01-01

    Differences between microbial pathogenesis in male and female hosts are well characterized in disease conditions connected to sexual transmission. However, limited biological insight is available on variances attributed to sex specificity in host-microbe interactions, and it is most often a minimized variable outside these transmission events. In this work, we studied two gut microbes—a pathogen, Mycobacterium avium subsp. paratuberculosis, and a probiotic, Lactobacillus animalis NP-51—and the interaction between each agent and the male and female gastrointestinal systems. This trial was conducted in BALB/c mice (n = 5 per experimental group and per sex at a given time point), with analysis at four time points over 180 days. Host responses to M. avium subsp. paratuberculosis and L. animalis were sensitive to sex. Cytokines that were significantly different (P ≤ 0.05) between the sexes included interleukin-1α/β (IL-1α/β), IL-17, IL-6, IL-10, IL-12, and gamma interferon (IFN-γ) and were dependent on experimental conditions. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and IL-13/23 showed no sex specificity. A metabolomics study indicated a 0.5- to 2.0-fold (log2 scale) increase in short-chain fatty acids (butyrate and acetate) in males and greater increases in o-phosphocholine or histidine from female colon tissues; variances distinct to each sex were observed with age or long-term probiotic consumption. Two genera, Staphylococcus and Roseburia, were consistently overrepresented in females compared to males; other species were specific to one sex but fluctuated depending on experimental conditions. The differences observed suggest that male and female gut tissues and microbiota respond to newly introduced microorganisms differently and that gut-associated microorganisms with host immune system responses and metabolic activity are supported by biology distinct to the host sex. PMID:24814797

  6. Superoxide dismutase activity of Mycobacterium avium, M. intracellulare, and M. scrofulaceum.

    PubMed Central

    Mayer, B K; Falkinham, J O

    1986-01-01

    Superoxide dismutase (EC 1.15.1.1) (SOD) activity has been detected in crude cell extracts of representative strains of the Mycobacterium avium, M. intracellulare, and M. scrofulaceum (MAIS) group. Polyacrylamide gel electrophoresis demonstrated a single SOD activity band for each of the MAIS strains, though there were differences in mobility. All M. avium and M. intracellulare and two of five M. scrofulaceum strains demonstrated a single activity band of identical mobility (Rf = 0.83), while the SOD activity band for the three remaining M. scrofulaceum strains migrated farther (Rf = 0.85). The differences in mobility correlated with differences in sensitivity to NaN3 and H2O2. The SOD activities of the majority of the MAIS strains which displayed the slower-migrating activity band were inhibited 22 to 81% after 15 min of exposure to 5 mM H2O2, suggesting that both iron and manganese may be present in a single enzyme. The SOD activities of the three M. scrofulaceum strains which had the faster-migrating activity band were inhibited 100% after only 5 min of exposure to 5 mM H2O2 and exhibited greater sensitivity to 5 and 10 mM NaN3, characteristics of an iron-containing SOD. A concentration of 1 mM KCN did not cause inhibition of enzyme activity in any of the MAIS strains tested. Extracellular SOD activity was detected in four of six MAIS strains and was shown to be identical in mobility to the SOD activity of the crude extracts. Images PMID:3744555

  7. Enabling a New Planning and Scheduling Paradigm

    NASA Technical Reports Server (NTRS)

    Jaap, John; Davis, Elizabeth

    2004-01-01

    without the intervention of a scheduling expert. The algorithm is tuned for the constraint hierarchies and the complex temporal relationships provided by the modeling schema. It has an extensive search algorithm which can exploit timing flexibilities and constraint and relationship options. (3) A web-based architecture allows multiple remote users to simultaneously model science and technology requirements and other users to model vehicle and hardware characteristics. The architecture allows the users to submit scheduling requests directly to the scheduling engine and immediately see the results. These three components are integrated so that science and technology experts with no knowledge of the vehicle or hardware subsystems and no knowledge of the internal workings of the scheduling engine have the ability to build and submit scheduling requests and see the results. The immediate feedback will hone the users' modeling skills and ultimately enable them to produce the desired timeline. This paper summarizes the three components of the enabling technology and describes how this technology would make a new paradigm possible.

  8. Further studies on the GS element. A novel mycobacterial insertion sequence (IS1612), inserted into an acetylase gene (mpa) in Mycobacterium avium subsp. silvaticum but not in Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Bull, T J; Sheridan, J M; Martin, H; Sumar, N; Tizard, M; Hermon-Taylor, J

    2000-12-20

    We have recently described the GS element, found in Mycobacterium avium subsp. paratuberculosis (MAP), Mycobacterium avium subsp. silvaticum (MAS) and some isolates of Mycobacterium avium subsp. avium serotype 2 (MAAs2), which contains a set of genes of low GC% content, putatively associated with the biosynthesis, modification and transference of fucose to cell wall glycopeptidolipids. Here we describe a further gene of low GC% content (mpa), within the GS element in MAP. mpa is a putative acetyltransferase with homology to genes directly responsible for host specificity and virulence in Salmonella typhimurium and Shigella flexneri. Unlike other GS genes, strong homologues of mpa have not been found in related species, including Mycobacterium tuberculosis (MTB). In MAP, mpa encodes an ORF of 445aa, however, in MAS and MAAs2 mpa contains a single inserted copy of a novel insertion sequence. This element (IS1612) has two sets of inverted repeats at each terminus and encodes two ORFs with good homologies to transposase and helper proteins of IS21 (E. coli) and IS1415 (R. erythropolis). Sequence comparisons between mpa in MAP and MAS indicate the target site for IS1612 is duplicated on insertion to give a direct repeat at each end of the element. Immediately, downstream of the mpa gene in both MAP and MAS are a group of three genes with good homology to the daunorubicin resistance cluster. This cluster has a high GC% content which suggests a 'border' for the GS element. A short motif present at the beginning of this cluster matches with an inverted repeat of this motif at the beginning of the first gene in the GS element. This encapsulates the whole of this group of low GC% genes in MAP and further suggests its cassette-like nature. Homologues of the GS element in MTB show a marked similarity of organisation, suggesting a parallel role for these genes in both pathogens.

  9. Bayesian evidence and predictivity of the inflationary paradigm

    NASA Astrophysics Data System (ADS)

    Gubitosi, Giulia; Lagos, Macarena; Magueijo, João; Allison, Rupert

    2016-06-01

    In this paper we consider the issue of paradigm evaluation by applying Bayes' theorem along the following nested hierarchy of progressively more complex structures: i) parameter estimation (within a model), ii) model selection and comparison (within a paradigm), iii) paradigm evaluation. In such a hierarchy the Bayesian evidence works both as the posterior's normalization at a given level and as the likelihood function at the next level up. Whilst raising no objections to the standard application of the procedure at the two lowest levels, we argue that it should receive a considerable modification when evaluating paradigms, when testability and fitting data are equally important. By considering toy models we illustrate how models and paradigms that are difficult to falsify are always favoured by the Bayes factor. We argue that the evidence for a paradigm should not only be high for a given dataset, but exceptional with respect to what it would have been, had the data been different. With this motivation we propose a measure which we term predictivity, as well as a prior to be incorporated into the Bayesian framework, penalising unpredictivity as much as not fitting data. We apply this measure to inflation seen as a whole, and to a scenario where a specific inflationary model is hypothetically deemed as the only one viable as a result of information alien to cosmology (e.g. Solar System gravity experiments, or particle physics input). We conclude that cosmic inflation is currently hard to falsify, but that this could change were external/additional information to cosmology to select one of its many models. We also compare this state of affairs to bimetric varying speed of light cosmology.

  10. Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

    PubMed Central

    Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

    1992-01-01

    Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the

  11. Mycobacterium avium subspecies paratuberculosis infection of cattle does not diminish peripheral blood-derived macrophage mycobactericidal activity.

    PubMed

    Hostetter, J; Zhang, W; Simutis, F

    2006-09-15

    Ruminants infected with Mycobacterium avium subspecies paratuberculosis consistently develop a multibacillary form of disease that is centered on the ileum. Mechanisms responsible for failure of macrophage function during multibacillary disease are incompletely characterized. Our data suggest that mycobactericidal functions are present, and potentially enhanced, in monocyte-derived macrophages from M. avium subsp. paratuberculosis infected cattle. Addition of CD4(+) T cells from infected animals to autologous in vitro infected macrophages did not increase bacterial killing. In contrast, CD4(+) T cells from non-infected animals did increase bacterial killing in autologous macrophages. In macrophages from both infected and non-infected cattle, bacterial killing appeared to be independent of interferon-gamma (IFN-gamma) and nitric oxide production.

  12. Immune response of poults following intranasal inoculation with Artvax vaccine and a formalin-inactivated Bordetella avium bacterin.

    PubMed

    Hofstad, M S; Jeska, E L

    1985-01-01

    Poults 3 weeks and older developed temporary tracheal resistance to intranasal challenge following inoculation of either Artvax vaccine or formalin-inactivated Bordetella avium bacterin by the intranasal and eyedrop routes. Resistance usually persisted for 3-4 weeks after B. avium challenge. However, with constant exposure to infected controls, the vaccinated birds eventually developed tracheal infection. Day-old poults did not respond to either the Artvax or the bacterin and were completely susceptible to challenge. Two-week-old poults responded to some degree, but poults 3 weeks old and older responded best. Poults inoculated with bacterin by aerosol or by drinking water did not respond as well as those inoculated by the intranasal and eyedrop routes. When poults were given a single subcutaneous injection at 3 weeks of age and challenged 2 weeks later, three of five resisted infection for 18 days.

  13. Localization of Mycobacterium avium-intracellulare within a skin lesion of bacillary angiomatosis in a patient with AIDS.

    PubMed

    Sagerman, P M; Relman, D A; Niroomand, F; Niedt, G W

    1992-09-01

    We report a 39-year-old man who had AIDS and who presented with an unusual cutaneous vascular lesion, which was clinically thought to be Kaposi's sarcoma. Histologically, the lesion was characterized by capillary proliferation and a mixed inflammatory infiltrate that included numerous histiocytes. The lesion was found to contain slender intracellular acid-fast bacilli, as well as plump extracellular Warthin-Starry-positive bacilli. The acid-fast bacilli were confirmed to be Mycobacterium avium-intracellulare by subsequent positive blood cultures for this organism. To further investigate the lesion, polymerase chain reaction DNA amplification and sequencing was performed, and the lesion was found to contain DNA sequences identical to those previously established for the agent of bacillary angiomatosis. The lesion is thought to represent a lesion of bacillary angiomatosis with secondary involvement by M. avium-intracellulare.

  14. A comparison of cell mediators and serum cytokines transcript expression between male and female mice infected with Mycobacterium avium subspecies paratuberculosis and/or consuming probiotics.

    PubMed

    Karunasena, Enusha; McMahon, Kevin W; Kurkure, Paresh C; Brashears, Mindy M

    2014-11-01

    The gut immune system is complex, and dysregulation leads to a number of disorders including inflammatory bowel syndrome and (in livestock) Johne's disease. Previous work has demonstrated that males and females respond differently to treatment with pathologic and probiotic microorganisms, suggesting that a 'one-size-fits-all' approach to treat GIT inflammation may be inadequate. While we had observed significant differences between males and females in terms of cytokine production, it remains unclear how these changes occur. To better understand the mechanisms, transcript expression of genes important to gut immunoregulation were monitored from male and female BALB/c mice consuming the probiotic Lactobacillus animalis (1 × 10(6) CFU g(-1) ) and infected with the gut pathogen, Mycobacterium avium subspecies paratuberculosis (1 × 10(7) CFU). Expression of transcripts analyzed included those important to the immune system, intestinal cell differentiation, and/or regulation. Males generally displayed increased expression of Th 2 and B-cell mediators, and females showed repressed cytokine expression after MAP infection (IL-6, TNF-α, IL-1 among others). Additionally, regulation of pro-inflammatory mediators in female mice consuming probiotics suggests females responded positively to L. animalis when compared to males. Therefore, we speculate that studying mechanistic changes associated with sex and immunoregulation in gastrointestinal tissues could further elucidate host response to microorganisms.

  15. Innate defensive behaviour and panic-like reactions evoked by rodents during aggressive encounters with Brazilian constrictor snakes in a complex labyrinth: behavioural validation of a new model to study affective and agonistic reactions in a prey versus predator paradigm.

    PubMed

    Guimarães-Costa, Raquel; Guimarães-Costa, Maria Beatriz; Pippa-Gadioli, Leonardo; Weltson, Alfredo; Ubiali, Walter Adriano; Paschoalin-Maurin, Tatiana; Felippotti, Tatiana Tocchini; Elias-Filho, Daoud Hibrahim; Laure, Carlos Júlio; Coimbra, Norberto Cysne

    2007-09-15

    Defensive behaviour has been extensively studied, and non-invasive methodologies may be interesting approaches to analyzing the limbic system function as a whole. Using experimental models of animals in the state of anxiety has been fundamental in the search for new anxiolytic and antipanic compounds. The aim of this present work is to examine a new model for the study of affective behaviour, using a complex labyrinth consisting of an arena and galleries forming a maze. Furthermore, it aims to compare the defensive behaviour of Wistar rats, Mongolian gerbils and golden hamsters in a complex labyrinth, as well as the defensive behaviour of Meriones unguiculatus in aggressive encounters with either Epicrates cenchria assisi or Boa constrictor amarali in this same model. Among species presently studied, the Mongolian gerbils showed better performance in the exploration of both arena and galleries of the labyrinth, also demonstrating less latency in finding exits of the galleries. This increases the possibility of survival, as well as optimizes the events of encounter with the predator. The duration of alertness and freezing increased during confrontation with living Epicrates, as well as the duration of exploratory behaviour in the labyrinth. There was an increase in the number of freezing and alertness behaviours, as well as in duration of alertness during confrontations involving E.c. assisi, compared with behavioural reactions elicited by jirds in presence of B.c. amarali. Interestingly, the aggressive behaviour of Mongolian gerbils was more prominent against B.c. amarali compared with the other Boidae snake. E.c. assisi elicited more offensive attacks and exhibited a greater time period of body movement than B.c. amarali, which spent more time in the arena and in defensive immobility than the E.c. assisi. Considering that jirds evoked more fear-like reaction in contact with E.c. assisi, a fixed E.c. assisi kept in a hermetically closed acrylic box was used as

  16. Testing paradigms of ecosystem change under climate warming in Antarctica.

    PubMed

    Melbourne-Thomas, Jessica; Constable, Andrew; Wotherspoon, Simon; Raymond, Ben

    2013-01-01

    Antarctic marine ecosystems have undergone significant changes as a result of human activities in the past and are now responding in varied and often complicated ways to climate change impacts. Recent years have seen the emergence of large-scale mechanistic explanations-or "paradigms of change"-that attempt to synthesize our understanding of past and current changes. In many cases, these paradigms are based on observations that are spatially and temporally patchy. The West Antarctic Peninsula (WAP), one of Earth's most rapidly changing regions, has been an area of particular research focus. A recently proposed mechanistic explanation for observed changes in the WAP region relates changes in penguin populations to variability in krill biomass and regional warming. While this scheme is attractive for its simplicity and chronology, it may not account for complex spatio-temporal processes that drive ecosystem dynamics in the region. It might also be difficult to apply to other Antarctic regions that are experiencing some, though not all, of the changes documented for the WAP. We use qualitative network models of differing levels of complexity to test paradigms of change for the WAP ecosystem. Importantly, our approach captures the emergent effects of feedback processes in complex ecological networks and provides a means to identify and incorporate uncertain linkages between network elements. Our findings highlight key areas of uncertainty in the drivers of documented trends, and suggest that a greater level of model complexity is needed in devising explanations for ecosystem change in the Southern Ocean. We suggest that our network approach to evaluating a recent and widely cited paradigm of change for the Antarctic region could be broadly applied in hypothesis testing for other regions and research fields.

  17. Testing Paradigms of Ecosystem Change under Climate Warming in Antarctica

    PubMed Central

    Melbourne-Thomas, Jessica; Constable, Andrew; Wotherspoon, Simon; Raymond, Ben

    2013-01-01

    Antarctic marine ecosystems have undergone significant changes as a result of human activities in the past and are now responding in varied and often complicated ways to climate change impacts. Recent years have seen the emergence of large-scale mechanistic explanations–or “paradigms of change”–that attempt to synthesize our understanding of past and current changes. In many cases, these paradigms are based on observations that are spatially and temporally patchy. The West Antarctic Peninsula (WAP), one of Earth’s most rapidly changing regions, has been an area of particular research focus. A recently proposed mechanistic explanation for observed changes in the WAP region relates changes in penguin populations to variability in krill biomass and regional warming. While this scheme is attractive for its simplicity and chronology, it may not account for complex spatio-temporal processes that drive ecosystem dynamics in the region. It might also be difficult to apply to other Antarctic regions that are experiencing some, though not all, of the changes documented for the WAP. We use qualitative network models of differing levels of complexity to test paradigms of change for the WAP ecosystem. Importantly, our approach captures the emergent effects of feedback processes in complex ecological networks and provides a means to identify and incorporate uncertain linkages between network elements. Our findings highlight key areas of uncertainty in the drivers of documented trends, and suggest that a greater level of model complexity is needed in devising explanations for ecosystem change in the Southern Ocean. We suggest that our network approach to evaluating a recent and widely cited paradigm of change for the Antarctic region could be broadly applied in hypothesis testing for other regions and research fields. PMID:23405116

  18. Cloning, sequencing, and expression of the mig gene of Mycobacterium avium, which codes for a secreted macrophage-induced protein.

    PubMed Central

    Plum, G; Brenden, M; Clark-Curtiss, J E; Pulverer, G

    1997-01-01

    Mycobacterium avium is an intracellular pathogen that has evolved to be a frequent cause of disseminated infection in immunocompromised patients. Although these bacilli are readily phagocytized, they are able to survive and even multiply within human macrophages. The process whereby mycobacteria circumvent the lytic functions of the macrophages is currently not well understood, but this is a key aspect in the pathogenicity of all pathogenic mycobacteria. Previously, we identified a gene in M. avium, designated mig (for macrophage-induced gene), the expression of which is induced when the bacilli grow in human macrophages (G. Plum and J. E. Clark-Curtiss, Infect. Immun. 62:476-483, 1994). In the present study we show that (i) the nucleotide sequence of the mig gene has an open reading frame of 295 amino acids with a strong bias for mycobacterial codon usage, (ii) the mig gene also codes for a putative signal peptide of 19 amino acid residues, (iii) mig is induced by acidity to be expressed as an early-secreted 30-kDa protein, and (iv) the Mig protein exhibits an AMP-binding domain signature. However, beyond this motif which is common to enzymes that activate a large variety of substrates, no homologies to known sequences are found. We also show that (v) Mycobacterium smegmatis strains expressing the Mig protein have a limited advantage for survival in macrophages. These findings may be concordant with a role of the mig gene in the virulence of M. avium. PMID:9353032

  19. Biofabrication: a 21st century manufacturing paradigm.

    PubMed

    Mironov, V; Trusk, T; Kasyanov, V; Little, S; Swaja, R; Markwald, R

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. PMID:20811099

  20. Think globally, research locally: paradigms and place in agroecological research.

    PubMed

    Reynolds, Heather L; Smith, Alex A; Farmer, James R

    2014-10-01

    Conducting science for practical ends implicates scientists, whether they wish it or not, as agents in social-ecological systems, raising ethical, economic, environmental, and political issues. Considering these issues helps scientists to increase the relevance and sustainability of research outcomes. As we rise to the worthy call to connect basic research with food production, scientists have the opportunity to evaluate alternative food production paradigms and consider how our research funds and efforts are best employed. In this contribution, we review some of the problems produced by science conducted in service of industrial agriculture and its associated economic growth paradigm. We discuss whether the new concept of "ecological intensification" can rescue the industrial agriculture/growth paradigm and present an emerging alternative paradigm of decentralized, localized, biodiversity-promoting agriculture for a steady-state economy. This "custom fit" agriculture engages constructively with complex and highly localized ecosystems, and we draw from examples of published work to demonstrate how ecologists can contribute by using approaches that acknowledge local agricultural practices and draw on community participation. PMID:25326612

  1. Think globally, research locally: paradigms and place in agroecological research.

    PubMed

    Reynolds, Heather L; Smith, Alex A; Farmer, James R

    2014-10-01

    Conducting science for practical ends implicates scientists, whether they wish it or not, as agents in social-ecological systems, raising ethical, economic, environmental, and political issues. Considering these issues helps scientists to increase the relevance and sustainability of research outcomes. As we rise to the worthy call to connect basic research with food production, scientists have the opportunity to evaluate alternative food production paradigms and consider how our research funds and efforts are best employed. In this contribution, we review some of the problems produced by science conducted in service of industrial agriculture and its associated economic growth paradigm. We discuss whether the new concept of "ecological intensification" can rescue the industrial agriculture/growth paradigm and present an emerging alternative paradigm of decentralized, localized, biodiversity-promoting agriculture for a steady-state economy. This "custom fit" agriculture engages constructively with complex and highly localized ecosystems, and we draw from examples of published work to demonstrate how ecologists can contribute by using approaches that acknowledge local agricultural practices and draw on community participation.

  2. Paradigm shifts in Medicare reform.

    PubMed

    Jones, S B; Etheredge, L

    1996-04-01

    Reforms passed by Congress and vetoed by the president during the past year would have accelerated initiatives already transforming Medicare. Operating in a rapidly changing insurance marketplace, Medicare is shifting from a social insurance model toward a private individual insurance model-expanding the number and type of alternative health plans it offers-and growing numbers of beneficiaries are enrolling in these plans. Such reforms, especially if bolstered by legislative reforms that are likely to resurface after the November elections, will rewrite the social contract enacted more than 30 years ago. They require fundamental shifts in ways of thinking about the federal government's responsibilities; the Medicare program's management; relations between the Medicare program and doctors, hospitals, and other health care providers; and the role of beneficiaries in the Medicare program. The likely deferral of further legislative attempts to reform Medicare affords an opportunity to step back and consider these ongoing changes. It is not easy to describe paradigm shifts accurately, but there are advantages to trying. First, conceptual comparisons can allow public discussion to go beyond budget scorekeeping and media soundbites to consider how different the Medicare program will be if it evolves in the new ways being proposed. Second, a conceptual framework can assist health policy analysts to target what to watch for in tracking changes, to assess the tradeoffs involved, and to advise about the needs for refining legislation. This paper includes examples of what to watch for in tracking the implemented changes. The paradigm shifts are summarized below, then described individually in terms of directions of change along a number of continuums. Note that complete paradigm shifts, from one end of a continuum to the other, are seldom completely realized nor even far advanced. But Medicare's ongoing reforms, accelerated by legislative proposals, seem likely predecessors of

  3. A New Paradigm for Groundwater Modeling

    NASA Astrophysics Data System (ADS)

    Li, S.; Liu, Q.; Afshari, S.

    2005-12-01

    In this talk, we present interim results from an on-going integrated NSF project to develop a new paradigm and a computational steering environment for real-time multi-scale groundwater modeling, data assimilation, information integration, and visualization. The new paradigm has the potential to significantly improve our ability to characterize and predict water and solute pathways and fluxes through geological formations and the fluxes across surface water and groundwater interfaces, to quantify the scale interactions that affect the response of aquifer systems to local and external forcing factors, and to develop model-based tools for integrated resources management. Despite the dramatic growth of computational capability over the past two decades - one that has allowed computational science to become a powerful tool for scientific discovery, our ability to model complex, 3D systems is still severely limited because of the following computational and conceptual challenges: The machine bottleneck. The computation in large-scale modeling, analysis, and visualization increases exponentially with the problem size and the level of details simulated and quickly becomes prohibitive for large problems. This is especially the case for multi-scale and coupled processes modeling, inverse modeling, and uncertainty analysis. The algorithmic bottleneck. Three-dimensional modeling based on a single numerical representation of a multi-scaled system faces an algorithmic bottleneck. The high dimensionality, especially when combined with distorted grids representing multiple scales of heterogeneity, anisotropy, complex stratigraphy, and singular stresses, translates into ill conditioned matrix systems, and causes a host of numerical problems. The scale and data assimilation problem. A fundamental problem in the analysis of groundwater systems is the interplay of data and modeling. Improving how data and models are used, especially across a multitude of scales, has proven to be

  4. A molecular beacon-based real-time NASBA assay for detection of Mycobacterium avium subsp. paratuberculosis in water and milk.

    PubMed

    Rodríguez-Lázaro, David; Lloyd, Joy; Herrewegh, Arnold; Ikonomopoulos, John; D'Agostino, Martin; Pla, Maria; Cook, Nigel

    2004-08-01

    A molecular beacon-based real-time NASBA assay for detection and identification of Mycobacterium avium subsp. paratuberculosis has been developed. It targets and amplifies sequences from the dnaA gene which are specific for this bacterium. The assay includes an internal amplification control, to allow identification of inhibited reactions. The assay was tested against 18 isolates of M. avium subsp. paratuberculosis, 17 other mycobacterial strains and 25 non-mycobacterial strains, and was fully selective in that it detected all the targets but none of the non-targets. The lowest number of cells which the assay can detect with 99% probability is 150-200 cells per reaction (as determined using pure culture suspensions). Using centrifugation and nucleic acid extraction as sample treatment, the assay was able to consistently detect 10(3) M. avium subsp. paratuberculosis cells in 20 ml artificially contaminated drinking water. With a simple detergent and enzymatic sample pretreatment before centrifugation and nucleic acid extraction, the assay was able to consistently detect 10(4) M. avium subsp. paratuberculosis cells in 20 ml artificially contaminated semi-skimmed milk. The assay will be a useful addition to the range of diagnostic tools available for the study of M. avium subsp. paratuberculosis.

  5. Datacubes as a Service Paradigm

    NASA Astrophysics Data System (ADS)

    Rossi, Angelo Pio; Baumann, Peter

    2016-04-01

    Spatio-temporal data sets often can be represented conveniently through datacubes as a common unifying paradigm. Flexible, scalable services can be offered based on the concept of a datacube query language while hiding the technicalities, thereby allowing user-friendly visual data interaction. One of today's most influential initiatives in Big Geo Data is EarthServer which is paving the way for flexible, scalable datacube services based on innovative NewSQL technology (Fig. 1). Researchers from Europe, the US and recently Australia have teamed up to rigorously materialize the datacube paradigm for Earth Observation, ocean, meteorological, and planetary science. EarthServer has established client and server technology for such spatio-temporal datacubes strictly based on the open datacube standards, OGC WCS and WPCS. The underlying scalable array engine, rasdaman, enables direct interaction, including 3-D visualization, what-if scenarios, common EO data processing, and general analytics on regular and irregular grids. Integration of datacube and metadata retrieval, together with advanced visualization based on NASA WorldWind, are geared towards an effective, user-friendly access and analysis. Conversely, EarthServer is significantly shaping the ISO, OGC, and INSPIRE Big Data standards landscape by being specification editor. Phase 1 of EarthServer has advanced scalable array data¬base technology into 100+ TB services; in phase 2, a federation of Petabyte datacubes is being built in Europe and Australia to perform ad-hoc querying and merging. Phase 1 reviewers have attested rasdaman to "significantly transform the way that scientists in different areas of Earth Science will be able to access and use data in a way that hitherto was not possible". Altogether, these large-scale deployments prove that datacubes are a convenient model for presenting users with a simple, consolidated view on the massive amount of data files gathered - "a cube tells more than a million

  6. Methodological issues in the psychology of religion: toward another paradigm?

    PubMed

    Belzen, Jacob A; Hood, Ralph W

    2006-01-01

    Recent evaluations have identified the psychology of religion as a field in crisis and have called for a new multilevel interdisciplinary paradigm. However, a critical meta-perspective on methods reveals a broad range of methodologies, each appropriate for particular levels of complexity in the psychology of religion. No single methodology is appropriate for every level, nor can higher levels of complexity be explained by data from lower levels. The authors identify the different types of research practiced in the psychology of religion and critically discuss philosophical presuppositions involved in two major methodological traditions, the empiricist-analytical and the hermeneutical, often identified as quantitative and qualitative traditions, respectively.

  7. Intracellular fate of Mycobacterium avium: use of dual-label spectrofluorometry to investigate the influence of bacterial viability and opsonization on phagosomal pH and phagosome-lysosome interaction.

    PubMed Central

    Oh, Y K; Straubinger, R M

    1996-01-01

    Mycobacterium avium is a facultative intracellular pathogen that can survive and replicate within macrophages. We tested the hypotheses that survival mechanisms may include alteration of phagosomal pH or inhibition of phagosome-lysosome fusion. M. avium was surface labeled with N-hydroxysuccinimidyl esters of carboxyfluorescein (CF) and rhodamine (Rho) to enable measurement of the pH of individual M. avium-containing phagosomes and the interactions of bacterium-containing phagosomes with labeled secondary lysosomes. CF fluorescence is pH sensitive, whereas Rho is pH insensitive; pH can be calculated from their fluorescence ratios. Surface labeling of M. avium did not affect viability in broth cultures or within J774, a murine macrophage-like cell line. By fluorescence spectroscopy, live M. avium was exposed to an environmental pH of approximately 5.7 at 6 h after phagocytosis, whereas similarly labeled Salmonella typhimurium, zymosan A, or heat-killed M. avium encountered an environmental pH of < 5.0. Video fluorescence and laser scanning confocal microscopy gave consistent pH results and demonstrated the heterogeneity of intracellular fate early in infection. pH became more homogeneous 6 h after infection. M. avium cells were coated with immunoglobulin G (IgG) or opsonized to investigate whether phagocytosis by the corresponding receptors would alter intracellular fate. Opsonized, unopsonized, and IgG-coated M. avium cells entered compartments of similar pH. Finally, the spatial distribution of intracellular bacteria and secondary lysosomes was compared. Only 18% of live fluorescent M. avium cells colocalized with fluorescent lysosomes, while 98% of heat-killed bacteria colocalized. Thus, both inhibition of phagosome-lysosome fusion and alteration of phagosomal pH may contribute to the intracellular survival of M. avium. PMID:8557358

  8. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    PubMed Central

    Hilborn, Elizabeth D.; Arduino, Matthew J.; Pruden, Amy; Edwards, Marc A.

    2015-01-01

    Background Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexisting risk factors and frequently require hospitalization. Objectives The objectives of this report are to alert professionals of the impact of OPPPs, the fact that 30% of the population may be exposed to OPPPs, and the need to develop means to reduce OPPP exposure. We herein present a review of the epidemiology and ecology of these three bacterial OPPPs, specifically to identify common and unique features. Methods A Water Research Foundation–sponsored workshop gathered experts from across the United States to review the characteristics of OPPPs, identify problems, and develop a list of research priorities to address critical knowledge gaps with respect to increasing OPPP-associated disease. Discussion OPPPs share the common characteristics of disinfectant resistance and growth in biofilms in water distribution systems or premise plumbing. Thus, they share a number of habitats with humans (e.g., showers) that can lead to exposure and infection. The frequency of OPPP-infected individuals is rising and will likely continue to rise as the number of at-risk individuals is increasing. Improved reporting of OPPP disease and increased understanding of the genetic, physiologic, and structural characteristics governing the persistence and growth of OPPPs in drinking water distribution systems and premise plumbing is needed. Conclusions Because broadly effective community-level engineering interventions for the control of OPPPs have yet to be identified, and because the number of at-risk individuals will continue to rise, it is likely that OPPP-related infections will continue to increase. However, it is possible that individuals can take measures (e.g., raise hot water heater temperatures and filter

  9. Effects of elevated CO(2) on growth and chloroplast proteins in Prunus avium.

    PubMed

    Wilkins, D.; Van Oosten, J.-J.; Besford, R. T.

    1994-01-01

    To predict the future carbon sequestering capacity of trees, we need information about the possible acclimatory mechanisms of plant growth and photosynthesis in rising atmospheric CO(2) under a variety of environmental conditions. We have, therefore, studied the growth response of a tree species (Prunus avium L. Stella (wild cherry)) to elevated CO(2) and characterized the associated changes in photosynthetic machinery of the leaf tissue. Self-pollinated seedlings and mature cuttings (clones) from the same parent plant of P. avium were grown for two consecutive growing seasons (about 60 days each) in ambient CO(2) (350 micro mol mol(-1) CO(2)) or elevated CO(2) (700 micro mol mol(-1) CO(2)) with a high or low nutrient supply. The degree of acclimation of leaf biochemistry and growth response to elevated CO(2) was dependent on the plant material (seedling or mature cutting) and nutrient supply. There was little or no growth response to elevated CO(2) in seedlings or cuttings in the low nutrient supply treatments, whereas, in both seasons, there was a strongly positive growth response to elevated CO(2) in seedlings and cuttings in the high nutrient supply regimes, resulting in increases in the root/shoot ratio and in carbon allocation to the roots. In contrast, the protein content and activity of ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco, EC 4.1.1.39) were down regulated in elevated CO(2). The loss of Rubisco on an area basis in plants in the elevated CO(2) treatments was compensated for at the canopy level by increased leaf area. The loss of Rubisco protein was accompanied by decreases in the contents of chlorophyll and the thylakoid membrane proteins D(1), D(2) and cytochrome f, which are involved in light harvesting and photo-electron transport. We conclude that, in the medium- to long-term, the initial stimulation of biomass production by elevated CO(2) may be increasingly offset by a lower photosynthetic capacity per unit leaf area in perennial

  10. Listening Fluency Before Speaking: An Alternative Paradigm.

    ERIC Educational Resources Information Center

    Nord, James, R.

    The foreign language instruction in the United States has followed a paradigm commonly called the "audio-lingual" method for almost twenty years. This paradigm is basically response-oriented and based upon structural linguistics and behavioral psychology. It focuses attention on speaking as the primary skill. It has not lived up to expectations.…

  11. Is This the Paradigm Shift We Need?

    ERIC Educational Resources Information Center

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  12. Towards a New Paradigm of Moral Personhood

    ERIC Educational Resources Information Center

    Frimer, Jeremy A.; Walker, Lawrence J.

    2008-01-01

    Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

  13. The cognitive paradigm and the immunological homunculus.

    PubMed

    Cohen, I R

    1992-12-01

    In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, during on concrete examples from the image of infection and the image of self, the immunological homunculus.

  14. Shifting Paradigms: From Flexner to Competencies.

    ERIC Educational Resources Information Center

    Carraccio, Carol; Wolfsthal, Susan D.; Englander, Robert; Ferentz, Kevin; Martin, Christine

    2002-01-01

    Reviewed the literature on competency-based medical education to: (1) understand the evolution of this educational paradigm; (2) assess the evidence to date of the efficacy of competency-based education; and (3) provide practical insights into how to accomplish full implementation and evaluation of the paradigm shift. (EV)

  15. Mercury biogeochemistry: Paradigm shifts, outstanding issues and research needs

    NASA Astrophysics Data System (ADS)

    Sonke, Jeroen E.; Heimbürger, Lars-Eric; Dommergue, Aurélien

    2013-05-01

    Half a century of mercury research has provided scientists and policy makers with a detailed understanding of mercury toxicology, biogeochemical cycling and past and future impacts on human exposure. The complexity of the global biogeochemical mercury cycle has led to repeated and ongoing paradigm shifts in numerous mercury-related disciplines and outstanding questions remain. In this review, we highlight some of the paradigm shifts and questions on mercury toxicity, the risks and benefits of seafood consumption, the source of mercury in seafood, and the Arctic mercury cycle. We see a continued need for research on mercury toxicology and epidemiology, for marine mercury dynamics and ecology, and for a closer collaboration between observational mercury science and mercury modeling in general. As anthropogenic mercury emissions are closely tied to the energy cycle (in particular coal combustion), mercury exposure to humans and wildlife are likely to persist unless drastic emission reductions are put in place.

  16. A New Paradigm For Testing Human And Machine Motion Perception

    NASA Astrophysics Data System (ADS)

    Papathomas, Thomas V.; Gorea, Andrei

    1989-08-01

    We present a new paradigm for studying motion perception. This approach is based on a class of stimuli that we devised for testing the relative strength of stimulus attributes (luminance, color, spatial frequency, orientation, binocular disparity, etc.) in eliciting motion perception by correspondence matching. In this class of stimuli, different attributes are matched simultaneously in the spatio-temporal domain in a systematic, algorithmic manner which allows each attribute to produce motion in an arbitrary direction (if, of course, it is a token for movement perception), independently of the other attributes. This results in animation sequences in which many different motion paths may co-exist, each path due to a different attribute. Such an arrangement allows a direct comparison of the strength of attributes in eliciting movement. Results from psychophysical experiments based on our paradigm can be used to develop complex motion detection models for machine vision systems which attempt to approximate human performance. Similar methods are discussed for studying stereopsis mechanisms.

  17. Developing sustainable software solutions for bioinformatics by the " Butterfly" paradigm.

    PubMed

    Ahmed, Zeeshan; Zeeshan, Saman; Dandekar, Thomas

    2014-01-01

    Software design and sustainable software engineering are essential for the long-term development of bioinformatics software. Typical challenges in an academic environment are short-term contracts, island solutions, pragmatic approaches and loose documentation. Upcoming new challenges are big data, complex data sets, software compatibility and rapid changes in data representation. Our approach to cope with these challenges consists of iterative intertwined cycles of development (" Butterfly" paradigm) for key steps in scientific software engineering. User feedback is valued as well as software planning in a sustainable and interoperable way. Tool usage should be easy and intuitive. A middleware supports a user-friendly Graphical User Interface (GUI) as well as a database/tool development independently. We validated the approach of our own software development and compared the different design paradigms in various software solutions.

  18. Alpha-1 Antitrypsin Deficiency: Beyond the Protease/Antiprotease Paradigm.

    PubMed

    Cosio, Manuel G; Bazzan, Erica; Rigobello, Chiara; Tinè, Mariaenrica; Turato, Graziella; Baraldo, Simonetta; Saetta, Marina

    2016-08-01

    From the discovery that alpha-1 antitrypsin (AAT) was an effective inhibitor of neutrophil elastase originated the classic paradigm of protease/antiprotease imbalance, linking lung destruction to the unopposed effect of proteases in patients with the deficiency. Notwithstanding its importance as an antiprotease, it has become evident that alpha-1 antitrypsin has important antiinflammatory and immune-regulatory activities, which may be critically involved in lung destruction. We review here recent evidence showing that, indeed, an important adaptive immune reaction is present in lungs with AAT deficiency, similar to the one seen in severe chronic obstructive pulmonary disease with normal AAT. On the basis of recent evidence from epidemiological, clinical, and pathogenetic studies, it is likely time to move on from the original protease/antiprotease hypothesis for the production of emphysema toward a more complex paradigm, involving the antiinflammatory and immune modulating functions of AAT. PMID:27564665

  19. Inflationary paradigm in trouble after Planck2013

    NASA Astrophysics Data System (ADS)

    Ijjas, Anna; Steinhardt, Paul J.; Loeb, Abraham

    2013-06-01

    Recent results from the Planck satellite combined with earlier observations from WMAP, ACT, SPT and other experiments eliminate a wide spectrum of more complex inflationary models and favor models with a single scalar field, as reported by the Planck Collaboration. More important, though, is that all the simplest inflaton models are disfavored statistically relative to those with plateau-like potentials. We discuss how a restriction to plateau-like models has three independent serious drawbacks: it exacerbates both the initial conditions problem and the multiverse-unpredictability problem and it creates a new difficulty that we call the inflationary "unlikeliness problem." Finally, we comment on problems reconciling inflation with a standard model Higgs, as suggested by recent LHC results. In sum, we find that recent experimental data disfavors all the best-motivated inflationary scenarios and introduces new, serious difficulties that cut to the core of the inflationary paradigm. Forthcoming searches for B-modes, non-Gaussianity and new particles should be decisive.

  20. Direct identification and discernment of Mycobacterium avium and Mycobacterium intracellulare using a real-time RNA isothermal amplification and detection method.

    PubMed

    Cui, Zhenling; Li, Yuanyuan; Cheng, Song; Yang, Hua; Lu, Junmei; Zhu, Honglei; Hu, Zhongyi

    2015-12-01

    The purpose of this work was to establish a real-time simultaneous amplification and testing method for identification and discernment of Mycobacterium avium and Mycobacterium intracellulare (SAT-MAC assay) and to evaluate the efficiency with which this method can detect isolated strains and clinical sputum specimens. The specific 16S rRNA sequences of M. avium and M. intracellulare were used as targets to design RNA probes and a reverse transcription primer containing T7 promoter. RNA isothermal amplification and real-time fluorescence detection were performed at 42 °C. SAT-MAC assay, culture tests on Lowenstein-Jensen (L-J) culture medium and PCR-sequencing were used to test the clinical isolated strains and sputum specimens. The limit of detection (LOD) of M. avium and M. intracellulare by SAT-MAC was found to be 30 CFU/mL and 20 CFU/mL. SAT-MAC showed high specificity in 21 species of mycobacteria standard strains and 5 species of non-mycobacteria bacteria. Using PCR-sequencing as the reference method, both rates of SAT-MAC assay for identifying M. avium and M. intracellulare from clinical isolates were 100% (259/259). Consistent with the results of L-J culture combined PCR-sequencing, the coincidence rate of SAT-MAC assay in clinical sputum specimens was 100% (369/369) for M. avium and 99.19% (366/369) for Mycobacterium intracellular. The SAT-MAC assay can identify and distinguish M. avium and M. intracellulare rapidly and accurately. It may be suitable for use in clinical microbiology laboratories.

  1. The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

    PubMed Central

    Babrak, Lmar; Danelishvili, Lia; Rose, Sasha J.; Kornberg, Tiffany

    2014-01-01

    “Mycobacterium avium subsp. hominissuis” is an opportunistic environmental pathogen that causes respiratory illness in immunocompromised patients, such as those with cystic fibrosis as well as other chronic respiratory diseases. Currently, there is no efficient approach to prevent or treat M. avium subsp. hominissuis infection in the lungs. During initial colonization of the airways, M. avium subsp. hominissuis forms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasion in vitro and in vivo. DNA microarray analysis was employed to identify genes associated with the microaggregate phenotype. The gene encoding microaggregate-binding protein 1 (MBP-1) (MAV_3013) is highly expressed during microaggregate formation. When expressed in noninvasive Mycobacterium smegmatis, MBP-1 increased the ability of the bacteria to bind to HEp-2 epithelial cells. Using anti-MBP-1 immune serum, microaggregate binding to HEp-2 cells was significantly reduced. By far-Western blotting, and verified by coimmunoprecipitation, we observed that MBP-1 interacts with the host cytoskeletal protein vimentin. As visualized by confocal microscopy, microaggregates, as well as MBP-1, induced vimentin polymerization at the site of bacterium-host cell contact. Binding of microaggregates to HEp-2 cells was inhibited by treatment with an antivimentin antibody, suggesting that MBP-1 expression is important for M. avium subsp. hominissuis adherence to the host cell. MBP-1 immune serum significantly inhibited M. avium subsp. hominissuis infection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized by M. avium subsp. hominissuis to bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy. PMID:25422262

  2. Genetic Structure of Mycobacterium avium subsp. paratuberculosis Population in Cattle Herds in Quebec as Revealed by Using a Combination of Multilocus Genomic Analyses

    PubMed Central

    Sohal, Jagdip Singh; Arsenault, Julie; Labrecque, Olivia; Fairbrother, Julie-Hélène; Roy, Jean-Philippe; Fecteau, Gilles

    2014-01-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of paratuberculosis, a granulomatous enteritis affecting a wide range of domestic and wild ruminants worldwide. A variety of molecular typing tools are used to distinguish M. avium subsp. paratuberculosis strains, contributing to a better understanding of M. avium subsp. paratuberculosis epidemiology. In the present study, PCR-based typing methods, including mycobacterial interspersed repetitive units/variable-number tandem repeats (MIRU-VNTR) and small sequence repeats (SSR) in addition to IS1311 PCR-restriction enzyme analysis (PCR-REA), were used to investigate the genetic heterogeneity of 200 M. avium subsp. paratuberculosis strains from dairy herds located in the province of Quebec, Canada. The majority of strains were of the “cattle type,” or type II, although 3 strains were of the “bison type.” A total of 38 genotypes, including a novel one, were identified using a combination of 17 genetic markers, which generated a Simpson's index of genetic diversity of 0.876. Additional analyses revealed no differences in genetic diversity between environmental and individual strains. Of note, a spatial and spatiotemporal cluster was evidenced regarding the distribution of one of the most common genotypes. The population had an overall homogeneous genetic structure, although a few strains stemmed out of the consensus cluster, including the bison-type strains. The genetic structure of M. avium subsp. paratuberculosis populations within most herds suggested intraherd dissemination and microevolution, although evidence of interherd contamination was also revealed. The level of genetic diversity obtained by combining MIRU-VNTR and SSR markers shows a promising avenue for molecular epidemiology investigations of M. avium subsp. paratuberculosis transmission patterns. PMID:24829229

  3. Genetic structure of Mycobacterium avium subsp. paratuberculosis population in cattle herds in Quebec as revealed by using a combination of multilocus genomic analyses.

    PubMed

    Sohal, Jagdip Singh; Arsenault, Julie; Labrecque, Olivia; Fairbrother, Julie-Hélène; Roy, Jean-Philippe; Fecteau, Gilles; L'Homme, Yvan

    2014-08-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of paratuberculosis, a granulomatous enteritis affecting a wide range of domestic and wild ruminants worldwide. A variety of molecular typing tools are used to distinguish M. avium subsp. paratuberculosis strains, contributing to a better understanding of M. avium subsp. paratuberculosis epidemiology. In the present study, PCR-based typing methods, including mycobacterial interspersed repetitive units/variable-number tandem repeats (MIRU-VNTR) and small sequence repeats (SSR) in addition to IS1311 PCR-restriction enzyme analysis (PCR-REA), were used to investigate the genetic heterogeneity of 200 M. avium subsp. paratuberculosis strains from dairy herds located in the province of Quebec, Canada. The majority of strains were of the "cattle type," or type II, although 3 strains were of the "bison type." A total of 38 genotypes, including a novel one, were identified using a combination of 17 genetic markers, which generated a Simpson's index of genetic diversity of 0.876. Additional analyses revealed no differences in genetic diversity between environmental and individual strains. Of note, a spatial and spatiotemporal cluster was evidenced regarding the distribution of one of the most common genotypes. The population had an overall homogeneous genetic structure, although a few strains stemmed out of the consensus cluster, including the bison-type strains. The genetic structure of M. avium subsp. paratuberculosis populations within most herds suggested intraherd dissemination and microevolution, although evidence of interherd contamination was also revealed. The level of genetic diversity obtained by combining MIRU-VNTR and SSR markers shows a promising avenue for molecular epidemiology investigations of M. avium subsp. paratuberculosis transmission patterns. PMID:24829229

  4. The Physical and Cognitive Paradigms in Information Retrieval Research.

    ERIC Educational Resources Information Center

    Ellis, David

    1992-01-01

    Explores the role of paradigms in information retrieval research and discusses the nature of a paradigm and the applicability of the paradigm concept to a multidisciplinary field such as information science. The features of the physical paradigm and the cognitive paradigm are outlined, and their origins, nature, and role are examined. (55…

  5. Bovine PGLYRP1 polymorphisms and their association with resistance to Mycobacterium avium ssp. paratuberculosis.

    PubMed

    Pant, S D; Verschoor, C P; Schenkel, F S; You, Q; Kelton, D F; Karrow, N A

    2011-08-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes a chronic, granulomatous inflammatory condition of the intestines in ruminants and wild-type species. It causes significant economic losses to the dairy and beef industries owing to reduced productivity, premature culling and mortality. Bovine peptidoglycan recognition protein 1 is an important pattern recognition molecule that is capable of directly killing microorganisms. The goal of this study was to identify single nucleotide polymorphisms (SNPs) in the gene encoding bovine peptidoglycan recognition protein 1 and to assess their association with susceptibility to MAP infection in dairy cattle. Blood and milk samples were collected from Holsteins in Southwestern and Eastern Ontario and tested for MAP infection using blood and milk ELISAs. A resource population consisting of 197 infected (S/P > 0.25) and 242 healthy (S/P < 0.10) cattle was constructed. Sequencing of pooled DNA was used to identify three SNPs (c.102G>C, c.480G>A and c.625C>A) that were genotyped in the resource population. Statistical analysis was performed using a logistic regression model fitting the additive and dominance effects of each SNP in the model. SNP c.480G>A (P = 0.054) was found to be associated with susceptibility to MAP infection. Cows with a copy of the major allele 'G' at this locus had an odds ratio of 1.51 (95% CI: 0.99-2.31) for being infected with MAP.

  6. The Association of Mycobacterium avium subsp. paratuberculosis with Inflammatory Bowel Disease

    PubMed Central

    Timms, Verlaine J.; Daskalopoulos, George; Mitchell, Hazel M.; Neilan, Brett A.

    2016-01-01

    The association of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) with Crohn’s disease is a controversial issue. M. paratuberculosis is detected by amplifying the IS900 gene, as microbial culture is unreliable from humans. We determined the presence of M. paratuberculosis in patients with Crohn’s disease (CD) (n = 22), ulcerative colitis (UC) (n = 20), aphthous ulcers (n = 21) and controls (n = 42) using PCR assays validated on bovine tissue. Culture from human tissue was also performed. M. paratuberculosis prevalence in the CD and UC groups was compared to the prevalence in age and sex matched non-inflammatory bowel disease controls. Patients and controls were determined to be M. paratuberculosis positive if all three PCR assays were positive. A significant association was found between M. paratuberculosis and Crohn’s disease (p = 0.02) that was not related to age, gender, place of birth, smoking or alcohol intake. No significant association was detected between M. paratuberculosis and UC or aphthous ulcers; however, one M. paratuberculosis isolate was successfully cultured from a patient with UC. We report the resistance of this isolate to ethambutol, rifampin, clofazamine and streptomycin. Interestingly this isolate could not only survive but could grow slowly at 5°C. We demonstrate a significant association between M. paratuberculosis and CD using multiple pre-validated PCR assays and that M. paratuberculosis can be isolated from patients with UC. PMID:26849125

  7. High concentrations of anthocyanins in genuine cherry-juice of old local Austrian Prunus avium varieties.

    PubMed

    Schüller, Elisabeth; Halbwirth, Heidi; Mikulic-Petkovsek, Maja; Slatnar, Ana; Veberic, Robert; Forneck, Astrid; Stich, Karl; Spornberger, Andreas

    2015-04-15

    Antioxidant activity and polyphenols were quantified in vapour-extracted juice of nine Austrian, partially endemic varieties of sweet cherry (Prunus avium): cv. 'Spätbraune von Purbach', cv. 'Early Rivers', cv. 'Joiser Einsiedekirsche', cv. 'Große Schwarze Knorpelkirsche' and four unidentified local varieties. Additionally the effect of storage was evaluated for six of the varieties. A variety showing the highest antioxidant capacity (9.64 μmol Trolox equivalents per mL), total polyphenols (2747 mg/L) and total cyanidins (1085 mg/L) was suitable for mechanical harvest and its juice did not show any losses of antioxidant capacity and total anthocyanin concentration during storage. The juice of cv. 'Große Schwarze Knorpelkirsche' had also high concentrations of total anthocyanins (873 mg/L), but showed substantial losses through storage. The local Austrian sweet cherry varieties from the Pannonian climate zone are particularly suitable for the production of processed products like cherry juice with high content of anthocyanins and polyphenols. PMID:25466109

  8. Search for Mycobacterium avium Subspecies paratuberculosis Antigens for the Diagnosis of Paratuberculosis

    PubMed Central

    Mon, María Laura; Viale, Mariana; Baschetti, Guido; Alvarado Pinedo, Fiorella; Gioffre, Andrea; Travería, Gabriel; Willemsen, Peter; Bakker, Douwe; Romano, María Isabel

    2012-01-01

    The aim of this study was to evaluate a wide panel of antigens of Mycobacterium avium subsp. paratuberculosis (MAP) to select candidates for the diagnosis of paratuberculosis (PTB). A total of 54 recombinant proteins were spotted onto nitrocellulose membranes and exposed to sera from animals with PTB (n = 25), healthy animals (n = 10), and animals experimentally infected with M. bovis (n = 8). This initial screening allowed us to select seven antigens: MAP 2513, MAP 1693, MAP 2020, MAP 0038, MAP 1272, MAP 0209c, and MAP 0210c, which reacted with sera from animals with PTB and showed little cross-reactivity with sera from healthy animals and animals experimentally infected with M. bovis. The second step was to evaluate the antigen cocktail of these seven antigens by ELISA. For this evaluation, we used sera from animals with PTB (n = 25), healthy animals (n = 26), and animals experimentally infected with M. bovis (n = 17). Using ELISA, the cocktail of the seven selected MAP antigens reacted with sera from 18 of the 25 animals with PTB and did not exhibit cross-reactivity with healthy animals and only low reactivity with animals with bovine tuberculosis. The combined application of these antigens could form part of a test which may help in the diagnosis of PTB. PMID:22792514

  9. Genome-Wide Diversity and Phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian Dairy Cattle.

    PubMed

    Ahlstrom, Christina; Barkema, Herman W; Stevenson, Karen; Zadoks, Ruth N; Biek, Roman; Kao, Rowland; Trewby, Hannah; Haupstein, Deb; Kelton, David F; Fecteau, Gilles; Labrecque, Olivia; Keefe, Greg P; McKenna, Shawn L B; Tahlan, Kapil; De Buck, Jeroen

    2016-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne's disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six "Bison type" isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Québec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale. PMID:26871723

  10. Persistence of Mycobacterium avium subspecies paratuberculosis in endangered Florida Key deer and Key deer habitat.

    PubMed

    Murray, Heidi L; Yabsley, Michael J; Keel, M Kevin; Manning, Elizabeth J B; Wilmers, Thomas J; Corn, Joseph L

    2014-04-01

    Mycobacterium avium subsp. paratuberculosis (MAP) was first reported in the endangered Key deer (Odocoileus virginianus clavium) in 1996 on Big Pine Key, Florida, USA. By 2008, eight additional MAP-positive Key deer had been identified on Big Pine Key and the nearby Newfound Harbor Keys. This study was conducted to determine if MAP was still present in Key deer and whether natural or man-made freshwater sources were contaminated with MAP. Between November 2009 and September 2012, MAP was isolated from 36/369 (10%) fecal samples collected from the ground throughout the Key deer range on Big Pine Key and the Newfound Harbor Keys, but all 36 positive samples were from Little Palm Island (36/142 [25%]). Only 1/729 (0.1%) environmental samples was positive; this was from the garden fountain on Little Palm Island (1/81 [1%]). In addition, MAP was detected in 3/43 (7%) necropsied Key deer, all from Little Palm Island (3/3 [100%]). Of these three Key deer, pooled samples from the ileum, cecum, and ileocecal lymph node from two were MAP-culture positive and feces from one of these were culture-positive. The third deer was only PCR-positive. Evidence of MAP was only detected on Little Palm Island during this sampling period and environmental contamination was limited.

  11. Composition and Potency Characterization of Mycobacterium avium subsp. paratuberculosis Purified Protein Derivatives

    PubMed Central

    Capsel, Randal T.; Thoen, Charles O.; Reinhardt, Timothy A.; Lippolis, John D.; Olsen, Renee; Stabel, Judith R.; Bannantine, John P.

    2016-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) purified protein derivatives (PPDs) are immunologic reagents prepared from cultured filtrates of the type strain. Traditional production consists of floating culture incubation at 37°C, organism inactivation by autoclaving, coarse filtration, and protein precipitation. Three traditional production PPDs were used in this study including lot 9801, which served as a reference and has been used in the field for decades. Alternative production PPDs (0902A and 0902B), in which the autoclaving step was removed, were also analyzed in this study. SDS-PAGE analysis revealed protein smearing in traditional PPDs, but distinct bands were observed in the alternative PPD preparations. Antibody bound distinct protein bands in the alternative PPDs by immunoblot analysis, whereas an immunoreactive smear was observed with the traditional PPDs. Mass spectrometry identified 194 proteins among three PPD lots representing the two different production methods, ten of which were present in all PPDs examined. Selected proteins identified by mass spectrometry were recombinantly expressed and purified from E. coli and evaluated by the guinea pig potency test. Seven recombinant proteins showed greater erythema as compared to the reference PPD lot 9801 in paired guinea pigs and were able to stimulate interferon-gamma production in blood from Johne’s positive animals. These results suggest that autoclaving culture suspensions is not a necessary step in PPD production and specific proteins could supplant the PPD antigen for intradermal skin testing procedures and for use as in-vitro assay reagents. PMID:27136199

  12. Diuretic effect of powdered Cerasus avium (cherry) tails on healthy volunteers.

    PubMed

    Hooman, Nakysa; Mojab, Faraz; Nickavar, Bahman; Pouryousefi-Kermani, Pouran

    2009-10-01

    In this study, the diuretic activity of powdered cherry stalk was evaluated in 13 healthy volunteers by means of their water balance. In addition to biochemical parameters, such as urinary electrolyte concentration, osmolality and any adverse reaction were determined. The capsules of cherry stalks were administered at an equivalent dose of 2.0 grams of the plant per person. Urinary biochemical determination was made of concentration of electrolytes (sodium, potassium, chloride and calcium), urinary volume and osmolality by standard laboratory procedures. Statistical evaluation was performed by Student's-t and Wilcoxon rank tests. After administration of cherry stalk, the mean of urine calcium, sodium, chloride, and urine volume increased, but the amount of urine potassium and urine osmolality did not change. No adverse reaction was observed. Powdered C. avium stalk increased mild urine volume confirming thus the claimed diuretic effect of the herb. Administration of cherry stalk caused urinary sodium and chloride rising less than loop diuretics but higher than the others. Because of rising calcium excretion, it should be used with cautious in those with urolithiasis. PMID:19783515

  13. Short communication: effect of homogenization on heat inactivation of Mycobacterium avium subspecies paratuberculosis in milk.

    PubMed

    Hammer, P; Kiesner, C; Walte, H-G C

    2014-01-01

    Mycobacterium avium ssp. paratuberculosis (MAP) can be present in cow milk and low numbers may survive high-temperature, short-time (HTST) pasteurization. Although HTST treatment leads to inactivation of at least 5 log10 cycles, it might become necessary to enhance the efficacy of HTST by additional treatments such as homogenization if the debate about the role of MAP in Crohn's disease of humans concludes that MAP is a zoonotic agent. This study aimed to determine whether disrupting the clumps of MAP in milk by homogenization during the heat treatment process would enhance the inactivation of MAP. We used HTST pasteurization in a continuous-flow pilot-plant pasteurizer and evaluated the effect of upstream, downstream, and in-hold homogenization on inactivation of MAP. Reduction of MAP at 72°C with a holding time of 28s was between 3.7 and 6.9 log10 cycles, with an overall mean of 5.5 log10 cycles. None of the 3 homogenization modes applied showed a statistically significant additional effect on the inactivation of MAP during HTST treatment.

  14. Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins.

    PubMed

    Sharma, B S; Abo-Ismail, M K; Schenkel, F S; You, Q; Verschoor, C P; Pant, S D; Karrow, N A

    2015-10-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in cattle that results in substantial financial losses to the cattle industry worldwide. Given that susceptibility to MAP infection is determined in part by genetics, marker-assisted selection may help in the breeding of animals that are more resistant to MAP infection. The toll-like receptor 4 gene (TLR4) was selected as a potential candidate gene because of its role in innate immunity and its involvement in MAP recognition and infection. The objective of this study, therefore, was to identify associations between TLR4 polymorphisms and susceptibility to MAP infection in Canadian Holstein cows. Two biologically relevant SNPs, including c.-226G>C in the 5'-untranslated region and the non-synonymous SNP c.2021C>T in the potential TIR domain, were selected for an association analysis with MAP infection status in 409 Canadian Holsteins. The haplotype C-T from these combined SNPs yielded significant association with susceptibility to MAP infection, supporting the involvement of TLR4 in susceptibility to MAP infection.

  15. Impact of the shedding level on transmission of persistent infections in Mycobacterium avium subspecies paratuberculosis (MAP).

    PubMed

    Slater, Noa; Mitchell, Rebecca Mans; Whitlock, Robert H; Fyock, Terry; Pradhan, Abani Kumar; Knupfer, Elena; Schukken, Ynte Hein; Louzoun, Yoram

    2016-01-01

    Super-shedders are infectious individuals that contribute a disproportionate amount of infectious pathogen load to the environment. A super-shedder host may produce up to 10,000 times more pathogens than other infectious hosts. Super-shedders have been reported for multiple human and animal diseases. If their contribution to infection dynamics was linear to the pathogen load, they would dominate infection dynamics. We here focus on quantifying the effect of super-shedders on the spread of infection in natural environments to test if such an effect actually occurs in Mycobacterium avium subspecies paratuberculosis (MAP). We study a case where the infection dynamics and the bacterial load shed by each host at every point in time are known. Using a maximum likelihood approach, we estimate the parameters of a model with multiple transmission routes, including direct contact, indirect contact and a background infection risk. We use longitudinal data from persistent infections (MAP), where infectious individuals have a wide distribution of infectious loads, ranging upward of three orders of magnitude. We show based on these parameters that the effect of super-shedders for MAP is limited and that the effect of the individual bacterial load is limited and the relationship between bacterial load and the infectiousness is highly concave. A 1000-fold increase in the bacterial contribution is equivalent to up to a 2-3 fold increase in infectiousness.

  16. Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn’s disease, cause or epiphenomenon?

    PubMed Central

    Liverani, Elisa; Scaioli, Eleonora; Cardamone, Carla; Dal Monte, Paola; Belluzzi, Andrea

    2014-01-01

    The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne’s disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn’s disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the “MAP-hypothesis”, analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven. PMID:25278700

  17. Short communication: Viable Mycobacterium avium subspecies paratuberculosis in retail artisanal Coalho cheese from Northeastern Brazil.

    PubMed

    Faria, A C S; Schwarz, D G G; Carvalho, I A; Rocha, B B; De Carvalho Castro, K N; Silva, M R; Moreira, M A S

    2014-07-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis and it potentially plays a role in Crohn's disease. In humans, the main route of transmission of MAP might be the intake of contaminated milk and dairy products. Considering that MAP has already been detected in many types of cheese in different counties, and that Coalho cheese is an important dairy product in northeastern Brazil, the aim of this study was to report the first detection of MAP in retail Coalho cheese in Brazil by PCR and culture. Of 30 retail Coalho cheese samples, 3 (10%) amplified fragments of a similar size to that expected (626 bp) were obtained and viable MAP was recovered by culture from 1 (3.3%) sample. The DNA from the positive culture sample was sequenced and showed 99% identity with the insertion sequence IS900 deposited in GenBank. It was possible to identify the presence of MAP-specific DNA in the analyzed samples for the first time in Brazil, and to recover viable cells from retail Coalho cheese.

  18. Mycobacterium avium Subspecies paratuberculosis: Human Exposure through Environmental and Domestic Aerosols

    PubMed Central

    Rhodes, Glenn; Richardson, Hollian; Hermon-Taylor, John; Weightman, Andrew; Higham, Andrew; Pickup, Roger

    2014-01-01

    Mycobacterium avium subspecies paratuberculosis (Map) causes Johne’s disease in animals and is significantly associated with Crohn’s disease (CD) in humans. Our previous studies have shown Map to be present in U.K. rivers due to land deposition from chronic livestock infection and runoff driven by rainfall. The epidemiology of CD in Cardiff showed a significant association with the River Taff, in which Map can be detected on a regular basis. We have previously hypothesized that aerosols from the river might influence the epidemiology of CD. In this preliminary study, we detected Map by quantitative PCR in one of five aerosol samples collected above the River Taff. In addition, we examined domestic showers from different regions in the U.K. and detected Map in three out of 30 independent samples. In detecting Map in river aerosols and those from domestic showers, this is the first study to provide evidence that aerosols are an exposure route for Map to humans and may play a role in the epidemiology of CD. PMID:25438013

  19. Experimental Infection of Goats with Mycobacterium avium subsp. hominissuis: a Model for Comparative Tuberculosis Research.

    PubMed

    Schinköthe, J; Möbius, P; Köhler, H; Liebler-Tenorio, E M

    2016-01-01

    Mycobacterium avium subsp. hominissuis (MAH) is an opportunistic pathogen that causes infections in man and animals. In this study, 18 goat kids were inoculated orally with a high dose of MAH. One group of goats (n = 9) developed severe clinical disease for up to 2-3 months post inoculation (mpi). At necropsy examination, there were ulcerative and granulomatous lesions in gut-associated lymphoid tissue and granulomas with extensive necrosis in the lymph nodes (LNs) of the cranial mesenteric lymphocentre (CMLNs). Culture revealed growth of MAH in all lesions with systemic spread. A second group of goats were healthy at the end of the trial (13 mpi); however, all had extensive granulomas in the CMLNs, but no extra-intestinal spread of bacteria. Moderate faecal shedding occurred in all goats up to 2 mpi. Microscopical characterization of the granulomas revealed solid non-necrotic, necrotic, calcified and fibrocalcified granulomas with resemblance to those seen in human and bovine tuberculosis. The two different courses of disease, with highly heterogenic lesions, systemic spread in goats with severe clinical disease and the development of granulomas of all stages in the surviving goats, makes the experimental infection of goats with MAH a valuable model for tuberculosis research. This model might allow new insights into host-pathogen interaction and anti-mycobacterial compound testing. PMID:27426001

  20. Mycobacterium avium ss. paratuberculosis Zoonosis - The Hundred Year War - Beyond Crohn's Disease.

    PubMed

    Sechi, Leonardo A; Dow, Coad Thomas

    2015-01-01

    The factitive role of Mycobacterium avium ss. paratuberculosis (MAP) in Crohn's disease has been debated for more than a century. The controversy is due to the fact that Crohn's disease is so similar to a disease of MAP-infected ruminant animals, Johne's disease; and, though MAP can be readily detected in the infected ruminants, it is much more difficult to detect in humans. Molecular techniques that can detect MAP in pathologic Crohn's specimens as well as dedicated specialty labs successful in culturing MAP from Crohn's patients have provided strong argument for MAP's role in Crohn's disease. Perhaps more incriminating for MAP as a zoonotic agent is the increasing number of diseases with which MAP has been related: Blau syndrome, type 1 diabetes, Hashimoto thyroiditis, and multiple sclerosis. In this article, we debate about genetic susceptibility to mycobacterial infection and human exposure to MAP; moreover, it suggests that molecular mimicry between protein epitopes of MAP and human proteins is a likely bridge between infection and these autoimmune disorders.

  1. Persistence of Mycobacterium avium subspecies paratuberculosis in endangered Florida Key deer and Key deer habitat.

    PubMed

    Murray, Heidi L; Yabsley, Michael J; Keel, M Kevin; Manning, Elizabeth J B; Wilmers, Thomas J; Corn, Joseph L

    2014-04-01

    Mycobacterium avium subsp. paratuberculosis (MAP) was first reported in the endangered Key deer (Odocoileus virginianus clavium) in 1996 on Big Pine Key, Florida, USA. By 2008, eight additional MAP-positive Key deer had been identified on Big Pine Key and the nearby Newfound Harbor Keys. This study was conducted to determine if MAP was still present in Key deer and whether natural or man-made freshwater sources were contaminated with MAP. Between November 2009 and September 2012, MAP was isolated from 36/369 (10%) fecal samples collected from the ground throughout the Key deer range on Big Pine Key and the Newfound Harbor Keys, but all 36 positive samples were from Little Palm Island (36/142 [25%]). Only 1/729 (0.1%) environmental samples was positive; this was from the garden fountain on Little Palm Island (1/81 [1%]). In addition, MAP was detected in 3/43 (7%) necropsied Key deer, all from Little Palm Island (3/3 [100%]). Of these three Key deer, pooled samples from the ileum, cecum, and ileocecal lymph node from two were MAP-culture positive and feces from one of these were culture-positive. The third deer was only PCR-positive. Evidence of MAP was only detected on Little Palm Island during this sampling period and environmental contamination was limited. PMID:24506424

  2. FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis

    PubMed Central

    Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F.; Goethe, Ralph

    2015-01-01

    The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator. PMID:25705205

  3. Host Transcriptional Profiles and Immunopathologic Response following Mycobacterium avium subsp. paratuberculosis Infection in Mice

    PubMed Central

    Shin, Min-Kyoung; Park, Hongtae; Shin, Seung Won; Jung, Myunghwan; Lee, Su-Hyung; Kim, Dae-Yong; Yoo, Han Sang

    2015-01-01

    Paratuberculosis or Johne’s disease is a chronic granulomatous enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. In the present study, we examined the host response to MAP infection in spleens of mice in order to investigate the host immunopathology accompanying host-pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and 6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger receptor, and complement components, suggesting an initial innate immune reaction, such as macrophage activation, bactericidal activity, and macrophage invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways related to the T cell response including ICOS-ICOSL signaling in T helper cells, calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell. These results provide information which furthers the understanding of the immunopathologic response to MAP infection in mice, thereby providing insights valuable for research into the pathogenesis for MAP infection. PMID:26439498

  4. Isolation and characterization of a novel bacteriophage against Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Basra, Simone; Anany, Hany; Brovko, Lioubov; Kropinski, Andrew M; Griffiths, Mansel W

    2014-10-01

    Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease, has a doubling time of 24 hours, making rapid detection very difficult. Mycobacteriophages can be used in the detection of disease-causing mycobacteria such as MAP. Isolation and sequencing the genomes of lytic MAP bacteriophages are important preliminary steps towards designing phage-based rapid detection assays for this bacterium. A simple optimized protocol was developed to allow reproducible production of confluent growth of MAP on plates within four to six weeks of incubation at 30 °C. This protocol was applied to the screening of environmental and fecal samples for bacteriophages inhibiting the growth of MAP. As a result, a lytic phage, vB_MapS_FF47, was isolated from bovine feces. FF47 contains a double-stranded DNA genome ~48 kb in length with 73 protein coding sequences. It does not carry temperate or known virulence genes. This phage was shown to be most closely related to Mycobacterium phage Muddy, isolated in South Africa, and Gordonia phage GTE2; however, it could not infect any of the tested Gordonia, Rhodococcus, or Nocardia spp. that GTE2 could. The protocols that were developed for growth and phage isolation have potential applications in a high-throughput screening for compounds inhibiting the growth of MAP. This work describes the first time that a phage was isolated against M. paratuberculosis.

  5. Ecology and genomic features of infection with Mycobacterium avium subspecies paratuberculosis in Egypt.

    PubMed

    Amin, Adel S; Hsu, Chung-Yi; Darwish, Samah F; Ghosh, Pallab; AbdEl-Fatah, Eman M; Behour, Tahani S; Talaat, Adel M

    2015-04-01

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of paratuberculosis, or Johne's disease, in cattle, with potential involvement in cases of Crohn's disease in humans. Johne's disease is found worldwide and is economically important for both beef and dairy industries. In an effort to characterize this important infection in Egypt, we analysed the ecological and genomic features of recent isolates of M. paratuberculosis. In this report, we examined 26 Holstein dairy herds distributed throughout Egypt, from 2010 to 2013. Using PCR analysis of faecal samples, we estimated a mean herd-level prevalence of 65.4 %, with animal-level infection that reached a mean of 13.6 % among animals suffering from diarrhoea. Whole genome sequencing of field isolates identified numerous single nucleotide polymorphisms among field isolates relative to the standard M. paratuberculosis K10 genome. Interestingly, the virulence of M. paratuberculosis isolates from Egypt revealed diverse virulence phenotypes in the murine model of paratuberculosis, with significant differences in tissue colonization, particularly during the chronic stage of infection. Overall, our analysis confirmed that Johne's disease is a newly identified problem in Egypt and indicated that M. paratuberculosis has potentially diverse genotypes that impact its virulence. Further ecological mapping and genomic analysis of M. paratuberculosis will enhance our understanding of the transmission and evolutionary dynamics of this pathogen under natural field conditions.

  6. Assessment of food as a source of exposure to Mycobacterium avium subspecies paratuberculosis (MAP).

    PubMed

    2010-07-01

    The National Advisory Committee on Microbiological Criteria for Foods assessed the importance of food as a source of exposure to Mycobacterium avium subspecies paratuberculosis (MAP). MAP is the causative agent of Johne's disease, which affects primarily the small intestine of all ruminants. The significance of MAP as a human pathogen is unknown and is being investigated by several research groups. This document also reviews the efficacy of current detection methods, processing interventions, and MAP inactivation. Research needs related to MAP are provided. The Committee reached the following conclusions: current methods for detection of MAP have significant limitations, and a standard method for the detection of viable MAP cells is needed. Aside from MAP-infected domestic ruminant animals, the organism is found infrequently. If MAP in cattle is controlled, the source of MAP in other animals, food, and water may largely be eliminated. Milk, particularly raw milk, may be a likely food source for human exposure to MAP. Given the prevalence of MAP in U.S. cattle herds, ground beef may be a potential source of MAP. Although humans may be exposed to MAP through a variety of routes, including food and the environment, the frequency and amount of exposure will require additional research. PMID:20615354

  7. Mycobacterium avium ss. paratuberculosis Zoonosis – The Hundred Year War – Beyond Crohn’s Disease

    PubMed Central

    Sechi, Leonardo A.; Dow, Coad Thomas

    2015-01-01

    The factitive role of Mycobacterium avium ss. paratuberculosis (MAP) in Crohn’s disease has been debated for more than a century. The controversy is due to the fact that Crohn’s disease is so similar to a disease of MAP-infected ruminant animals, Johne’s disease; and, though MAP can be readily detected in the infected ruminants, it is much more difficult to detect in humans. Molecular techniques that can detect MAP in pathologic Crohn’s specimens as well as dedicated specialty labs successful in culturing MAP from Crohn’s patients have provided strong argument for MAP’s role in Crohn’s disease. Perhaps more incriminating for MAP as a zoonotic agent is the increasing number of diseases with which MAP has been related: Blau syndrome, type 1 diabetes, Hashimoto thyroiditis, and multiple sclerosis. In this article, we debate about genetic susceptibility to mycobacterial infection and human exposure to MAP; moreover, it suggests that molecular mimicry between protein epitopes of MAP and human proteins is a likely bridge between infection and these autoimmune disorders. PMID:25788897

  8. A population genetic analysis of chloroplast DNA in wild populations of Prunus avium L. in Europe.

    PubMed

    Mohanty, A; Martín, J P; Aguinagalde, I

    2001-10-01

    A population genetic study of chloroplast DNA was carried out in 23 wild populations of Prunus avium sampled from several European deciduous forests. An analysis of approx. 9% of the chloroplast genome detected mostly insertion-deletion mutations and one point mutation. In all, 16 haplotypes were detected. Six haplotypes were shared by two or more populations and 10 were unique. One haplotype was present in 21 of the 23 populations and 161 of 211 individuals, which probably indicates its ancient origin. The level of population subdivision, using unordered and ordered alleles, was low, GSTC=0.29 and NSTC=0.33, respectively. The difference between GSTC and NSTC is nonsignificant, indicating an absence of correlation between haplotype phylogeny and geographical distribution. The absence of phylogeographic structure in wild cherry may be attributed to long distance gene flow among populations by birds, animals and anthropogenic activities. The minimum-length spanning tree depicting the phylogenetic relationships between the haplotypes indicates the possible existence of two lineages represented by the haplotypes H3 and H4. The information about homogeneity or heterogeneity of populations in terms of haplotype constitution and detection of rare haplotypes in some populations will be useful for formulation of conservation and management strategies of wild cherry.

  9. Survey of Mycobacterium avium subspecies paratuberculosis in road-killed wild carnivores in Portugal.

    PubMed

    Matos, Ana Cristina; Figueira, Luis; Martins, Maria Helena; Loureiro, Filipa; Pinto, Maria Lurdes; Matos, Manuela; Coelho, Ana Cláudia

    2014-12-01

    A survey to determine the occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in wild carnivores in Portugal was conducted by testing samples from road-killed animals between 2009 and 2012. Postmortem examinations were performed and tissues were collected from wild carnivores representing four families and six different species, with a total of 74 animals analyzed. Cultures were performed by using Löwenstein-Jensen and Middlebrook 7H11 solid media and acid-fast isolates were identified by polymerase chain reaction (PCR) and mycobactin dependency characteristics. Tissues were also screened for MAP by directly extracting DNA and testing for the MAP-specific sequences. The occurrence of infected animals (an animal had at least one tissue that was positive for culture or direct PCR) was 27.0% (n = 20). MAP was isolated from culture of 25 tissue samples (3.8%) and was detected by direct PCR in 40 (6.0%) samples. Infection was recorded in 5/6 studied species: 7/49 (14.3%) red foxes (Vulpes vulpes), 3/3 (100%) beech martens (Martes foina), 2/4 (50.0%) Eurasian otters (Lutra lutra), 7/15 (46.7%) Egyptian mongooses (Herpestes ichneumon), and 1/1 (100%) European badger (Meles meles). These species represent three different taxonomic families: Canidae (14.3% were positive), Mustelidae (75.0% were positive), and Herpestidae (46.7% were positive). The results of this study confirm the presence of MAP infection in wild carnivores in Portugal. PMID:25632662

  10. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius

    PubMed Central

    Johnston, Christopher D.; Bannantine, John P.; Govender, Rodney; Endersen, Lorraine; Pletzer, Daniel; Weingart, Helge; Coffey, Aidan; O'Mahony, Jim; Sleator, Roy D.

    2014-01-01

    It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease. PMID:25237653

  11. Effect of temperature on pollen tube kinetics and dynamics in sweet cherry, Prunus avium (Rosaceae).

    PubMed

    Hedhly, A; Hormaza, J I; Herrero, M

    2004-04-01

    Prevailing ambient temperature during the reproductive phase is one of several important factors for seed and fruit set in different plant species, and its consequences on reproductive success may increase with global warming. The effect of temperature on pollen performance was evaluated in sweet cherry (Prunus avium L.), comparing as pollen donors two cultivars that differ in their adaptation to temperature. 'Sunburst' is a cultivar that originated in Canada with a pedigree of cultivars from Northern Europe, while 'Cristobalina' is a cultivar native to southeast Spain, adapted to warmer conditions. Temperature effects were tested either in controlled-temperature chambers or in the field in a plastic cage. In both genotypes, an increase in temperature reduced pollen germination, but accelerated pollen tube growth. However, a different genotypic response, which reflected the overall adaptation of the pollen donor, was obtained for pollen tube dynamics, expressed as the census of the microgametophyte population that successfully reached the base of the style. While both cultivars performed similarly at 20°C, the microgametophyte population was reduced at 30°C for Sunburst and at 10°C for Cristobalina. These results indicate a differential genotypic response to temperature during the reproductive phase, which could be important in terms of the time needed for a plant species to adapt to rapid temperature changes.

  12. FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis.

    PubMed

    Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F; Goethe, Ralph

    2015-01-01

    The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator.

  13. Macrophage polarization in cattle experimentally exposed to Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Thirunavukkarasu, Shyamala; de Silva, Kumudika; Begg, Douglas J; Whittington, Richard J; Plain, Karren M

    2015-12-01

    Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease (JD) in cattle, has significant impacts on the livestock industry and has been implicated in the etiology of Crohn's disease. Macrophages play a key role in JD pathogenesis, which is driven by the manipulation of host immune mechanisms by MAP. A change in the macrophage microenvironment due to pathogenic or host-derived stimuli can lead to classical (M1) or alternative (M2) polarization of macrophages. In addition, prior exposure to antigenic stimuli has been reported to alter the response of macrophages to subsequent stimuli. However, macrophage polarization in response to MAP exposure and its possible implications have not been previously addressed. In this study, we have comprehensively examined monocyte/macrophage polarization and responsiveness to antigens from MAP-exposed and unexposed animals. At 3 years post-exposure, there was a heterogeneous macrophage activation pattern characterized by both classical and alternate phenotypes. Moreover, subsequent exposure of macrophages from MAP-exposed cattle to antigens from MAP and other mycobacterial species led to significant variation in the production of nitric oxide, interleukin-10 and tumour necrosis factor α. These results indicate the previously unreported possibility of changes in the activation state and responsiveness of circulating monocytes/macrophages from MAP-exposed cattle.

  14. On deaf ears, Mycobacterium avium paratuberculosis in pathogenesis Crohn’s and other diseases

    PubMed Central

    Davis, William C

    2015-01-01

    The historic suggestion that Mycobacterium avium subsp. paratuberculosis (Map) might be a zoonotic pathogen was based on the apparent similarity of lesions in the intestine of patients with Crohn’s disease (CD) with those present in cattle infected with Map, the etiological agent of Johne’s disease. Reluctance to fully explore this possibility has been attributed to the difficulty in demonstrating the presence of Map in tissues from patients with CD. Advances in technology have resolved this problem and revealed the presence of Map in a significant proportion of patients with CD and other diseases. The seminal finding from recent investigations, however, is the detection of Map in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans. PMID:26730151

  15. Host gene expression for Mycobacterium avium subsp. paratuberculosis infection in human THP-1 macrophages.

    PubMed

    Shin, Min-Kyoung; Shin, Seung Won; Jung, Myunghwan; Park, Hongtae; Park, Hyun-Eui; Yoo, Han Sang

    2015-07-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, which causes considerable economic loss in the dairy industry and has a possible relationship to Crohn's disease (CD) in humans. As MAP has been detected in retail pasteurized milk samples, its transmission via milk is of concern. Despite its possible role in the etiology of CD, there have been few studies examining the interactions between MAP and human cells. In the current study, we applied Ingenuity Pathway Analysis to the transcription profiles generated from a murine model with MAP infection as part of a previously conducted study. Twenty-one genes were selected as potential host immune responses, compared with the transcriptional profiles in naturally MAP-infected cattle, and validated in MAP-infected human monocyte-derived macrophage THP-1 cells. Of these, the potential host responses included up-regulation of genes related to immune response (CD14, S100A8, S100A9, LTF, HP and CHCIL3), up-regulation of Th1-polarizing factor (CCL4, CCL5, CXCL9 and CXCL10), down-regulation of genes related to metabolism (ELANE, IGF1, TCF7L2 and MPO) and no significant response of other genes (GADD45a, GPNMB, HMOX1, IFNG and NQO1) in THP-1 cells infected with MAP. PMID:25877879

  16. Detection of Mycobacterium avium subspecies paratuberculosis in several herds of Arctic Caribou (Rangifer tarandus ssp.).

    PubMed

    Forde, Taya; Orsel, Karin; De Buck, Jeroen; Côté, Steeve D; Cuyler, Christine; Davison, Tracy; Elkin, Brett; Kelly, Allicia; Kienzler, Martin; Popko, Richard; Taillon, Joëlle; Veitch, Alasdair; Kutz, Susan

    2012-10-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is a common pathogen in domestic ruminants that causes granulomatous inflammation of the small intestine leading to emaciation and wasting. Clinical disease (Johne's disease) is also reported for several wild ruminant species. Between 2007 and 2009 we collected 561 fecal samples from caribou (Rangifer tarandus ssp.) representing 10 herds of migratory caribou, two herds of caribou from Greenland, and three populations of boreal woodland caribou. Feces were tested for MAP by bacterial culture and PCR targeting the IS900 insertion sequence. In total, 31 samples from eight different populations representing all three ecotypes were found positive for MAP by PCR, with one sample from the Rivière-aux-Feuilles herd also being culture positive for the type II (cattle) strain. The proportion of positive animals was particularly high in the Akia-Maniitsoq herd in Greenland, and Rivière-aux-Feuilles and Riviè re-George herds in northeastern Canada (23.4, 11.5, and 10.0%, respectively). Our results indicate that MAP is present in several caribou herds of different ecotypes in northern Canada and Greenland and that MAP circulates within wildlife populations that do not have ongoing contact with domestic livestock. The epidemiology, pathogenicity, and effects on the health of caribou in northern ecosystems remain unknown.

  17. Seroprevalence and risk factors of Mycobacterium avium subspecies paratuberculosis infection in domestic sika deer in China.

    PubMed

    Meng, Qing-Feng; Li, Ying; Yang, Fan; Yao, Gui-Zhi; Qian, Ai-Dong; Wang, Wei-Li; Cong, Wei

    2015-06-01

    Paratuberculosis or Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic infectious granulomatous enteritis of ruminants and other animals, which has a worldwide occurrence, but little is known of MAP infection in domestic sika deer in Jilin Province, China. The objective of the present investigation was to examine seroprevalence and risk factors of MAP infection in Jilin Province. Serum samples collected from 1400 sika deer from 16 sika deer herds were collected in the 4 districts of the province between May 2013 and August 2014 and were tested independently for the presence of antibodies against MAP. A total of 247 (17.64 %) sika deer tested positive for MAP antibodies using a commercially available enzyme immunoassay kit. The management level of farm and collecting region of sika deer was the main risk factor associated with MAP infection. The present study revealed the seroprevalence of MAP infection in sika deer in Jilin Province, China, which provided the baseline data for taking comprehensive countermeasures and measures in effectively preventing and controlling MAP infection in sika deer.

  18. Seroprevalence and risk factors of Mycobacterium avium subspecies paratuberculosis infection in domestic sika deer in China.

    PubMed

    Meng, Qing-Feng; Li, Ying; Yang, Fan; Yao, Gui-Zhi; Qian, Ai-Dong; Wang, Wei-Li; Cong, Wei

    2015-06-01

    Paratuberculosis or Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic infectious granulomatous enteritis of ruminants and other animals, which has a worldwide occurrence, but little is known of MAP infection in domestic sika deer in Jilin Province, China. The objective of the present investigation was to examine seroprevalence and risk factors of MAP infection in Jilin Province. Serum samples collected from 1400 sika deer from 16 sika deer herds were collected in the 4 districts of the province between May 2013 and August 2014 and were tested independently for the presence of antibodies against MAP. A total of 247 (17.64 %) sika deer tested positive for MAP antibodies using a commercially available enzyme immunoassay kit. The management level of farm and collecting region of sika deer was the main risk factor associated with MAP infection. The present study revealed the seroprevalence of MAP infection in sika deer in Jilin Province, China, which provided the baseline data for taking comprehensive countermeasures and measures in effectively preventing and controlling MAP infection in sika deer. PMID:25904509

  19. Mycobacterium avium subsp. paratuberculosis is not discerned in diabetes mellitus patients in Hyderabad, India.

    PubMed

    Rani, Pittu Sandhya; Doddam, Sankara Narayana; Agrawal, Sashank; Hasnain, Seyed E; Sechi, Leonardo A; Kumar, Ashutosh; Ahmed, Niyaz

    2014-07-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is an obligate intracellular pathogen. It causes chronic intestinal inflammation in ruminants known as Johne's disease and is associated with human Crohn's disease. Furthermore, association of MAP with other autoimmune diseases, such as type-1 diabetes, has been established in patients from Sardinia (Italy) which is a MAP endemic and genetically isolated region. Due to largest livestock population and consequently high MAP prevalence amidst a very high diabetes incidence in India, we sought to test this association on a limited number of patient samples from Hyderabad. Our results of ELISA with MAP lysate and MAP-specific protein MAP3738c as well as PCR/real-time PCR of MAP-specific sequences IS900 and/or f57 indicated that, in contrast to Sardinian diabetic patients, MAP infection in blood is not discerned in diabetic patients in Hyderabad. The association of a mycobacterial trigger with diabetes therefore could well be a population-specific phenomenon, highly dependent on genetic repertoire and the environment of susceptible populations. However, a larger study is needed in order to confirm this.

  20. Genomic variations associated with attenuation in Mycobacterium avium subsp. paratuberculosis vaccine strains

    PubMed Central

    2013-01-01

    Background Mycobacterium avium subspecies paratuberculosis (MAP) whole cell vaccines have been widely used tools in the control of Johne’s disease in animals despite being unable to provide complete protection. Current vaccine strains derive from stocks created many decades ago; however their genotypes, underlying mechanisms and relative degree of their attenuation are largely unknown. Results Using mouse virulence studies we confirm that MAP vaccine strains 316 F, II and 2e have diverse but clearly attenuated survival and persistence characteristics compared with wild type strains. Using a pan genomic microarray we characterise the genomic variations in a panel of vaccine strains sourced from stocks spanning over 40 years of maintenance. We describe multiple genomic variations specific for individual vaccine stocks in both deletion (26–32 Kbp) and tandem duplicated (11–40 Kbp) large variable genomic islands and insertion sequence copy numbers. We show individual differences suitable for diagnostic differentiation between vaccine and wild type genotypes and provide evidence for functionality of some of the deleted MAP-specific genes and their possible relation to attenuation. Conclusions This study shows how culture environments have influenced MAP genome diversity resulting in large tandem genomic duplications, deletions and transposable element activity. In combination with classical selective systematic subculture this has led to fixation of specific MAP genomic alterations in some vaccine strain lineages which link the resulting attenuated phenotypes with deficiencies in high reactive oxygen species handling. PMID:23339684

  1. Ulcerative colitis and Crohn's disease: is Mycobacterium avium subspecies paratuberculosis the common villain?

    PubMed Central

    2010-01-01

    Mycobacterium avium, subspecies paratuberculosis (MAP) causes a chronic disease of the intestines in dairy cows and a wide range of other animals, including nonhuman primates, called Johne's ("Yo-knee's") disease. MAP has been consistently identified by a variety of techniques in humans with Crohn's disease. The research investigating the presence of MAP in patients with Crohn's disease has often identified MAP in the "negative" ulcerative colitis controls as well, suggesting that ulcerative colitis is also caused by MAP. Like other infectious diseases, dose, route of infection, age, sex and genes influence whether an individual infected with MAP develops ulcerative colitis or Crohn's disease. The apparently opposite role of smoking, increasing the risk of Crohn's disease while decreasing the risk of ulcerative colitis, is explained by a more careful review of the literature that reveals smoking causes an increase in both diseases but switches the phenotype from ulcerative colitis to Crohn's disease. MAP as the sole etiologic agent of both ulcerative colitis and Crohn's disease explains their common epidemiology, geographic distribution and familial and sporadic clusters, providing a unified hypothesis for the prevention and cure of the no longer "idiopathic" inflammatory bowel diseases. PMID:21167058

  2. Survey of Mycobacterium avium subspecies paratuberculosis in road-killed wild carnivores in Portugal.

    PubMed

    Matos, Ana Cristina; Figueira, Luis; Martins, Maria Helena; Loureiro, Filipa; Pinto, Maria Lurdes; Matos, Manuela; Coelho, Ana Cláudia

    2014-12-01

    A survey to determine the occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in wild carnivores in Portugal was conducted by testing samples from road-killed animals between 2009 and 2012. Postmortem examinations were performed and tissues were collected from wild carnivores representing four families and six different species, with a total of 74 animals analyzed. Cultures were performed by using Löwenstein-Jensen and Middlebrook 7H11 solid media and acid-fast isolates were identified by polymerase chain reaction (PCR) and mycobactin dependency characteristics. Tissues were also screened for MAP by directly extracting DNA and testing for the MAP-specific sequences. The occurrence of infected animals (an animal had at least one tissue that was positive for culture or direct PCR) was 27.0% (n = 20). MAP was isolated from culture of 25 tissue samples (3.8%) and was detected by direct PCR in 40 (6.0%) samples. Infection was recorded in 5/6 studied species: 7/49 (14.3%) red foxes (Vulpes vulpes), 3/3 (100%) beech martens (Martes foina), 2/4 (50.0%) Eurasian otters (Lutra lutra), 7/15 (46.7%) Egyptian mongooses (Herpestes ichneumon), and 1/1 (100%) European badger (Meles meles). These species represent three different taxonomic families: Canidae (14.3% were positive), Mustelidae (75.0% were positive), and Herpestidae (46.7% were positive). The results of this study confirm the presence of MAP infection in wild carnivores in Portugal.

  3. MDMA and the "ecstasy paradigm".

    PubMed

    Cole, Jon C

    2014-01-01

    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  4. Antiphospholipid antibodies: Paradigm in transition

    PubMed Central

    Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Ahn, Yeon S; Kelley, Roger E; Zivadinov, Robert; Maghzi, Amir H; Etemadifar, Masoud; Mousavi, Seyed Ali; Minagar, Alireza

    2009-01-01

    Objectives This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. Organization After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. Conclusion The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology. PMID:19154576

  5. Dealing with a Paradigm Shift

    PubMed Central

    Pack, Allan I.

    2015-01-01

    Recent changes in policies by insurance companies with respect to mandating home sleep apnea testing rather than in-laboratory studies have a large impact on the financial viability of clinical sleep centers. Coping with this disruptive change requires forward planning. First, it is important to be well positioned with respect to facilities so that these can be quickly downsized to control costs. There is also a need to develop, in advance, an accredited home sleep study program so that centers can respond to the rapidly changing environment. Following the change there is a need to control costs by rapidly downsizing the technology workforce. Technologists can be retrained for other essential roles. Centralizing the precertification process with knowledgeable, well-trained staff and a robust auditing process is an essential component. The approach taken at the University of Pennsylvania to this change is described as is how one can ensure continued financial viability of a comprehensive sleep center program in a major academic medical center. Citation: Pack AI. Dealing with a paradigm shift. J Clin Sleep Med 2015;11(8):925–929. PMID:26094918

  6. Proteome-scale identification and characterization of mitochondria targeting proteins of Mycobacterium avium subspecies paratuberculosis: Potential virulence factors modulating host mitochondrial function.

    PubMed

    Rana, Aarti; Kumar, Devender; Rub, Abdur; Akhter, Yusuf

    2015-07-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of Johne's Disease among ruminants. During the course of infection, it expresses a number of proteins for its successful persistence inside the host that cause variety of physiological abnormalities in the host. Mitochondrion is one of the attractive targets for pathogenic bacteria. Employing a proteome-wide sequence and structural signature based approach we have identified 46 M. avium subsp. paratuberculosis proteins as potential targets for the host mitochondrial targeting. These may act as virulence factors modulating mitochondrial physiology for bacterial survival and immune evasion inside the host cells.

  7. In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid.

    PubMed Central

    Casal, M J; Rodriguez, F C; Luna, M D; Benavente, M C

    1987-01-01

    The in vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae (M. chelonei) to ticarcillin in combination with calvulanic acid (CA) was studied by the agar dilution method. All the M. tuberculosis, M. bovis, and M. africanum strains were inhibited at a ticarcillin concentration of 32 micrograms/ml or lower in combination with 5 micrograms of CA. M. chelonae and M. avium strains proved resistant to more than 128 micrograms of ticarcillin plus 5 micrograms of CA per ml. M. fortuitum strains needed 128 micrograms of ticarcillin plus 5 micrograms of CA to inhibit approximately 30% of the isolates. PMID:3105441

  8. Monsoon-Enso Relationships: A New Paradigm

    NASA Technical Reports Server (NTRS)

    Lau, K. M.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    This article is partly a review and partly a new research paper on monsoon-ENSO relationship. The paper begins with a discussion of the basic relationship between the Indian monsoon and ENSO dating back to the work of Sir Gilbert Walker up to research results in more recent years. Various factors that may affect the monsoon-ENSO, relationship, including regional coupled ocean-atmosphere processes, Eurasian snow cover, land-atmosphere hydrologic feedback, intraseasonal oscillation, biennial variability and inter-decadal variations, are discussed. The extreme complex and highly nonlinear nature of the monsoon-ENSO relationship is stressed. We find that for regional impacts on the monsoon, El Nino and La Nina are far from simply mirror images of each other. These two polarities of ENSO can have strong or no impacts on monsoon anomalies depending on the strength of the intraseasonal oscillations and the phases of the inter-decadal variations. For the Asian-Australian monsoon (AAM) as a whole, the ENSO impact is effected through a east-west shift in the Walker Circulation. For rainfall anomalies over specific monsoon areas, regional processes play important roles in addition to the shift in the Walker Circulation. One of the key regional processes identified for the boreal summer monsoon is the anomalous West Pacific Anticyclone (WPA). This regional feature has similar signatures in interannual and intraseasonal time scales and appears to determine whether the monsoon-ENSO relationship is strong or weak in a given year. Another important regional feature includes a rainfall and SST dipole across the Indian Ocean, which may have strong impact on the austral summer monsoon. Results are shown indicating that monsoon surface wind forcings may induce a strong biennial signal in ENSO and that strong monsoon-ENSO coupling may translate into pronounced biennial variability in ENSO. Finally, a new paradigm is proposed for the study of monsoon variability. This paradigm provides

  9. Leprosy: too complex a disease for a simple elimination paradigm.

    PubMed Central

    Lockwood, Diana N. J.; Suneetha, Sujai

    2005-01-01

    Can leprosy be eliminated? This paper considers the question against the background of the WHO programme to eliminate leprosy. In 1991 the World Health Assembly set a target of eliminating leprosy as a public health problem by 2000. Elimination was defined as reaching a prevalence of < 1 case per 10 000 people. The elimination programme has been successful in delivering highly effective antibiotic therapy worldwide. However, despite this advance, new-case detection rates remain stable in countries with the highest rates of endemic leprosy, such as Brazil and India. This suggests that infection has not been adequately controlled by antibiotics alone. Leprosy is perhaps more appropriately classed as a chronic stable disease than as an acute infectious disease responsive to elimination strategies. In many countries activities to control and treat leprosy are being integrated into the general health-care system. This reduces the stigma associated with leprosy. However, leprosy causes long-term immunological complications, disability and deformity. The health-care activities of treating and preventing disabilities need to be provided in an integrated setting. Detecting new cases and monitoring disability caused by leprosy will be a challenge. One solution is to implement long-term surveillance in selected countries with the highest rates of endemic disease so that an accurate estimate of the burden of leprosy can be determined. It is also critical that broad-based research into this challenging disease continues until the problems are truly solved. PMID:15798849

  10. Navigating complex decision spaces: Problems and paradigms in sequential choice

    PubMed Central

    Walsh, Matthew M.; Anderson, John R.

    2015-01-01

    To behave adaptively, we must learn from the consequences of our actions. Doing so is difficult when the consequences of an action follow a delay. This introduces the problem of temporal credit assignment. When feedback follows a sequence of decisions, how should the individual assign credit to the intermediate actions that comprise the sequence? Research in reinforcement learning provides two general solutions to this problem: model-free reinforcement learning and model-based reinforcement learning. In this review, we examine connections between stimulus-response and cognitive learning theories, habitual and goal-directed control, and model-free and model-based reinforcement learning. We then consider a range of problems related to temporal credit assignment. These include second-order conditioning and secondary reinforcers, latent learning and detour behavior, partially observable Markov decision processes, actions with distributed outcomes, and hierarchical learning. We ask whether humans and animals, when faced with these problems, behave in a manner consistent with reinforcement learning techniques. Throughout, we seek to identify neural substrates of model-free and model-based reinforcement learning. The former class of techniques is understood in terms of the neurotransmitter dopamine and its effects in the basal ganglia. The latter is understood in terms of a distributed network of regions including the prefrontal cortex, medial temporal lobes cerebellum, and basal ganglia. Not only do reinforcement learning techniques have a natural interpretation in terms of human and animal behavior, but they also provide a useful framework for understanding neural reward valuation and action selection. PMID:23834192

  11. Ostracism Online: A social media ostracism paradigm.

    PubMed

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism.

  12. Two complementary paradigms for analysing population dynamics.

    PubMed Central

    Krebs, Charles J

    2002-01-01

    To understand why population growth rate is sometimes positive and sometimes negative, ecologists have adopted two main approaches. The most common approach is through the density paradigm by plotting population growth rate against population density. The second approach is through the mechanistic paradigm by plotting population growth rate against the relevant ecological processes affecting the population. The density paradigm is applied a posteriori, works sometimes but not always and is remarkably useless in solving management problems or in providing an understanding of why populations change in size. The mechanistic paradigm investigates the factors that supposedly drive density changes and is identical to Caughley's declining population paradigm of conservation biology. The assumption that we can uncover invariant relationships between population growth rate and some other variables is an article of faith. Numerous commercial fishery applications have failed to find the invariant relationships between stock and recruitment that are predicted by the density paradigm. Environmental variation is the rule, and non-equilibrial dynamics should force us to look for the mechanisms of population change. If multiple factors determine changes in population density, there can be no predictability in either of these paradigms and we will become environmental historians rather than scientists with useful generalizations for the population problems of this century. Defining our questions clearly and adopting an experimental approach with crisp alternative hypotheses and adequate controls will be essential to building useful generalizations for solving the practical problems of population management in fisheries, wildlife and conservation. PMID:12396513

  13. The cognitive paradigm ontology: design and application.

    PubMed

    Turner, Jessica A; Laird, Angela R

    2012-01-01

    We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project ( www.brainmap.org ) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community.

  14. Sensitive and specific enzyme-linked immunosorbent assay for detecting serum antibodies against Mycobacterium avium subsp. paratuberculosis in fallow deer.

    PubMed

    Prieto, José M; Balseiro, Ana; Casais, Rosa; Abendaño, Naiara; Fitzgerald, Liam E; Garrido, Joseba M; Juste, Ramon A; Alonso-Hearn, Marta

    2014-08-01

    The enzyme-linked immunosorbent assay (ELISA) is the diagnostic test most commonly used in efforts to control paratuberculosis in domestic ruminants. However, commercial ELISAs have not been validated for detecting antibodies against Mycobacterium avium subsp. paratuberculosis in wild animals. In this study, we compared the sensitivities and specificities of five ELISAs using individual serum samples collected from 41 fallow deer with or without histopathological lesions consistent with paratuberculosis. Two target antigenic preparations were selected, an ethanol-treated protoplasmic preparation obtained from a fallow deer M. avium subsp. paratuberculosis isolate (ELISAs A and B) and a paratuberculosis protoplasmic antigen (PPA3) (ELISAs C and D). Fallow deer antibodies bound to the immobilized antigens were detected by using a horseradish peroxidase (HRP)-conjugated anti-fallow deer IgG antibody (ELISAs A and C) or HRP-conjugated protein G (ELISAs B and D). A commercially available assay, ELISA-E, which was designed to detect M. avium subsp. paratuberculosis antibodies in cattle, sheep, and goats, was also tested. Although ELISAs A, C, and E had the same sensitivity (72%), ELISAs A and C were more specific (100%) for detecting fallow deer with lesions consistent with paratuberculosis at necropsy than was the ELISA-E (87.5%). In addition, the ELISA-A was particularly sensitive for detecting fallow deer in the latent stages of infection (62.5%). The antibody responses detected with the ELISA-A correlated with both the severity of enteric lesions and the presence of acid-fast bacteria in gut tissue samples. In summary, our study shows that the ELISA-A can be a cost-effective diagnostic tool for preventing the spread of paratuberculosis among fallow deer populations.

  15. Cytokine Gene Expression in Peripheral Blood Mononuclear Cells and Tissues of Cattle Infected with Mycobacterium avium subsp. paratuberculosis: Evidence for an Inherent Proinflammatory Gene Expression Pattern

    PubMed Central

    Coussens, Paul M.; Verman, Nitin; Coussens, Marc A.; Elftman, Michael D.; McNulty, Amanda M.

    2004-01-01

    In cattle and other ruminants, infection with the intracellular pathogen Mycobacterium avium subsp. paratuberculosis results in a granulomatous enteritis (Johne's disease) that is often fatal. The key features of host immunity to M. avium subsp. paratuberculosis infection include an appropriate early proinflammatory and cytotoxic response (Th1-like) that eventually gives way to a predominant antibody-based response (Th2-like). Clinical disease symptoms often appear subsequent to waning of the Th1-like immune response. Understanding why this shift in the immune response occurs and the underlying molecular mechanisms involved is critical to future control measures and diagnosis. Previous studies have suggested that M. avium subsp. paratuberculosis may suppress gene expression in peripheral blood mononuclear cells (PBMCs) from infected cows, despite a continued inflammatory reaction at sites of infection. In the present study, we tested the hypothesis that exposure to M. avium subsp. paratuberculosis suppresses a proinflammatory gene expression pattern in PBMCs from infected cows. To do this, we examined expression of genes encoding interleukin-1α (IL-1α), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-16, and IL-18, as well as genes encoding gamma interferon (IFN-γ), transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α), in PBMCs, intestinal lesions, and mesenteric lymph nodes of cattle naturally infected with M. avium subsp. paratuberculosis. Cytokine gene expression in these cells and tissues was compared to expression in similar cells and tissues from control uninfected cattle. Our comprehensive results demonstrate that for most cytokine genes, including the genes encoding IFN-γ, TGF-β, TNF-α, IL-1α, IL-4, IL-6, IL-8, and IL-12p35, differential expression in PBMCs from infected and control cattle did not require stimulation with M. avium subsp. paratuberculosis. In fact, stimulation with M. avium subsp. paratuberculosis tended

  16. Fuzzy Hybrid Deliberative/Reactive Paradigm (FHDRP)

    NASA Technical Reports Server (NTRS)

    Sarmadi, Hengameth

    2004-01-01

    This work aims to introduce a new concept for incorporating fuzzy sets in hybrid deliberative/reactive paradigm. After a brief review on basic issues of hybrid paradigm the definition of agent-based fuzzy hybrid paradigm, which enables the agents to proceed and extract their behavior through quantitative numerical and qualitative knowledge and to impose their decision making procedure via fuzzy rule bank, is discussed. Next an example performs a more applied platform for the developed approach and finally an overview of the corresponding agents architecture enhances agents logical framework.

  17. Contemporary Treatment Paradigms in Keratoconus.

    PubMed

    McGhee, Charles N J; Kim, Bia Z; Wilson, Peter J

    2015-10-01

    The past 20 years have witnessed an explosion in our knowledge of keratoconus, accompanied by a radical transformation of management options. A 2-hit hypothesis proposes an underlying genetic predisposition coupled with external environmental factors, including eye rubbing and atopy. The variable prevalence and natural history have been better defined including significant cone progression in middle age. Therefore, current management must include early diagnosis, regular monitoring, and treatment of environmental cofactors. Spectacles and contact lenses remain fundamental to the optical management of keratoconus. Intrastromal corneal ring segments have been increasingly used, providing improvement in the corneal shape, corrected visual acuity, and contact lens wear. However, like contact lenses, intrastromal corneal ring segments do not treat the underlying disease process. Therefore, current approaches must also consider treatments to minimize keratoconus progression. Fortunately, there is increasing evidence that corneal collagen crosslinking will halt or slow progression in most cases. Until relatively recently, penetrating keratoplasty was the preferred intervention for advanced keratoconus, with long-term success in the region of 90%; however, the greatest risk of failure remains endothelial allograft rejection. Deep anterior lamellar keratoplasty has emerged in the new millennium as a preferred approach to conserve the host endothelium and avoid rejection. Nonetheless, the overall superiority of deep anterior lamellar keratoplasty compared with penetrating keratoplasty, in terms of optical and survival benefits, is still debated. This perspective provides an overview of our current knowledge of keratoconus and current management options. A step-ladder approach to managing keratoconus is outlined to provide the practitioner with a contemporary management paradigm.

  18. New Paradigms for Asteroid Formation

    NASA Astrophysics Data System (ADS)

    Johansen, A.; Jacquet, E.; Cuzzi, J. N.; Morbidelli, A.; Gounelle, M.

    Asteroids and meteorites provide key evidence on the formation of planetesimals in the solar system. Asteroids are traditionally thought to form in a bottom-up process by coagulation within a population of initially kilometer-scale planetesimals. However, new models challenge this idea by demonstrating that asteroids of sizes from 100 to 1000 km can form directly from the gravitational collapse of small particles that have organized themselves in dense filaments and clusters in the turbulent gas. Particles concentrate passively between eddies down to the smallest scales of the turbulent gas flow and inside large-scale pressure bumps and vortices. The streaming instability causes particles to take an active role in the concentration, by piling up in dense filaments whose friction on the gas reduces the radial drift compared to that of isolated particles. In this chapter we review new paradigms for asteroid formation and critically compare them against the observed properties of asteroids as well as constraints from meteorites. Chondrules of typical sizes from 0.1 to 1 mm are ubiquitous in primitive meteorites and likely represent the primary building blocks of asteroids. Chondrule-sized particles are nevertheless tightly coupled to the gas via friction and are therefore hard to concentrate in large amounts in the turbulent gas. We review recent progress on understanding the incorporation of chondrules into the asteroids, including layered accretion models where chondrules are accreted onto asteroids over millions of years. We highlight in the end 10 unsolved questions in asteroid formation where we expect that progress will be made over the next decade.

  19. Purification and chemical characterisation of a cell wall-associated β-galactosidase from mature sweet cherry (Prunus avium L.) fruit.

    PubMed

    Gerardi, Carmela; Blando, Federica; Santino, Angelo

    2012-12-01

    Using four different chromatographic steps, β-galactosidase was purified from the ripe fruit of sweet cherry to apparent electrophoretic homogeneity with approximately 131-fold purification. The Prunus avium β-galactosidase showed an apparent molecular mass of about 100 kDa and consisted of four different active polypeptides with pIs of about 7.9, 7.4, 6.9 and 6.4 as estimated by native IEF and β-galactosidase-activity staining. The active polypeptides were individually excised from the gel and subjected to SDS-PAGE. Each of the four native enzymes showing β-galactosidase activity was composed of two polypeptides with an estimated mass of 54 and 33 kDa. Both of these polypeptides were subjected to N-terminal amino acid sequence analysis. The 54 kDa polypeptide of sweet cherry β-galactosidase showed a 43% identity with the 44 kDa subunit of persimmon and apple β-galactosidases and the 48 kDa subunit of carambola galactosidase I. The sweet cherry β-galactosidase exhibited a strict specificity towards p-nitrophenyl β-D-galactopyranoside, a pH optimum of 4.0 and K(m) and V(max) values of 0.42 mM and 4.12 mmol min(-1) mg(-1) of protein respectively with this substrate. The enzyme was also active towards complex glycans. Taken together the results of this study prompted a role for this class of enzymes on sweet cherry fruit ripening and softening.

  20. Evolutionary psychology: the emperor's new paradigm.

    PubMed

    Buller, David J

    2005-06-01

    For some evolutionary psychology is merely a field of inquiry, but for others it is a robust paradigm involving specific theories about the nature and evolution of the human mind. Proponents of this paradigm claim to have made several important discoveries regarding the evolved architecture of the mind. Highly publicized discoveries include a cheater-detection module, a psychological sex difference in jealousy, and motivational mechanisms underlying parental love and its lapses, which purportedly result in child maltreatment. In this article, I argue that the empirical evidence for these "discoveries" is inconclusive, at best. I suggest that, as the reigning paradigm in evolutionary psychology has produced questionable results, the evolutionary study of human psychology is still in need of a guiding paradigm.

  1. The safety implications of emerging software paradigms

    SciTech Connect

    Suski, G.J.; Persons, W.L.; Johnson, G.L.

    1994-10-01

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants.

  2. Yakov Zeldovich and the Cosmic Web Paradigm

    NASA Astrophysics Data System (ADS)

    Einasto, Jaan

    2016-10-01

    I discuss the formation of the modern cosmological paradigm. In more detail I describe the early study of dark matter and cosmic web and the role of Yakov Zeldovich in the formation of the present concepts on these subjects.

  3. A Paradigm for Research in Education.

    ERIC Educational Resources Information Center

    Holmberg, Borje

    1982-01-01

    Examines the effect of researcher value judgments on the aims, methods, and objects of educational research. The author proposes a paradigm for scholarly educational research on the use of the scientific method. (AM)

  4. MICROHABITAT REVIEWED: ANALYSIS OF A PARADIGM

    EPA Science Inventory

    Small mammal microhabitat partitioning research has greatly influenced vertebrate community ecologists. It is not a stretch to assert that there exists a 'microhabitat paradigm' among small mammal specialists; sympatry among small mammal species is enabled by differential use of...

  5. Engineering paradigms and anthropogenic global change

    NASA Astrophysics Data System (ADS)

    Bohle, Martin

    2016-04-01

    This essay discusses 'paradigms' as means to conceive anthropogenic global change. Humankind alters earth-systems because of the number of people, the patterns of consumption of resources, and the alterations of environments. This process of anthropogenic global change is a composite consisting of societal (in the 'noosphere') and natural (in the 'bio-geosphere') features. Engineering intercedes these features; e.g. observing stratospheric ozone depletion has led to understanding it as a collateral artefact of a particular set of engineering choices. Beyond any specific use-case, engineering works have a common function; e.g. civil-engineering intersects economic activity and geosphere. People conceive their actions in the noosphere including giving purpose to their engineering. The 'noosphere' is the ensemble of social, cultural or political concepts ('shared subjective mental insights') of people. Among people's concepts are the paradigms how to shape environments, production systems and consumption patterns given their societal preferences. In that context, engineering is a means to implement a given development path. Four paradigms currently are distinguishable how to make anthropogenic global change happening. Among the 'engineering paradigms' for anthropogenic global change, 'adaptation' is a paradigm for a business-as-usual scenario and steady development paths of societies. Applying this paradigm implies to forecast the change to come, to appropriately design engineering works, and to maintain as far as possible the current production and consumption patterns. An alternative would be to adjust incrementally development paths of societies, namely to 'dovetail' anthropogenic and natural fluxes of matter and energy. To apply that paradigm research has to identify 'natural boundaries', how to modify production and consumption patterns, and how to tackle process in the noosphere to render alterations of common development paths acceptable. A further alternative

  6. Interfacial inhibition of macromolecular interactions: nature's paradigm for drug discovery.

    PubMed

    Pommier, Yves; Cherfils, Jacqueline

    2005-03-01

    One of nature's strategies for interfering with molecular interactions is to trap macromolecules in transition states with their partners in dead-end complexes that are unable to complete their biological function. This type of inhibition, which we refer to as "interfacial inhibition", is illustrated by two natural inhibitors, brefeldin A (BFA) and camptothecin (CPT), whose modes of action have been elucidated fully in structural studies. Interfacial inhibition occurs at the protein-protein interface in the case of BFA and at the protein-DNA interface in the case of CPT. In both systems, the drugs take advantage of transient structural and energetic conditions created by the macromolecular complex, which give rise to "hot-spots" for drug binding. In addition to these examples, several natural compounds such as forskolin, tubulin inhibitors and immunophilins target protein interfaces. We propose that interfacial inhibition is a paradigm for the discovery of drugs that interfere with macromolecular complexes.

  7. Adaptive Systems Engineering: A Medical Paradigm for Practicing Systems Engineering

    SciTech Connect

    R. Douglas Hamelin; Ron D. Klingler; Christopher Dieckmann

    2011-06-01

    From its inception in the defense and aerospace industries, SE has applied holistic, interdisciplinary tools and work-process to improve the design and management of 'large, complex engineering projects.' The traditional scope of engineering in general embraces the design, development, production, and operation of physical systems, and SE, as originally conceived, falls within that scope. While this 'traditional' view has expanded over the years to embrace wider, more holistic applications, much of the literature and training currently available is still directed almost entirely at addressing the large, complex, NASA and defense-sized systems wherein the 'ideal' practice of SE provides the cradle-to-grave foundation for system development and deployment. Under such scenarios, systems engineers are viewed as an integral part of the system and project life-cycle from conception to decommissioning. In far less 'ideal' applications, SE principles are equally applicable to a growing number of complex systems and projects that need to be 'rescued' from overwhelming challenges that threaten imminent failure. The medical profession provides a unique analogy for this latter concept and offers a useful paradigm for tailoring our 'practice' of SE to address the unexpected dynamics of applying SE in the real world. In short, we can be much more effective as systems engineers as we change some of the paradigms under which we teach and 'practice' SE.

  8. Managing Balloon Projects - A Changing Paradigm: A Retrospective Look

    NASA Astrophysics Data System (ADS)

    Black, R. K.; Smith, I. S.

    With the advent of the Ultra-Long Duration Balloon (ULDB) capability and balloons being offered as a carrier for NASA Explorer class missions, a fundamental shift in the way balloon mission projects are managed will be required. This shift will ensure the performance and reliability of the science instrument, balloon vehicle, flight system, and ground control center to support a science mission of up to 100 days in duration. The current ``design to capability'' paradigm, with minimal management oversight, has traditionally worked well for many years in flying scientific instruments on balloons at low cost with medium to high risk. Newer, more complex science instruments and missions, such as those developed under NASA's Explorers Program, will require a radical shift to a much more formal ``design to requirements'' management paradigm. This paper will attempt to take a retrospective look at the formality imposed by the Explorers Program and determine what management elements are needed to assure the success of the current ``design to capability'' missions without increasing significant cost. This paradigm shift is intended to support the successful accomplishment of balloon missions on schedule, within budget, and lower risk, while enhancing and satisfying the success criteria and requirements of the primary customer, the Principal Investigator. This shift to a ``Explorer-like'' formality paradigm will require development of a cohesive mission management organization, organizing an effective system engineering process that links science requirements to instrument and flight system performance, implementing a cost effective performance assurance program, and exerting cost control over all aspects of the mission. All of these elements need to be addressed within a context of a strong commitment to meeting schedule within the constrained budgets.

  9. [Paradigm shift in higher education].

    PubMed

    Csóka, Mária

    2009-08-30

    The fast changes that took place in the last quarter of the 20th century made the professionals dealing with pedagogy realize that our school system followed the economical changes in terms of training supply and the matter of education very slowly, if at all; let alone the educational methods. We had to realize that the maintaining of this conservative system is not rational, education has become the most important part of the globalisational competition and the key to the 21st century is learning. Accordingly, the spatial and temporal expenditure of education has become a new trend, namely lifelong learning (LLL). The social needs on education have increased, the expectations of economy and employers have changed: knowledge has become the fund of competitiveness. In this process, universities have got an accentuated role: in addition to being the place of undergraduate training they have become the site of postgraduate courses for the increasing graduate adult masses. Therefore, reform processes have started in a number of European countries in the nineties. The Bologna Declaration signed on 19th June 1999 set a common direction for these reforms, with its signatories aiming to establish a standard European Higher Education Area with harmonized and comparable educational systems by 2010. However, the administrative change itself is not enough to reach the goals; a formal innovation has to be followed by a reform of the contents which means reformation of higher education. In recent years, Hungarian colleges and universities have worked out their educational programs that are suitable for the new structure; it is only the new educational programs that started from 1st September 2006. The author determines the most important parts of the reform of the training system of Semmelweis University Faculty of Health Sciences, which are the following: redrawing of the training philosophy and paradigm, the reform of the training structure of macro level (cognition

  10. [Paradigm shift in higher education].

    PubMed

    Csóka, Mária

    2009-08-30

    The fast changes that took place in the last quarter of the 20th century made the professionals dealing with pedagogy realize that our school system followed the economical changes in terms of training supply and the matter of education very slowly, if at all; let alone the educational methods. We had to realize that the maintaining of this conservative system is not rational, education has become the most important part of the globalisational competition and the key to the 21st century is learning. Accordingly, the spatial and temporal expenditure of education has become a new trend, namely lifelong learning (LLL). The social needs on education have increased, the expectations of economy and employers have changed: knowledge has become the fund of competitiveness. In this process, universities have got an accentuated role: in addition to being the place of undergraduate training they have become the site of postgraduate courses for the increasing graduate adult masses. Therefore, reform processes have started in a number of European countries in the nineties. The Bologna Declaration signed on 19th June 1999 set a common direction for these reforms, with its signatories aiming to establish a standard European Higher Education Area with harmonized and comparable educational systems by 2010. However, the administrative change itself is not enough to reach the goals; a formal innovation has to be followed by a reform of the contents which means reformation of higher education. In recent years, Hungarian colleges and universities have worked out their educational programs that are suitable for the new structure; it is only the new educational programs that started from 1st September 2006. The author determines the most important parts of the reform of the training system of Semmelweis University Faculty of Health Sciences, which are the following: redrawing of the training philosophy and paradigm, the reform of the training structure of macro level (cognition

  11. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    NASA Astrophysics Data System (ADS)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  12. Searching for a new paradigm in health care delivery.

    PubMed

    Neff, K E; Moser, D R

    1993-01-01

    The cartoon character Pogo, uttering his now famous line, "We have met the enemy and it is us," might well have been referring to the dilemmas that we face today in American health care. A major source of our current difficulties in solving these admittedly complex problems lies in our way of thinking about, or conceptualizing, health care and health care delivery. We are caught in an old paradigm that is simply not adequate for dealing with the health care delivery problems of the '90s, not to mention those of the 21st Century. PMID:10129386

  13. The Underlying Social Dynamics of Paradigm Shifts.

    PubMed

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  14. The Underlying Social Dynamics of Paradigm Shifts

    PubMed Central

    Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm. PMID:26418255

  15. Thermal inactivation profiles of Mycobacterium avium subsp. paratuberculosis in lamb skeletal muscle homogenate fluid.

    PubMed

    Whittington, Richard J; Waldron, Anna; Warne, Darian

    2010-01-31

    Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in livestock and there is a debate about its role in humans in chronic inflammatory bowel disorders such as Crohn's disease, but the relationship remains unproven. Nevertheless livestock health authorities in many countries aim to lower the prevalence of this infection to reduce potential contamination of the human food supply. MAP may occur in bovine milk and data on thermal inactivation suggest pasteurisation is an effective process. Recently MAP has been identified in skeletal muscle of cattle and sheep but there are no data on its thermal inactivation in these substrates. In this study the inactivation of MAP was studied in a fluid homogenate of lamb skeletal muscle at temperatures previously identified as being relevant to cooking processes applied by domestic consumers. A PCR thermocycler was used to ensure accurate temperatures and rapid heat exchange, while radiometric culture was used to ensure sensitive detection of viable MAP for determination of D and z values. Among the two predominant strains of MAP, S and C, D(55) ranged from 56 to 89 min, D(60) was 8 to 11 min, D(65) was 26 to 35s while D(70) was 1.5 to 1.8s. Values for z were 4.21C degrees for the S strain and 4.51C degrees for the C strain. At temperatures of 65-70 degrees C, MAP appeared to be less heat tolerant in skeletal muscle fluid than in previous reports using milk as the medium. The total thermal exposure of MAP during baking of a sample of 16 leg-of-lamb roasts in domestic ovens was determined to result in more than 20 log reductions in most cases, that is the product was microbiologically safe. Based on the models used in this study, there is a low probability of survival of MAP provided that red meat is cooked to recommended standards. PMID:19896745

  16. A Mycobacterium avium subsp. paratuberculosis Predicted Serine Protease Is Associated with Acid Stress and Intraphagosomal Survival

    PubMed Central

    Kugadas, Abirami; Lamont, Elise A.; Bannantine, John P.; Shoyama, Fernanda M.; Brenner, Evan; Janagama, Harish K.; Sreevatsan, Srinand

    2016-01-01

    The ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although, studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophages and MAC-T cells that coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increased bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5) conditions, compared to the parent strain. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted. PMID:27597934

  17. SNP genotyping of animal and human derived isolates of Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Wynne, James W; Beller, Christie; Boyd, Victoria; Francis, Barry; Gwoźdź, Jacek; Carajias, Marios; Heine, Hans G; Wagner, Josef; Kirkwood, Carl D; Michalski, Wojtek P

    2014-08-27

    Mycobacterium avium subsp. paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic granulomatous enteritis that affects ruminants worldwide. While the ability of MAP to cause disease in animals is clear, the role of this bacterium in human inflammatory bowel diseases remains unresolved. Previous whole genome sequencing of MAP isolates derived from human and three animal hosts showed that human isolates were genetically similar and showed a close phylogenetic relationship to one bovine isolate. In contrast, other animal derived isolates were more genetically diverse. The present study aimed to investigate the frequency of this human strain across 52 wild-type MAP isolates, collected predominantly from Australia. A Luminex based SNP genotyping approach was utilised to genotype SNPs that had previously been shown to be specific to the human, bovine or ovine isolate types. Fourteen SNPs were initially evaluated across a reference panel of isolates with known genotypes. A subset of seven SNPs was chosen for analysis within the wild-type collection. Of the seven SNPs, three were found to be unique to paediatric human isolates. No wild-type isolates contain these SNP alleles. Interestingly, and in contrast to the paediatric isolates, three additional adult human isolates (derived from adult Crohn's disease patients) also did not contain these SNP alleles. Furthermore we identified two SNPs, which demonstrate extensive polymorphism within the animal-derived MAP isolates. One of which appears unique to ovine and a single camel isolate. From this study we suggest the existence of genetic heterogeneity between human derived MAP isolates, some of which are highly similar to those derived from bovine hosts, but others of which are more divergent.

  18. Short communication: Evaluation of sampling socks for detection of Mycobacterium avium ssp. paratuberculosis on dairy farms.

    PubMed

    Wolf, R; Orsel, K; De Buck, J; Kanevets, U; Barkema, H W

    2016-04-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, a production-limiting disease in cattle. Detection of infected herds is often done using environmental samples (ES) of manure, which are collected in cattle pens and manure storage areas. Disadvantages of the method are that sample accuracy is affected by cattle housing and type of manure storage area. Furthermore, some sampling locations (e.g., manure lagoons) are frequently not readily accessible. However, sampling socks (SO), as used for Salmonella spp. testing in chicken flocks, might be an easy to use and accurate alternative to ES. The objective of the study was to assess accuracy of SO for detection of MAP in dairy herds. At each of 102 participating herds, 6 ES and 2 SO were collected. In total, 45 herds had only negative samples in both methods and 29 herds had ≥1 positive ES and ≥1 positive SO. Furthermore, 27 herds with ≥1 positive ES had no positive SO, and 1 herd with no positive ES had 1 positive SO. Bayesian simulation with informative priors on sensitivity of ES and MAP herd prevalence provided a posterior sensitivity for SO of 43.5% (95% probability interval=33-58), and 78.5% (95% probability interval=62-93) for ES. Although SO were easy to use, accuracy was lower than for ES. Therefore, with improvements in the sampling protocol (e.g., more SO per farm and more frequent herd visits), as well as improvements in the laboratory protocol, perhaps SO would be a useful alternative for ES. PMID:26851860

  19. Where Are All the Mycobacterium avium Subspecies paratuberculosis in Patients with Crohn's Disease?

    PubMed Central

    Pierce, Ellen S.

    2009-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease. PMID:19325887

  20. Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis.

    PubMed

    Hempel, Randy J; Bannantine, John P; Stabel, Judith R

    2016-01-01

    Johne's disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection.