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  • 1
    Language: English
    In: PloS one, 2015, Vol.10(4), pp.e0124373
    Description: Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans. Cationic APs are attracted to the negatively charged bacterial cell surface. In other gram-negative bacteria, modification of lipopolysaccharide or lipooligosaccharide (LOS) by the addition of positively charged moieties, such as phosphoethanolamine (PEA), confers AP resistance by means of electrostatic repulsion. H. ducreyi LOS has PEA modifications at two sites, and we identified three genes (lptA, ptdA, and ptdB) in H. ducreyi with homology to a family of bacterial PEA transferases. We generated non-polar, unmarked mutants with deletions in one, two, or all three putative PEA transferase genes. The triple mutant was significantly more susceptible to both α- and β-defensins; complementation of all three genes restored parental levels of AP resistance. Deletion of all three PEA transferase genes also resulted in a significant increase in the negativity of the mutant cell surface. Mass spectrometric analysis revealed that LptA was required for PEA modification of lipid A; PtdA and PtdB did not affect PEA modification of LOS. In human inoculation experiments, the triple mutant was as virulent as its parent strain. While this is the first identified mechanism of resistance to α-defensins in H. ducreyi, our in vivo data suggest that resistance to cathelicidin LL-37 may be more important than defensin resistance to H. ducreyi pathogenesis.
    Keywords: Bacterial Proteins -- Genetics ; Drug Resistance, Bacterial -- Genetics ; Ethanolaminephosphotransferase -- Genetics ; Haemophilus Ducreyi -- Genetics ; Lipid A -- Metabolism
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Infection and immunity, June 2011, Vol.79(6), pp.2324-34
    Description: Haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance in H. ducreyi. We found a proton motive force-dependent effect on H. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC rendered H. ducreyi more sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. The mtrC mutant 35000HPmtrC exhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type by trans-complementation with mtrC. Similar phenotypes were reported in a cpxA mutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. A cpxR mutant had wild-type levels of antimicrobial peptide resistance; a cpxA mutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrC was more sensitive than the cpxA mutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrC had lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism in H. ducreyi and shows that LL-37 resistance in H. ducreyi is multifactorial.
    Keywords: Antimicrobial Cationic Peptides -- Metabolism ; Bacterial Outer Membrane Proteins -- Immunology ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Regulon -- Genetics
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 3
    Description: Indiana University-Purdue University Indianapolis (IUPUI) Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans. Cationic APs are attracted to the negatively charged bacterial cell surface. In other gram-negative bacteria, modification of lipopolysaccharide or lipooligosaccharide (LOS) by the addition of positively charged moieties, such as phosphoethanolamine (PEA), confers AP resistance by means of electrostatic repulsion. H. ducreyi LOS has PEA modifications at two sites, and we identified three genes (lptA, ptdA, and ptdB) in H. ducreyi with homology to a family of bacterial PEA transferases. We generated non-polar, unmarked mutants with deletions in one, two, or all three putative PEA transferase genes. Mutants with deletions in two PEA transferase genes were significantly more susceptible to β-defensins, and the triple mutant was significantly more susceptible to both α- and β-defensins, but not LL-37; complementation of all three genes restored parental levels of AP resistance. Deletion of all three PEA transferase genes also resulted in a significant increase in the negativity of the mutant cell surface, suggesting these three genes contribute to the addition of positively charged moieties on the cell surface. Mass spectrometric analysis revealed that LptA was required for PEA modification of lipid A; PtdtA and PtdB did not affect PEA modification of LOS. In human inoculation experiments, the triple mutant was as virulent as its parent strain. While this is the first identified mechanism of resistance to α-defensins in H. ducreyi, our in vivo data suggest that resistance to cathelicidin may be more important than defensin resistance to H. ducreyi pathogenesis.
    Keywords: Haemophilus Ducreyi ; Phosphoethanolamine Transferase ; Antimicrobial Peptide Resistance
    Source: Networked Digital Library of Theses and Dissertations
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  • 4
    In: Nova Law Review, Wntr, 1995, Vol.19(2), p.667-678
    Keywords: Elderly -- Psychological Aspects ; Geriatric Psychiatry -- Laws, Regulations And Rules ; Civil Commitment ; Mentally Ill Persons
    ISSN: 1049-0248
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  • 5
    Language: English
    In: Arthritis Care & Research, 15 October 2004, Vol.51(5), pp.763-773
    Description: OBJECTIVE: To examine the strength of the association between different measures of health-related quality of life (HRQOL), disability, pain, and well-being in children with chronic arthritis. To evaluate whether HRQOL scores vary as a function of disability status beyond chance. To assess the quality of the parent proxy report for HRQOL as compared with disability, pain, and well-being.METHODS: Measures of HRQOL (visual analog scale [VAS] of health, Pediatric Quality of Life Inventory [PedsQL], Juvenile Arthritis Quality of Life Questionnaire (JAQQ), and modified standard gamble technique [SG]), disability (Childhood Health Assessment Questionnaire), VAS of pain, and VAS of well-being (VAS-well) were completed by the parents (n = 119) and patients 〉 or =8 years (SG: 〉 or =12 years).RESULTS: HRQOL was highest when measured by the SG, whose utilities were no more than weakly correlated with any of the other outcomes. The values of all other HRQOL measures were at least moderately correlated with each other and with the VAS-well. Irrespective of the measure used, disability was associated with significantly decreased HRQOL. There was fair to good agreement and moderate consistency of the HRQOL ratings (SG: fair consistency) between patients and parents with marked differences between health domains.CONCLUSION: HRQOL measured by the PedsQL, JAQQ, and VAS are moderately to highly correlated with each other in children with chronic arthritis. The children's HRQOL significantly decreases with increasing disability. Despite more pronounced differences for some health domains, parents are moderate to good proxy reporters of HRQOL, disability, and well-being of children with chronic arthritis.
    Keywords: Quality Of Life ; Pedsql ; Jaqq ; Standard Gamble ; Children ; Arthritis
    ISSN: 0004-3591
    E-ISSN: 1529-0131
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  • 6
    Language: English
    In: Arthritis and rheumatism, 15 October 2004, Vol.51(5), pp.763-73
    Description: To examine the strength of the association between different measures of health-related quality of life (HRQOL), disability, pain, and well-being in children with chronic arthritis. To evaluate whether HRQOL scores vary as a function of disability status beyond chance. To assess the quality of the parent proxy report for HRQOL as compared with disability, pain, and well-being. Measures of HRQOL (visual analog scale [VAS] of health, Pediatric Quality of Life Inventory [PedsQL], Juvenile Arthritis Quality of Life Questionnaire (JAQQ), and modified standard gamble technique [SG]), disability (Childhood Health Assessment Questionnaire), VAS of pain, and VAS of well-being (VAS-well) were completed by the parents (n = 119) and patients 〉 or =8 years (SG: 〉 or =12 years). HRQOL was highest when measured by the SG, whose utilities were no more than weakly correlated with any of the other outcomes. The values of all other HRQOL measures were at least moderately correlated with each other and with the VAS-well. Irrespective of the measure used, disability was associated with significantly decreased HRQOL. There was fair to good agreement and moderate consistency of the HRQOL ratings (SG: fair consistency) between patients and parents with marked differences between health domains. HRQOL measured by the PedsQL, JAQQ, and VAS are moderately to highly correlated with each other in children with chronic arthritis. The children's HRQOL significantly decreases with increasing disability. Despite more pronounced differences for some health domains, parents are moderate to good proxy reporters of HRQOL, disability, and well-being of children with chronic arthritis.
    Keywords: Health Status Indicators ; Arthritis -- Diagnosis
    ISSN: 0004-3591
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 7
    Language: English
    In: Personality and Individual Differences, 1996, Vol.21(5), pp.785-789
    Description: Two models of emotion (Positive Affect/Negative Affect and Bioinformational) were compared to determine whether information obtained using one model could be used to make inferences about the other. Results did not support the suggested relationship between these 2 models. It may be misleading to assume that data obtained by measuring dimensions from one model can be used to make inferences about dimensions of the other model. (Original abstract-amended)
    Keywords: Psychology
    ISSN: 0191-8869
    E-ISSN: 1873-3549
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  • 8
    Language: English
    In: Developmental Dynamics, September 1998, Vol.213(1), pp.140-146
    Description: Lens regeneration in vivo is restricted to some urodeles only. After removal of the lens, this remarkable event is initiated from the dorsal iris. The pigmented epithelial cells from the dorsal iris dedifferentiate and subsequently transdifferentiate to form the regenerating lens. This property of the dorsal iris implies specific regulation along the dorsal‐ventral axis. To date, no known genes are known to be specifically expressed in the dedifferentiating cells and to be involved in lens regeneration. In this paper, we show that FGFR‐1 expression and function is correlated with the process of lens regeneration from the dorsal iris. Following lentectomy, FGFR‐1 protein is specifically present in the dedifferentiating pigment epithelial cells in the dorsal iris, but is absent from the ventral iris. Subsequently, FGFR‐1 protein is present throughout the process of lens regeneration and fiber differentiation. Furthermore, we show that an FGFR‐1‐specific inhibitor is able to inhibit the process of transdifferentiation and lens regeneration. In this sense, FGFR‐1 can be regarded as the first known lens regeneration‐associated factor. © 1998 Wiley‐Liss, Inc.
    Keywords: Fgfr‐1 ; Lens Regeneration ; Fgfr‐1 Inhibitor
    ISSN: 1058-8388
    E-ISSN: 1097-0177
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  • 9
    Language: English
    In: Developmental Dynamics, December 2000, Vol.219(4), pp.588-593
    Description: Prompted by the actions of retinoids and their receptors in gene regulation, in the developing eye and especially in the lens, we have undertaken a detailed study to examine the effects of retinoids on urodele lens regeneration. First, we examined the effects of exogenous retinoids. It was found that exogenous retinoids had no significant effect on lens regeneration. However, when synthesis of retinoic acid was inhibited by disulfiram, or when the function of the retinoid receptors was impaired by using a RAR antagonist, the process of lens regeneration was dramatically affected. In the majority of the cases, lens regeneration was inhibited and lens morphogenesis was disrupted. In a few cases, we were also able to observe ectopic lens regeneration from places other than the normal site, which is from the dorsal iris. The most spectacular case was the regeneration of a lens from the cornea, an event possible only in premetamorphic frogs. These data show that inhibition of retinoid receptors is paramount for the normal course and distribution of lens regeneration. We have also examined expression of RAR‐delta during lens regeneration. This receptor was expressed highly in the regenerating lens only. Therefore, it seems that this receptor is specific for the regeneration process and consequently such expression correlates well with the effects of RAR inhibition observed in our studies. © 2000 Wiley‐Liss, Inc.
    Keywords: Newt ; Lens ; Regeneration ; Retinoids
    ISSN: 1058-8388
    E-ISSN: 1097-0177
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  • 10
    Language: English
    In: The Astrophysical Journal, 2010, Vol.708(2), pp.1241-1253
    Description: We present Hubble Space Telescope /Near-Infrared Camera and Multi-Object Spectrometer photometry, and low-resolution K -band spectra of the GLIMPSE9 stellar cluster. The newly obtained color-magnitude diagram shows a cluster sequence with H K S = 1 mag, indicating an interstellar extinction A = 1.6 ± 0.2 mag. The spectra of the three brightest stars show deep CO band heads, which indicate red supergiants with spectral type M1-M2. Two 09-B2 supergiants are also identified, which yield a spectrophotometric distance of 4.2 ± 0.4 kpc. Presuming that the population is coeval, we derive an age between 15 and 27 Myr, and a total cluster mass of 1600 ± 400 M , integrated down to 1 M . In the vicinity of GLIMPSE9 are several H  II regions and supernova remnants, all of which (including GLIMPSE9) are probably associated with a giant molecular cloud (GMC) in the inner galaxy. GLIMPSE9 probably represents one episode of massive star formation in this GMC. We have identified several other candidate stellar clusters of the same complex.
    ISSN: 0004-637X
    E-ISSN: 1538-4357
    Source: IOPscience (IOP Publishing)
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