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Duquesne University
1.
Rose, Katherine Marie.
The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation.
Degree: MS, Pharmacology, 2012, Duquesne University
URL: https://dsc.duq.edu/etd/1121
► Neuroinflammation is a common pathology found in patients with Parkinson's disease (PD). PD involves a loss of dopamine (DA) neurons and an increase in activated…
(more)
▼ Neuroinflammation is a common pathology found in patients with Parkinson's disease (PD). PD involves a loss of dopamine (DA) neurons and an increase in activated microglia with subsequent proinflammatory cytokine secretion in the substantia nigra (SN) and striatum. A loss of DA neurons is found in the offspring of animals exposed prenatally to the bacteriotoxin,
lipopolysaccharide (LPS) (Ling et al., 2002). Activation of the extracellular regulated kinases, ERK1/2 and ERK5, the downstream targets in the mitogen-activated protein kinase (MAPK) pathway, has been shown to be involved in the dysregulation of the inflammatory process (Cuschieri and Maier, 2005). Consequently, LPS-induced activation of ERK1/2 and ERK5 may cause an increase in production and secretion of proinflammatory cytokines in activated microglia. LPS-mediated activation of ERK1/2 has been shown to be decreased by the phytochemical resveratrol (Zhang et al., 2010). However, the effect of LPS or resveratrol on ERK5 signaling has not been explored. The purpose of this study was to determine (1) the effect of resveratrol on LPS-induced dopaminergic deficits in pups exposed prenatally to LPS, (2) the impact of resveratrol on LPS-induced BV-2 microglial cell activation and (3) the roles of ERK1/2 and ERK5 in resveratrol mediated inhibition of LPS-induced BV-2 cell activation. To test our hypothesis, pregnant rats received an intraperitoneal (i.p.) injection 10, 000 EU/kg LPS at gestational day 10.5 (E10.5) and were fed a resveratrol-enriched diet for 20 days (E3 - E22.5). LPS-induced dopaminergic deficits in pups exposed prenatally at postnatal day 21 (P21), but not at P10 or P40. These deficits were exhibited by a loss of striatal 3, 4-dihydroxyphenylacetic acid (DOPAC) and DA content and tyrosine hydroxylase (TH) expression in the P21 animals. However, dietary resveratrol supplementation increased TH expression, DA and DOPAC levels in the P21 pups following prenatal exposure to LPS. Thus, these data suggest that resveratrol treatment may restore the homeostasis of the DA neuronal system in vivo. However, contrary to previous reports it was determined in vitro that LPS-mediated BV-2 activation and ERK1/2 phosphorylation was not inhibited by resveratrol pretreatment. Interestingly, at 6 hours the MEK inhibitor U0126 decreased LPS-mediated ERK1/2 activation and TNF-α release. ERK5 was not activated by LPS, but preliminary data suggest that the MEK5 inhibitor BIX02189 inhibited LPS-induced TNF-α release. Therefore, BIX02189 may be inhibiting a distinct pathway in our model. Overall, these studies suggest that the use of dietary resveratrol supplementation may be protective against LPS-induced loss of striatal dopaminergic deficits in a time-dependent manner and inhibition of ERK signaling may reduce LPS-mediated microglial activation.
Advisors/Committee Members: Jane E. Cavanaugh, Patrick Flaherty, Lauren O'Donnell, Christopher K. Surratt.
Subjects/Keywords: Lipopolysaccharide; Resveratrol
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APA (6th Edition):
Rose, K. M. (2012). The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation. (Masters Thesis). Duquesne University. Retrieved from https://dsc.duq.edu/etd/1121
Chicago Manual of Style (16th Edition):
Rose, Katherine Marie. “The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation.” 2012. Masters Thesis, Duquesne University. Accessed January 28, 2021.
https://dsc.duq.edu/etd/1121.
MLA Handbook (7th Edition):
Rose, Katherine Marie. “The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation.” 2012. Web. 28 Jan 2021.
Vancouver:
Rose KM. The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation. [Internet] [Masters thesis]. Duquesne University; 2012. [cited 2021 Jan 28].
Available from: https://dsc.duq.edu/etd/1121.
Council of Science Editors:
Rose KM. The Effect of Resveratrol on Lipopolysaccharide-induced Dopaminergic Deficits and BV-2 Cell Activation. [Masters Thesis]. Duquesne University; 2012. Available from: https://dsc.duq.edu/etd/1121

Texas A&M University
2.
Kahn, Meredith K.
Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge.
Degree: MS, Animal Science, 2014, Texas A&M University
URL: http://hdl.handle.net/1969.1/154113
► Eighteen Quarter Horses were utilized in a randomized complete design for a 28 d experiment to evaluate age-related effects on inflammation and cartilage turnover after…
(more)
▼ Eighteen Quarter Horses were utilized in a randomized complete design for a 28 d experiment to evaluate age-related effects on inflammation and cartilage turnover after induction of a single inflammatory insult using
lipopolysaccharide (LPS). Horses were grouped by age, with yearlings (yearling; n = 3 males, n = 3 females), 2 to 3 yr olds (2/3; n = 2 males, n = 4 females), and mature 5 to 8 yr olds (mature; n = 2 males, n = 4 females). On d 0, all horses were housed individually and fed diets that met or exceeded NRC (2007) requirements. On d 14, horses were challenged with an intra-articular injection of LPS. Carpal joints were randomly assigned to receive 0.5 ng LPS solution obtained from E. coli O55:B5, or 0.8mL sterile lactated Ringer’s solution as a contralateral control. Synovial fluid was collected prior to LPS injection at pre-injection h 0 (PIH 0) and 6, 12, 24, 168, and 336 h post-injection. Samples were later analyzed using commercial ELISA kits for prostaglandin E2 (PGE2), collagenase cleavage neoepitope (C2C), and carboxypropeptide of type II collagen (CPII). Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were monitored over the first 24 h and carpal circumference and surface temperature were recorded with additional measurements at 168 and 336 h. Data were analyzed using PROC MIXED procedure of SAS.
Values for RT, HR, and RR were within normal range. HR and RT were influenced by age (P < 0.01), while RR was unaffected by age (P ≤ 0.21). Joint circumference was not influenced by age (P = 0.84), but circumference and surface temperature increased (P < 0.01) over time across all age groups. Synovial PGE2 concentrations tended (P = 0.09) to be influenced by age with yearlings having lower (P = 0.03) concentrations than mature horses. Synovial C2C concentrations were affected by age with yearlings and 2/3 yr olds having lower (P < 0.01) concentrations than mature horses. Concentrations of synovial CPII were influenced by age with yearlings and 2/3 yr old having lower (P ≤ 0.02) concentrations than mature horses. Ratios of CPII:C2C were influenced by age with mature and 2/3 yr old horses having increased (P < 0.01) values compared to yearlings. These results indicate that inflammation and corresponding cartilage turnover in response to LPS administration vary with age.
Advisors/Committee Members: Coverdale, Josie A (advisor), Lucia, Jessica L. (committee member), Welsh, Thomas H. (committee member), Wickersham, Tryon A. (committee member).
Subjects/Keywords: Age; Horse; Lipopolysaccharide; Inflammation; Cartilage
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kahn, M. K. (2014). Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/154113
Chicago Manual of Style (16th Edition):
Kahn, Meredith K. “Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge.” 2014. Masters Thesis, Texas A&M University. Accessed January 28, 2021.
http://hdl.handle.net/1969.1/154113.
MLA Handbook (7th Edition):
Kahn, Meredith K. “Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge.” 2014. Web. 28 Jan 2021.
Vancouver:
Kahn MK. Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge. [Internet] [Masters thesis]. Texas A&M University; 2014. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1969.1/154113.
Council of Science Editors:
Kahn MK. Age-Related Effects on Markers of Inflammation and Cartilage Metabolism in Response to an Intra-Articular Lipopolysaccharide Challenge. [Masters Thesis]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/154113

Texas A&M University
3.
Lucia, Jessica Lauren.
Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses.
Degree: PhD, Animal Science, 2013, Texas A&M University
URL: http://hdl.handle.net/1969.1/149284
► This project established an in vivo method to identify and manipulate expression of markers of osteoarthritis (OA). Specifically, strategies that predictably induce joint inflammation to…
(more)
▼ This project established an in vivo method to identify and manipulate expression of markers of osteoarthritis (OA). Specifically, strategies that predictably induce joint inflammation to evaluate dietary methods of OA prevention in young horses have yet to be accomplished. Therefore, the 3 studies described herein were conducted to determine effectiveness of an intra-articular
lipopolysaccharide (LPS) challenge on markers of inflammation and cartilage metabolism in young horses and potential of dietary glucosamine hydrochloride (HCl) to mitigate these alterations. In the first study, horses were challenged with 0.25 ng or 0.50 ng of intra-articular LPS solution or lactated ringer’s solution (control). Injection of LPS increased inflammation based on synovial prostaglandin E2 (PGE2) concentrations. Carboxypeptide of type II collagen (CPII), a maker of type II collagen synthesis, also increased in a dose-dependent manner. However, clinical parameters of health were not influenced and remained within normal ranges. Carpal circumference increased in response to repeated arthrocentesis. Lameness scores increased with LPS injection when compared to controls. This model of joint inflammation (0.5 ng LPS) was used in the second study to evaluate potential chondroprotective effects of oral glucosamine HCl supplementation in yearling horses. Specifically, the oral absorption of glucosamine HCl versus saline was determined by nasogastric dosing and incorporation of dietary glucosamine HCl into plasma and synovial fluid over time. Plasma and synovial fluid concentrations of glucosamine tended to increase over the 98-d period. In the third study, yearlings were challenged with intra-articular LPS to determine the potential of glucosamine HCl to mitigate inflammation when compared to contralateral joints. Injection of LPS increased synovial PGE2 and cartilage biomarkers CPII and collagenase cleavage neopeptide (C2C), a marker of type II collagen degradation. Oral glucosamine HCl decreased PGE2 and C2C concentrations, but increased levels of CPII. Results of these 3 studies provide a clearer understanding of joint inflammation and cartilage turnover in young horses and demonstrated a potential role of oral glucosamine to mitigate these effects and possibly prevent OA in horses.
Advisors/Committee Members: Coverdale, Josie A (advisor), Welsh, Thomas H (committee member), Arnold, Carolyn E (committee member), Heird, James C (committee member).
Subjects/Keywords: lipopolysaccharide; cartilage; inflammation; horse
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lucia, J. L. (2013). Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/149284
Chicago Manual of Style (16th Edition):
Lucia, Jessica Lauren. “Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses.” 2013. Doctoral Dissertation, Texas A&M University. Accessed January 28, 2021.
http://hdl.handle.net/1969.1/149284.
MLA Handbook (7th Edition):
Lucia, Jessica Lauren. “Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses.” 2013. Web. 28 Jan 2021.
Vancouver:
Lucia JL. Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses. [Internet] [Doctoral dissertation]. Texas A&M University; 2013. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1969.1/149284.
Council of Science Editors:
Lucia JL. Influence of an Intra-articular Lipopolysaccharide Challenge on Markers of Inflammation and Cartilage Metabolism and the Ability of Oral Glucosamine to Mitigate these Alterations in Young Horses. [Doctoral Dissertation]. Texas A&M University; 2013. Available from: http://hdl.handle.net/1969.1/149284

Texas A&M University
4.
Duarte, Iris.
Characterization of a Broad Host Range Tailocin from Burkholderia.
Degree: PhD, Plant Pathology, 2012, Texas A&M University
URL: http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11636
► Members of the Burkholderia cepacia complex (Bcc) are plant and human opportunistic pathogens. Essentially all Bcc isolates demonstrate in vitro broad-spectrum antibiotic resistance. In fact,…
(more)
▼ Members of the Burkholderia cepacia complex (Bcc) are plant and human opportunistic pathogens. Essentially all Bcc isolates demonstrate in vitro broad-spectrum antibiotic resistance. In fact, many clinical isolates are resistant to all currently available antibiotics, rendering therapy ineffective. There is a substantial need to develop new antimicrobial therapies. The potential use of phage-tail-like high molecular weight bacteriocins, or "tailocins", as alternative anti-bacterial agents against Bcc was investigated. A tailocin, designated Bcep0425, produced by B.cenocepacia strain BC0425 was determined to have broad host range activity against members of the Bcc. Targeted mutagenesis of genes involved in the biosynthesis of the bacterial
lipopolysaccharide (LPS) was conducted to determine the receptor site and it was determined that L-rhamnose and alpha-glucose associated with the LPS core were the receptors. Genetic analysis and targeted mutagenesis of the tailocin encoding genes was conducted in the host strain, B. cenocepacia BC0425, to determine the genetic organization of the tailocin Bcep0425 gene cluster and to confirm gene functions. We report for the first time genes involved in replication and integration that are associated with a pyocin/tailocin gene cluster. Additionally, a new class (IV) of holin was identified as part of the lysis cassette. Genetic analysis of the tailocin encoding genes revealed a high degree of similarity to defective phages identified in sequenced Burkholderia genomes. Two novel transcriptional regulators, bctN and bctR, along with recA were found to be involved in the induction of Bcep0425. Numerous studies have focused on the characterization of pyocins from Pseudomonas, but there have been no molecular investigations of tailocins from Burkholderia. This constitutes the first molecular characterization of a phage tail-like bacteriocin from Burkholderia.
Advisors/Committee Members: Gonzalez, Carlos F. (advisor), Scholthof, Herman B. (committee member), Gross, Dennis C. (committee member), Young, Ryland F. (committee member).
Subjects/Keywords: bacteriocin; Burkholderia; lipopolysaccharide; tailocin
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Duarte, I. (2012). Characterization of a Broad Host Range Tailocin from Burkholderia. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11636
Chicago Manual of Style (16th Edition):
Duarte, Iris. “Characterization of a Broad Host Range Tailocin from Burkholderia.” 2012. Doctoral Dissertation, Texas A&M University. Accessed January 28, 2021.
http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11636.
MLA Handbook (7th Edition):
Duarte, Iris. “Characterization of a Broad Host Range Tailocin from Burkholderia.” 2012. Web. 28 Jan 2021.
Vancouver:
Duarte I. Characterization of a Broad Host Range Tailocin from Burkholderia. [Internet] [Doctoral dissertation]. Texas A&M University; 2012. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11636.
Council of Science Editors:
Duarte I. Characterization of a Broad Host Range Tailocin from Burkholderia. [Doctoral Dissertation]. Texas A&M University; 2012. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11636

University of Guelph
5.
Taylor, Véronique Louise.
Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa.
Degree: PhD, Department of Molecular and Cellular Biology, 2016, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9578
► Lipopolysaccharide of Pseudomonas aeruginosa is capped by highly diverse O-specific antigens (OSA). Differences in the OSA are the basis for classifying P. aeruginosa into 20…
(more)
▼ Lipopolysaccharide of Pseudomonas aeruginosa is capped by highly diverse O-specific antigens (OSA). Differences in the OSA are the basis for classifying P. aeruginosa into 20 distinct serotypes. OSA is synthesized by the Wzx/Wzy-dependent pathway wherein O-units are polymerized by Wzy with either α- or β- intramolecular linkages to chain-lengths regulated by Wzz1 or Wzz2 whereas the polymer is ligated by WaaL a lipid-anchor forming mature LPS. Infection of P. aeruginosa by the D3 bacteriophage results in serotype conversion by altering the intramolecular linkage from α- to β- due to the expression of an inhibitor of α-polymerase (Iap), and a β-polymerase (Wzyβ). The inner membrane topologies of WaaL and Wzyβ were determined experimentally using a dual-reporter capable of PhoA-LacZ activity to screen the subcellular localization of random and site-targeted 3’ truncations. Twelve transmembrane segments (TMS) and a large periplasmic loop were identified for WaaL. Wzyβ contained 10 TMS and two large periplasmic loops (PL3 and PL4). Both WaaL and Wzyβ possessed residues essential for an inverting glycosyltransferase reaction. The topology of Wzyβ supports the proposed “catch-and-release” mechanism of Wzy proteins. Wzyβ is therefore resistant to Iap inhibition due to using a different reaction mechanism.By titrating Iap expression it was determined that Iap inhibition occurs after Wzyα was inserted into the inner membrane. Specificity of the Iap to the O2 serogroup is supported by sequence similarity between Iap and the N’ terminal TMS of only cognate Wzz proteins. Iap appears to function by disrupting the proposed Wzz/Wzy interaction. In a separate project, we developed an algorithm for in silico serotyping of P. aeruginosa based on unique sequences in the OSA clusters. This method was used to type >80 P. aeruginosa strains with published genome sequences. We discovered a unique genomic island among O12 strains with a multidrug-resistance phenotype, and collected evidence of concomitant transfer of the O12 OSA cluster and antibiotic resistance genes from an ancestral clone, PA7. The presence of this island accounts for the geographic dissemination of the O12 serotype in hospital settings. In summary, this research furthered the understanding of mechanisms which drive O-antigen diversity in P. aeruginosa.
Advisors/Committee Members: Lam, Joseph S. (advisor).
Subjects/Keywords: microbiology; lipopolysaccharide; bacteriophage; membrane proteins
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Taylor, V. L. (2016). Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa. (Doctoral Dissertation). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9578
Chicago Manual of Style (16th Edition):
Taylor, Véronique Louise. “Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa.” 2016. Doctoral Dissertation, University of Guelph. Accessed January 28, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9578.
MLA Handbook (7th Edition):
Taylor, Véronique Louise. “Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa.” 2016. Web. 28 Jan 2021.
Vancouver:
Taylor VL. Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa. [Internet] [Doctoral dissertation]. University of Guelph; 2016. [cited 2021 Jan 28].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9578.
Council of Science Editors:
Taylor VL. Molecular and Biochemical Investigation of Mechanisms that propel O-antigen Diversity in Pseudomonas aeruginosa. [Doctoral Dissertation]. University of Guelph; 2016. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9578

University of Manitoba
6.
Kroeker, Angela.
Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity.
Degree: Animal Science, 2012, University of Manitoba
URL: http://hdl.handle.net/1993/8611
► The effects of induced subacute ruminal acidosis (SARA) using grain pellet-based (GPI) and alfalfa pellet-based diet models on systemic immunological parameters were evaluated in nonlactating…
(more)
▼ The effects of induced subacute ruminal acidosis (SARA) using grain pellet-based (GPI) and alfalfa pellet-based diet models on systemic immunological parameters were evaluated in nonlactating Holstein cows. The systemic immunological parameters analysed in this study included rectal temperature, blood cell leukogram, expression of
lipopolysaccharide (LPS) recognition receptors on leukocytic cells, and plasma and serum proteins. Also, blood biochemistry was analysed. There were no significant differences in rectal temperature, blood cell leukogram, expression of LPS recognition receptors and fibrinogen or haptoglobin concentrations between control and SARA induction treatments. Concentrations of serum amyloid A and
lipopolysaccharide-binding protein increased while total protein concentrations decreased in response to GPI SARA compared to control. Blood glucose and urea concentrations increased and decreased, respectively, with GPI SARA treatment. Grain pellet-induced SARA resulted in changes to serum proteins and acute phase proteins but did not affect other systemic immunological parameters suggesting a localized inflammatory response was initiated.
Advisors/Committee Members: Rodriguez-Lecompte, Juan Carlos (Animal Science) (supervisor), Plaizier, Kees (Animal Science) Ominski, Kim (Animal Science) O, Karmin (Animal Science) Holley, Rick (Food Science) (examiningcommittee).
Subjects/Keywords: Subacute ruminal acidosis; Lipopolysaccharide; CD14
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Kroeker, A. (2012). Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/8611
Chicago Manual of Style (16th Edition):
Kroeker, Angela. “Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity.” 2012. Masters Thesis, University of Manitoba. Accessed January 28, 2021.
http://hdl.handle.net/1993/8611.
MLA Handbook (7th Edition):
Kroeker, Angela. “Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity.” 2012. Web. 28 Jan 2021.
Vancouver:
Kroeker A. Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity. [Internet] [Masters thesis]. University of Manitoba; 2012. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1993/8611.
Council of Science Editors:
Kroeker A. Systemic immune responses to intestinal-derived lipopolysaccharide (LPS) during subacute ruminal acidosis (SARA) and their possible role in innate immunity. [Masters Thesis]. University of Manitoba; 2012. Available from: http://hdl.handle.net/1993/8611

Virginia Tech
7.
Morris, Matthew.
Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide.
Degree: PhD, Genetics, Bioinformatics, and Computational Biology, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/64253
► The innate immune system depends for its effectiveness on the function of specialized pattern recognition receptors which enable it to target pathogens for destruction on…
(more)
▼ The innate immune system depends for its effectiveness on the function of specialized pattern recognition receptors which enable it to target pathogens for destruction on the basis of conserved molecular patterns such as flagellin or
lipopolysaccharide (LPS). Specifically, LPS is recognized by the Toll-like receptor 4 (TLR4), activating a signaling pathway which triggers the production of both pro- and anti-inflammatory mediators. Very low doses of LPS, however, preferentially induce pro-inflammatory cytokines, which can lead to persistent low-grade inflammation, a contributing factor in a host of chronic diseases. The mild pro-inflammatory skewing induced by super-low-dose LPS also potentiates the inflammatory response to later challenge with a higher dose of LPS in a phenomenon known as the "Shwartzman reaction" or "endotoxin priming". We investigated the mechanisms involved in pro-inflammatory skewing by super-low-dose LPS in THP-1 cells and found it to be governed by a regulatory circuit of competitive inhibition between glycogen synthase kinase 3 (GSK3) and Akt, which promote the activity of the transcription factors FoxO1 and CREB, respectively. Super-low-dose LPS mildly activated FoxO1 and pro-inflammatory gene transcription without inducing anti-inflammatory genes or activating CREB, and this pro-inflammatory skewing could be abolished by inhibition of GSK3 or direct activation of CREB. We then examined the dynamics of the LPS response at various different dosages in murine bone-marrow-derived macrophages (BMDM). The pro-inflammatory cytokine IL-12 was most strongly induced by intermediate LPS dosages, with very low or high doses inducing less robust IL-12 production. Knockout of the inhibitory TLR4 pathway molecules Lyn or IRAK-M resulted in sustained induction of IL-12 by high doses of LPS. By activating CREB, we were able to reduce inflammation in WT BMDM, and saw that this corresponded with increased phosphorylation of CREB. Overall, we are confident that this subnetwork is an important switch regulating the resolution of inflammation in response to TLR4 stimulation. Furthermore, we propose that endotoxin priming is an example of the generalized capacity of all signaling networks to recall prior states, and that an appreciation for the history and context of exposure to stimuli is critical for the understanding of signaling behavior.
Advisors/Committee Members: Li, Liwu (committeechair), Lu, Chang (committee member), Yuan, Lijuan (committee member), Tyson, John J. (committee member).
Subjects/Keywords: Immunology; lipopolysaccharide; signaling; monocyte; macrophage
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morris, M. (2014). Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/64253
Chicago Manual of Style (16th Edition):
Morris, Matthew. “Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 28, 2021.
http://hdl.handle.net/10919/64253.
MLA Handbook (7th Edition):
Morris, Matthew. “Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide.” 2014. Web. 28 Jan 2021.
Vancouver:
Morris M. Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10919/64253.
Council of Science Editors:
Morris M. Molecular mechanisms responsible for the dynamic modulation of macrophage responses to varying dosages of lipopolysaccharide. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/64253

University of Saskatchewan
8.
Kent-Dennis, Coral.
Molecular and metabolic effects of local immune activation in the ruminal epithelium.
Degree: 2020, University of Saskatchewan
URL: http://hdl.handle.net/10388/13045
► Modern dairy and beef cattle efficiently produce large quantities of high value products, milk and meat respectively, for human consumption. In order to meet the…
(more)
▼ Modern dairy and beef cattle efficiently produce large quantities of high value products, milk and meat respectively, for human consumption. In order to meet the energy demands of production, cattle are fed diets consisting of rapidly fermentable carbohydrates. As a result, ruminal acidosis may occur. The acidotic conditions in the ruminal fluid can result in compromised barrier function and, potentially, translocation of microbes and microbe-associated molecular patterns, (MAMP) from the lumen across the ruminal epithelium. Translocation of microbes or MAMP may lead to an interaction with the ruminal epithelial cells (REC), thus inducing a local, pro-inflammatory response. However, little is known about the capability of REC to initiate such a response as well as the effects of inflammation on the physiological functions of the ruminal epithelium. The objective of this research was to assess the inflammatory response of the ruminal epithelium and to investigate the potential effects of inflammation on nutrient uptake and metabolism using in vivo, ex vivo and primary cell culture models.
In Chapter 3, ruminal papillae biopsies were collected from beef heifers following induction of subacute ruminal acidosis (SARA). The papillae were used to evaluate differential gene expression and toll-like receptor (TLR) 4 quantification. Despite an increase in ruminal fluid concentration of LPS, gene expression of inflammatory molecules and immunohistofluorescent analysis of TLR4 protein expression indicated an anti-inflammatory response 2 d following the SARA challenge.
The Ussing chamber model was used in Chapter 4 to explore the effects of LPS exposure on the inflammatory response and the potential effects on butyrate flux and metabolism. Analysis of gene expression suggested that the pro-inflammatory response to LPS may have been suppressed or prevented by the epithelial barrier. In tissue exposed to LPS, butyrate flux tended to increase linearly (P = 0.063); however, production of β-hydroxybutyrate (BHB) was not affected (P = 0.21), suggesting that the impact of LPS exposure on metabolism of the ruminal epithelium was minimal.
To further evaluate REC responses to LPS exposure, a cell culture model was established (Chapter 5). Using that model in Chapter 6, I evaluated the effects of dose, duration, and timing of LPS exposure on viability and gene expression of pattern recognition receptors (PRR), pro-inflammatory cytokines, chemokines, and other immunomodulatory molecules in cultured primary REC. There was no indication that LPS negatively impacted cell viability, but exposure to LPS increased TLR2 and TLR4 expression and induced a pro-inflammatory response. Results suggested that the REC response was influenced by LPS dose and duration of exposure, and that gene expression may have been regulated to prevent an excessive pro-inflammatory response and potential damage to the cells.
In Chapter 7, cultured REC were exposed to LPS when grown with or without the addition of short-chain fatty acids (SCFA) to the cell culture media…
Advisors/Committee Members: Penner, Gregory B, Buchanan, Fiona, Mutsvangwa, Tim, Van Kessel, Andrew, Griebel, Philip.
Subjects/Keywords: Rumen Epithelium Inflammation Lipopolysaccharide Metabolism
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MLA ·
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Export
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APA (6th Edition):
Kent-Dennis, C. (2020). Molecular and metabolic effects of local immune activation in the ruminal epithelium. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/13045
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kent-Dennis, Coral. “Molecular and metabolic effects of local immune activation in the ruminal epithelium.” 2020. Thesis, University of Saskatchewan. Accessed January 28, 2021.
http://hdl.handle.net/10388/13045.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kent-Dennis, Coral. “Molecular and metabolic effects of local immune activation in the ruminal epithelium.” 2020. Web. 28 Jan 2021.
Vancouver:
Kent-Dennis C. Molecular and metabolic effects of local immune activation in the ruminal epithelium. [Internet] [Thesis]. University of Saskatchewan; 2020. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10388/13045.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kent-Dennis C. Molecular and metabolic effects of local immune activation in the ruminal epithelium. [Thesis]. University of Saskatchewan; 2020. Available from: http://hdl.handle.net/10388/13045
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin
9.
-6509-0842.
Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae.
Degree: PhD, Microbiology, 2017, University of Texas – Austin
URL: http://dx.doi.org/10.26153/tsw/684
► Produced by all domains of life, cationic antimicrobial peptides (CAMPs) are the most ubiquitous antibacterial compound in nature. In higher order eukaryotes CAMPs are critical…
(more)
▼ Produced by all domains of life, cationic antimicrobial peptides (CAMPs) are the most ubiquitous antibacterial compound in nature. In higher order eukaryotes CAMPs are critical components of innate immunity. Unicellular eukaryotes and prokaryotes use CAMPs for competitive exclusion in ecological niches. Some classes of CAMPs, such as polymyxins, are used as last-resort antibiotics in the treatment of bacterial infections. However, many bacteria have evolved resistance mechanisms to the toxic effects of CAMPs. For example, the current pandemic strain of Vibrio cholerae (O1 El Tor) is resistant to polymyxins, whereas the previous pandemic strain (O1 classical) is polymyxin sensitive. For decades how El Tor V. cholerae evolved polymyxin resistance was unknown, until the recent identification of a three-gene operon responsible for >100-fold improvement in resistance to polymyxin B. Classical strains lack a functional version of this operon. Renamed almEFG, this operon was shown to be necessary for the esterification of one, sometimes two, glycine residues to the major Gram-negative surface molecule
lipopolysaccharide (LPS). Covalent attachment of glycine to LPS likely prevents CAMP binding through minimization of the negatively charged bacterial surface, since the amine terminus of glycine or diglycine remains freely exposed. Here, a mechanistic description of the almEFG operon is provided. Guided by predictive models, AlmF is shown to be a genuine aminoacyl carrier protein. Also identified is the V. cholerae enzyme required for post-translational activation of AlmF to a functional carrier protein. A combination of biochemical approaches reveal that AlmE specifically adds glycine to activated AlmF. Ultimately, AlmG transfers glycine from glycyl-AlmF to the lipid A membrane anchor of surface-displayed LPS in vivo, a process that evidence indicates can be done sequentially for diglycine LPS modification. The trio of proteins in the AlmEFG system forms a chemical pathway that resembles the division of labor observed in non-ribosomal peptide synthetases. They also bear striking resemblance to a related Gram-positive cell-wall remodeling strategy that promotes CAMP resistance. This biochemical study has the power to inform therapeutics against V. cholerae infection and provides a highly detailed mechanism of Gram-negative CAMP resistance.
Advisors/Committee Members: Trent, Michael Stephen (advisor), Davies, Bryan William (advisor), Brodbeld, Jennifer (committee member), Barrick, Jeffrey (committee member), Whiteley , Marvin (committee member).
Subjects/Keywords: Lipopolysaccharide; Non-ribosomal peptide synthetase
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
-6509-0842. (2017). Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://dx.doi.org/10.26153/tsw/684
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Chicago Manual of Style (16th Edition):
-6509-0842. “Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae.” 2017. Doctoral Dissertation, University of Texas – Austin. Accessed January 28, 2021.
http://dx.doi.org/10.26153/tsw/684.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
MLA Handbook (7th Edition):
-6509-0842. “Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae.” 2017. Web. 28 Jan 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
-6509-0842. Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2017. [cited 2021 Jan 28].
Available from: http://dx.doi.org/10.26153/tsw/684.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Council of Science Editors:
-6509-0842. Enzymology of a three gene pathway required for cationic antimicrobial peptide resistance by Vibrio cholerae. [Doctoral Dissertation]. University of Texas – Austin; 2017. Available from: http://dx.doi.org/10.26153/tsw/684
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Iowa State University
10.
Horst, Erin Andrea.
The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows.
Degree: 2020, Iowa State University
URL: https://lib.dr.iastate.edu/etd/18141
► Nutrient partitioning towards productive processes (i.e., milk synthesis, growth, and reproduction) concomitant with diluting maintenance costs are key to profitable animal agriculture. During immune activation,…
(more)
▼ Nutrient partitioning towards productive processes (i.e., milk synthesis, growth, and reproduction) concomitant with diluting maintenance costs are key to profitable animal agriculture. During immune activation, the hierarchy of coordinated nutrient trafficking is reprioritized towards the immune system at the expense of production. Dairy cows encounter frequent immune challenges, as bacterial insults can originate from a myriad of sources including the uterus, mammary gland, lungs, and gastrointestinal tract. Regardless of origin, immune activation hinders animal welfare and mounting evidence suggests it plays a role in many undesirable phenotypes post-calving (i.e., decreased DMI, increased NEFA, hypocalcemia). Following activation, most leukocytes undergo a metabolic shift from oxidative phosphorylation to aerobic glycolysis (a phenomenon known as the “Warburg effect”) and begin consuming copious amounts of glucose. To ensure adequate glucose delivery to activated leukocytes, several well-characterized metabolic adjustments are employed including: increased insulin and glucagon levels, increased skeletal muscle catabolism, hypertriglyceridemia, and hypoketonemia. The energetic burden of immune activation is intensified by a simultaneous decrease in feed intake and thus reduced intestinally derived nutrients. Identifying dietary strateiges with potential to alleviate the negative consequences of immune activation on metabolism and production are of interest. As part of this dissertation, supplementation of dietary zinc hydroxychlrode, zinc amino acid complex, and chromium propionate were evaluated in feed-restricted or LPS-infused cows. In addition to energetic metabolism, immune activation induces a marked and sustained decrease in circulating calcium (Ca). In this dissertation we have demonstrated that the total Ca deficit was ~20 g during an acute (12 hour) and intense model of immune activation. Infection-induced hypocalcemia is a species conserved response, yet, it remains largely unknown what role Ca plays during infection and why it abruptly decreases during immune activation. Evidence suggests it may be a protective strategy to prevent a hyperinflammatory systemic response. Based upon the literature and our supporting work we suggest that post-calving hypocalcemia can be explained, at least partially, by inflammation. In addition to hypocalcemia, research in rodents suggests that inflammation may also be involved in fatty liver development. A final objective of this dissertation was to evaluate if inflammation affected liver fat accumulation in artificially-induced hyperlipidemic cows. In summary, immune activation negatively influences metabolic, hormonal, and Ca homeostasis and these alterations closely mimic changes observed in poorly transitioning dairy cows. Having a better understanding of the impact of immune activation on nutrient trafficking and Ca homeostasis will provide foundational information for developing strategies aimed at minimizing production losses during infection.
Subjects/Keywords: Calcium; Fatty liver; Lipopolysaccharide
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Horst, E. A. (2020). The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/18141
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Horst, Erin Andrea. “The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows.” 2020. Thesis, Iowa State University. Accessed January 28, 2021.
https://lib.dr.iastate.edu/etd/18141.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Horst, Erin Andrea. “The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows.” 2020. Web. 28 Jan 2021.
Vancouver:
Horst EA. The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows. [Internet] [Thesis]. Iowa State University; 2020. [cited 2021 Jan 28].
Available from: https://lib.dr.iastate.edu/etd/18141.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Horst EA. The influence of immune activation on energetic and calcium homeostasis in Holstein dairy cows. [Thesis]. Iowa State University; 2020. Available from: https://lib.dr.iastate.edu/etd/18141
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
Blake, Bertani Robert.
Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>.
Degree: PhD, Microbiology, 2019, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1563470856804902
► The cell envelope of bacteria mediates their interaction with the outside world and determines what can enter the cell. Gram-negative bacteria have a cell…
(more)
▼ The cell envelope of bacteria mediates their
interaction with the outside world and determines what can enter
the cell. Gram-negative bacteria have a cell envelope defined by
two membranes: an inner membrane, which surrounds the cytoplasm,
and an outer membrane, which together with the inner membrane
delimits an additional cellular compartment termed the periplasm.
The inner membrane of Gram-negative bacteria is primarily composed
of a phospholipid bilayer. The outer membrane, in contrast,
contains phospholipids in its inner leaflet, and the essential
glycolipid
lipopolysaccharide (LPS) in the outer leaflet. The
presence of LPS in the outer leaflet renders the outer membrane
relatively impermeable, and therefore grants the cell resistance to
noxious compounds in the environment, such as antibiotics. LPS is
synthesized in the cytoplasmic face of the inner membrane, though
it can also undergo non-stoichiometric modifications in the
periplasmic face, and must thereafter be transported across the
rest of the cell envelope. Transversal of the inner membrane by LPS
is mediated by the ATP-binding cassette transporter MsbA. LPS
extraction from the inner membrane, and subsequent transport across
the rest of the cell envelope, is mediated by the LPS transport, or
Lpt, complex. The Lpt complex is composed of eight proteins: a
dimer of LptB in the cytoplasm that binds and hydrolyzes ATP to
drive LPS transport; two transmembrane domains, LptF and LptG,
which form a cavity in the inner membrane that accepts LPS and
extracts it; LptC, LptA, and LptD, which form a bridge across the
periplasm to allow the hydrophobic portion of LPS to traverse the
aqueous periplasm; and LptE, which in conjunction with LptD
facilitates the transport of LPS across the outer
membrane. Here, we describe work in which we
dissect the molecular mechanisms by which the Lpt system’s inner
membrane complex, LptB2FGC, interacts with LPS. In chapter two, we
describe the identification of a residue within LptG, K34, which is
critical for LPS transport. Through structure-function and
suppressor analyses, we show K34 of LptG mediates early contact
with unmodified LPS as it enters the cavity formed by LptF and
LptG. Further, our results imply that modified LPS interacts with
the transporter distinctly from unmodified LPS.
Chapter three describes the structure of the LptB2FGC
inner membrane complex, as determined by X-ray crystallography, and
defines the path LPS takes to the periplasmic bridge of the Lpt
system through site-specific crosslinking. We show that the
transmembrane anchor of LptC intercalates between transmembrane
domains LptF and LptG and is ergo likely to be functionally
involved in transport. Further, the periplasmic bridge is
preferentially coupled to LptF, rather than LptG.
In chapter four, we utilized a mutant producing LptG
altered at residue K34 to perform suppressor analysis and further
elucidate how the LptB2FGC complex interacts with LPS. We found
that increased LPS production could suppress the defects produced
by this…
Advisors/Committee Members: Ruiz, Natividad (Advisor).
Subjects/Keywords: Microbiology; lipopolysaccharide; LPS; lipopolysaccharide transport; LPS transport; ABC transporter; cell envelope
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Blake, B. R. (2019). Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1563470856804902
Chicago Manual of Style (16th Edition):
Blake, Bertani Robert. “Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>.” 2019. Doctoral Dissertation, The Ohio State University. Accessed January 28, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1563470856804902.
MLA Handbook (7th Edition):
Blake, Bertani Robert. “Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>.” 2019. Web. 28 Jan 2021.
Vancouver:
Blake BR. Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>. [Internet] [Doctoral dissertation]. The Ohio State University; 2019. [cited 2021 Jan 28].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1563470856804902.
Council of Science Editors:
Blake BR. Investigations of the early stages of transport by the
transenvelope lipopolysaccharide transporter in <i>E.
coli</i>. [Doctoral Dissertation]. The Ohio State University; 2019. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1563470856804902

Ruhr Universität Bochum
12.
Langklotz, Sina.
Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases.
Degree: 2011, Ruhr Universität Bochum
URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-35208
► Durch regulierte Proteolyse kann das zelluläre Proteom schnell und effektiv an die jeweiligen Umweltbedingungen angepasst werden. In Bakterien wird der Energieabhängige Abbau von Proteinen durch…
(more)
▼ Durch regulierte Proteolyse kann das zelluläre
Proteom schnell und effektiv an die jeweiligen Umweltbedingungen
angepasst werden. In Bakterien wird der Energieabhängige Abbau von
Proteinen durch die spezifische Substraterkennung von
AAA+-Proteasen (ATPases associated with various cellular
activities) ermöglicht. Während die Protease FtsH in der inneren
Membran verankert ist, handelt es sich bei Lon um eine
cytoplasmatische Protease. FtsH kontrolliert in Escherichia coli
unter anderem die Hitzeschockantwort und die Biosynthese von
Lipopolysacchariden durch Degradation der Proteine RpoH und LpxC.
Im Rahmen dieser Arbeit wurde (i) die Substraterkennung von RpoH
durch FtsH, (ii) die Konservierung der Regulation der LPS-Synthese
über Proteolyse in verschiedenen Gram-negativen Bakterien sowie
(iii) die Substratvielfalt von FtsH analysiert. Weiterhin konnte
gezeigt werden, dass der Replikationsinhibitor CspD in E. coli über
Lon-abhängige Proteolyse reguliert wird.
Advisors/Committee Members: Biologie.
Subjects/Keywords: Proteolyse; Proteasen; Lipopolysaccharide; Hitzeschock;
Gram-negative Bakterien
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Langklotz, S. (2011). Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-35208
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Langklotz, Sina. “Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases.” 2011. Thesis, Ruhr Universität Bochum. Accessed January 28, 2021.
http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-35208.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Langklotz, Sina. “Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases.” 2011. Web. 28 Jan 2021.
Vancouver:
Langklotz S. Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases. [Internet] [Thesis]. Ruhr Universität Bochum; 2011. [cited 2021 Jan 28].
Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-35208.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Langklotz S. Substrate diversity and substrate recognition of the
bacterial FtsH and Lon proteases. [Thesis]. Ruhr Universität Bochum; 2011. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-35208
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universiteit Utrecht
13.
Hofland, T.
Recognition of LPS by TLR4: potential for anti-inflammatory therapies.
Degree: 2014, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/298967
► LPS molecules of marine bacteria show distinct structures from terrestrial bacteria, due to the different environment that marine bacteria live in. Because of these different…
(more)
▼ LPS molecules of marine bacteria show distinct structures from terrestrial bacteria, due to the different environment that marine bacteria live in. Because of these different structures, lipid A molecules from marine bacteria are most often poor stimulators of the Toll-like receptor 4 (TLR4) pathway. Due to their low stimulatory potential, these lipid A molecules could be used to antagonize TLR4 signaling in sepsis patients, where this immune response is amplified and unregulated. Antagonizing lipid A molecules might be used for future therapies against sepsis, therapies that currently do not exist. In this review, the structural differences of terrestrial and marine lipid A molecules are described. Furthermore, the consequences of structural differences on immune recognition will be discussed, thereby relating the antagonizing potential of marine lipid A molecules to their structure. Finally, since clinical trials built on antagonizing lipid A molecules have proven unsuccessful, we propose to focus on different aspects of the TLR4 signaling pathway when searching for new potential drugs. Furthermore, we put forward the notion that bacteria probably already produce inhibitors of TLR4 signaling, making these bacterial products interesting molecules to investigate for future sepsis therapies.
Advisors/Committee Members: Nijland, R..
Subjects/Keywords: lipopolysaccharide; lipid A; Toll-like receptor 4
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hofland, T. (2014). Recognition of LPS by TLR4: potential for anti-inflammatory therapies. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/298967
Chicago Manual of Style (16th Edition):
Hofland, T. “Recognition of LPS by TLR4: potential for anti-inflammatory therapies.” 2014. Masters Thesis, Universiteit Utrecht. Accessed January 28, 2021.
http://dspace.library.uu.nl:8080/handle/1874/298967.
MLA Handbook (7th Edition):
Hofland, T. “Recognition of LPS by TLR4: potential for anti-inflammatory therapies.” 2014. Web. 28 Jan 2021.
Vancouver:
Hofland T. Recognition of LPS by TLR4: potential for anti-inflammatory therapies. [Internet] [Masters thesis]. Universiteit Utrecht; 2014. [cited 2021 Jan 28].
Available from: http://dspace.library.uu.nl:8080/handle/1874/298967.
Council of Science Editors:
Hofland T. Recognition of LPS by TLR4: potential for anti-inflammatory therapies. [Masters Thesis]. Universiteit Utrecht; 2014. Available from: http://dspace.library.uu.nl:8080/handle/1874/298967

University of Alberta
14.
Krajacic, Aleksandra.
Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat.
Degree: PhD, Centre for Neuroscience, 2011, University of Alberta
URL: https://era.library.ualberta.ca/files/r207tq51t
► Injury to the cervical spinal cord is a devastating event that results in a transient to permanent loss of sensory and motor functions following injury.…
(more)
▼ Injury to the cervical spinal cord is a devastating
event that results in a transient to permanent loss of sensory and
motor functions following injury. Moderate recovery has been
reported to occur in individuals and in animal models after spinal
cord injury (SCI). One approach to promote recovery after SCI is
rehabilitative training. This thesis examines the relation of
reaching training with adaptive changes (i.e. plasticity) and
functional recovery following SCI. In my first experiment, I
investigated whether plasticity of the corticospinal tract (CST) is
the cause for reaching recovery after ablation of the dorsal and
lateral CST. Rats that received reaching training were
significantly better in reaching than their untrained counterparts.
A relesion of the CST revealed that the reaching recovery mainly
depended on plasticity of the CST itself. Since it is controversial
whether training should be initiated immediately after SCI, I
investigated whether a delayed initiation of reaching training
after SCI is beneficial. I compared the reaching success of rats
that received reaching training on day 4 post SCI with rats that
received training on day 12 post SCI. I found that the reaching
success in rats that either received reaching training on day 4 or
12 following SCI was similar. Lastly, I investigated whether
training efficacy is declined in chronically injured rats. Since it
has been shown that the inflammatory response after SCI declines,
it is questionable whether there is a relation between the
inflammatory response after SCI and training efficacy. In my last
experiment I injected chronically injured rats with a substance
that induces a systemic inflammation. I found that rehabilitative
reaching training in chronic injured rats only resulted in an
improved reaching recovery when the training was combined with the
administration of the substance that induces inflammation
(lipopolysaccharide). Although there are still unanswered questions
regarding the underlying mechanism for functional recovery after
SCI, the results of this thesis could be used as a basic to improve
future rehabilitative training strategies and therefore improve the
quality of life in individuals that suffer from SCI.
Subjects/Keywords: reaching; corticospinal; spinal cord injury; lipopolysaccharide
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Krajacic, A. (2011). Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/r207tq51t
Chicago Manual of Style (16th Edition):
Krajacic, Aleksandra. “Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat.” 2011. Doctoral Dissertation, University of Alberta. Accessed January 28, 2021.
https://era.library.ualberta.ca/files/r207tq51t.
MLA Handbook (7th Edition):
Krajacic, Aleksandra. “Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat.” 2011. Web. 28 Jan 2021.
Vancouver:
Krajacic A. Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat. [Internet] [Doctoral dissertation]. University of Alberta; 2011. [cited 2021 Jan 28].
Available from: https://era.library.ualberta.ca/files/r207tq51t.
Council of Science Editors:
Krajacic A. Rehabilitative reaching training and plasticity following
spinal cord injury in the adult rat. [Doctoral Dissertation]. University of Alberta; 2011. Available from: https://era.library.ualberta.ca/files/r207tq51t

University of Georgia
15.
Foote, Matthew Ian.
Structural modification of E. Coli lipid A and KDO-lipid IVA.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/26896
► Lipopolysaccharides from gram negative bacteria are responsible for signal transduction for the proinflammatory response in cells by initiating formation of TLR4/MD-2 protein complexes. Excess LPS…
(more)
▼ Lipopolysaccharides from gram negative bacteria are responsible for signal transduction for the proinflammatory response in cells by initiating formation of TLR4/MD-2 protein complexes. Excess LPS can lead to septic shock, a condition with
often fatal results. Lipid A, the inner diglucosamine region of LPS, is responsible for a majority of LPS endotoxicity. A precursor, lipid IVA, behaves as an antagonist for LPS binding. Through molecular modeling, specific alterations to the lipid A
structure can be designed that may allow tuning of lipid A activity. KDO, a sialic acid derivative naturally covalently linked to lipid A in LPS, can improve endotoxic activity in lipid A. KDO was therefore covalently linked to lipid IVA to investigate
its effects on lipid IVA antagonistic acitiviy. Analogues of E. coli lipid A and KDO-lipid IVA were synthesized using divergent and partially divergent synthetic schemes.
Subjects/Keywords: LIPID; LIPOPOLYSACCHARIDE; ESCHERICHIA COLI; TLR4; MD-2
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Foote, M. I. (2014). Structural modification of E. Coli lipid A and KDO-lipid IVA. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26896
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Foote, Matthew Ian. “Structural modification of E. Coli lipid A and KDO-lipid IVA.” 2014. Thesis, University of Georgia. Accessed January 28, 2021.
http://hdl.handle.net/10724/26896.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Foote, Matthew Ian. “Structural modification of E. Coli lipid A and KDO-lipid IVA.” 2014. Web. 28 Jan 2021.
Vancouver:
Foote MI. Structural modification of E. Coli lipid A and KDO-lipid IVA. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10724/26896.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Foote MI. Structural modification of E. Coli lipid A and KDO-lipid IVA. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26896
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
16.
Miller, Sinead Emily.
Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii.
Degree: MS, Biomedical Engineering, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/14665
► Gold nanoparticles (AuNPs) were functionalized for rapid binding of Acinetobacter baumannii (A. baumannii), a Gram-negative bacterium. AuNPs were functionalized with colistin (Col), a polycationic antibiotic,…
(more)
▼ Gold nanoparticles (AuNPs) were functionalized for rapid binding of Acinetobacter baumannii (A. baumannii), a Gram-negative bacterium. AuNPs were functionalized with colistin (Col), a polycationic antibiotic, using a two-step self-assembly process, in which heterobifunctional polyethylene glycol (PEG) was used as a linker. Colistin was successfully conjugated to the AuNPs (Col-PEG-AuNP), as validated by dynamic light scattering (DLS) and proton nuclear magnetic resonance (H1 NMR). Images taken using a scanning transmission electron microscope (STEM), in combination with x-ray energy dispersive spectroscopy (EDS), confirmed binding of Col-PEG-AuNPs to the cell wall of A. baumannii. Results generated from a rapid binding assay indicated that the reaction rate of Col-PEG-AuNP complexation with A. baumannii reached half-maximum saturation in approximately 7 minutes. Quantitative measurement of the kinetics of Col-PEG-AuNP binding to A. baumannii is essential to inform the design of colistin-functionalized magnetic nanoparticles for magnetic separation of nanoparticle-bound A. baumannii.
Advisors/Committee Members: Frederick R. Haselton (committee member), Todd D. Giorgio (Committee Chair).
Subjects/Keywords: Lipopolysaccharide; Gram-negative; Multi-Drug Resistance; Gold
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Miller, S. E. (2015). Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Miller, Sinead Emily. “Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii.” 2015. Thesis, Vanderbilt University. Accessed January 28, 2021.
http://hdl.handle.net/1803/14665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Miller, Sinead Emily. “Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii.” 2015. Web. 28 Jan 2021.
Vancouver:
Miller SE. Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii. [Internet] [Thesis]. Vanderbilt University; 2015. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1803/14665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Miller SE. Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter baumannii. [Thesis]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/14665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

McMaster University
17.
Vasanthan, Tarushika.
IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY.
Degree: MSc, 2013, McMaster University
URL: http://hdl.handle.net/11375/13473
► The pathophysiology of how a maternal infection induces fetal inflammation and subsequently premature birth is a growing area of research. The ex-vivo dual closed-loop…
(more)
▼ The pathophysiology of how a maternal infection induces fetal inflammation and subsequently premature birth is a growing area of research. The ex-vivo dual closed-loop placental perfusion model has been widely used to study placental physiology. To address the association between bacterial chorioamnionitis and fetal inflammation, TNF-α induction following lipopolysaccharide (LPS) challenge – a pyrogen of Gram-negative origin – was measured in the perfusion model. Preliminary analysis of perfusates unexpectedly revealed markedly elevated levels of TNF-α in control and LPS-treated groups indicating contamination of material(s) capable of activating innate immune responses. To identify source(s) driving high background TNF-α expression in perfusates, bovine serum albumin (BSA) – the chief component of the perfusion media – the perfusion system and the materno-feto-placental unit were independently examined. To validate a cleaning protocol effective in LPS removal, acid-base and oxidative depyrogenation techniques were also additionally assessed in the perfusion system. Using TNF-α as a surrogate marker of contamination, high background TNF-α expression in previously conducted placental perfusions were attributed to (1) LPS contaminated perfusion media and (2) LPS build up in the perfusion system. Additionally, results from depyrogenation experiments revealed both acid-base and oxidative techniques effectively reduced LPS buildup in the perfusion system to levels that were in accordance with FDA guidelines for medical equipment (< 0.5 EU/mL). Thus, to circumvent LPS-derived contamination placentas should be perfused using endotoxin-free perfusion media and the perfusion system should be cleaned with acid-base or oxidative depyrogenation techniques prior to its use.
Master of Science (MSc)
Advisors/Committee Members: Fusch, Christoph, Medical Sciences.
Subjects/Keywords: placental perfusion model; lipopolysaccharide; depyrogenation; cytokine
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Vasanthan, T. (2013). IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/13473
Chicago Manual of Style (16th Edition):
Vasanthan, Tarushika. “IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY.” 2013. Masters Thesis, McMaster University. Accessed January 28, 2021.
http://hdl.handle.net/11375/13473.
MLA Handbook (7th Edition):
Vasanthan, Tarushika. “IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY.” 2013. Web. 28 Jan 2021.
Vancouver:
Vasanthan T. IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY. [Internet] [Masters thesis]. McMaster University; 2013. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/11375/13473.
Council of Science Editors:
Vasanthan T. IDENTIFYING FACTORS DRIVING TNF-α EXPRESSION IN THE DUAL CLOSED LOOP EX-VIVO PLACENTAL PERFUSION MODEL: A METHODOLOGICAL STUDY. [Masters Thesis]. McMaster University; 2013. Available from: http://hdl.handle.net/11375/13473

McMaster University
18.
Stokes, Jonathan Michael.
EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES.
Degree: PhD, 2016, McMaster University
URL: http://hdl.handle.net/11375/20502
► The widespread emergence of antibiotic resistance determinants for nearly all drug classes threatens human health on a global scale. It is therefore essential to discover…
(more)
▼ The widespread emergence of antibiotic resistance determinants for nearly all drug classes threatens human health on a global scale. It is therefore essential to discover antibiotics with novel functions that are less likely to be influenced by pre-existing resistance mechanisms. An emerging approach to identify inhibitors of investigator-defined cellular processes involves screening compounds for antimicrobial activity under non-standard growth conditions. Indeed, by growing cells under conditions of stress, inhibitors of specific cellular targets can be enriched, thereby allowing for the identification of molecules with predictable activities in the complex environment of the cell. Here, I exploit cold stress in Escherichia coli to identify molecules targeting ribosome biogenesis and outer membrane biosynthesis. First, through a screen of 30,000 small molecules for growth inhibition exclusively at 15°C, I was able to identify the first small molecule inhibitor of bacterial ribosome biogenesis, lamotrigine. Second, by leveraging the idiosyncratic cold sensitivity of E. coli to vancomycin, I developed a novel screening technology designed to enrich for non-lethal inhibitors of Gram- negative outer membrane biosynthesis. From this platform, I identified pentamidine as an efficient outer membrane perturbant that was able to potentiate Gram-positive antibiotics against Gram-negative pathogens, similar to the polymyxins. Remarkably, however, this compound was able to overcome mcr-1 mediated polymyxin resistance. Together, this thesis highlights the utility of exploiting the bacterial cold stress response in antibiotic discovery.
Thesis
Doctor of Philosophy (PhD)
Advisors/Committee Members: Brown, Eric David, Biochemistry and Biomedical Sciences.
Subjects/Keywords: cold stress; ribosome biogenesis; outer membrane; lipopolysaccharide
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Stokes, J. M. (2016). EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/20502
Chicago Manual of Style (16th Edition):
Stokes, Jonathan Michael. “EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES.” 2016. Doctoral Dissertation, McMaster University. Accessed January 28, 2021.
http://hdl.handle.net/11375/20502.
MLA Handbook (7th Edition):
Stokes, Jonathan Michael. “EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES.” 2016. Web. 28 Jan 2021.
Vancouver:
Stokes JM. EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/11375/20502.
Council of Science Editors:
Stokes JM. EXPLOITING COLD SENSITIVITY IN ESCHERICHIA COLI TO IDENTIFY NOVEL ANTIBACTERIAL MOLECULES. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/20502

University of Edinburgh
19.
Hunter, Catriona Mhairi.
MicroRNA regulation of macrophage activation.
Degree: PhD, 2017, University of Edinburgh
URL: http://hdl.handle.net/1842/31027
► Macrophages are mononuclear phagocytic cells that have diverse roles within the body. Tissue specific macrophages, e.g. Kupffer cells, microglia and osteoclasts, have roles in tissue…
(more)
▼ Macrophages are mononuclear phagocytic cells that have diverse roles within the body. Tissue specific macrophages, e.g. Kupffer cells, microglia and osteoclasts, have roles in tissue homeostasis, while circulating macrophages play an important role in the innate immune system. Macrophages detect the presence of pathogen associated molecular patterns (PAMPs) via a range of receptors known collectively as pathogen recognition receptors (PRRs). Detection of pathogens causes the macrophages to become ‘activated,’ during which the macrophages undergo extreme morphological and translational changes that enable the pathogen to be neutralised and other immune system components to be recruited. Macrophage activation must be carefully regulated and promptly resolved, as chronic inflammation is damaging to the host. MicroRNAs have emerged as one mechanism by which activation is regulated. MicroRNAs are small, non-coding pieces of RNA that function as a post-transcriptional regulatory mechanism. Their action is exerted through binding with a complementary region in the 3’ untranslated region (3’UTR) of the target mRNA. This binding, facilitated by the ribonuclear protein complex RISC, prevents successful translation of the mRNA into its protein product. MicroRNAs have been shown to function across species, throughout development and during the adult life-span. In the immune system, microRNAs are known to be required for correct formation of germinal centres and normal development of B- and T-cells. MicroRNAs have also been shown to be differentially regulated during macrophage activation with different stimuli. In particular, miR-155, miR-146a and miR-21 are associated with macrophage activation by lipopolysaccharide (LPS). The objective of this work was to further understand the role of microRNAs during macrophage activation with LPS. Two approaches were adopted. Firstly, the regulation of individual microRNAs in LPS-activated bone marrow derived macrophages (BMDMs) was characterised by the use of illumina small RNA sequencing. Secondly, the requirement of the global microRNA population during macrophage biology was investigated through the use of DGCR8 and Dicer knockout systems. In keeping with the large number of changes reported in mRNA translation upon activation, expression of >400 microRNAs were found to be differentially regulated by exposure to LPS. Twelve of these microRNAs were chosen for further study (miR- 142-3p, -146a, -15b, -155, -16, -191, -21, -27b, -30b, -322-5p, -378 and -7a). Individual knock-down of these microRNAs in the RAW264.7 macrophage-like cell line mostly demonstrated subtle, rather than dramatic changes to the activation marker genes studied by RT-QPCR analysis. However, knock-down of miR-146a, -15b, - 155 and -191 were able to significantly alter the expression of the activation marker genes (Tnf-a, Cox2, Cxcl2, Il-6 and Saa3). Interestingly, knock-down of miR-142-3p, miR-146a and miR-155 appeared to show cross-regulation of these microRNAs. The cell index (CI) data suggested that miR-191 and…
Subjects/Keywords: 636.089; microRNA; macrophage; activation; lipopolysaccharide; LPS
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hunter, C. M. (2017). MicroRNA regulation of macrophage activation. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/31027
Chicago Manual of Style (16th Edition):
Hunter, Catriona Mhairi. “MicroRNA regulation of macrophage activation.” 2017. Doctoral Dissertation, University of Edinburgh. Accessed January 28, 2021.
http://hdl.handle.net/1842/31027.
MLA Handbook (7th Edition):
Hunter, Catriona Mhairi. “MicroRNA regulation of macrophage activation.” 2017. Web. 28 Jan 2021.
Vancouver:
Hunter CM. MicroRNA regulation of macrophage activation. [Internet] [Doctoral dissertation]. University of Edinburgh; 2017. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/1842/31027.
Council of Science Editors:
Hunter CM. MicroRNA regulation of macrophage activation. [Doctoral Dissertation]. University of Edinburgh; 2017. Available from: http://hdl.handle.net/1842/31027

Harvard University
20.
Garner, Ronald Aaron.
Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure.
Degree: PhD, Chemistry and Chemical Biology, 2014, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991
► Lipopolysaccharide (LPS) is the glycolipid that comprises the outer leaflet of the Gram-negative outer membrane (OM). Because it is essential in nearly all Gram-negative species,…
(more)
▼ Lipopolysaccharide (LPS) is the glycolipid that comprises the outer leaflet of the Gram-negative outer membrane (OM). Because it is essential in nearly all Gram-negative species, and because it is responsible for making these bacteria impervious to many types of antibiotics, LPS biogenesis has become an important area of research. While its biosynthesis at the cytoplasmic face of the inner membrane (IM) is well studied, the process by which it is removed from the IM, transported across the aqueous periplasmic compartment, and specifically inserted into the outer leaflet of the OM is only beginning to be understood. This transport process is mediated by the essential seven-protein LPS transport (Lpt) complex, LptA/B/C/D/E/F/G. The OM portion of the exporter, LptD/E, is a unique plug-and-barrel protein complex in which LptE, a lipoprotein, sits inside of LptD, a β-barrel integral membrane protein. LptD is of particular interest, as it is the target of an antibiotic in Pseudomonas aeruginosa.
Part I of this thesis investigates how the cell forms the two non-consecutive disulfide bonds that connect LptD's C-terminal β-barrel to its N-terminal soluble domain. These disulfides, one of which is almost universally conserved among Gram-negatives, are essential for cell viability. Here, we show that an intermediate oxidation state with non-native disulfide bonds accumulates in the absence of LptE and in strains defective in either LptE or LptD. We then demonstrate that this observed intermediate is on-pathway and part of the native LptD oxidative folding pathway. Using a defective mutant of DsbA, the protein that introduces disulfide bonds into LptD, we are able to identify additional intermediates in the LptD oxidative folding pathway. We ultimately demonstrate that the disulfide rearrangement that activates the LptD/E complex occurs following an exceptionally slow β-barrel assembly step and is dependent on the presence of LptE.
Part II describes work towards obtaining X-ray crystal structures of the LptD N-terminal domain and LptD/E complex. Expression construct and purification optimization enabled the production of stable LptD/E in quantities that make crystallography feasible. Numerous precipitants, detergents, and additives were screened, ultimately resulting in protein crystals that diffract to a resolution of 3.85 Å.
Chemistry and Chemical Biology
Advisors/Committee Members: Kahne, Daniel (advisor), Gaudet, Rachelle (committee member), Denic, Vladimer (committee member).
Subjects/Keywords: Biochemistry; Biology; Lipopolysaccharide; LptD; LptE; Outer Membrane
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Garner, R. A. (2014). Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991
Chicago Manual of Style (16th Edition):
Garner, Ronald Aaron. “Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure.” 2014. Doctoral Dissertation, Harvard University. Accessed January 28, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991.
MLA Handbook (7th Edition):
Garner, Ronald Aaron. “Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure.” 2014. Web. 28 Jan 2021.
Vancouver:
Garner RA. Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure. [Internet] [Doctoral dissertation]. Harvard University; 2014. [cited 2021 Jan 28].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991.
Council of Science Editors:
Garner RA. Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure. [Doctoral Dissertation]. Harvard University; 2014. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991

University of Guelph
21.
Hunt, Brittany.
Investigation of the Expression of the O:54 antigen from Salmonella enterica.
Degree: MS, Department of Molecular and Cellular Biology, 2013, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/7624
► WbbF is a proposed member of the synthase family of dual glycosyltransferase-exporter proteins. WbbF assembles the O:54 antigen from Salmonella enterica. The wb*O:54 operon (encoding…
(more)
▼ WbbF is a proposed member of the synthase family of dual glycosyltransferase-exporter proteins. WbbF assembles the O:54 antigen from Salmonella enterica. The wb*O:54 operon (encoding wbbE, wbbF and mnaA) is found on a naturally-occuring plasmid (pWQ799). Previous research suggested only WbbE and WbbF are necessary for O:54 antigen assembly due to the presence of a chromosomal gene encoding WecB, a functional homolog of MnaA. WecB and MnaA synthesize the essential UDP-ManNAc donor. However, this study determined optimal production of O:54 in E. coli was dependent on the presence of MnaA. A growth defect was observed in cells producing O:54 antigen, but unable to ligate it to the
lipopolysaccharide acceptor (due to ΔwaaL). Cells recovered growth over time via mutations that turned off (or down) O:54 antigen biosynthesis. During this study, a cysteine-free version of WbbF that retained function was established, providing a key resource for future topology mapping experiments.
Advisors/Committee Members: Whitfield, Chris (advisor).
Subjects/Keywords: O-antigen; lipopolysaccharide; synthase; O:54; WbbF
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hunt, B. (2013). Investigation of the Expression of the O:54 antigen from Salmonella enterica. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/7624
Chicago Manual of Style (16th Edition):
Hunt, Brittany. “Investigation of the Expression of the O:54 antigen from Salmonella enterica.” 2013. Masters Thesis, University of Guelph. Accessed January 28, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/7624.
MLA Handbook (7th Edition):
Hunt, Brittany. “Investigation of the Expression of the O:54 antigen from Salmonella enterica.” 2013. Web. 28 Jan 2021.
Vancouver:
Hunt B. Investigation of the Expression of the O:54 antigen from Salmonella enterica. [Internet] [Masters thesis]. University of Guelph; 2013. [cited 2021 Jan 28].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/7624.
Council of Science Editors:
Hunt B. Investigation of the Expression of the O:54 antigen from Salmonella enterica. [Masters Thesis]. University of Guelph; 2013. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/7624

Harvard University
22.
Moison, Eileen.
Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes.
Degree: PhD, 2018, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129126
► The study of Gram-negative bacteria is important for developing an understanding of both bacterial physiology and to develop new drugs to treat Gram-negative bacterial infections.…
(more)
▼ The study of Gram-negative bacteria is important for developing an understanding of both bacterial physiology and to develop new drugs to treat Gram-negative bacterial infections. One unique aspect of Gram-negative bacteria is the outer membrane, which is an asymmetric membrane composed of lipopolysaccharide (LPS) in the outer leaflet. This dissertation develops new fluorescent tools based on the antibiotic polymyxin B and applies it to studies of LPS biogenesis in whole cells. The development of these tools enables a novel understanding of LPS localization in whole cells, which was not previously possible with established analytical methods. Through a more detailed understanding of perturbations to LPS localization, we have been able to more specifically elucidate the impact on LPS biogenesis by both new and established antimicrobial compounds. We have also used a fluorescent polymyxin B derivative to also enable an appreciation of antibiotic hypersensitivity and tolerance that is difficult to normally isolate within a population, and which indicates a regulatory link between outer membrane and cell wall biogenesis.
Chemistry and Chemical Biology
Advisors/Committee Members: Kahne, Daniel (advisor), Losick, Richard (committee member), Mitchison, Timothy (committee member).
Subjects/Keywords: Bacteria; Polymyxin B; Antibiotics; Lipopolysaccharide; Outer membrane
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moison, E. (2018). Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129126
Chicago Manual of Style (16th Edition):
Moison, Eileen. “Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes.” 2018. Doctoral Dissertation, Harvard University. Accessed January 28, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129126.
MLA Handbook (7th Edition):
Moison, Eileen. “Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes.” 2018. Web. 28 Jan 2021.
Vancouver:
Moison E. Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes. [Internet] [Doctoral dissertation]. Harvard University; 2018. [cited 2021 Jan 28].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129126.
Council of Science Editors:
Moison E. Polymyxin B as a Tool to Study Gram-Negative Bacterial Phenotypes. [Doctoral Dissertation]. Harvard University; 2018. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129126

Univerzitet u Beogradu
23.
Lalić, Ivana M., 1986-.
Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša.
Degree: Medicinski fakultet, 2019, Univerzitet u Beogradu
URL: https://fedorabg.bg.ac.rs/fedora/get/o:19142/bdef:Content/get
► Medicina - Histologija i embriologija / Medicine - Histology and Embryology
Lipopolisaharid (LPS) je glavna komponenta spoljašnje membrane Gram negativnih bakterija. Prepoznavanje LPS-a inicira intracelularne…
(more)
▼ Medicina - Histologija i embriologija / Medicine -
Histology and Embryology
Lipopolisaharid (LPS) je glavna komponenta
spoljašnje membrane Gram negativnih bakterija. Prepoznavanje LPS-a
inicira intracelularne signalne puteve koji dovode do transkripcije
gena i oslobaĊanja proinflamatornih medijatora. Dobro je poznato da
kljuĉnu ulogu u imunskom odgovoru na LPS ima receptor TNFR1 (tumor
necrosis factor receptor-1), kao i da TNFR1-/- (tumor necrosis
factor receptor-1 knockout) miševi pokazuju rezistenciju na
endotoksiĉni šok ĉak i nakon tretmana letalnim dozama LPS-a.
Dosadašnja istraţivanja su pokazala da LPS izaziva migraciju
nekoliko ćelijskih tipova unutar slezine. MeĊutim, nema podataka o
uticaju LPS-a na populaciju B i T limfocita koji se nalaze u
crvenoj pulpi slezine miša. Nedavna studija istakla je znaĉaj
hemokina CCL20 u brzoj akumulaciji B limfocita u slezini miša nakon
sistemske administracije Nod1 agoniste, koji izaziva sistemsku
inflamaciju in vivo. Cilj: Ispitivanje uticaja sistemske
administracije LPS-a na broj B i T limfocita u crvenoj pulpi
slezine miša, kao i na strukturnu organizaciju bele pulpe slezine,
24 h nakon tretmana. Osim toga, cilj ove studije bio je da ispita
uticaj sistemske administracije LPS-a na ekspresiju gena za
hemokine i proinflamatorne citokine u slezini miša 1 h, 2 h i 24 h
nakon tretmana. Dodatni cilj bio je da se ispitaju potencijalne
promene u ekspresiji hemokina CCL20 u slezini miša 2 h nakon
sistemske administracije LPS-a, kao i da se odredi lokalizacija
ćelija koje bi u ovim uslovima proizvodile CCL20. Materijal i
metode: Eksperimenti su izvoĊeni na wild-type miševima soja C57BL/6
i TNFR1-/- miševima istog soja. Za ispitivanje uticaja sistemske
administracije LPS-a na broj B i T limfocita u crvenoj pulpi
slezine, kao i na strukturnu organizaciju bele pulpe slezine,
formirane su ĉetiri grupe ţivotinja: netretirani wild-type miševi
(n=5), tretirani wild-type miševi (n=5), netretirani TNFR1-/-
miševi (n=5) i tretirani TNFR1-/- miševi (n=5). Tretman ţivotinja
podrazumevao je ubrizgavanje u repnu venu LPS-a E. coli (soj
055:B5) rastvorenog u fosfatnom puferu, u dozi 2,5 μg/g telesne
mase...
Advisors/Committee Members: Milićević, Novica, 1952-.
Subjects/Keywords: lymphocyte; red pulp; chemokine; lipopolysaccharide;
spleen; mouse
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lalić, Ivana M., 1. (2019). Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:19142/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lalić, Ivana M., 1986-. “Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša.” 2019. Thesis, Univerzitet u Beogradu. Accessed January 28, 2021.
https://fedorabg.bg.ac.rs/fedora/get/o:19142/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lalić, Ivana M., 1986-. “Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša.” 2019. Web. 28 Jan 2021.
Vancouver:
Lalić, Ivana M. 1. Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša. [Internet] [Thesis]. Univerzitet u Beogradu; 2019. [cited 2021 Jan 28].
Available from: https://fedorabg.bg.ac.rs/fedora/get/o:19142/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lalić, Ivana M. 1. Uticaj sistemske administracije lipopolisaharida na
strukturne, celularne i molekularne karakteristike slezine
miša. [Thesis]. Univerzitet u Beogradu; 2019. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:19142/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Bath
24.
Wickens, Robin.
The role of NLRP3 signalling in the pathology of depression.
Degree: PhD, 2017, University of Bath
URL: https://researchportal.bath.ac.uk/en/studentthesis/the-role-of-inflammsasome-signalling-in-the-pathology-of-depression(493e4784-a3e9-4751-854a-22fa2734b99e).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715257
► Neuroinflammation is considered to be an important underlying process in the pathology of major depressive disorder (MDD) within a subpopulation of patients. MDD is associated…
(more)
▼ Neuroinflammation is considered to be an important underlying process in the pathology of major depressive disorder (MDD) within a subpopulation of patients. MDD is associated with increased levels of proinflammatory cytokines in the blood, and cytokine-based treatments can induce depression. In mice, the induction of systemic inflammation with lipopolysaccharide (LPS) can induce depressive-like behaviours that are associated with symptoms of MDD. Microglia mediate the neuroinflammatory response within the brain and have a critical role in inflammation-induced depressive- like behaviours. Microglia within the brain exist in low O2 conditions (~5 %), though experimentation in vitro is typically carried out in high O2 conditions (20 %). The NLRP3 inflammasome is a molecular complex central to the production of the proinflammatory cytokine IL-1β and the propagation of the inflammatory response. NLRP3 inflammasome activity has been implicated in chronic stress and inflammation-based models of depressive-like behaviours in mice. The aims of this thesis were to study LPS-induced depressive-like behaviour in C57BL/6J mice, the role of NLRP3 in the behavioural output and the influence of oxygen (O2) availability on NLRP3 inflammasome activity in microglia cell cultures. Acute LPS induced depressive-like behaviours were observed in hedonia-based tasks but not in the forced swim test (FST). However, acute LPS induces a brief period of inflammation that does not address the sustained nature of depression. A FST depressive-like behaviour was observed in a novel 3-day increasing dose LPS model of sustained inflammation, whilst circumventing the development of LPS tolerance. The LPS-induced sickness was partially dependent upon NLRP3, though the resulting depressive-like behaviour was not. NLRP3 inflammasome signalling in microglia was studied in 5 % O2 conditions to replicate the hypoxic environment within the brain. Primary microglia isolated from mixed glial cultures by mild trypsinisation exhibited functional NLRP3 inflammasome expression and activity. When exposed to 5 % O2 (24 hours), NLRP3 inflammasome activity and adenosine triphosphate (ATP)-induced cell death was attenuated, whilst the production of other proinflammatory cytokines were unaffected. These data demonstrate the O2 sensitivity of NLRP3 inflammasome signalling in microglia. This thesis demonstrates a novel model of sustained inflammation and that inhibiting NLRP3 signalling may provide a target for attenuating neuroinflammation and the resulting behavioural changes. The importance of understanding the influence of O2 in microglia function and neuroinflammation was highlighted by the sensitivity of NLRP3 inflammasome activity to low O2.
Subjects/Keywords: 616.89; NLRP3; Neuroinflammation; Depression; Microglia; Mice; Lipopolysaccharide
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wickens, R. (2017). The role of NLRP3 signalling in the pathology of depression. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/the-role-of-inflammsasome-signalling-in-the-pathology-of-depression(493e4784-a3e9-4751-854a-22fa2734b99e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715257
Chicago Manual of Style (16th Edition):
Wickens, Robin. “The role of NLRP3 signalling in the pathology of depression.” 2017. Doctoral Dissertation, University of Bath. Accessed January 28, 2021.
https://researchportal.bath.ac.uk/en/studentthesis/the-role-of-inflammsasome-signalling-in-the-pathology-of-depression(493e4784-a3e9-4751-854a-22fa2734b99e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715257.
MLA Handbook (7th Edition):
Wickens, Robin. “The role of NLRP3 signalling in the pathology of depression.” 2017. Web. 28 Jan 2021.
Vancouver:
Wickens R. The role of NLRP3 signalling in the pathology of depression. [Internet] [Doctoral dissertation]. University of Bath; 2017. [cited 2021 Jan 28].
Available from: https://researchportal.bath.ac.uk/en/studentthesis/the-role-of-inflammsasome-signalling-in-the-pathology-of-depression(493e4784-a3e9-4751-854a-22fa2734b99e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715257.
Council of Science Editors:
Wickens R. The role of NLRP3 signalling in the pathology of depression. [Doctoral Dissertation]. University of Bath; 2017. Available from: https://researchportal.bath.ac.uk/en/studentthesis/the-role-of-inflammsasome-signalling-in-the-pathology-of-depression(493e4784-a3e9-4751-854a-22fa2734b99e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715257

Virginia Tech
25.
Ceh, Carrie Ann.
Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves.
Degree: MSin Life Sciences, Dairy Science, 2019, Virginia Tech
URL: http://hdl.handle.net/10919/91447
► Dairy calves are born with an under-developed stomach. The stomach has four compartments: the rumen, reticulum, omasum, and abomasum. The rumen is the largest component…
(more)
▼ Dairy calves are born with an under-developed stomach. The stomach has four compartments: the rumen, reticulum, omasum, and abomasum. The rumen is the largest component where finger-like projections called papillae grow to absorb nutrients for the calf. It is vital to the calf that the rumen develops not only the papillae to absorb nutrients but also to foster a microbe-rich environment so the microbes can act as a defense mechanism for the calf to aid in fighting disease. While it is known that things like solid feed support the development of the rumen, the mechanism behind how that is happening still remains unclear in the literature. The objective of this study was first to better understand the relationships that exist in the literature between dietary, environmental, and ruminal factors, and second to investigate the claim that certain components of the bacteria in the rumen are stimulating rumen development independently and additively with sodium butyrate. In order to investigate the relationships amongst the dietary, environmental, and ruminal parameters, a computer program called R Studio was used to analyze over 30 different models that extracted data from a database that included a collection of 36 studies from the literature. This is also known as a meta-analysis. The associations of interest that we found were: average daily gain (ADG) of the calf was associated with daily forage intake, calves that were weaned, total starter intake, and total MR intake. Feed efficiency of the calf was associated with the weight of the ruminal contents, daily forage, milk replacer (MR), and starter intakes, percent of the diet composed of starter, and total starter intake. Daily forage intake was associated with the percent of the diet that was starter or MR. Daily starter intake was associated with acid detergent fiber in the starter, a pelleted starter (versus a texturized starter), diets including starter and forage (versus a MR only diet), and the percent of the diet that was MR. Daily MR intake was associated with the percentage of the diet that was starter, final body weight (BW), ruminal propionate concentration, and daily starter intake. These relationships emphasized that although dietary and environmental factors are more closely associated with calf performance, ruminal factors such as rumen contents and volatile fatty acid concentrations appear to have additional, additive influences on calf performance. The second part of the study objective was to explore an idea that, to our knowledge, has not been published in the literature. In the second study, 24 dairy calves were challenged with oral doses of a gram-negative bacteria
lipopolysaccharide (LPS), and a short-chain fatty acid sodium butyrate. The hypothesis in this study was that the LPS and sodium butyrate would trigger metabolic pathways on the rumen cell membranes to a greater extent together, versus independently, to increase the amount of cells growing. Calves were assigned to one of four treatments: control (CON), butyrate (BUTY), LPS only (LPS-O),…
Advisors/Committee Members: Daniels, Kristy M. (committeechair), White, Robin (committee member), Hanigan, Mark Daniel (committee member), Jiang, Honglin (committee member).
Subjects/Keywords: calf; dairy; lipopolysaccharide; meta-analysis; rumen development
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ceh, C. A. (2019). Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/91447
Chicago Manual of Style (16th Edition):
Ceh, Carrie Ann. “Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves.” 2019. Masters Thesis, Virginia Tech. Accessed January 28, 2021.
http://hdl.handle.net/10919/91447.
MLA Handbook (7th Edition):
Ceh, Carrie Ann. “Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves.” 2019. Web. 28 Jan 2021.
Vancouver:
Ceh CA. Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves. [Internet] [Masters thesis]. Virginia Tech; 2019. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10919/91447.
Council of Science Editors:
Ceh CA. Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves. [Masters Thesis]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/91447

University of St. Andrews
26.
Dong, Haohao.
Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
.
Degree: 2015, University of St. Andrews
URL: http://hdl.handle.net/10023/7338
► Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) of Gram-negative bacteria and plays a fundamental role in protecting the bacteria from harsh…
(more)
▼ Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) of
Gram-negative bacteria and plays a fundamental role in protecting the bacteria from
harsh environments and toxic compounds. The LPS transport system is responsible
for transporting LPS from the periplasmic side of the inner membrane (IM) to the
OM, in a process involving seven LptA-LptG proteins. The current model for
lipopolysaccharide transport (Lpt) suggests that LPS is initially extracted by a four-protein complex, LptBCFG, from the inner membrane to the periplasm, where LptA
mediates further transport to the OM. Another two protein complex, LptD/E,
catalyses the assembly of LPS at the OM cell surface. However, the details of this
transport mechanism have remained unknown, mainly due to a lack of structural
information.
In chapter 1 and 2 of this thesis, I report materials and methods for all LptD/E, and
Schmallenberg virus (SBV) nucleoprotein (NP) experiments and the theories and
software that were used in determining structures of LptD/E, SBV NP and the SBV
NP/RNA complex.
In chapter 3 of this thesis, I report the first crystal structure of the outer membrane
protein LptD/E complex. LptD forms a 26-strand ß-barrel in a closed form and LptE
is a roll-like structure located inside LptD to form “barrel and plug” architecture.
Through structural analysis, function assay and molecular dynamics simulation, we
proposed a mechanism in which the hydrophilic head of LPS molecule, including the
oligosaccharide core and the O antigen, directly penetrates through the hydrophilic ß-
barrel whilst the hydrophobic lipid A tail is inserted into an intramembrane hole, with
a lateral opening between strand ß1 and ß26 of the LptD. LptE may assist this
process.
In chapter 4, I report the crystal structure of the SBV NP in two conformations:
tetrameric when the protein was purified under native conditions, and trimeric when
denatured and refolded during purification. The SBV NP has a novel fold and we
have also identified that the N-terminal arm is crucial for RNA binding, and the N- and the C-terminal arm is essential for RNA multimerisation with adjacent protomers
and for viral RNA encapsidation.
Chapter 5 describes the crystal structure of SBV NP in complex with a 42 nucleotide
long RNA (polyU). This ribonucleoprotein (RNP) complex was crystallized as a ring-like tetramer with each protomer bound to 11 ribonucleotides. Eight of these
nucleotides are bound in a positively charged cleft between N- and C- terminal
domains and three are bound in the N-terminal arm. I also compared the structure to
that of other NPs from negative-sense RNA viruses, and found that SBV NP
sequesters RNA using a different mechanism. Furthermore, the structure suggests that
when RNA binds the protein, there are conformational changes in the RNA-binding
cleft, and in the N- and C-terminal arms. Thus our results reveal a novel mechanism
of RNA encapsidation by orthobunyaviruses NP.
Advisors/Committee Members: Naismith, Jim (advisor).
Subjects/Keywords: Lipopolysaccharide;
Bunyaviruses;
LptD/E;
Schmallenberg virus
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dong, H. (2015). Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
. (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/7338
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dong, Haohao. “Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
.” 2015. Thesis, University of St. Andrews. Accessed January 28, 2021.
http://hdl.handle.net/10023/7338.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dong, Haohao. “Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
.” 2015. Web. 28 Jan 2021.
Vancouver:
Dong H. Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
. [Internet] [Thesis]. University of St. Andrews; 2015. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10023/7338.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dong H. Structural and functional studies of bacterial outer membrane lipopolysaccharide insertion and Schmallenberg virus replication
. [Thesis]. University of St. Andrews; 2015. Available from: http://hdl.handle.net/10023/7338
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech
27.
Yuan, Ruoxi.
Dynamic Programming of Innate Immunity in Health and Disease.
Degree: PhD, Biomedical and Veterinary Sciences, 2016, Virginia Tech
URL: http://hdl.handle.net/10919/82925
► Whether innate immune cells may be adapted into potential memory states has becoming an important question in the field of immunity. Although previous conceptual paradigm…
(more)
▼ Whether innate immune cells may be adapted into potential memory states has becoming an important question in the field of immunity. Although previous conceptual paradigm failed to acknowledge this important question, emerging clinical and basic observations have started to shed intriguing clues to shake the previous dogma regarding innate immunity of being "simple", "raw", "first-line defense with no memory". We have aimed to further address this fundamental issue in this dissertation work, under the close guidance of Dr. Liwu Li. We have chosen to use the model system of Toll-Like-Receptor (TLR) signaling networks within primary monocytes.
TLRs play fundamental roles in sensing pathogen-associated molecular patterns (PAMPs) and modulation of innate immunity.
Lipopolysaccharide (LPS), an endotoxin found on the cell membrane of gram-negative bacteria, is the ligand of TLR4 and induces a range of inflammatory as well as anti-inflammatory responses. Higher dosages of LPS were known to cause robust yet transient expression of pro-inflammatory mediators. On the other hand, the effects of super-low dose LPS, commonly manifested in humans with adverse health conditions, have been largely ignored in the basic research field. Super-low dose LPS may skew host immune environment into a mild non-resolving pro-inflammatory state, which is a risk factor for inflammatory diseases such as atherosclerosis, compromised wound healing, and elevated risks for sepsis.
Our central hypothesize is that monocytes may be adapted by super-low dose LPS into a non-resolving low-grade inflammatory state conducive for the pathogenesis of inflammatory diseases. We have employed both in vitro cell culture system as well as in vivo disease models to test this hypothesis.
For the in vitro system, we have cultured primary murine monocytes with increasing signal strength of LPS. Monocyte phenotypes such as the expression of key inflammatory mediators including cytokines, chemokines, and cellular surface markers were studied. Potential molecular and cellular mechanisms were examined. We revealed a novel low-grade inflammatory monocyte phenotype termed ML adapted by super-low dose LPS, mediated through IRF5.
For the in vivo system, we have employed both acute and chronic models of inflammation. For the chronic model, we have tested the effects of super-low dose LPS on monocyte polarization in vivo, as well as its contribution to the pathogenesis of atherosclerosis. Furthermore, we have tested the effects of programmed monocytes on wound healing. For the acute model, we have tested the effects of pre-conditioning with super-low dose LPS on the subsequence risks of sepsis elicited by cecal ligation and puncture. We have demonstrated aggravated atherosclerosis, compromised wound healing, and increased sepsis mortality in mice pre-conditioned with super-low dose LPS.
Taken together, our findings reveal that monocytes can be differentially programmed into distinct states, depending on the signal strength of LPS. The differential…
Advisors/Committee Members: Ahmed, S. Ansar (committeechair), Li, Liwu (committeechair), LeRoith, Tanya (committee member), Luo, Xin (committee member).
Subjects/Keywords: lipopolysaccharide; inflammation; monocytes; atherosclerosis; sepsis; wound healing.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yuan, R. (2016). Dynamic Programming of Innate Immunity in Health and Disease. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/82925
Chicago Manual of Style (16th Edition):
Yuan, Ruoxi. “Dynamic Programming of Innate Immunity in Health and Disease.” 2016. Doctoral Dissertation, Virginia Tech. Accessed January 28, 2021.
http://hdl.handle.net/10919/82925.
MLA Handbook (7th Edition):
Yuan, Ruoxi. “Dynamic Programming of Innate Immunity in Health and Disease.” 2016. Web. 28 Jan 2021.
Vancouver:
Yuan R. Dynamic Programming of Innate Immunity in Health and Disease. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2021 Jan 28].
Available from: http://hdl.handle.net/10919/82925.
Council of Science Editors:
Yuan R. Dynamic Programming of Innate Immunity in Health and Disease. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/82925
28.
Ranc, Anne-Gaëlle.
Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila.
Degree: Docteur es, Micro-organismes. Interactions. Infections, 2018, Lyon
URL: http://www.theses.fr/2018LYSE1010
► Legionella pneumophila (Lp) est une bactérie ubiquitaire dans les environnements aqueux et responsable d’une pneumopathie potentiellement sévère : la légionellose. La majorité des souches impliquées…
(more)
▼ Legionella pneumophila (Lp) est une bactérie ubiquitaire dans les environnements aqueux et responsable d’une pneumopathie potentiellement sévère : la légionellose. La majorité des souches impliquées appartiennent au sérogroupe 1 (Lp1) et à un sous- groupe spécifique de souches portant un épitope particulier dites mAb3/1+. Cependant, la différence de distribution entre les souches retrouvées dans l’environnement et celles impliquées en clinique n’est pas clairement élucidée. Notre travail a porté sur la détection de deux facteurs de virulence de Lp. Nous avons voulu mettre en évidence l’existence de Phenols Soluble Modulines (PSMs), peptides uniquement décrit chez Staphylocoques et avons ainsi pu démontrer l’activité de peptides prédits par analyse in silico chez Lp capables d’activer la réponse inflammatoire par la voie du NF-?B et sont dotés d’une action cytotoxique. Notre deuxième axe d’étude a porté sur le lipopolysaccharide (LPS) de Lp. Afin de vérifier si la prédominance de certaines souches était liée à un biais diagnostique, nous avons voulu tout d’abord vérifier la sensibilité de 3 tests urinaires diagnostiques envers le LPS extrait de souches de différents sous- groupes de Lp1 et sérogroupes de Lp et avons ainsi pu montrer que ces tests sont capables de détecter tous les LPS de Lp1. La sensibilité envers le LPS des autres sérogroupes est très variable mais reste insuffisante pour permettre leur détection. Nous avons ensuite utilisé ces LPS extraits pour vérifier la réponse immunitaire innée en fonction des souches de Lp1. Ainsi les souches mAb3/1+ activent moins le système immunitaire que les souches mAb3/1-, ce qui pourrait expliquer alors une moins bonne clairance de ces souches permettant leur multiplication à l’origine d’une infection. Au final, notre travail a permis d’étudier deux facteurs de virulence potentiels au sein de Lp, pouvant expliquer partiellement la prédominance de certaines souches en pathologie humaine
Legionella pneumophila (Lp) is a ubiquitous intracellular bacterium found widely in the environment and is the cause of an opportunistic infection named legionellosis. The majority of the strains involved belong to serogroup 1 (Lp1) and to a specific subgroup named mAb3/1+, linked to a specific epitope expressed at the cell membrane. However the distribution difference between the strains found in the environment and the ones involved in pathology is not fully understood. We here studied two virulence factors of Lp. We first demonstrated the existence of Phenols Soluble Modulines (PSMs), smalls peptides that only have been described for Staphylococcus and found that the peptides that were predicted for Lp by in silico analysis were able to activate the innate immune response by NF-?B pathway and were able to have a cytotoxic activity. We also studied the lipopolysaccharide (LPS) of Lp. To found out if the predominance of some strains was linked to a diagnosis biais, we first evaluated the sensitivity of 3 urinary antigens tests against extracted LPS of strains belonging to all the…
Advisors/Committee Members: Jarraud, Sophie (thesis director), Lina, Gérard (thesis director).
Subjects/Keywords: Legionella pneumophila; PSMs; Lipopolysaccharide; Facteurs de virulence; Legionella pneumophila; PSMs; Lipopolysaccharide; Virulence factors; 579
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ranc, A. (2018). Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2018LYSE1010
Chicago Manual of Style (16th Edition):
Ranc, Anne-Gaëlle. “Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila.” 2018. Doctoral Dissertation, Lyon. Accessed January 28, 2021.
http://www.theses.fr/2018LYSE1010.
MLA Handbook (7th Edition):
Ranc, Anne-Gaëlle. “Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila.” 2018. Web. 28 Jan 2021.
Vancouver:
Ranc A. Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila. [Internet] [Doctoral dissertation]. Lyon; 2018. [cited 2021 Jan 28].
Available from: http://www.theses.fr/2018LYSE1010.
Council of Science Editors:
Ranc A. Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée : Phenol Soluble Modulines caracterisation and role of lipopolysaccharide in innate immune response to Legionella pneumophila. [Doctoral Dissertation]. Lyon; 2018. Available from: http://www.theses.fr/2018LYSE1010
29.
Rideau, Aline.
Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge.
Degree: Docteur es, Neurosciences, 2012, Université Montpellier I
URL: http://www.theses.fr/2012MON1T011
► Introduction: L'injection ip de lipopolysaccharide (LPS) d'E.coli à la rate gestante aboutit à un phénotype cognitivo-comportemental de pathologies neuropsychiatriques chez la progéniture mâle. L'objectif principal…
(more)
▼ Introduction: L'injection ip de lipopolysaccharide (LPS) d'E.coli à la rate gestante aboutit à un phénotype cognitivo-comportemental de pathologies neuropsychiatriques chez la progéniture mâle. L'objectif principal était de vérifier l'hypothèse d'une atteinte structurelle et d'un déséquilibre entre excitation et inhibition dans l'hippocampe. L'objectif secondaire était de dégager des stratégies thérapeutiques ciblées.Méthodes: 500 μg/kg de LPS d'E.coli de sérotype O55:B5 ou 2 ml/kg de sérum physiologique étaient injectés ip à la rate au 19e jour de gestation. La progéniture mâle était étudiée à différents stades du développement. L'étude structurelle reposait sur de l'immunohistochimie, l'étude fonctionnelle sur des enregistrements électro-physiologiques de l'activité des cellules pyramidales de l'aire CA1. L'effet protecteur de la N-acétylcystéine (NAC) donnée po à la rate gestante après l'injection de LPS était testé. Résultats: Les animaux soumis à un stress prénatal par le LPS présentaient une désorganisation durable de la couche pyramidale de l'aire CA3, un déficit transitoire de neurones exprimant la reeline, une altération de la dépression à long terme des synapses glutamatergiques (LTDe) liée à un déficit des récepteurs NMDA et du système GABAergique. Un inhibiteur de la recapture du GABA parvenait à corriger les anomalies de la LTDe. La NAC prévenait les anomalies cyto-architecturales.Conclusion: Cette thèse confirme l'impact d'un stress immuno-inflammatoire maternel sur la structure et la fonction hippocampique. Elle démontre l'intérêt d'un traitement prénatal par la NAC et de la modulation du tonus GABAergique pour corriger les troubles cognitifs associés.
Introduction: A late gestational exposure to lipopolysaccharide (LPS) leads to a behavioral and cognitive phenotype of neuropsychiatric disorders in male offspring. The main goal was to test the hypothesis of structural damage and imbalance between excitation and inhibition in the hippocampus. The secondary goal was to identify targeted therapeutic strategies.Methods: Pregnant rats were ip injected with either 500 μg/kg LPS from E.coli O55:B5 or 2 ml/kg saline vehicle on gestational day 19. Male offspring were studied at different developmental stages. The structural study was based on immunohistochemistry, the functional study on electrophysiological recordings of the activity of pyramidal cells in the CA1 area. The protective effect of N-acetylcysteine (NAC) given to pregnant rats after LPS injection was tested.Results: In male offspring, LPS induced late gestational immune challenge led to sustainable disarray of the pyramidal layer in the CA3 area, transient deficit of reelin expressing neurons, impaired long term depression of glutamatergic synapses (LTDe), due to NMDA receptor and GABAergic system dysfunction. An inhibitor of GABA reuptake completely restored plasticity lost after prenatal stress. NAC prevented cyto-architectural abnormalities.Conclusion: This thesis confirms the impact of a late prenatal immune challenge on hippocampal…
Advisors/Committee Members: Barbanel, Gérard (thesis director), Cambonie, Gilles (thesis director).
Subjects/Keywords: Lipopolysaccharide; Gaba; Glutamate; Plasticité synaptique; Hippocampe; Lipopolysaccharide; Gaba; Glutamate; Synaptic plasticity; Hippocampus
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
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APA (6th Edition):
Rideau, A. (2012). Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON1T011
Chicago Manual of Style (16th Edition):
Rideau, Aline. “Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed January 28, 2021.
http://www.theses.fr/2012MON1T011.
MLA Handbook (7th Edition):
Rideau, Aline. “Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge.” 2012. Web. 28 Jan 2021.
Vancouver:
Rideau A. Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Jan 28].
Available from: http://www.theses.fr/2012MON1T011.
Council of Science Editors:
Rideau A. Dysfonction glutamatergique et GABAergique dans l'hippocampe après un stress immuno-inflammatoire prénatal chez le rat : hippocampal GABAergic and glutamatergic deficiency after LPS prenatal immune challenge. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON1T011
30.
Pfister, Hélène.
Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei.
Degree: Docteur es, Chimie organique, 2014, Université Paris Descartes – Paris V
URL: http://www.theses.fr/2014PA05P619
► Avec 800 000 morts par année, les maladies diarrhéiques sont la seconde cause de mortalité chez les enfants de moins de cinq ans. La shigellose,…
(more)
▼ Avec 800 000 morts par année, les maladies diarrhéiques sont la seconde cause de mortalité chez les enfants de moins de cinq ans. La shigellose, causée par des bactéries Gram négatif appelées Shigella, est l’une des quatre grandes maladies entériques touchant cette population. L’infection naturelle protège contre la réinfection et la composante polysaccharidique du lipopolysaccharide bactérien est la principale cible de l’immunité humorale. Chez S. sonnei, espèce prévalente dans les pays en développement et développés, ce polysaccharide spécifique, à caractère zwitterionique, a pour unité répétitive un disaccharide composé de deux hexosamines rares : l’acide 2-acétamido-2-désoxy-L-altruronique (A) et le 2-acétamido-4-amino-2,4,6-tridésoxy-D-galactose (B, aussi appelé AAT) associés par des liens glycosidiques 1,2-trans (I). ->4-a-L-AltpNAcA-(1->3)-b-D-FucpNAc4N-(1-> (I). Ces travaux s’intègrent dans un programme visant le développement d’un vaccin issu de sucres de synthèse à couverture large contre les infections par Shigella. Le premier objectif de la stratégie développée contre les infections par S. sonnei est l’identification des épitopes saccharidiques, cibles des anticorps protecteurs. Dans ce but, nous avons entrepris la synthèse d’une diversité de fragments du polysaccharide d’intérêt. Des synthèses multi-grammes de précurseurs orthogonalement protégés des monosaccharides A et B ont été mises au point afin d’accéder aux intermédiaires donneurs et accepteurs impliqués dans les étapes de glycosylation. En particulier, deux voies originales d’accès au précurseur B ont été développées. D’autre part, l’optimisation des conditions de glycosylation et d’oxydation a conduit à un bloc disaccharidique AB compatible avec la synthèse d’oligosaccharides d’ordres supérieurs. Les synthons mono- et disaccharidiques identifiés ont été validés à travers l’obtention de quatre disaccharides portant ou non des modifications de la répartition des charges, de deux trisaccharides ainsi que d’un tétrasaccharide.
800,000 children die each year of diarrhoeal diseases, making it the second cause of death among children under five. Shigellosis, caused by a Gram negative bacterium, Shigella, is one of the four major forms of diarrhoeal diseases in this population. Natural infection protects against reinfection and the humoral response is primarily directed against the specific polysaccharide moiety of the bacterial lipopolysaccharide. S. sonnei, the prevalent species in developed and transitional countries, displays a zwitterionic polysaccharide, whose disaccharide repeating unit is made of two rare aminosugars: a 2-acetamido-2-deoxy-L-altruronic acid (A) and a 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (B, AAT) 1,2-trans linked to one another (I). ->4-a-L-AltpNAcA-(1->3)-b-D-FucpNAc4N-(1-> (I). This work is part of the program aimed at the development of a synthetic carbohydrate-based broad coverage vaccine against Shigella infections. In order to define the protective epitopes located on the O-specific polysaccharide of S. sonnei,…
Advisors/Committee Members: Mulard, Laurence (thesis director).
Subjects/Keywords: AAT; Glycosylation; Lipopolysaccharide; Oligosaccharide; Oxydation; Zwitterion; Shigella; AAT; Glycosylation; Lipopolysaccharide; Oligosaccharide; Oxidation; Zwitterion; Shigella; 616.935 5061
Record Details
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Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pfister, H. (2014). Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2014PA05P619
Chicago Manual of Style (16th Edition):
Pfister, Hélène. “Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei.” 2014. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed January 28, 2021.
http://www.theses.fr/2014PA05P619.
MLA Handbook (7th Edition):
Pfister, Hélène. “Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei.” 2014. Web. 28 Jan 2021.
Vancouver:
Pfister H. Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2014. [cited 2021 Jan 28].
Available from: http://www.theses.fr/2014PA05P619.
Council of Science Editors:
Pfister H. Synthèse d'oligosaccharides représentatifs de l'antigène O de Shigella sonnei : Synthesis of oligosaccharides fragments of the o-specific polysaccharide of shigella sonnei. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2014. Available from: http://www.theses.fr/2014PA05P619
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