65 research outputs found
Numerical simulation of brine migration in the vicinity of a potash mine
The development and results of a 3-D site-specific groundwater flow and transport study of the Potash Corporation of Saskatchewan Incorporated Cory Division Potash Mine (PCS Cory Mine) and surrounding area are presented. The mine is located approximately 10 km southwest of Saskatoon, Saskatchewan, Canada. The objectives of the study are to simulate, analyze and predict the extent of brine migration, originating from the PCS Cory Mine Waste Management Area (WMA), in the groundwater flow system.
The hydrogeology of interest to the study is Late Cretaceous to Quaternary in age. A 3-D finite element mesh representing the hydrogeology of the study area is constructed. The FEMWATER code is used to simulate steady-state and transient groundwater flow and solute transport processes. Calibration of the model using observed hydraulic heads is reported.
Fifty years of brine plume migration at the PCS Cory Mine WMA, beginning in 1969, are simulated. Detailed analysis of the position and concentration of the brine plume in the surficial stratified deposits, the Floral Aquifer, the Judith River Aquifer and in vertical cross-sections are conducted for the years 1979, 1986, 1995 and 2019. Analysis of the base case model indicates that after 50 years of simulated brine transport, the contaminant plume migrated past the freshwater bypass ditch in the surficial stratified deposits and infiltrates the Floral Aquifer reaching concentrations in excess of 100 g/L.
Sensitivity studies indicate that the engineered containment devices are ineffective at inhibiting brine plume migration. These studies also show that brine mounding in the tailings pile is a critical control on plume migration to the Floral Aquifer and in vertical section. Varying the coefficient of tortuosity has little effect on brine migration
The effects of plasmid DNA and immunostimulatory CpG motifs on immune surveillance in sheep lymph nodes
This Ph.D. dissertation examined the effects of bacterial DNA on immune surveillance in ovine lymph nodes (LN). The first study identified long-term changes in lymph nodes following exposure to plasmid DNA. Treated lymph nodes were heavier and had larger medullary areas. Furthermore, medullary cord thickness and medullary sinus width as well as germinal center size and number were increased in plasmid treated lymph nodes.
To determine whether bacterial DNA altered cell trafficking through lymph nodes, the efferent lymphatic of the prescapular LN of sheep was cannulated and cells were collected. Intradermal injection of as little as 4 ìg of plasmid DNA
expressing the green fluorescent protein of jellyfish (eGFP) caused a marked increase in the cell trafficking through the prescapular lymph node. A dose-Âdependent facet existed for this response, as the increase in cell trafficking response persisted longer with 40 ìg or 400 ìg of plasmid-eGFP than with 4 ìg. This increased cell trafficking was independent of green fluorescent protein expression as both pCAN1-eGFP and pCAN1 induced similar responses.
Increased cell traffic induced by bacterial DNA was further characterized by determining whether bacterial DNA form was critical for this response. Treatment with intact plasmid (circular) DNA induced the greatest increase in cell traffic. In contrast, when plasmid DNA was digested with restriction enzymes into linear fragments of DNA, then cell trafficking was not significantly increased.
Numerous studies have shown that immunostimulatory guanosine-cytosine (CpG) motifs activate cells in vitro and can improve protective immune responses in vivo. Therefore we tested the hypothesis that the presence of immunostimulatory CpG motifs within plasmids was responsible for altering cell trafficking. It was shown that plasmids with added immunostimulatory CpG sequences affected cell trafficking in a dose-dependent manner. The injection of 40 ìg pBISIA-88 caused an increase in cell trafficking while injecting 400 ìg pBISIA-88 failed to increase cell flow above control levels.
Analysis of cell populations collected in efferent lymph gives insight into treatment effects on immune surveillance. This is well-studied following treatment with antigen and in general, antigen induces a selective movement of cells into lymph that occurs 24 hours post-treatment. In contrast, plasmid DNA induced a
rapid, non-selective movement of lymphocytes through the lymph node, suggesting that bacterial DNA and antigen may affect cell trafficking by different mechanisms and thereby have distinct effects on immune surveillance.
Short-term effects of bacterial DNA on lymph node architecture and cellular composition were also investigated to determine whether an increase in cell trafficking was associated with structural changes within the lymph node. While it was shown that bacterial DNA induced changes within a lymph node, including an increased number of germinal centers and an increased frequency of CD72+CD21+ B cells, these changes were not correlated to increased cell trafficking.
In summary, bacterial DNA altered immune surveillance in sheep lymph nodes by changing cell traffic and lymph node architecture and composition. Many of these responses differed from responses observed by others following antigen treatment. The present observations suggest that bacterial DNA can function as an
important signal to modulate immune surveillance and host responses to infections by pathogens
Catheterization of Intestinal Loops in Ruminants
The intestine is a complex structure that is involved not only in absorption of nutrients, but also acts as a barrier between the individual and the outside world. As such, the intestine plays a pivotal role in immunosurveillance and protection from enteric pathogens. Investigating intestinal physiology and immunology commonly employs 'intestinal loops' as an experimental model. The majority of these loop models are non-recovery surgical procedures that study short-term (<24 hr) changes in the intestine (1-3). We previously created a recovery intestinal loop model to specifically measure long-term (<6 mo) immunological changes in the intestine of sheep following exposure to vaccines, adjuvants, and viruses (4). This procedure localized treatments to a specific 'loop', allowing us to sample this area of the intestine. A significant drawback of this method is the single window of opportunity to administer treatments (i.e. at the time of surgery). Furthermore, samples of both the intestinal mucosa and luminal contents can only be taken at the termination of the project. Other salient limitations of the above model are that the surgical manipulation and requisite post-operative measures (e.g. administration of antibiotics and analgesics) can directly affect the treatment itself and/or alter immune function, thereby confounding results. Therefore, we modified our intestinal loop model by inserting long-term catheters into the loops. Sheep recover fully from the procedure, and are unaffected by the exteriorized catheters. Notably, the establishment of catheters in loops allows us to introduce multiple treatments over an extended interval, following recovery from surgery and clearance of drugs administered during surgery and the post-operative period
Non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses
<p>Abstract</p> <p>Background</p> <p>The development of efficacious alternatives to antimicrobial growth promoters (AGP) in livestock production is an urgent issue, but is hampered by a lack of knowledge regarding the mode of action of AGP. The belief that AGP modulate the intestinal microbiota has become prominent in the literature; however, there is a lack of experimental evidence to support this hypothesis. Using a chlortetracycline-murine-<it>Citrobacter rodentium </it>model, the ability of AGP to modulate the intestinal immune system in mammals was investigated.</p> <p>Results</p> <p><it>C. rodentium </it>was transformed with the tetracycline resistance gene, <it>tet</it>O, and continuous oral administration of a non-therapeutic dose of chlortetracycline to mice did not affect densities of <it>C. rodentium </it>CFU in feces throughout the experiment or associated with mucosal surfaces in the colon (i.e. at peak and late infection). However, chlortetracycline regulated transcription levels of Th1 and Th17 inflammatory cytokines in a temporal manner in <it>C. rodentium</it>-inoculated mice, and ameliorated weight loss associated with infection. In mice inoculated with <it>C. rodentium</it>, those that received chlortetracycline had less pathologic changes in the distal colon than mice not administered CTC (i.e. relative to untreated mice). Furthermore, chlortetracycline administration at a non-therapeutic dose did not impart either prominent or consistent effects on the colonic microbiota.</p> <p>Conclusion</p> <p>Data support the hypothesis that AGP function by modulating the intestinal immune system in mammals. This finding may facilitate the development of biorationale-based and efficacious alternatives to AGP.</p
Comparative variation within the genome of Campylobacter jejuni NCTC 11168 in human and murine hosts
Sherpa Romeo green journal. Open access, distributed under the terms of the Creative Commons Attibution License.Campylobacteriosis incited by
C. jejuni
is a significant enteric disease of human beings. A person working with two reference
strains of
C. jejuni
National Collection of Type Cultures (NCTC) 11168 developed symptoms of severe enteritis including
bloody diarrhea. The worker was determined to be infected by
C. jejuni
. In excess of 50 isolates were recovered from the
worker’s stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on
comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with
a
C. jejuni
NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv) is the genome
sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve
contingency loci conferring phase variations were detected in the genome of
C. jejuni
. Specific and robust single nucleotide
polymorphism (SNP) changes in the human host were also observed in two loci (Cj0144c, Cj1564). In mice inoculated with
an isolate of
C. jejuni
NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci,
mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in
the human host reverted in mice. Genetic variations occurring in the genome of
C. jejuni
in mice corresponded to increased
densities of
C. jejuni
cells associated with cecal mucosa. In conclusion,
C. jejuni
NCTC 11168-GSv was found to be highly
virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were
selected for in the genome of
C. jejuni
, and many were not maintained in mice. Information obtained in the current study
provides new information on host-specific genetic adaptation by
C. jejuni
.Ye
Considerations in Surgical Management of Pediatric Obstructive Sleep Apnea: Tonsillectomy and Beyond
Obstructive sleep apnea (OSA) is an increasingly recognized disorder with a reported incidence of 5.7% in children. Tonsillectomy (with or without adenoidectomy) in pediatric OSA in otherwise healthy non-obese children has a success rate of approximately 75%. However, the cure rate reported for all children undergoing tonsillectomy varies from 51% to 83%. This article reviews the history of tonsillectomy, its indications, techniques, various methods, risks, and successes. The article also explores other surgical options in children with residual OSA post-tonsillectomy
The Effects of Plasmid DNA and Immunostimulatory CpG Motifs on Immune Surveillance in Sheep Lymph Nodes
This Ph.D. dissertation examined the effects of bacterial DNA on immune surveillance in ovine lymph nodes (LN). The first study identified long-term changes in lymph nodes following exposure to plasmid DNA. Treated lymph nodes were heavier and had larger medullary areas. Furthermore, medullary cord thickness and medullary sinus width as well as germinal center size and number were increased in plasmid treated lymph nodes.To determine whether bacterial DNA altered cell trafficking through lymph nodes, the efferent lymphatic of the prescapular LN of sheep was cannulated and cells were collected. Intradermal injection of as little as 4 ìg of plasmid DNA expressing the green fluorescent protein of jellyfish (eGFP) caused a marked increase in the cell trafficking through the prescapular lymph node. A dose-dependent facet existed for this response, as the increase in cell trafficking response persisted longer with 40 ìg or 400 ìg of plasmid-eGFP than with 4 ìg. This increased cell trafficking was independent of green fluorescent protein expression as both pCAN1-eGFP and pCAN1 induced similar responses.Increased cell traffic induced by bacterial DNA was further characterized by determining whether bacterial DNA form was critical for this response. Treatment with intact plasmid (circular) DNA induced the greatest increase in cell traffic. In contrast, when plasmid DNA was digested with restriction enzymes into linear fragments of DNA, then cell trafficking was not significantly increased. Numerous studies have shown that immunostimulatory guanosine-cytosine (CpG) motifs activate cells in vitro and can improve protective immune responses in vivo . Therefore we tested the hypothesis that the presence of immunostimulatory CpG motifs within plasmids was responsible for altering cell trafficking. It was shown that plasmids with added immunostimulatory CpG sequences affected cell trafficking in a dose-dependent manner. The injection of 40 ìg of pBISIA-88 caused an increase in cell trafficking while injecting 400 ìg pBISIA-88 failed to increase cell flow above control levels.Analysis of cell populations collected in efferent lymph gives insight into treatment effects on immune surveillance. This is well-studied following treatment with antigen and in general, antigen induces a selective movement of cells into lymph that occurs 24 hours post-treatment. In contrast, plasmid DNA induced a rapid, non-selective movement of lymphocytes through the lymph node, suggesting that bacterial DNA and antigen may affect cell trafficking by different mechanisms and thereby have distinct effects on immune surveillance.Short-term effects of bacterial DNA on lymph node architecture and cellular composition were also investigated to determine whether an increase in cell trafficking was associated with structural changes within the lymph node. While it was shown that bacterial DNA induced changes within a lymph node, including and increased number of germinal centers and an increased frequency of CD72*CD21* B cells, these changes were not correlated to increased cell trafficking.In summary, bacterial DNA altered immune surveillance in sheep lymph nodes by changing cell traffic and lymph node architecture and composition. Many of these responses differed from responses observed by others following antigen treatment. The present observations suggest that bacterial DNA can function as an important signal to modulate immune surveillance and host responses to infections by pathogens
Long-Term Catheterization of the Intestinal Lymph Trunk and Collection of Lymph in Neonatal Pigs
MOESM1 of Impacts of resistant starch and wheat bran consumption on enteric inflammation in relation to colonic bacterial community structures and short-chain fatty acid concentrations in mice
Additional file 1. Supplemental tables and figure
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