MOOSE POPULATION DYNAMICS DURING 20 YEARS OF DECLINING HARVEST IN BRITISH COLUMBIA

Licenced harvest of moose (Alces alces) in British Columbia, Canada declined by approximately half over the 20-year period from 1996–2015. To better understand changes in moose populations coinciding with this period of declining harvest, we modelled population dynamics within 31 Game Management Zones (GMZs). We used aerial survey data (180 density and 159 composition surveys) combined with licensed harvest to develop 4 competing statistical models to assess population dynamics based on constant parameters and temporal trends in calf:cow ratios at 6 months, juvenile survival from 6–18 months, or cow survival. The models indicated that moose populations declined (λ < 1) in 7 GMZs (23%) from 1996–2005 and in 22 GMZs (71%) from 2006–2015. Over the 20-year period, the best model was fit with declining trends in calf:cow ratios in 8 GMZs, declining juvenile survival in 6 GMZs, and declining cow survival in 8 GMZs. Population growth rate was slightly reduced in those GMZs where licenced antlerless (cow and calf) hunting occurred but was not considered the primary factor causing population decline. Total licenced bull harvest influenced bull:cow ratios that were significantly lower in 2006–2015 (mean = 37:100) than 1995–2005 (mean = 48:100); significant predictive relationships existed between harvest rates and bull:cow ratios. Provincial moose numbers and harvest were highly correlated (r = 0.81) suggesting that declining harvest was a reaction to declining population trends. We found that the provincial moose population increased 6% from 1996–2005, subsequently declined 32% from 2006–2015, and declined 29% overall during the 20-year study period

Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic helicobacter pyloriInfection

Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to Helicobacter pylori bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse H. pylori SS1 infection model. Following infection, MAIT cells accumulated to high numbers in the gastric mucosa of wild-type C57BL/6 mice, and this was even more pronounced in MAIT TCR transgenic mice or in C57BL/6 mice where MAIT cells were preprimed by Ag exposure or prior infection. Gastric MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated with accelerated gastritis characterized by augmented recruitment of neutrophils, macrophages, dendritic cells, eosinophils, and non-MAIT T cells and by marked gastric atrophy. Similarly treated MR1−/− mice, which lack MAIT cells, showed significantly less gastric pathology. Thus, we demonstrate the pathogenic potential of MAIT cells in Helicobacter-associated immunopathology, with implications for other chronic bacterial infections

Assessment of Helicobacter pylori antioxidant enzymes as therapeutic targets

© 2012 Dr. Andrew William StentHelicobacter pylori is a significant gastric pathogen in humans, with gastritis and gastric neoplasia frequently resulting from chronic colonisation. The organism is reliant on its antioxidant enzyme system for survival, and this thesis proposes that components of this system – namely, the antioxidant enzymes superoxide dismutase (HpSOD), catalase (HpKatA), and thiolperoxidase (HpTpx) - present a viable therapeutic target in H. pylori infection. Using a pET Escherichia coli expression system, recombinant forms of the three enzymes from H. pylori were created and then trialled as vaccine antigens administered with an appropriate adjuvant via systemic and mucosal routes. Moreover, in order to assess for synergistic action, the enzymes were assessed both individually and in combination. These trials demonstrated that superoxide dismutase and thiolperoxidase are protective antigens, but no additional protection was observed with the combination vaccine. The essential requirement for the antioxidant system in H. pylori further led to speculation that inhibition of enzyme function may be an alternative mode of therapy. Monoclonal antibodies directed against the three enzymes were generated via hybridomas derived from hyperimmunised mice. Antibodies were characterised by class and isotype, binding properties and ability to inhibit enzyme function, in order to determine the most promising candidates for therapeutic trials. After demonstrating the presence of systemic antibodies at the gastrointestinal mucosal surface in a mouse trial, the candidate antibodies were administered via intraperitoneal injection to mice infected with H. pylori. Although the antibody therapy did not impair colonisation, there was a significant increase in a number of pro-inflammatory cytokines within gastric tissue following administration of the anti-HpSOD antibody. Investigating further, it was found that incubation of macrophages in the presence of recombinant HpSOD attenuated the cytokine response to lipopolysaccharide. These findings suggested that HpSOD may possess previously undescribed immunosuppressive properties, potentially facilitating long-term colonization. Possible pathway mechanisms are discussed, as well as supportive findings from work on other chronic pathogens

Fluctuation of clinical signs with near-syncopal episodes in a dog with gliomatosis cerebri: a diagnostic challenge

A 2-year-old Bull Mastiff cross Boxer neutered male dog was evaluated because of 2-month history of non-progressive right head tilt and mild vestibular ataxia. MRI of the brain revealed a faint T2W, FLAIR, DWI and ADC heterogenous hyperintense and T1W isointense intra-axial lesion with indistinct margins at the level of the pons and medulla oblongata. The lesion did not show any susceptibility artefact on T2* GRE images or contrast enhancement and CSF analysis was normal. Analysis of the spectra from MRS of the thalamus not promptly available at the time of the MRI study revealed a decreased level of NAA, as seen in people with gliomatosis cerebri. The dog represented 3 weeks later and, on this occasion, displayed left-sided head tilt, left-sided postural reaction deficits and near-syncopal episodes associated with state of confusion. Repeated MRI revealed a larger non-enhancing intra-axial lesion with a more hyperintense signal than previously described. CSF was normal and PCR of CSF for infectious diseases was negative. Thoracic and abdominal computed tomography did not reveal any primary or metastatic process. Immunosuppressive treatment was attempted and the dog remained stable over 5 days, then developed generalized tonic-clonic seizures which led to status epilepticus and death. Histopathology supported the diagnosis of gliomatosis cerebri. Gliomatosis cerebri remains difficult to diagnose ante-mortem, due to the broad age of onset and the variable duration and wide range of clinical signs. The mismatch between MRI findings and clinical presentation, the fluctuating clinical signs with near-syncopal episodes associated with a state of confusion, the presence of an infiltrative brain disease as depicted on MR imaging and a normal CSF analysis, should prompt the clinician to consider possible diagnosis of a widespread infiltrative neoplasm. Although, MRS may help narrow the differential diagnosis in favor of a neoplastic lesion, the overall prognosis remains poor

Risk Factors for Exercise-Associated Sudden Cardiac Death in Thoroughbred Racehorses

Cardiac arrhythmias resulting in sudden cardiac death (SCD) are an important cause of racehorse fatalities. The objective of this study was to determine risk factors for SCD in Thoroughbreds by evaluating a sample with a policy of mandatory post-mortem following racing or training fatalities. Risk factors were compared between case horses with SCD (n = 57) and control horses with other fatal injury (OFI, n = 188) by univariable and multivariable logistic regression. Survival in years for horses with SCD was compared to OFI using the Kaplan–Meier method with log rank test. The following variables were most important in the multiple logistic model: Horses with SCD were more likely to die during training than during racing, SCD (42/57, 74%) vs. OFI (82/188, 44%; odds ratio [OR], 95% confidence interval [CI], 2.5, 1.2–5.4; p = 0.01), had fewer lifetime starts, median (interquartile range [IQR]), SCD (3.0 [0.0–9.0]) vs. OFI (9.0 [0.0–22.8]; OR, 95% CI, 0.96, 0.9–1.0; p = 0.02 and were less likely to be entire (uncastrated) males, SCD 9/57 (16%) vs. OFI (46/188, 25%; OR, 95% CI, 0.47, 0.1–0.9; p = 0.03). Survival in years (median (IQR)) for horses with SCD was 3.6 (3.1–4.4), which was shorter than OFI (4.5 [3.1–6.0], hazard ratio, 95%CI, 1.6,1.2–2.3; p < 0.001). SCD occurs more commonly in training than racing, which suggests exercise intensity is less important in precipitating this fatality. In this study, SCD occurred early in the careers of affected horses

Increased Levels of ER Stress and Apoptosis in a Sheep Model for Pulmonary Fibrosis Are Alleviated by In Vivo Blockade of the KCa3.1 Ion Channel

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease, characterized by progressive damage to the lung tissues. Apoptosis and endoplasmic reticulum stress (ER stress) in type II alveolar epithelial cells (AECs) and lung macrophages have been linked with the development of IPF. Therefore, apoptosis- and ER stress-targeted therapies have drawn attention as potential avenues for treatment of IPF. The calcium-activated potassium ion channel KCa3.1 has been proposed as a potential therapeutic target for fibrotic diseases including IPF. While KCa3.1 is expressed in AECs and macrophages, its influence on ER stress and apoptosis during the disease process is unclear. We utilized a novel sheep model of pulmonary fibrosis to demonstrate that apoptosis and ER stress occur in type II AECs and macrophages in sheep with bleomycin-induced lung fibrosis. Apoptosis in type II AEC and macrophages was identified using the TUNEL method of tagging fragmented nuclear DNA, while ER stress was characterized by increased expression of GRP-78 ER chaperone proteins. We demonstrated that apoptosis and ER stress in type II AECs and macrophages increased significantly 2 weeks after the final bleomycin infusion and remained high for up to 7 weeks post-bleomycin injury. Senicapoc treatment significantly reduced the rates of ER stress in type II AECs and macrophages that were resident in bleomycin-infused lung segments. There were also significant reductions in the rates of apoptosis of type II AECs and macrophages in the lung segments of senicapoc-treated sheep. In vivo blockade of the KCa3.1 ion channel alleviates the ER stress and apoptosis in type II AECs and macrophages, and this effect potentially contributes to the anti-fibrotic effects of senicapoc