Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients.

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Apolipoprotein C-II (APOC2) is an obligatory cofactor for lipoprotein lipase (LPL), the major enzyme catalyzing plasma triglyceride hydrolysis. We have created an apoc2 knockout zebrafish model, which mimics the familial chylomicronemia syndrome (FCS) in human patients with a defect in the APOC2 or LPL gene. In this study, we measured plasma levels of free cholesterol (FC) and cholesterol esters (CE) and found that apoc2 mutant zebrafish have a significantly higher FC to CE ratio (FC/CE), when compared to the wild type. Feeding apoc2 mutant zebrafish a low-fat diet reduced triglyceride levels but not the FC/CE ratio. In situ hybridization and qPCR results demonstrated that the hepatic expression of lecithin-cholesterol acyltransferase (lcat), the enzyme responsible for esterifying plasma FC to CE, and of apolipoprotein A-I, a major protein component of HDL, were dramatically decreased in apoc2 mutants. Furthermore, the FC/CE ratio was significantly increased in the whole plasma and in a chylomicron-depleted fraction of human FCS patients. The FCS plasma LCAT activity was significantly lower than that of healthy controls. In summary, this study, using a zebrafish model and human patient samples, reports for the first time the defect in plasma cholesterol esterification associated with LPL deficiency

Development of a real-time immuno-PCR assay for the quantification of environmental contaminants

This thesis outlines the development of two universal real-time immuno-PCR (RT-iPCR) assays for application in agriculture. The first RT-iPCR was developed for the sensitive quantification of 17β-estradiol in water. Using a universal iPCR method and polyclonal antibodies, 17β-estradiol was accurately quantified at concentrations ranging from 1 pg mL-1 to 10 μg mL-1, with a limit of detection of 0.7 pg mL-1. The RT-iPCR assay provided an 800-fold increase in sensitivity as well as an expanded working range compared to the corresponding enzyme-linked immunosorbent assay. Antibodies were swapped with antibodies specific to P. brassicae for the quantification of clubroot resting spores using the same RT-iPCR assay. P. brassicae resting spores were quantified in the range of 50 to 10 000 spores, with a detection limit of 29 spores. Both RT-iPCR showed equal or improved sensitivity compared to other published analytical methods, with expanded linear working ranges and high-throughput capabilities.Agriculture and Agri-Foods Canad

Development of non-linear guidance algorithms for asteroids close-proximity operations

In this paper, we discuss non-linear methodologies that can be employed to devise real-time algorithms suitable for guidance and control of spacecrafts during asteroid close-proximity operations. Combination of optimal and sliding control theory provide the theoretical framework for the development of guidance laws that generates thrust commands as function of the estimated spacecraft state. Using a Lyapunov second theorem one can design non-linear guidance laws that are proven to be globally stable against unknown perturbations with known upper bound. Such algorithms can be employed for autonomous targeting of points of the asteroid surface (soft landing , Touch-And-Go (TAG) maneuvers). Here, we theoretically derived and tested the Optimal Sliding Guidance (OSG) for close-proximity operations. The guidance algorithm has its root in the generalized ZEM/ZEV feedback guidance and its mathematical equations are naturally derived by a proper definition of a sliding surface as function of Zero-Effort-Miss and Zero-Effort-Velocity. Thus, the sliding surface allows a natural augmentation of the energy-optimalguidance via a sliding mode that ensures global stability for the proposed algorithm. A set of Monte Carlo simulations in realistic environment are executed to assess the guidance performance in typical operational scenarios found during asteroids close-proximity operations. OSG is shown to satisfy stringent requirements for asteroid pinpoint landing and sampling accuracy

Advancing the Sunulator Analysis Tool to Support Australian Solar Energy Initiatives

In partnership with the Alternative Technology Association (ATA), our team developed the groundwork to advance the Sunulator , a program ATA designed to analyse feasibility of Australian solar energy initiatives. We provided a set of representative locations and data to be integrated into Sunulator\u27s programming, necessary to expand its functionality to all Australian states and territories. We then offered interface and function recommendations for Sunulator based on user feedback gathered via interviews and online surveys

Salivary pH as a marker of plasma adiponectin concentrations in Women

<p>Abstract</p> <p>Background</p> <p>Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status.</p> <p>Method</p> <p>Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH.</p> <p>Results</p> <p>Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p < 0.001). The proportion of the variance of plasma adiponectin levels explained by the salivary pH (R²) was 10.8% (p < 0.001). Plasma adiponectin levels progressively increased across salivary pH quartiles (p = 0.005).</p> <p>Conclusions</p> <p>These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.</p

The lipoprotein/lipid profile is modulated by a gene–diet interaction effect between polymorphisms in the liver X receptor-α and dietary cholesterol intake in French-Canadians

Genetic and nutritional factors interact together and modulate the plasma lipid profile. We identified variations in the gene encoding the liver X receptor α (LXRα) and investigated their effects on the plasma lipoprotein/lipid profile. We also examined whether the association between cholesterol intake and plasma lipid profile was modulated by LXRα variants. The LXRα gene was sequenced in thirty-five French-Canadian men with high plasma total cholesterol (>5·0 mmol/l) and LDL-cholesterol (>3·5 mmol/l) concentrations. Dietary cholesterol was obtained from a food-frequency questionnaire. The LXRα c.-115G>A, c.-840C>A and c.-1830T>C genotypes were determined by direct sequencing in 732 subjects. Molecular screening of the LXRα gene revealed sixteen variants. Genotypes c.-115G>A, c.-840C>A and c.-1830T>C (rare allele frequency of 14·3 %, 14·2 % and 11·0 %, respectively) were analysed further. Plasma total cholesterol concentrations were higher in carriers of the -115A, -840A and -1830C allele, compared with the -115G/G, -840C/C and -1830T/T homozygotes (P ≤ 0·05). In a model including the c.-115G>A polymorphism, cholesterol intake, the interaction term c.-115G>A × cholesterol intake (mg/d) and covariates, LXRα-115G>A explained 1·8 % and 2·1 % of the variance in total cholesterol and LDL-cholesterol concentrations (P = 0·02 and P = 0·01), whereas the interaction term explained 2·9 % (P = 0·002) and 2·8 % (P = 0·005), respectively. When subjects were divided into four groups according to the median of cholesterol (290·8 mg) and -115G>A genotypes, high cholesterol intake was associated with higher cholesterol levels in -115A carriers. Similar results were observed for c.-840C>A and c.-1830T>C. These results suggest that cholesterol intake interacts with LXRα variants to modulate the plasma lipid profile

Saguenay Youth Study : a multi-generational approach to studying virtual trajectories of the brain and cardio-metabolic health

This paper provides an overview of the Saguenay Youth Study (SYS) and its parental arm. The overarching goal of this effort is to develop trans-generational models of developmental cascades contributing to the emergence of common chronic disorders, such as depression, addictions, dementia and cardio-metabolic diseases. Over the past 10 years, we have acquired detailed brain and cardio-metabolic phenotypes, and genome-wide genotypes, in 1029 adolescents recruited in a population with a known genetic founder effect. At present, we are extending this dataset to acquire comparable phenotypes and genotypes in the biological parents of these individuals. After providing conceptual background for this work (transactions across time, systems and organs), we describe briefly the tools employed in the adolescent arm of this cohort and highlight some of the initial accomplishments. We then outline in detail the phenotyping protocol used to acquire comparable data in the parents

Size-dependent rheology of type-I collagen networks

We investigate the system size dependent rheological response of branched type I collagen gels. When subjected to a shear strain, the highly interconnected mesh dynamically reorients, resulting in overall stiffening of the network. When a continuous shear strain is applied to a collagen network, we observe that the local apparent modulus, in the strain-stiffening regime, is strongly dependent on the gel thickness. In addition, we demonstrate that the overall network failure is determined by the ratio of the gel thickness to the mesh size. These findings have broad implications for cell-matrix interactions, the interpretation of rheological tissue data, and the engineering of biomimetic scaffolds.Comment: 3 pages, 4 figures, to appear in Biophysical Journal Letters, September 201