Matching Items (58)

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Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

Description

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H[subscript 2]O[subscript 2]) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

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  • 2015-06-09

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Growing Mya-1 T Cells for Adoptive Immunotherapy

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CD4+CD25+ FOXP3+ cells are recognized as the most reliable regulatory T cell subset. However, the intracellular nature of the FOXP3 transcription factor limits its use for the isolation or selection

CD4+CD25+ FOXP3+ cells are recognized as the most reliable regulatory T cell subset. However, the intracellular nature of the FOXP3 transcription factor limits its use for the isolation or selection of viable regulatory T cells for adoptive immunotherapy. Nuclear localization of FOXP3 has been more strongly associated with induced regulatory T cell (Treg) function than increased expression of FOXP3 alone. Several different cell culture methods and T cell activation techniques can induce increased expression of FOXP3 in a variety of T cell models, but Rapamycin (an mTOR inhibitor) was recently shown to differentially induce nuclear localization of FOXP3 when compared with IL-10 and TGFβ. Feline Tregs have been well characterized and share many of the phenotypic and functional characteristics of murine and human Tregs. We cultured feline Mya-1 T cells in conditions that would differentially promote effector or regulatory phenotypes and correlated nuclear localization of FOXP3 with other quantitative morphologic features using imaging flow cytometry. We compared the morphologic features of cells with high intra-nuclear concentrations of FOXP3 cultured without IL-2, with IL-2, and with IL-2 and Rapamycin before and after non-specific antigenic stimulation with Concanavalin-A. This analysis may help identify a population of pure regulatory T cells that would be more likely to maintain regulatory function following in-vitro expansion and activation. Furthermore, the feline T cell model could help elucidate important differences between murine and human Treg cells that would further translational efforts in adoptive immunotherapy. Now, we ask if nuclear localization of FOXP3 could be used to identify other morphologic differences between activated effector and regulatory T cells using a feline T cell line.

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  • 2018-05

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Doxorubicin Induced Cardiotoxicity and High Intensity Aerobic Exercise

Description

Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation

Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and ADP concentrations and decreased ATP concentration. mTOR is active in cellular growth and remodeling. These proteins are cellular kinases with cascades that are influenced by one another. Exercise preconditioning may diminish the cardiotoxic effects on these proteins. Female, Ovariectomized Sprague-Dawley rats (N=33) were randomized to: Exercise+DOX (EX+DOX, n=9); Exercise+Vehicle (EX+VEH, n=8); Sedentary+DOX (SED+DOX, n=8); and Sedentary+Vehicle (SED+VEH, n=8) groups. DOX (4mg/kg) or VEH (saline) intraperitoneal injections were administered bi-weekly (cumulative dose of 12mg/kg). VEH animals received body weight matched volumes of saline based on dosing in animals receiving DOX. Exercise (EX) animals underwent high intensity (85-95% VO2 peak) interval training (HIIT) (4x4 min bouts) separated by low intensity (50-60% VO2max) intervals (2 min bouts) 5 days per week. Exercise began 1 week prior to the first injection and was continued throughout the study. Rats were euthanized 5 days after the last injection. Left ventricular tissue was isolated, processed into lysate and used for western blot analyses [2x2 ANOVA; (α=0.05)]. DOX induced significant phosphorylation of Akt and mTOR (p=0.035; p=0.032) only in SED+DOX rats, but unchanged in EX+DOX rats. No significant differences (p=0.374) in AMPK phosphorylation were observed between groups. Exercise Preconditioning prevents some DOX-induced changes in the cardiac mTOR signaling pathway implicated in pathological remodeling.

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  • 2017-05

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Is it Hunger or Hormones? Association of Plasma Ghrelin Levels with Eating Behaviors and Weight Cycling History in Obese and Overweight Women

Description

Weight cycling (WC) is characterized by repeated bouts of weight loss followed by regain. WC has been associated with a number of adverse health consequences and is a risk factor

Weight cycling (WC) is characterized by repeated bouts of weight loss followed by regain. WC has been associated with a number of adverse health consequences and is a risk factor for cardiovascular disease. Body weight regulation is complex. Little is known about why women who intentionally lose weight are so likely to regain their weight back. Humans are motivated by a variety of psychological pressures as well as physiological stimuli that influence eating behaviors and weight control. One of the complex factors that has been shown to predict weight regain, in weight-reduced individuals, is hunger. Ghrelin is a known gastrointestinal hormone that rises during weight loss and is a strong trigger of hunger and increased appetite. Increased ghrelin levels have been associated with disordered eating behaviors and active weight loss. The Three Factor Eating Questionnaire (TFEQ-R18) describes elements that may affect hunger and satiety. These factors are: cognitive restraint (CR, defined as regulating food intake because of weight maintenance), uncontrolled eating (UE, defined as difficulty in regulating eating), and emotional eating (EE, refers to the tendency to eat more than needed because of mood state). Objective: The purpose of this study was to explore the associations of fasting plasma ghrelin with eating behaviors and weight cycling in overweight and obese women. Methods: This is a cross-sectional observation of women aged 20-60 years who completed a Weight and Lifestyle Inventory (WALI) and the TFEQ-R18. Women provided a 12-h fasting blood sample and plasma ghrelin was measured using a commercial radioimmunoassay (ELISA kit Cat# EZGRA-88k). Intra- and inter-assay CVs were 88.4% + 13.8% and 84.4% + 8.4% respectively. Descriptive data were computed and Pearson correlations were assessed adjusting for age and body weight (SPSS, v23). Results: A WC Index (WCI) was computed as number of WC reported x the amount of weight lost per cycle. 61 women (mean age: 39.3 + 11 yr; BMI: 31.4 + 7; WCI: 70 + 60; range = 0 to 253) completed questionnaires. Ghrelin was significantly and negatively correlated to weight (R= -0.25, P = 0.03), BMI (R= -0.32, P = .006), UE (R = -0.29, p = 0.02), and EE (R = -0.29, p = 0.04). Ghrelin was not significantly related to WCI. WCI was not significantly correlated with any TFEQ-18 subscales. Conclusion: In this observational study, lower ghrelin was associated with higher UE and EE. Thus physiological hunger sensations from ghrelin secretion, is not a likely stimulus of eating behavior in these women. There are a host of psychological triggers, such as stress, loneliness, guilt, anger etc. that may enhance eating. Future research will need to explore what psychological triggers influence eating behavior and why obese women are resistant to the powerful physiological hunger cues of ghrelin.

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  • 2016-05

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Effects of urbanization on the nutritional physiology and gut microbiome of house sparrows (Passer domesticus)

Description

The natural habitat as well as the food abundance and food sources of avian species is changing due to urbanization, and such anthropocentric actions could lead to devastating impacts on

The natural habitat as well as the food abundance and food sources of avian species is changing due to urbanization, and such anthropocentric actions could lead to devastating impacts on bird populations. As changes in distribution and nutrition are thought to be related to the gut microbiome, the goal of this study was to determine the relationship between nutritional markers, including body mass, gizzard mass, triglycerides, free glycerol and glycogen, and the gut microbiome in urban and rural house sparrows (Passer domesticus), to understand physiological differences between urban and rural house sparrows. We hypothesized that increased access to human refuse, through urbanization, may significantly alter the gut microbiome and thus, the nutritional physiology-the effects of foods on metabolism-of urban birds. Fecal samples were collected from rural (n=13) and urban (n=7) birds to characterize the gut microbiome and plasma samples were collected to measure nutritional markers using commercially available kits. Following euthanasia, liver samples were collected to measure triglycerides, free glycerol and glycogen. While there were no significant differences in circulating triglycerides or free glycerol between populations, urban birds had significantly greater blood glucose (p=0.046) compared to rural birds, when normalized to body mass. Additionally, rural birds had significantly more plasma uric acid (p=0.016) and liver free glycerol (p=0.044). Higher blood glucose suggests greater accessibility to carbohydrates in an urban setting or higher rates of gluconeogenesis. Uric acid is a byproduct of purine catabolism and a potent antioxidant. Thus, higher uric acid suggests that rural birds may utilize more protein for energy. Finally, higher liver free glycerol in rural birds suggests they metabolize more fat but could also indicate that urban birds have greater glycerol gluconeogenesis, which may consume free glycerol resulting in higher glucose concentrations. However, the current study does not provide evidence for this as there were no significant differences in the gluconeogenic enzyme PEPCK-C levels between urban and rural house sparrows (p= 0.165). While triglyceride, glucose, and uric acid levels differed between urban and rural birds, there were additionally no significant differences in the gut microbiome, indicating that although nutritional physiology can be affected by distribution and varying food availability and sources, differences in the gut microbiome are evident at the phyla level.

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Date Created
  • 2018-05

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Exposure to Artificial Light at Night Increases Innate Immunity During Development in a Precocial Bird

Description

Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it

Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it may significantly alter the seasonal/daily physiological rhythms or behaviors of animals. There has been considerable interest in the impacts of ALAN on health in humans and lab animals, but most such work has centered on adults and we know comparatively little about effects on young animals. We exposed 3-week-old king quail (Excalfactoria chinensis) to a constant overnight blue-light regime for 6 weeks and assessed weekly bactericidal activity of plasma against Escherichia coli - a commonly employed metric of innate immunity in animals. We found that chronic ALAN exposure significantly increased immune function, and that this elevation in immune performance manifested at different developmental time points in males and females. These results counter the pervasive notion that overnight light exposure is universally physiologically harmful to diurnal organisms and indicate that ALAN can provide sex-specific, short-term immunological boosts to developing animals.

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Date Created
  • 2017-12

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Lenalidomide modulates high fat diet induced inflammation in human vascular smooth muscle cells

Description

Vascular inflammation plays a key role in the development and progression of cardiovascular disease. High fat diet has been associated with cardiovascular risk (1). Therefore, as poor nutrition and poor

Vascular inflammation plays a key role in the development and progression of cardiovascular disease. High fat diet has been associated with cardiovascular risk (1). Therefore, as poor nutrition and poor diet become more widespread, the number of people at risk to cardiovascular disease increases. We hypothesized that using the cancer drug lenalidomide would reverse the inflammation caused by high fat conditions. Human aortic vascular smooth muscle cells were used as an in vitro model to analyze the effect of lenalidomide on high fat diet induced inflammation. Palmitate, a saturated fatty acid was used to induce inflammation. Since lenalidomide has been shown to inhibit cytokine production and attenuate oxidative stress, we investigated whether lenalidomide alters select markers of vascular inflammation in vascular smooth muscle treated with high fat exposure using palmitate. These markers were cyclooxygenase-2 (COX-2) protein levels, TNF-α pro-inflammatory cytokine levels, and superoxide ions. Lenalidomide (5 µM) reversed COX-2 protein expression in cells exposed to high fat conditions (100 µM palmitate). In conclusion, high fat exposure elicits an inflammatory response in cultured primary human vascular smooth muscle, but this response appears to be independent of local cytokine or ROS production. Lenalidomide, although effective at reversing palmitate-induced COX-2, alone augments the pro-inflammatory mediators, COX-2 and TNF-α as well as promotes oxidative stress independent of high fat exposure in human vascular smooth muscle cells.

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  • 2017-12

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The Effect of Glucocorticoids on Insulin Resistance in Rat Skeletal Muscle via TXNIP

Description

Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has

Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2
diabetes. Experiments including polymerase chain reaction, western blotting, and glycogen
synthase analysis were conducted to determine if exposure to higher doses of dexamethasone, a
glucocorticoid, induces insulin resistance in cultured rat skeletal muscle via interaction with
thioredoxin-interacting protein (TXNIP). Treatment with dexamethasone was shown to cause
mild increases in TXNIP while a definitive increase or decrease in insulin signaling was unable
to be determined.

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Date Created
  • 2020-05

Comparing Nutritional Physiology and Bioavailable Nutrients between Rural and Urban Populations of Callipepla gambelii

Description

This study is an exploration of the nutritional physiology of Gambel's quail, Callipepla gambelii, in terms of the comparison of rural and urban area populations of this gallinaceous species, and

This study is an exploration of the nutritional physiology of Gambel's quail, Callipepla gambelii, in terms of the comparison of rural and urban area populations of this gallinaceous species, and the employment of in situ study by design. The health of quail populations is of interest as a resource to recreational enthusiasts, hunters, stakeholders, as well as agencies charged with their management. Quail are the only resident small avian game species known to be native to the southwest that is depended upon by management agencies for recreational opportunities. The condition of the Gambel's quail populations determine regulatory actions with respect to recreational quailing opportunities and these quail represent a species which shows adjustment to human expansion. The combination of morphologic, physical, and plasma nutrient data gathered from samples during this study are hypothesized to show a difference between rural and urban populations of C. gambelii. The hypothesis is that urban quail will display morphological differences, and nutrient differences that are crucial to quail fitness, therefore, potential selective differences. Ground and ambient air temperatures are hypothesized to be higher in urban areas andthus these measurements were taken for site comparison. Plasma nutrient concentrations between rural and urban populations of adult male Gambel's quail were compared for potential existing variations in nutrition. The blood nutrient assays are expected to display increased plasma concentrations of constituents such as glucose, lipids, and proteins, which are known to be involved in growth, reproductive success, and general fitness in the urban quail populations. Morphological data was collected to examine the potential differences in the physical attributes of the sampled quail. A fitness advantage in male Gambel's quail living within urban areas is hypothesized to be associated with differences in plasma nutrients and morphology. The potentially differing plasma nutrients in samples of the C. gambelii in urban versus rural environments is believed to be affected by, and to indicate, differing nutrient availability. Body mass and length, chest circumference as well as skin temperatures were measured to assess potential differences in these outward physical attributes. The urban quail are hypothesized to have reproductive and/or natural selective advantages where their measured morphology may show physical size differences. Differences in the physical attributes of the male Gambel's quail that live in urban areas may be supported through measured morphologic attributes.

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Date Created
  • 2015-12

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Effects of Urbanization and Sex on Color and Disease in the House Finch (Haemorhous mexicanus)

Description

Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a

Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal expression in female animals. We measured carotenoid-based plumage coloration and coccidian (Isospora spp) parasite burden in desert and city populations of house finches to examine urban impacts on male and female health and attractiveness. In earlier work, we showed that male house finches are less colorful and more parasitized in the city, and we again detected that pattern in this study for males. However, though city females are also less colorful than their rural counterparts, we found that rural females were more parasitized. Also, regardless of sex and unlike rural birds, more colorful birds in the city were more heavily infected with coccidia. These results show that urban environments can disrupt signal honesty in female animals and highlight the need for more studies on how cities affect disease and condition-dependent traits in both male and female animals.

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Date Created
  • 2016-05