Publications by authors named "Emily Graff"

The mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat color genes, there is no apparent homolog for in other mammals. We show that the is caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of the ( ) gene.

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  • ADT-1004 is a new oral prodrug that effectively inhibits tumor growth and RAS activation in pancreatic ductal adenocarcinoma (PDAC) models without causing significant toxicity.
  • It works by blocking ERK phosphorylation in tumor cells, showing effectiveness against various KRAS mutations and increasing immune cell presence in the tumor microenvironment.
  • ADT-1004’s broad antitumor activity and selectivity for KRAS mutant tumors make it a promising candidate for clinical trials in treating PDAC, potentially outperforming existing KRAS inhibitors.
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Fibroblast growth factors (FGFs) are a group of structurally homologous yet functionally pleiotropic proteins. Canonical and intracellular FGFs have primarily autocrine or paracrine effects. However, the FGF19 subfamily, composed of FGF15/19, FGF21, and FGF23, act as endocrine hormones that regulate bile acid, metabolic, and phosphorus homeostasis, respectively.

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  • Microbial population structures in fecal samples are crucial for gut microbiome research and disease diagnosis, with two main collection methods: fecal loop and litter box.
  • A study analyzed fecal samples from 10 cats using both methods, revealing that the fecal loop method had a lower yield of microbial DNA, but no major differences in contamination or microbial diversity between the two.
  • The findings suggest that collecting fecal samples from the litter box within 6 hours post-defecation is a reliable and effective method for microbiome studies.
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Alzheimer's disease (AD) is characterized by brain plaques, tangles, and cognitive impairment. AD is one of the most common age-related dementias in humans. Progress in characterizing AD and other age-related disorders is hindered by a perceived dearth of animal models that naturally reproduce diseases observed in humans.

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  • * In a study, obese male-neutered cats were given an FGF21 mimetic or saline for 14 days, showing significant weight loss (~5.93%) in the FGF21 group and some positive trends in liver health.
  • * The research indicates that FGF21 may help in managing obesity in cats, but more studies are needed to explore its effects on related liver conditions.
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Nonalcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), is the most common chronic liver disease. Yet, the molecular mechanisms for the progression of steatosis to NASH remain largely undiscovered. Thus, there is a need for identifying specific gene and pathway changes that drive the progression of NAFLD.

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Background: Fecal specimens are critical for disease screening, diagnosis, and gut microbiome research. For domestic cats, lubricants are often necessary to obtain a sufficient quantity of sample. However, the effect of lubrication on feline microbiome analysis has not been assessed.

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Objective: To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses.

Animals: 6 healthy geldings.

Procedures: A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms.

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  • Obesity is a rising issue in domestic cats, linked to various health risks such as insulin resistance and cardiovascular disease, with around 45% of cats affected.
  • A study using whole-genome sequencing on fecal samples from overweight and normal cats revealed a significant reduction in microbial diversity and specific changes in gut bacteria associated with obesity.
  • The findings suggest a dysbiosis in obese cat microbiomes, highlighting potential markers for obesity and providing insights for future treatments as current options like exercise and calorie restriction are limited.
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Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15).

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  • - Adipose tissue expansion is key to understanding metabolic issues, but there isn't a standard method to measure adipocyte (fat cell) size accurately.
  • - The study compared three methods: a classic digital camera approach and two whole-slide analysis methods (one proprietary and one open-source), finding that the classic method identified significantly fewer adipocytes, leading to higher statistical variances.
  • - Whole-slide analysis methods, especially the open-source software, showed higher accuracy and consistency in measuring adipocyte size, making them preferable to avoid errors associated with smaller sample sizes.
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Obesity is an immunometabolic disease associated with chronic inflammation and the dysregulation of pro- and anti-inflammatory cytokines. One hallmark of obesity is reduced concentrations of the anti-inflammatory adipokine, adiponectin. Pharmacologic doses of niacin produce multiple metabolic benefits, including attenuating high-fat diet (HFD)-induced adipose tissue inflammation and increasing adiponectin concentrations.

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Obesity is a major public health concern and overconsumption of unhealthy fats and sugary beverages are contributing factors. Time-restricted feeding can reduce obesity-associated pathophysiological parameters by limiting the time of food consumption; however, the effects of time-restricted sugary water consumption are unknown. To examine whether liquid calorie restriction impacts metabolic health, we measured metabolic parameters in mice provided liquid sugar at various intervals during the active phase.

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Nonalcoholic fatty liver disease (NAFLD) is a very common disorder affecting between 20 and 30% of adults in the United States. However, there is no effective pharmacotherapy for treating NAFLD. Niacin, a water-soluble vitamin (B3), at pharmacological doses, decreases hepatic triglyceride (TG) content in NAFLD through inhibition of diacylglycerol acyltransferase 2, a key enzyme that catalyzes the final step in TG synthesis.

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Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen in a specialized compression chamber leading to hyperoxia. This treatment modality is associated with anti-inflammatory, antioxidant, and healing properties in people and laboratory animals. However, there are relatively few reports that evaluate the effects of HBOT in companion animals.

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Objective: Methionine restriction (MR) decreases inflammation and improves markers of metabolic disease in rodents. MR also increases hepatic and circulating concentrations of fibroblast growth factor 21 (FGF21). Emerging evidence has suggested that FGF21 exerts anti-inflammatory effects.

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Background: Obesity is a major public health concern that can result from diets high in fat and sugar, including sugar sweetened beverages. A proposed treatment for dietary-induced obesity is time-restricted feeding (TRF), which restricts consumption of food to specific times of the 24-hour cycle. Although TRF shows great promise to prevent obesity and the development of chronic disease, the effects of TRF to reverse metabolic changes and the development of NAFLD in animal models of a Western diet with sugary water consumption is not known.

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The hydroxycarboxylic acid receptors (HCA1-3) are a family of G-protein-coupled receptors that are critical for sensing endogenous intermediates of metabolism. All three receptors are predominantly expressed on adipocytes and mediate anti-lipolytic effects. In addition to adipocytes, HCA2 is highly expressed on immune cells, including macrophages, monocytes, neutrophils and dermal dendritic cells, among other cell types.

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nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.

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The western blotting technique for transfer and detection of proteins, named following the discovery of southern and northern blotting for DNA- and RNA-blotting, respectively, has traditionally relied on the use of X-ray films to capture chemiluminescence. Recent advancements use super-cooled charge coupled devices (CCD) cameras to capture both chemiluminescence and fluorescence images, which exhibit a greater dynamic range compared to traditional X-ray film. Chemiluminescence detected by a CCD camera records photons and displays an image based on the amount of light generated as a result of a dynamic chemical reaction.

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Background: Evaluation of the bone marrow is needed for complete staging in dogs with multicentric large-cell lymphoma, but is often omitted in clinical practice.

Objectives: The objective was to determine if routine peripheral blood findings, including microscopic evaluation of blood smears, can predict the presence of bone marrow involvement in dogs with lymphoma.

Methods: Hematologic data including evaluation of blood smears and bone marrow aspirates from 107 dogs newly diagnosed with large-cell lymphoma were retrospectively evaluated.

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  • Researchers created a mouse model (Ca-PBL-SCID) to study the canine immune system by injecting canine lymphocytes into irradiated NSG mice.
  • The engraftment was analyzed using flow cytometry to track different types of canine lymphocytes like helper T cells, cytotoxic T cells, and B cells, showing that certain cells were present as early as day 1 and varied over time.
  • Despite successful engraftment, about 30% of the mice developed anemia and thrombocytopenia between days 28 and 52, indicating the occurrence of graft versus host disease, similar to findings in human models.
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