The myeloid-specific transcription factor, CCAAT/enhancer-binding protein epsilon (C/EBPε) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPε-deficient mice are severely affected by infection with S. aureus, and C/EBPε...
This paper presents a brief discussion on the phenomenon of exercise-induced insulin sensitization, including the effects of exercise on insulin-stimulated glucose uptake and potential mechanisms mediating these effects. Originally created for KIN 481 (Writing Intensive Curriculum course).
We report the first systems biology investigation of regulators controlling arterial plaque macrophage transcriptional
changes in response to lipid lowering in vivo in two distinct mouse models of atherosclerosis regression. Transcriptome
measurements from plaque macrophages from the Reversa mouse were integrated with measurements from an aortic
transplant-based mouse model of...
Age is a recognized risk factor for amyotrophic lateral sclerosis (ALS), a paralytic disease characterized by progressive loss of motor neurons and neuroinflammation. A hallmark of aging is the accumulation of senescent cells. Yet, the pathogenic role of cellular senescence in ALS remains poorly understood. In rats bearing the ALS-linked...
Pseudocapillaria tomentosa is a nematode that parasitizes Danio rerio, causing major disease that affects the economic commodities of fish industries and destroys experimental results at research facilities. There is a critical need for a rapid and sensitive diagnostic assay to test for P. tomentosa in D. rerio populations. PCR primers...
Excess fat intake can increase lipid oxidation and expression of mitochondrial proteins, indicating remodeling of the mitochondrial proteome. Yet intermediates of lipid oxidation also accumulate, indicating a relative insufficiency to completely oxidize lipids. We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes in lipid oxidation following high-fat...
To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint....
The gut microbiome influences human disease including Type 2 diabetes, obesity and metabolic syndrome and interacts with the innate immune system. The human cathelicidin antimicrobial peptide (hCAMP), an important component of the innate immune system, and vitamin D and xanthohumol, a natural compound found in beer hops, regulate its expression....
The Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) began development of a broad-spectrum antiviral countermeasure against deliberate use of high-consequence viral hemorrhagic fevers (VHFs) in 2016. The effort featured comprehensive preclinical research, including laboratory testing and rapid advancement of lead molecules into nonhuman primate (NHP)...
Altered skeletal muscle fat metabolism is linked to changes in skeletal muscle insulin sensitivity. Whereby the accumulation of bioactive signaling lipids (i.e., diacylglycerols and ceramides) within skeletal muscle are negatively associated with insulin sensitivity and the exercise-induced changes to fatty acid trafficking are related to improved skeletal muscle insulin action....
Spent hemp biomass (SHB) is a byproduct of the cannabinoid oil production which currently is not approved as a livestock feed ingredient. The 2018 Farm Bill defined the difference between varieties of the cannabis sativa plant as either non-hemp cannabis or hemp which has equal to or less than 0.3...
Human epidermal growth factor receptor 2 (HER2), a member of the receptor tyrosine kinase (RTK) family, is frequently dysregulated in a variety of cancers. Overexpression of the receptor leads to increased cell proliferation and resistance to cell death due to downstream signaling effects. Proteasomal degradation of HER2 results in the...
A significant proportion of the population of the United States suffers from chronic pain, a category of disease that is not yet well understood by healthcare professionals. A majority of this group is made up of women; individuals who often have to convince healthcare professionals that their symptoms are real...
Background: Antimicrobial peptides (AMPs) are synthesized and secreted by immune and epithelial cells that are constantly exposed to environmental microbes. AMPs are essential for barrier defense and deficiencies lead to increased susceptibility to infection. In addition to their ability to disrupt the integrity of bacterial, viral and fungal membranes, AMPs...
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:803-811. doi 10.1172/JCI30142.
37. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH
While monocytes are vital for host defense against pathogens, in cases of non-resolving inflammation, monocytes and their differentiated progeny can secrete tissue-damaging factors, present auto-antigens, and promote the inflammatory response. In this study, a systems biology approach was used to map human monocyte gene regulatory regions by integrating expression quantitative...
While monocytes are vital for host defense against pathogens, in cases of non-resolving inflammation, monocytes and their differentiated progeny can secrete tissue-damaging factors, present auto-antigens, and promote the inflammatory response. In this study, a systems biology approach was used to map human monocyte gene regulatory regions by integrating expression quantitative...
Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The...
Microglia and reactive astrocytes accumulate in the spinal cord of rats expressing the Amyotrophic lateral sclerosis (ALS)-linked SOD1ᴳ⁹³ᴬ mutation. We previously reported that the rapid progression of paralysis in ALS rats is associated with the appearance of prolifer- ative astrocyte-like cells that surround motor neurons. These cells, designated as Aberrant...
Acute myeloid leukemia (AML) is a blood malignancy characterized by a differentiation and proliferation defect of myeloid progenitors leading to accumulation of myeloid blasts. It is one of the most common leukemias in adults. Trametinib (Mekinist) is a small molecule inhibitor that targets MEK1 (MAP2K1) and MEK2 (MAPK2K2). It has...
Many pharmaceuticals have negative effects on biota when released into the environment. For example, recent work has shown that the commonly prescribed antidiabetic drug, metformin (N,N-dimethylbiguanide), has endocrine disrupting effects on fish. However, effects of metformin on aquatic primary producers are poorly known. We exposed cultured isolates of a freshwater...
In this study, we characterize the behavioral response of larval zebrafish (Danio rerio) to the noxious chemical allyl isothiocyanate (AITC), an agonist of the nociceptive TRPA1 ion channel, and utilize AITC as an aversive stimulus in an associative learning paradigm. We find that larvae exposed to AITC in both a...
Immature T cells, known as thymocytes, undergo development through successive stages in the thymus and the periphery to become functional mature T cells. These stages are regulated by sequence specific transcription factors (SSTFs). Two such SSTFs, BCL11B and TCF-1, are both known master regulators of thymopoiesis, which is also known...
The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell...
Dietary restriction (DR) is the gold standard intervention used to delay aging, and much recent research has focused on
the identification of possible DR mimetics. Energy sensing pathways, including insulin/IGF1 signaling, sirtuins, and
mammalian Target of Rapamycin (mTOR), have been proposed as pathways involved in the antiaging actions of DR,...
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2013;123:3272–3291. doi:10.1172/JCI67674
7. Fok WC, Zhang Y, Salmon AB, et al. Short-term treatment with
Mycobacterium avium subsp. hominissuis is an opportunistic pathogen that is associated with biofilm-related infections of the respiratory tract and is difficult to treat. In recent years, extracellular DNA (eDNA) has been found to be a major component of bacterial biofilms, including many pathogens involved in biofilm-associated infections. To date, eDNA...
Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of mutants in human macrophages, and...
Background: Ctip2 is crucial for epidermal homeostasis and protective barrier formation in developing mouse embryos. Selective ablation of Ctip2 in epidermis leads to increased transepidermal water loss (TEWL), impaired epidermal proliferation, terminal differentiation, as well as altered lipid composition during development. However, little is known about the role of Ctip2...
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic granulomatous enteritis that plagues domestic and wild ruminants globally. During the silent stages of Johne’s disease, infected animals intermittently shed bacteria for years prior to clinical diagnosis during advanced disease stages. This strategy allows MAP to...
Skeletal muscles provide several functions, including, yet not limited to, voluntary body movement and locomotion, posture and body position, and soft tissue support. Skeletal muscles also play a role in metabolism, requiring energy to facilitate contraction. Each skeletal muscle serves a different purpose despite seeming to perform the same task....
Triple-negative breast cancer (TNBC) is a particularly aggressive molecular subtype of malignant cells that tends to proliferate quickly and is commonly resistant to traditional chemotherapy leading to relapses in prognosis more frequently than other forms of breast cancer (BCa) [1][2][3]. Current treatment options include surgical resection of cancerous tissue and...
The COVID-19 pandemic has shed a light on the need for people to trust in medical science. With the need for 70% of Americans to be vaccinated to achieve herd immunity but 30% have reported vaccine hesitancy, now more than ever do we need to redouble our efforts to ensure...
An estimated total of 30.3 million people have diabetes in the United States, a disease characterized by chronic elevation in blood glucose which over time, can lead to a host of health problems. Currently the most common types of diabetes are type 1, type 2, and gestational. The principal hormone...
The analysis of oxidative stress-induced post-translational modifications remains challenging due to the chemical diversity of these modifications, the possibility of the presence of positional isomers and the low stoichiometry of the modified proteins present in a cell or tissue proteome. Alcoholic liver disease (ALD) is a multifactorial disease in which...
Background:
Nonalcoholic fatty liver disease (NAFLD) is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH,...
Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN...
Background:
Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a...
Alzheimer’s Disease (AD) is a neurodegenerative pathology currently affecting nearly 44 million individuals worldwide, yet there are not currently any effective treatments or preventions for AD despite the rapid development in our understanding of the disease over the last four decades. The medical and sanitary innovations of the last century...
Osteoporosis is a common metabolic bone disease, affecting a third of women and a fifth of men over age 65. In the US, annual health care costs associated with osteoporosis are estimated to be over $20 billion. Osteoporosis is associated with increased fracture risk, which has been demonstrated to predict...
Bone is much more than a simple, static organ. While its classical functions of mineral storage, organ protection, and locomotion still hold true, further studies into the skeleton have revealed a dynamic system capable of signaling, communication, remodeling, and responding to various stimuli. Overall skeletal health is critically important to...
Neisseria gonorrhoeae is the sexually transmitted pathogen responsible for millions of cases of gonorrhea worldwide each year. Rapidly-spreading antibiotic resistance is diminishing the ability to effectively treat a disease with significant consequences to female and male reproductive health, as well as to neonatal well-being. A protective vaccine has the potential...
The diverse community of bacteria living within and on host organisms, known as the microbiome, has an important role in maintaining host health. Dysbiosis, known as a change in the healthy community of the microbiome, has been associated with a number of diseases across host organisms and body sites including...
Nutrigenomics is a branch of nutrition that seeks to elucidate the relationship between dietary components and expression of genes. Certain bioactive compounds present in the diet have the potential to modulate transcription of genes through their interactions with ligand-dependent nuclear receptors, a series of transcriptional regulators capable of sensing intracellular...
Xanthohumol, a prenylated flavonoid found in hops and beer, possesses a long-standing reputation to improve health. Xanthohumol’s cytotoxicity to a wide variety of cancer cell lines is well-established. Herein we provide further insight into the cytotoxicity of not only xanthohumol, but also its non-estrogenic derivatives, to a number of colonic...
The goal of this dissertation was to improve our abilities in acquiring critical in vivo data by establishing embryo-larva zebrafish as an exemplary model to quantitatively evaluate cancer progression. The living environment that encompasses a tumor has a significant effect on how cancer develops, grows and metastasizes. In order to...
Alcohol is a widely consumed, nonessential, bioactive nutrient with end-organ effects on the skeleton. Moderate levels of alcohol consumption are generally associated with increased bone mineral density (BMD), whereas higher intake levels result in reduced bone formation, bone loss, and increased risk for osteoporotic fracture. Given the negative impact of...
Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g.,...
Nucleic acid therapeutics has cemented itself as one of the most efficacious and robust avenues for treatment of a wide range of diseases from vaccine development to treatment of liver, retina, cancer applications. Non-viral mediated gene delivery using lipid-based nanoparticle (LNP) carriers has proven its compatibility with addressing unexpected, fast...
Over the past century, life expectancy in the United States has dramatically increased leading to an increasingly aging population with people reaching, and spending more years in ‘old age’. While this unprecedented shift in population demographics represents great strides for humanity, it is not without cost. One consequence of longer...
Exposure to ultraviolet (UV) radiation is a primary cause of melanoma and non-melanoma skin cancer and thus represents a critical public health concern. Skin cancer risk behavior research lacks an instrument designed to assess health beliefs about UV exposure that may increase skin cancer risk by increasing risky UV exposure...
Health benefits obtained from consumption of fruits and vegetables have the potential to improve the lifestyle of individuals. The walnut is a polyunsaturated fatty acid (PUFA)-rich whole food that is readily available in the U.S and has been shown to potentially reduce risk of Metabolic Syndrome. Furthermore, consumption of polyphenol...