Medicine and Health Sciences Commons^™

Krüppel-Like Factor 2 Is Required For Normal Mouse Cardiac Development, Aditi R. Chiplunkar, Tina K. Lung, Yousef Alhashem, Benjamin A. Koppenhaver, Fadi N. Salloum, Rakesh C. Kukreja, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2−/− embryos die earlier, by E11.5. E9.5 FVB/N KLF2−/− hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

A Twin Study Of Early-Childhood Asthma In Puerto Ricans, Supinda Bunyavanich, Judy L. Silberg, Jessica Lasky-Su, Nathan A. Gillespie, Nancy E. Lange, Glorisa Canino, Juan C. Celedon

Human and Molecular Genetics Publications

Background

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood.

Objective

To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤3 years old.

Methods

678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages …

Targeted Apoptotic Effects Of Thymoquinone And Tamoxifen On Xiap Mediated Akt Regulation In Breast Cancer, Shashi Rajput, B. N. P. Kumar, Siddik Sarkar, Subhasis Das, Belal Azab, Prasanna K. Santhekadur, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher, Mahitosh Mandal

Human and Molecular Genetics Publications

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. …

Lipopolysaccharide-Induced Neuronal Activation In The Paraventricular And Dorsomedial Hypothalamus Depends On Ambient Temperature, Samuel P. Wanner, Kyoko Yoshida, Vladimir A. Kulchitsky, Andrei I. Ivanov, Kazuyuki Kanosue, Andrej A. Romanovsky

Human and Molecular Genetics Publications

Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS). To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously) either in a thermoneutral (30°C) or cool (24°C) environment. At 30°C, LPS caused fever; at 24°C, the same dose caused profound hypothermia. Both fever and hypothermia were …

Fyn-Dependent Gene Networks In Acute Ethanol Sensitivity, Sean P. Farris, Michael F. Miles

Pharmacology and Toxicology Publications

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex …

Contribution Of Nadph Oxidase To Membrane Cd38 Internalization And Activation In Coronary Arterial Myocytes, Ming Xu, Xiao-Xue Li, Joseph K. Ritter, Justine M. Abais, Yang Zhang, Pin-Lan Li

Pharmacology and Toxicology Publications

The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase …

Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew

Theses and Dissertations

The main psychoactive and therapeutic effects of Δ9-tetrahydrocannabinol (THC) are mediated through cannabinoid type 1 receptors (CB1Rs). The therapeutic uses of THC are mitigated by the development of tolerance to these therapeutic effects, whereas tolerance does not readily develop to some of the side-effects of THC, like motor impairment and reward. The development of tolerance occurs through adaptations at CB1Rs, which include desensitization (G-protein uncoupling) and downregulation (receptor degradation). Brain region-dependent differences in THC-mediated adaptations are proposed to explain the differences in tolerance to various THC-mediated effects. These studies focused on whether ΔFosB, a stable transcription factor, could regulate CB1R …

Early Adolescent Nicotine Exposure Has Long-Lasting Effects On Cocaine-Induced Behaviors In Mice, Mai Alajaji

Theses and Dissertations

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in …

Factors That Lead To The Immunotherapy Gap In Multiple Sclerosis Testing, Karthika Solai

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Multiple sclerosis is a disease that affects the central nervous system. Most doctors and scientists believe that it is an autoimmune disease. Simply put, the immune system attacks the nerves in a person’s body, thereby causing myelin damage, inflammation, and neurodegeneration. The plaque that then builds up on the nerves is scar tissue created when the wounds made by the immune system heal. It is this plaque that inhibits communication between the axons in the body and causes the symptoms of MS, which includes problems with movement, pain, vision problems, trouble swallowing, fatigue, and heat sensitivity (Baker et al., 2011, …

Examining The Relationship Between Particulate Matter, Nitrogen Oxide, Carbon Oxides, Sulfur Dioxide And Hypertension In Urban Areas In India: A Review, Hiren Kolli

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

While blood pressure may be decreasing around the world, it has been on the rise in India (Kounteya, 2012). According to the World Health Organization, the average blood pressure went down by 2.7mm Hg among women globally, while increasing by 2.4mm Hg in India. In men, blood pressure decreased by 2.3mm Hg globally in the past three decades but increased by 2.2mm Hg in India (Kounteya, 2012). Almost three-quarters of people with hypertension live in developing countries with limited health resources where there is very low awareness of hypertension, and India is one of these countries. Hypertension is the leading …

Discovering Protein Functions And Career Goals: The Suppressor Sike, Rebekah Rifareal

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Discovering IMSD was accidental. I was having a routine advising appointment and discussing future careers when the topic surfaced. At the time, I had no clue about what I wanted to do, so my advisor suggested that I explore research and encouraged me to apply for the program.