Lysine Specific Demethylase-1 And The Brahma Chromatin Remodeling Complex Regulate Conserved Signaling Pathways During Drosophila Wing Development, Brenda Jean Curtis
The conserved SWI/SNF chromatin remodeling complex uses the energy from ATP hydrolysis to alter local chromatin environments by disrupting DNA-histone contacts. The Drosophila SWI/SNF counterpart, the Brahma complex, has been shown to have an essential role in regulating the proper expression of many developmentally important genes, including those required for eye and wing tissue morphogenesis. A temperature sensitive mutation in one of the core subunits, SNR1 (SNF5/Ini1/SMARC B1), results in reproducible wing patterning phenotypes that can be enhanced and suppressed by extragenic mutations. SNR1 functions as a regulatory subunit to modulate chromatin remodeling activities of the ...
Aging Effects On Acute Lung Inflammation After Burn Injury, 2010 Loyola University Chicago
Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini
The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged ...
Phospholipase D Signaling In T Cells, 2010 Loyola University Chicago
Phospholipase D Signaling In T Cells, Uma Chandrasekaran
Antigen stimulation of T lymphocytes induces the activation of phospholipase D (PLD) signaling. Phospholipase D (PLD) is a phosphodiesterase that catalyzes the conversion of phosphatidyl choline (PC) to phosphatidic acid (PA). PA is an important lipid second messenger and is known to mediate a variety of cellular functions. However, the specific role of PA in T lymphocytes has not been established. Previous studies indicated differential requirement for TCR induced PLD signaling in regulatory and non-regulatory T cells. Inhibition of TCR induced PLD signal preferentially suppressed the growth of non-regulatory T cells while allowing the proliferation of regulatory T cells in ...
B Lymphocyte Development In Galt, 2010 Loyola University Chicago
B Lymphocyte Development In Galt, Venkata Arunachalam Yeramilli
In rabbits, the primary antibody repertoire is generated in the gut-associated lymphoid tissues (GALT), where bone marrow (BM)-derived B cells undergo a proliferative expansion and somatically diversify the immunoglobulin genes. Unlike in other species, B lymphopoiesis in rabbit arrests a few months after birth, and it is unclear how the peripheral B cell compartment is maintained when there is no influx of newly-made B cells from the BM.
For my dissertation, I investigated how B cells develop in the GALT of rabbits, and how they are maintained in adults after the arrest of lymphopoiesis. To identify cellular signals that ...
Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, 2010 Loyola University Chicago
Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, John Karavitis
Extensive evidence indicates that alcohol (ethanol) consumption affects human health by altering normal physiological functions of the immune system. This study investigated the effect of a single in vivo exposure of macrophages to clinically relevant levels of ethanol (1.2 and 2.2 g/kg). Following 3 hour exposure, both doses of ethanol decreased ex vivo TNFα production by splenic and alveolar macrophages (AMs). Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNFα production at 3 and 6 hours post ethanol administration, as well as decreased IL-6 and IL-12 production after 6 hours, compared control treated ...
Hypervirulent Clostridium Difficile Strains: Adherence, Toxin Production And Sporulation, 2010 Loyola University Chicago
Hypervirulent Clostridium Difficile Strains: Adherence, Toxin Production And Sporulation, Michelle Marie Merrigan
Clostridium difficile is a leading cause of nosocomial infections, and recently emerged "hypervirulent" C. difficile strains have caused epidemics worldwide. We hypothesized that multiple factors were responsible for this phenotype, particularly the interaction of C. difficile with the epithelial cell, as well as toxin production and sporulation.
To test if host interaction varied in HV strains, we developed a quantitative host-cell adherence assay, and found that while C. difficile strains varied in adherence to human intestinal epithelial cells, hypervirulent strains were not significantly more adherent than other strains. The bacterial surface protein SlpA varied in both size and amount between ...
Characterization Of Tram, A Required Bacteroides Fragilis Conjugal Apparatus Protein That Interacts With The B. Fragilis Putative Coupling Protein Bcta And The B. Fragilis Relaxase Protein Bmph, 2010 Loyola University Chicago
Characterization Of Tram, A Required Bacteroides Fragilis Conjugal Apparatus Protein That Interacts With The B. Fragilis Putative Coupling Protein Bcta And The B. Fragilis Relaxase Protein Bmph, Mai Thi Thanh Nguyen
Bacteroides spp. organisms, the most prominent bacteria of the human colon, are reservoirs of antibiotic resistance genes which promiscuously transfer within and from the genus via conjugation. The B. fragilis clinical isolate LV23 harbors a 37kb conjugative transposon, BTF-37. Two important conjugal apparatus proteins encoded by BTF-37 are BctA, a predicted coupling protein (CP) that powers DNA translocation, and ORF7 (TraM). In this study, we demonstrated that TraM exhibits characteristics of a required conjugal apparatus protein including 1) upregulated expression under conjugation conditions; 2) localization to the bacterial inner membrane; 3) interaction with the putative coupling protein BctA and the ...
Morphogenesis Of The Bacillus Anthracis Spore, 2010 Loyola University Chicago
Morphogenesis Of The Bacillus Anthracis Spore, Michael Mallozzi
With the ability to shut down metabolism, survive exposure to high degrees of heat, ultra-violet and ionizing radiation, digestive enzymes, and antimicrobials, the bacterial spore is one of the most-resistant forms of life on earth. Although most spores are harmless, several species' spores cause serious diseases such as tetanus, anthrax, gas gangrene, botulism, and diarrhea. Spore-forming bacteria differentiate into spores in response to stresses (especially starvation) in a multi-stage developmental pathway involving the coordinated expression of hundreds of genes and the formation of specialized protective organelles which surround and protect the spore during dormancy. The Bacillus anthracis spore (the causative ...
Involvement Of The Nmda Receptor In Moderate Ethanol Preconditioning-Dependent Neuroprotection From Amyloid-Beta In Vitro, 2010 Loyola University Chicago
Involvement Of The Nmda Receptor In Moderate Ethanol Preconditioning-Dependent Neuroprotection From Amyloid-Beta In Vitro, Robert Matthew Mitchell
Alzheimer's disease (AD) is a progressive, mentally crippling, and eventually fatal form of dementia with growing prevalence in aging populations. In 2009 it was estimated that 5.3 million Americans have AD, with 5.1 million older than age 65 and 200,000 under 65. That accounts for 1 in 8 adults over 65. Furthermore, AD costs Americans 148 billion dollars in direct expenses, and is the leading cause of dementia and the 6th leading cause of death. Since improved medical care in general is increasing average life span and age is the primary risk factor for AD, there ...
Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, 2010 Loyola University Chicago
Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, Sahadev A. Shankarappa
Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5 ...
Hindbrain Serotonin Neurons Activate 5-Ht1a Receptors In The Nucleus Tractus Solitarius (Nts) To Modulate Sympathetic And Ventilatory Recovery Following Hypotensive Hemorrhage, 2010 Loyola University Chicago
Hindbrain Serotonin Neurons Activate 5-Ht1a Receptors In The Nucleus Tractus Solitarius (Nts) To Modulate Sympathetic And Ventilatory Recovery Following Hypotensive Hemorrhage, Ling-Hsuan Kung
Trauma is the leading cause of death of young people in the United States. Most such deaths result either from the initial blood loss or from secondary reperfusion injury following resuscitation.
Currently, the standard treatments for hypovolemic shock include volume resuscitation and using of vasoconstrictors to raise pressure. However, these treatments can exacerbate reperfusion injury, and require technical care when apply to patients. Therefore, novel therapies that can safely restore perfusion pressure are needed.
Our lab has found that 5-HT1A-receptor agonist, 8-OH-DPAT, increases perfusion pressure and improves acid-base balance in hypovolemic rats by stimulation of sympathetic-mediated increases in venous tone ...
The Tumor Suppressor Pkcδ Is Critical For Uv-Induced G2/M Checkpoint Activation And Apoptosis, 2010 Loyola University Chicago
The Tumor Suppressor Pkcδ Is Critical For Uv-Induced G2/M Checkpoint Activation And Apoptosis, Edward Lewis Lagory
Protein kinase C delta (PKCδ) is an essential component of the intrinsic apoptotic program. Following DNA damage, such as exposure to UV radiation, PKCδ is cleaved in a caspase-dependent manner, generating a constitutively active catalytic fragment (PKCδ-cat) which is necessary and sufficient for keratinocyte (KC) apoptosis. We found that in addition to inducing apoptosis, expression of PKCδ-cat caused a pronounced G2/M cell cycle arrest in both primary human KCs and immortalized HaCaT cells. Consistent with a G2/M arrest, PKCδ-cat induced phosphorylation of Cdk1 (Tyr15), a critical event in the G2/M checkpoint. Treatment with the ATM/ATR inhibitor ...
Deconstructing Ihf-Mediated Inhibition Of The Complex Acs Promoter, 2010 Loyola University Chicago
Deconstructing Ihf-Mediated Inhibition Of The Complex Acs Promoter, David S. Thach
acs encodes a high affinity enzyme that permits survival during carbon starvation. As befits a survival gene, its transcription is subject to complex regulation. Previously, the Wolfe lab reported that CRP activates acs transcription by binding tandem DNA sites located upstream of the major acsP2 promoter and that the nucleoid protein IHF binds three specific sites located just upstream. The most proximal site (IHF III) exhibits reduced transcription compared to the full-length promoter or to a construct lacking all three IHF sites. The goal of my research was to understand how IHF III inhibits CRP-dependent acs transcription. First, I helped ...
Gabab Regulation Of Methamphetamine-Induced Associative Learning, 2010 Loyola University Chicago
Gabab Regulation Of Methamphetamine-Induced Associative Learning, Robin Michelle Voigt
Addiction is a chronic, relapsing disorder for which strikingly few effective therapies exist, and there are no FDA-approved pharmacotherapies for methamphetamine (Meth) addition. There is an immense need to identify the neurobiological underpinnings of psychostimulant addiction and develop efficacious drug therapies to compliment the current mainstay treatment of behavioral/cognitive therapy.
Re-exposure to cues associated with psychostimulants (e.g., drug paraphernalia) increase neuronal activity and can elicit drug-craving and -seeking; an effect which is profound and long-lasting. A mechanism to disrupt those brain processes which are necessary to maintain the association may reduce the incidence of cue-elicited relapse.
Conditioned place ...
Polyomavirus Enhancer Activator 3 (Pea3), A Member Of The Ets Family Of Transcription Factors, Is A Transcriptional Activator Of Notch-1 And Notch-4 In Breast Cancer: An Opportunity For Novel Combinational Therapy, 2010 Loyola University Chicago
Polyomavirus Enhancer Activator 3 (Pea3), A Member Of The Ets Family Of Transcription Factors, Is A Transcriptional Activator Of Notch-1 And Notch-4 In Breast Cancer: An Opportunity For Novel Combinational Therapy, Anthony George Clementz
Women diagnosed with triple-negative breast cancer have the worst overall prognosis and frequently present with metastatic tumors. To date, there are no targeted therapies available to combat this aggressive form of breast cancer due to the lack of expression of well-known targets such as ER-alpha, PR, or HER2/neu. Therefore, there is an immediate need to identify novel targets that are responsible for the proliferation, survival, and invasive phenotype. Notch-1 and Notch-4, both potent breast oncogenes, are overexpressed in triple-negative breast cancers-associated with the poorest overall survival. PEA3 (polyomavirus enhancer activator 3), a member of the Ets family of transcription ...
Developmental Characterization Of Cara Mitad: A Drosophila Nuclear Receptor Co-Regulator, 2010 Loyola University Chicago
Developmental Characterization Of Cara Mitad: A Drosophila Nuclear Receptor Co-Regulator, Chhavi Chauhan
In insects and vertebrates, hormone titers drive cellular proliferation and differentiation events that guide proper development. Nuclear receptors (NR) respond to these hormone signals by activating cascades of gene expression, along with coregulator protein complexes. In Drosophila melanogaster, fluctuating titers of the steroid hormone ecdysone are responsible for coordinating the timing of organismal development. Despite major advances in our understanding of Drosophila NR activities, we lack essential knowledge of the coregulators that are required for their proper function.
We have recently identified the Drosophila cara mitad (cmi) (`dear half') gene. The deduced CMI protein is closely related to the N-terminal ...
The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., 2010 Loyola University Chicago
The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., Sandra Eliasz
Thoracic malignancies are one of the deadliest of all cancers, being the leading cause of cancer death in the Western world. Thoracic malignancies arise from different tissues; however the most common are of epithelial (commonly referred to as non-small cell lung cancer, or NSCLC), neuroendocrine (small cell lung cancer, or SCLC) and mesothelial origin (malignant mesothelioma, or MM). The DNA oncogenic virus Simian Virus 40 (SV40) has been shown to cooperate with environmental oncogenic fibers in the onset of MM. Insulin like growth factor-1 (IGF-1) signaling plays a central role in all thoracic malignancies and in the process of SV40-mediated ...
Mechanisms Of Ipsapirone-Mediated Neuroprotection Of Ethanol-Treated Fetal Rhombencephalic Neurons: Role Of Endogenous Antioxidants, Jongho Lee
Prenatal exposure to ethanol can cause serious damage to the developing central nervous system. Both in vivo and in vitro studies demonstrate the vulnerability of the developing serotonergic system to the damaging effects of ethanol. However, treatment with a serotonin-1A (5-HT1A) agonist prevents the ethanol-associated apoptosis in developing 5-HT neurons. One mechanism by which 5-HT1A agonists exert their neuroprotective effects appears to involve activation of the phosphatidylinositol 3'kinase (PI-3K) pro-survival pathway and activation of NF-κB dependent anti-apoptotic genes. Additional NF-κB dependent genes might also be involved with the neuroprotective effects of ipsapirone.
There is also considerable evidence that ethanol ...
Notch Signaling Is Important In The Survival, Proliferation, And Self-Renewal Of The Putative Breast Cancer Stem Cell Population, 2010 Loyola University Chicago
Notch Signaling Is Important In The Survival, Proliferation, And Self-Renewal Of The Putative Breast Cancer Stem Cell Population, Peter Grudzien
Numerous studies have identified stem-like cells, termed cancer stem cells (CSCs), in breast tumors and established cell lines. It has been hypothesized that CSCs are responsible for breast cancer formation, progression and recurrence; therefore, a deeper understanding of the signaling pathways regulating CSC survival will benefit development of novel therapeutic strategies. Notch signaling, which is dysregulated in breast cancer and has been implicated in mammary stem cell self-renewal, and can be effectively blocked by gamma-secretase inhibitors (GSIs). While GSIs are currently in clinical trials for breast cancer, it is not fully understood how these compounds will affect CSCs or if ...
New Cyclophanes As Supramolecular Scaffolds: The Synthesis Of Tribenzo-1,4,7-Triazacyclononatriene., 2010 Loyola University Chicago
New Cyclophanes As Supramolecular Scaffolds: The Synthesis Of Tribenzo-1,4,7-Triazacyclononatriene., Andria M. Panagopoulos
Supramolecular chemistry involves the formation of complex molecular entities that have the capacity to participate in specific molecular recognition of guest molecules. A commonly employed scaffold in supramolecular chemistry is the trimeric crown-shaped molecule cyclotriveratrylene (CTV). CTV has been studied extensively for its capability of binding a number of smaller organic and organometallic guests within its bowl-shaped cleft and has been used as a building block enabling the construction of more complex cryptophanes. The goal of this research is the synthesis and characterization of a novel cyclophane, tribenzo-1,4,7-triazacyclononene and derivatives thereof. These new cyclophanes should have greater versatility ...