Medicine and Health Sciences Commons^™

Thomas Jefferson University, Department Of Pathology, Anatomy And Cell Biology, Oral Administration Of Apigenin Inhibits Metastasis Through Akt/P70s6k1/Mmp-9 Pathway In Orthotopic Ovarian Tumor Model., Jun He, Qing Xu, Min Wang, Chongyong Li, Xu Qian, Zhumei Shi, Ling-Zhi Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Apigenin, a flavonoid commonly present in the daily diet, is known for its potential anti-tumor properties. However, the effect of apigenin via oral administration on tumor growth and metastasis remains unknown. In this study we developed an orthotopic ovarian tumor model in nude mice to test the effect of apigenin oral administration, and showed that apigenin inhibited the micrometastasis of cancer cells in the animal tumor model. To understand the mechanism of apigenin in inhibiting metastasis, we found that apigenin greatly inhibited MMP-9 expression and p-AKT and p-p70S6K1 levels in the tumor tissues compared to the control group. We further …

Loss Of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration And Alzheimer's Disease-Related Tau Phosphorylation Via Par-1., Kanae Iijima-Ando, Michiko Sekiya, Akiko Maruko-Otake, Yosuke Ohtake, Emiko Suzuki, Bingwei Lu, Koichi M Iijima

Farber Institute for Neuroscience Faculty Papers

Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease (AD); however, what pathological conditions trigger tau abnormality in AD is not fully understood. A reduction in the number of mitochondria in the axon has been implicated in AD. In this study, we investigated whether and how loss of axonal mitochondria promotes tau phosphorylation and toxicity in vivo. Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 …

Glucose Decouples Intracellular Ca2+ Activity From Glucagon Secretion In Mouse Pancreatic Islet Alpha-Cells., Sylvain J Le Marchand, David W Piston

Farber Institute for Neuroscience Faculty Papers

The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+)](i)) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+)](i) and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP) channel activity but not on tetrodotoxin-sensitive Na(+) channels. …

Testosterone Treatment Fails To Accelerate Disease In A Transgenic Mouse Model Of Spinal And Bulbar Muscular Atrophy., Erica S Chevalier-Larsen, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone …

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

Synergetic Effect Of Recoverin And Calmodulin On Regulation Of Rhodopsin Kinase., Ilya I Grigoriev, Ivan I Senin, Natalya K Tikhomirova, Konstantin E Komolov, Sergei E Permyakov, Evgeni Yu Zernii, Karl-Wilhelm Koch, Pavel P Philippov

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation of photoactivated rhodopsin by rhodopsin kinase (RK or GRK1), a first step of the phototransduction cascade turnoff, is under the control of Ca(2+)/recoverin. Here, we demonstrate that calmodulin, a ubiquitous Ca(2+)-sensor, can inhibit RK, though less effectively than recoverin does. We have utilized the surface plasmon resonance technology to map the calmodulin binding site in the RK molecule. Calmodulin does not interact with the recoverin-binding site within amino acid residues M1-S25 of the enzyme. Instead, the high affinity calmodulin binding site is localized within a stretch of amino acid residues V150-K175 in the N-terminal regulatory region of RK. Moreover, …

Role Of Myosin Light Chain Kinase In Binge Ethanol And Burn Injury-Induced Intestinal Barrier Dysfunction, Anita Zahs

Dissertations

Ethanol is a common factor in traumatic injury, including burn injury. Previous studies from our laboratory indicate that ethanol increases both pulmonary and gastrointestinal inflammation as well as susceptibility to infection in burn-injured mice; however, the mechanisms of these responses are not entirely known. Moreover, after burn injury, bacteria and their products leak out of the intestinal lumen and into the bloodstream. These bacteria can disperse throughout the body leading to pulmonary damage, acute lung injury, sepsis, and death. Ethanol in combination with burn injury has been shown to decrease intestinal barrier function greater than either insult alone. Long (210 …

Resveratrol + Ethanol Preconditioning And Neuroprotection, Nastaran Khodaie

Master's Theses

Our lab established that moderate ethanol preconditioning (MEP) for 6 days blocked the Aâ25-35 toxicity in cerebellar mixed cell cultures and It has been shown that MEP cause the up regulation of the pre-survival enzymes such as proxiredoxin2 (PRX2), which suggests MEP can activate the cell survival pathways against upcoming toxins.

This study was performed to verify the possible combinatory effect of ethanol and resveratrol against Aâ25-35 toxicity. Both ethanol and resveratrol sub-protective concentrations were detected against Aâ25-35 in cerebellar mixed cell cultures. The combination of sub-protective levels of ethanol and resveratrol showed the significantly reduction in number of Aâ25-35 …

The Impact Of Algal Community Succession, Taxonomic Composition And Biomass Accrual, On Denitrification Potential Of Stream Periphyton, Allison Daley

Master's Theses

We investigated the relationship between algal taxonomy, community succession and biomass accrual and denitrification potential (DNP) within stream periphyton. Field research was conducted in 6 DuPage County, II forest preserve streams with diverse physical and chemical characteristics and in an experiment in the artificial stream facility at Loyola University Chicago in which 2 sets of streams were amended with nutrients and compared to an unamended set of streams. Algal communities in the field study streams were sampled over 12 weeks late spring/summer and NMDS ordination plots identified 4 distinct communities. Correlations with algal community NMDS axis scores and the relative …

Signals From Intraventricular Depth Electrodes Can Control A Brain-Computer Interface, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

A Brain-Computer Interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans have used scalp-recorded electroencephalography (EEG). We have recently demonstrated that signals from intracranial electrocorticography (ECoG) and stereotactic depth electrodes (SDE) in the hippocampus can be used to control a BCI P300 Speller paradigm. We report a case in which stereotactic depth electrodes positioned in the ventricle were able to obtain viable signals for a BCI. Our results demonstrate that event-related potentials from intraventricular electrodes can be used to reliably control the …

Heart Rate And Accelerometry During Singles Footbag Net Play, Christopher Michael Siebert

Dissertations and Theses

This investigation examined the heart rate responses and movement characteristics of experienced footbag net players during singles play. Footbag net is a net/court sport similar to volleyball, but it is played with a footbag (e.g., Hacky-Sack^TM) using only the feet. In singles footbag net, players are allowed either one or two kicks to propel the footbag over the net. Subjects were 15 males and 1 female, ranging in age from 18- 60 years, with a mean age of 33.6 years. Subjects played two games of singles footbag net using two different scoring systems: "sideout" scoring and "rally" scoring. …

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …

Neuron To Microglia Communication; A Study Of Cx3cl1 Signaling Implications In Cognitive Function, Inflammation, And Neurodegeneration, Joshua M. Morganti

USF Tampa Graduate Theses and Dissertations

As a consequence of aging, the brain is subject to chronic neuroinflammatory conditions. The resident immune cells of the brain, microglia, act similarly to peripheral macrophages to protect the brain from insults, infection, and physical trauma. However, without proper regulation of their respective host defense mechanisms, these actions can become neurotoxic. In the healthy brain neurons have several signaling systems that directly interact with microglia in order to maintain a calming influence upon their actions, one of particular interest is the chemokine CX3CL1. This chemokine is found predominantly on neurons, while its cognate receptor CX3CR1 is found exclusively on microglia. …

Maternal Immune Dysregulation In The Pathogenesis Of Neurodevelopmental Disorders: Interleukin-6 As A Central Mechanism And Therapeutic Target Of Flavonoids, Ellisa Carla Parker-Athill

USF Tampa Graduate Theses and Dissertations

Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has …

Effects Of G-Csf On Monocytes And Neurons: In Vitro And In Vivo Studies In A Mouse Model Of Alzheimer's Disease, Amanda Renee Pennington

USF Tampa Graduate Theses and Dissertations

G-CSF is routinely used to treat neutropenia/leukopenia or to increase hematopoietic stem cell generation in bone marrow donors. G-CSF and its receptor, G-CSFR, are produced by various cell types both in the peripheral circulation and within brain. As a consequence, exogenous administration of G-CSF results in a broad spectrum of effects involving hematopoietic, immune and central nervous systems.

G-CSF administration in a mouse model of Alzheimer's disease (AD) has revealed both cognitive benefits and disease modifying effects: a) decreased Aβ plaque burden, b) increased microgliosis, c) increased neurogenesis and d) improved performance in radial arm water maze (RAWM). In clinical …

Sugar Consumption And Cognitive Aging In The Swedish Adoption/Twin Study Of Aging, Shyam Seetharaman

USF Tampa Graduate Theses and Dissertations

Abstract

Consumption of foods high in sugar content has been linked with the development of metabolic abnormalities such as cardiovascular disease and type II diabetes, major sources of global health concerns. Although the detrimental consequences of high intake of sugar on abnormal metabolic processes are established, it is not known how this association affects (or accelerates) cognitive aging.

The current project was based on data from the Swedish Adoption/Twin Study of Aging (SATSA) to test the hypothesis that high refined sugar intake contributes to accelerated trajectories of cognitive decline assessed longitudinally. Trajectories of cognitive change were assessed as a function …

Behavioral And Immunological Phenotypes Of Transgenic Mice Overexpressing Human Secreted Amyloid Precursor Protein Alpha: Implications For Autism, Antoinette R. Bailey

USF Tampa Graduate Theses and Dissertations

Autism is a heterogeneous neurodevelopmental disorder that is characterized by impaired social interaction and communication as well as restricted and repetitive behaviors and focused interests. In addition to the cardinal behavioral characteristics observed for diagnosis, autistic individuals exhibit a number of comorbid conditions as well as a variety of aberrant immunological features. Recent studies report that plasma from autistic children contained elevated levels of secreted amyloid precursor protein alpha (sAPP-á), the á-secretase cleavage product of the amyloid precursor protein (APP) which is ubiquitously expressed in the brain, spleen, thymus and other organs. Interestingly, the sAPP-á fragment functions as a neurotrophic …

Efficacy Of Increased Ube3a Protein Levels In The Brain In Rescuing The Phenotype Of An Angelman Syndrome Mouse, Jennifer L. Daily

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS), a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes an E6-AP ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve …

Evidence For A Non-Genomic Action Of Testosterone In Skeletal Muscle Which May Improve Athletic Performance: Implications For The Female Athlete, J R Dent, D K Fletcher, Michael Mcguigan

Research outputs 2012

This review will focus on the proposed second mode of testosterone action (now termed non-genomic) that appears to occur independently of the traditional transcriptional mechanism in mammalian skeletal muscle cells which may enhance skeletal muscle contractile properties. This mechanism of testosterone action differs from the traditional pathway, originating at the cell membrane, having a rapid onset of action, requiring second messengers to execute its effects and is insensitive to inhibitors of traditional androgen receptor action, transcription and protein synthesis. Importantly, unlike the traditional action of testosterone in skeletal muscle, this non-genomic pathway is shown to have a direct acute effect …

Multiple Γ-Secretase Product Peptides Are Coordinately Increased In Concentration In The Cerebrospinal Fluid Of A Subpopulation Of Sporadic Alzheimer's Disease Subjects, Saori Hata, Miyako Taniguchi, Yi Piao, Takeshi Ikeuchi, Anne Fagan, David Holtzman, Randall Bateman, Hamid Sohrabi, Ralph Martins, Sam Gandy, Katsuya Urakami, Toshiharu Suzuki

Research outputs 2012

Background: Alcadeinα (Alcα) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Results: Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alcα, we determined levels of …

Predicting Re-Intubation In Patients Who Self Extubate In The Icu, John Reed Rrt, Kenneth Miller Med, Rrt-Nps, Robert Leshko Bs,Rrt, Michael J. Weiss Mph

Patient Care Services / Nursing

No abstract provided.

Sedation Safety Using Clinical Practice Guidelines, Bonnie Wasilowsky Bspa-Hca, Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Faculty Publications 2011, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 812 publications.

Mir-145 Directly Targets P70s6k1 In Cancer Cells To Inhibit Tumor Growth And Angiogenesis., Qing Xu, Ling-Zhi Liu, Xu Qian, Qi Chen, Yue Jiang, Dan Li, Lihui Lai, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

MiR-145 can regulate cell apoptosis, proliferation, neural development and stem cell differentiation. Previous studies indicate that miR-145 is downregulated in human colon cancer cells. However, the molecular mechanisms of miR-145 used to regulate colon carcinogenesis and angiogenesis remain to be clarified. Here, we show that the expression of miR-145 is downregulated in colon and ovarian cancer tissues and cell lines. MiR-145 inhibits p70S6K1 post-transcriptional expression by binding to its 3'-UTR. The angiogenic factors hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), which are downstream molecules of p70S6K1, are decreased by miR-145 overexpression. P70S6K1 rescues miR-145-suppressed HIF-1 and VEGF …

Blood-Brain Barrier Abnormalities Caused By Hiv-1 Gp120: Mechanistic And Therapeutic Implications., Jean-Pierre Louboutin, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs). These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and …

Graft Versus Host Disease Of The Brain Following Allogeneic Stem Cell Transplant For Myelodysplastic Syndrome, Janet Yoo, Lindsay Simon, Zi-Xuan Wang, Phd, Lawrence C. Kenyon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only very rarely been described in the literature. We report an unusual case …

Integrative Gene Regulatory Network Analysis Reveals Light-Induced Regional Gene Expression Phase Shift Programs In The Mouse Suprachiasmatic Nucleus., Haisun Zhu, Rajanikanth Vadigepalli, Rachel Rafferty, Gregory E Gonye, David R Weaver, James S Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We use the multigenic pattern of gene expression across suprachiasmatic nuclei (SCN) regions and time to understand the dynamics within the SCN in response to a circadian phase-resetting light pulse. Global gene expression studies of the SCN indicate that circadian functions like phase resetting are complex multigenic processes. While the molecular dynamics of phase resetting are not well understood, it is clear they involve a "functional gene expression program", e.g., the coordinated behavior of functionally related genes in space and time. In the present study we selected a set of 89 of these functionally related genes in order to further …

Lung Carcinoma In The Era Of Personalized Medicine: The Role Of Cytology., Maureen F Zakowski, Marluce Bibbo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In 2004, three groups working independently [1–3] , almost simultaneously, reported remarkable findings: that activating mutations in the epidermal growth factor receptor (EGFR) were common in certain lung carcinomas and that these mutations correlated with the response of those lung tumors to therapy with gefitinib and erlotinib, both EGFR tyrosine kinase inhibitors (TKIs). This was the first time driver mutations in lung cancer that responded to targeted therapy had been identified, marking the beginning of a new era of personalized medicine in lung cancer. Prior to the discovery of these mutations, patients had been treated with EGFR TKIs but predicting …

Cop9 Signalosome Component Jab1/Csn5 Is Necessary For T Cell Signaling Through Lfa-1 And Hiv-1 Replication., Shigemi M Kinoshita, Peter O Krutzik, Garry P Nolan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To determine critical host factors involved in HIV-1 replication, a dominant effector genetics approach was developed to reveal signaling pathways on which HIV-1 depends for replication. A large library of short peptide aptamers was expressed via retroviral delivery in T cells. Peptides that interfered with T cell activation-dependent processes that might support HIV-1 replication were identified. One of the selected peptides altered signaling, lead to a difference in T cell activation status, and inhibited HIV-1 replication. The target of the peptide was JAB1/CSN5, a component of the signalosome complex. JAB1 expression overcame the inhibition of HIV-1 replication in the presence …

Knockdown Of Ki-67 By Dicer-Substrate Small Interfering Rna Sensitizes Bladder Cancer Cells To Curcumin-Induced Tumor Inhibition., Sivakamasundari Pichu, Swapna Krishnamoorthy, Andrei Shishkov, Bi Zhang, Peter Mccue, Biddanda C Ponnappa

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma …