Medical Physiology Commons^™

A Developmental Cycle Masks Output From The Circadian Oscillator Under Conditions Of Choline Deficiency In Neurospora, Mi Shi, Luis F. Larrondo, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

In Neurospora, metabolic oscillators coexist with the circadian transcriptional/translational feedback loop governed by the FRQ (Frequency) and WC (White Collar) proteins. One of these, a choline deficiency oscillator (CDO) observed in chol-1 mutants grown under choline starvation, drives an uncompensated long-period developmental cycle ( approximately 60-120 h). To assess possible contributions of this metabolic oscillator to the circadian system, molecular and physiological rhythms were followed in liquid culture under choline starvation, but these only confirmed that an oscillator with a normal circadian period length can run under choline starvation. This finding suggested that long-period developmental cycles elicited by nutritional stress …

Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou

Neuroscience, Cell Biology & Physiology Faculty Publications

AIM: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans, and it is highly invasive. Doxycycline, first identified as an antimicrobial agent, is a nonspecific inhibitor of matrix metalloproteinases (MMPs). Our objective was to investigate the anti-MMP effect of doxycycline at therapeutically acceptable levels on glioma cells in vitro.

METHODS: The MTT assay was used to determine the anti-proliferative effects of doxycycline. MMP2 activity and expression were determined by gelatinase zymography and real-time quantitative RT-PCR, respectively. Cell invasion was assessed by Matrigel invasion assay.

RESULTS: Doxycycline exerted mild anti-proliferative effects on all three glioma cell lines …

The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau

Dartmouth Scholarship

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa …

Retroviral Vector And Cell-Based Assay For Measuring The Mutation Rate Of Retroviruses Employing Same, Dawn P. Wooley, Kelly Jo Huang

Neuroscience, Cell Biology & Physiology Faculty Publications

Lentiviral-based retrovirus vectors and an in vivo mutation rate assay employing them. More particularly, an assay for directly determining the in vivo mutation rate of HIV-1.

Is Gene Therapy A Good Therapeutic Approach For Hiv-Positive Patients?, Jai G. Marathe, Dawn P. Wooley

Neuroscience, Cell Biology & Physiology Faculty Publications

Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and …

Depression: Relationships To Sleep Paralysis And Other Sleep Disturbances In A Community Sample, Mariana Szklo-Coxe, Terry Young, Laurel Finn, Emmanuel Mignot

Community & Environmental Health Faculty Publications

Sleep disturbances are important correlates of depression, with epidemiologic research heretofore focused on insomnia and sleepiness. This epidemiologic study’s aim was to investigate, in a community sample, depression’s relationships to other sleep disturbances: sleep paralysis (SP), hypnagogic/hypnopompic hallucinations (HH), cataplexy – considered rapid eye movement-related disturbances – and automatic behavior (AB). Although typical of narcolepsy, these disturbances are prevalent, albeit under-studied, in the population. Cross-sectional analyses (1998–2002), based on Wisconsin Sleep Cohort Study population-based data from 866 participants (mean age 54, 53% male), examined: depression (Zung Self-Rating Depression Scale), trait anxiety (Spielberger State-Trait Anxiety Inventory, STAI-T ≥ 75th percentile), and …

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …