Missing Letters: Seven stories and one novella

My MFA thesis, entitled MISSING LETTERS, consists of seven short stories and one novella. These pieces are arranged to reflect a variety of tone and style; The first story, Tale of the Ill Ook Ook, is strictly comedic and serves as a parody of adult book stores. The emphasis is on humor rather than eroticism; The second story is Trouble on the Farm, which is intense in its treatment of a troubled runaway teen with murder and vengeance on his mind; Story number three, The Romans, is a children\u27s story, featuring Scotty, the protagonist who headlines my first published novel, SCOTTY AND THE GYPSY BANDIT. A sense of morality motors through this and story number seven, The Lemonade Stand. . Both are constructed in a sparse, lean style that reflects the simplistic yet morally compromised world of childhood; Wanda Waits is a dark, tightly structured tale concerning a hit man who would prefer a different line of work, but the money is too good for him to quit; Joie de Vivre tells the story of a strained father/daughter relationship with a dead mother as its centerpiece; Are We There Yet? is a light-hearted satire of the Book of Exodus, with a considerable amount of wordplay and puns, featuring a Las Vegas setting; The operative theme of my novella, Odd Bodkins, is the dissipation of a marriage brought on by a third party. It strives for a more literary-like style

Deletion of TSPO resulted in change of metabolomic profile in retinal pigment epithelial cells

Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD

Brief increases in corticosterone affect morphology, stress responses, and telomere length, but not post-fledging movements, in a wild songbird

Organisms are frequently exposed to challenges during development, such as poor weather and food shortage. Such challenges can initiate the hormonal stress response, which involves secretion of glucocorticoids. Although the hormonal stress response helps organisms deal with challenges, long-term exposure to high levels of glucocorticoids can have morphological, behavioral, and physiological consequences, especially during development. Glucocorticoids are also associated with reduced survival and telomere shortening. To investigate whether brief, acute exposures to glucocorticoids can also produce these phenotypic effects in free-living birds, we exposed wild tree swallow (Tachycineta bicolor) nestlings to a brief exogenous dose of cort once per day for five days and then measured their morphology, baseline and stress-induced corticosterone levels, and telomere length. We also deployed radio tags on a subset of nestlings, which allowed us to determine the age at which tagged nestlings left the nest (fledged) and their pattern of presence and absence at the natal site during the post-breeding period. Corticosterone-treated nestlings had lower mass, higher baseline and stress-induced corticosterone, and reduced telomeres; other metrics of morphology were affected weakly or not at all. Our treatment resulted in no significant effect on survival to fledging, fledge age, or age at first departure from the natal site, and we found no negative effect of corticosterone on inter-annual return rate. These results show that brief acute corticosterone exposure during development can have measurable effects on phenotype in free-living tree swallows. Corticosterone may therefore mediate correlations between rearing environment and phenotype in developing organisms, even in the absence of prolonged stressors.Comment: 35 pages, 4 figures, 1 appendi

Orbitofrontal epilepsy: Electroclinical analysis of surgical cases and literature review

Clinical and electrographic data were reviewed on 2 of our patients with orbitofrontal epilepsy who were seizure free at 5-year follow-up, and on 2 similar patients from the literature. One of our patients was lesional, and the other was nonlesional. Interictal EEG discharges were lateralized to the side of invasively recorded orbitofrontal seizures in the nonlesional case. In this case, no clinical manifestations occurred until the orbitofrontal discharge had spread to the opposite orbitofrontal and both mesial temporal areas. Unresponsiveness or arrest of activity were the initial manifestations of complex partial seizures in both cases. The 2 cases from the literature with long-term seizure-free follow-up had little impairment of awareness and displayed vigorous motor automatisms. Interictal epileptiform activity was bifrontally synchronous in 1 case. Ipsilateral frontotemporal discharges were seen in both. Invasive ictal epileptiform activity appeared maximal in the ipsilateral orbitofrontal region in both patients. No consistent electrographic or clinical pattern characterized these 4 cases. Seizures of orbitofrontal origin may be characterized by either unresponsiveness associated with oroalimentary automatisms or limited alteration of awareness and associated with vigorous motor automatisms. Invasive monitoring of the orbitofrontal cortex should be considered in nonlesional cases with complex partial seizures that show nonlocalizing ictal patterns and interictal frontal or frontotemporal epileptiform discharges. Copyright (C) 2004 S. Karger AG, Basel

A General Model for Binary Cell Fate Decision Gene Circuits with Degeneracy: Indeterminacy and Switch Behavior in the Absence of Cooperativity

BACKGROUND: The gene regulatory circuit motif in which two opposing fate-determining transcription factors inhibit each other but activate themselves has been used in mathematical models of binary cell fate decisions in multipotent stem or progenitor cells. This simple circuit can generate multistability and explains the symmetric "poised" precursor state in which both factors are present in the cell at equal amounts as well as the resolution of this indeterminate state as the cell commits to either cell fate characterized by an asymmetric expression pattern of the two factors. This establishes the two alternative stable attractors that represent the two fate options. It has been debated whether cooperativity of molecular interactions is necessary to produce such multistability. PRINCIPAL FINDINGS: Here we take a general modeling approach and argue that this question is not relevant. We show that non-linearity can arise in two distinct models in which no explicit interaction between the two factors is assumed and that distinct chemical reaction kinetic formalisms can lead to the same (generic) dynamical system form. Moreover, we describe a novel type of bifurcation that produces a degenerate steady state that can explain the metastable state of indeterminacy prior to cell fate decision-making and is consistent with biological observations. CONCLUSION: The general model presented here thus offers a novel principle for linking regulatory circuits with the state of indeterminacy characteristic of multipotent (stem) cells

Glacial cycles promote greater dispersal, which can help explain larger clutch sizes, in north temperate birds

Earth’s glacial history and patterns in the life history traits of the planet’s avifauna suggest the following interpretations of how recent geological history has affected these key characteristics of the biota: 1) Increased colonizing ability has been an important advantage of increased dispersal, and life history strategies are better categorized by dispersive colonizing ability than by their intrinsic growth rates; 2) Birds of the North Temperate Zone show a greater tendency to disperse, and they disperse farther, than tropical or south temperate birds; 3) Habitat changes associated with glacial advance and retreat selected for high dispersal ability, particularly in the North; and 4) Selection for greater dispersal throughout the unstable Pleistocene has also resulted in other well-recognized life history contrasts, especially larger clutch sizes in birds of North Temperate areas