published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Biological Sciences / Master / Master of Philosophy

The purpose of the present study was to determine whether computer-based cognitive bias modification (CBM) procedures could alter appraisal style toward viewing events from a big picture perspective and thereby influence emotional reactivity. Big picture appraisal entails viewing difficult situations and one's reactions to them in terms of a larger context. Appraisal training was implicit in that participants completed a series of vignettes, framed as a reading comprehension task, which trained either a big picture perspective or a personal/evaluative focus. When subsequently confronted with novel vignettes, participants produced interpretations that were consistent with assigned training condition. In addition, participants trained in big picture as compared to personal/evaluative appraisal subsequently demonstrated less emotional reactivity to a stressful task. / text

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14 pp. / This publication summarizes the results of a three year research study that evaluated whether the turf water duties mandated by the Arizona Department of Water Resources provide adequate water to grow acceptable quality turf in the Tucson and Phoenix areas.

It has been shown that maximal, bilateral efforts result in both a force and EMG deficit when compared to maximal, unilateral activation of the same musculature. It is unclear whether this deficit is the result of interactions of central or peripheral origin. The first aim study investigated the bilateral performance index (BPI (%) = [100 x bilateral force/(right unilateral + left unilateral forces)] - 100) for maximal, isometric, extensor torques about the knee joint in three groups of subjects: untrained (never lifted weights), cyclists (leg musculature trained reciprocally), and weightlifters (legs trained bilaterally). The BPI for the weightlifters (+7.0 ± 5.0%) was significantly (p < 0.05) greater than the BPI of the cyclists (-4.0 ± 6.3%) or the untrained subjects (-9.7 ± 5.2%). These results indicate that the inhibitory mechanisms previously proposed to act during bilateral efforts are inadequate, and that excitatory factors must be present to achieve a BPI > 0. The second aim study showed that the BPI can be altered as a result of three weeks of bilateral isometric strength training. The BPI's for the control and unilateral training groups were not significantly different pre- to posttraining. However, the BPI of the bilateral training group increased significantly (p < 0.05) from -3.7 ± 6.9% prior to training, to +4.2 ± 4.4% after training. These findings indicate that bilateral strength training can alter the relationship between unilateral and bilateral force output. The third aim study demonstrated that subjects with a positive BPI (+6.8 ± 4.3%) responded differently to an afferent perturbation (electrical stimulation) than subjects with a negative BPI (-10.0 ± 5.2%). The negative BPI group showed a 5.7 ± 3.4% facilitation in force during contralateral electrical stimulation. This was significantly (p < 0.05) less than the 16.5 ± 7.5% facilitation shown by the positive BPI group. These results indicate that afferent feedback can alter the force output in the contralateral limb, and may thereby play a role in unilateral-bilateral force differences.

Previous genetic evidence suggested that RecA was required in SOS mutagenesis for its regulatory role and perhaps some other nonregulatory role (Mount, 1977; Blanco et al., 1982). I undertook a genetic study which confirmed the above studies and provided further evidence that RecA protein appeared to have a dual "role in mutagenesis; first, the cleavage of LexA repressor for the derepression of specific SOS genes and second, one or more additional role(s). For these studies a new phage mutagenesis assay was developed which allows rapid scoring of SOS mutagenesis in a large number of host mutants. I next conducted a genetic analysis to determine if the newly defined RecA mutagenesis function was separable by mutation from the numerous other phenotypes which are known to be influenced by RecA protein. From the study of recA mutants it appears that the RecA mutagenesis function(s) is genetically separable from the following RecA phenotypes: LexA cleavage, lambda cI repressor cleavage, UV resistance and homologous recombination. In addition, I discovered that the LexA cleavage function and lambda cI cleavage function is also separable. I also studied in some detail the novel genetic properties that I uncovered for recA432 mutant strains. recA432 was defined as a mutagenesis defective allele (Kato and Shinoura, 1977). LexA cleavage in recA432 cells was more easily induced that in recA⁺ cells, causing lethal filamentation of these mutant cells even at very low UV doses. I concluded that the basis for the Mut⁻ phenotype was this strain's propensity to lethally filament, which complicated the detection of mutant cells. In another set of experiments, I examined the regulatory requirements for SOS mutagenesis and Weigle phage-reactivation; I wanted to determine which SOS operons must be derepressed for this process. lexA(Ind⁻) mutant cells are defective in mutagenesis because they cannot derepress specific SOS genes required in this process. I found that the selective derepression of umuDC was sufficient to restore mutagenesis to these lexA(Ind⁻) mutants; however, derepression of umuDC and recA was required for phage reactivation.

Several feeding-related factors can affect taste sensitivity or preferences and therefore may be part of a homeostatic regulatory mechanism. Cholecystokinin (CCK), a hormone which reduces food intake in several species, has also been postulated to interact with the orosensory characteristics of food. To test this hypothesis, the effects of CCK-8 and food deprivation on the short-term intakes of water, sucrose solutions (0.05 to 1.0 M), and saline solutions (0.05 and 0.15 M) were determined. In most cases, CCK (2 μg/kg) reduced sucrose intake when measured either as the amount consumed or the number of licks in a short period (nine minutes). Additionally, CCK reduced the intake of 0.15 M NaCl in satiated rats and water intake in both hungry and satiated rats. Rats usually consumed more sucrose when hungry than when satiated or fed ad libitum; CCK-induced suppression of intake, however, was generally greater in the satiated or ad libitum conditions than in the hungry condition. There was no systematic effect of sucrose concentration on the amount of CCK-induced suppression of intake, which suggests that CCK regulates rather than interferes with ingestion. To determine whether the CCK-induced suppression is due to a change in the peripheral taste signal, the integrated chorda tympani responses to sucrose and NaCl tastes were recorded in rats anesthetized with either urethane, Innovar-Vet, or a combination of urethane and alpha-chloralose. The only significant effect of CCK was the slight increase in the initial response to 0.3 M sucrose after the infusion of a total of 10 μg of CCK-8 into rats anesthetized with Innovar-Vet. In general, therefore, the effect of CCK on sucrose intake does not appear to be due to a peripheral taste change; an analysis of single taste fibers, however, would be more conclusive. An examination of the effects of CCK on central gustatory and reward areas might yet provide a mechanism for the CCK effect on taste-motivated ingestion.

This report describes the development and use of an expression vector system based on the single-stranded DNA bacteriophage M13. A derivative of M13mp8, designated M13mp8/P, was prepared in which the promoter and N-terminal codons of bacterial genes may be fused to a portion of β-galactosidase, resulting in an easily scorable phenotype. Because transcription from the inserted promoter remains responsive to the host regulatory system, it is simple to screen mutagenized phage for isolates with aberrant regulatory phenotypes, and to determine the mutational changes by dideoxy sequence analysis. The feasibility of this method was demonstrated by identification of a large number of mutations in the regulatory regions of two genes, recA and lexA. Base substitutions that altered the phenotype of recombinant phage were identified both in the single LexA repressor binding site of recA and in the two binding sites of lexA, as well as in other sites that likely affect translational efficiency. My results suggest that this method will be generally useful for mutational analysis of transcriptional and translational regulatory elements. The mutants that were isolated by the above approach were used to investigate the specificity of LexA protein binding by quantifying the repressibility of a several mutant recA and lexA operator/promoter regions fused to the E. coli galactokinase (galK) gene. The results of this analysis indicated that two sets of four nucleotides (terminal nucleotide contacts), one set at each extreme end of the operator, are most critical for repressor binding. In addition, our results indicate that the repressor-operator interaction is symmetric in nature, in that mutations at symmetrically equivalent positions in the recA operator had comparable effects on repressibility. The inferred symmetry of the interaction justified the reevaluation of the consensus sequence by half-site comparison, which yielded the half-site consensus: (5') CTGTATAT. Although the first four positions of this half-site sequence have the greatest effect on LexA repressor binding, the last four are well conserved among binding sites and appear to modulate repressor affinity. The role of the terminal nucleotide contacts and the mechanism by which the internal sequences affect repressor binding is discussed.

Transposons were first discovered as "jumping genes" by Barbara McClintock, who continued to study them in maize through the 1940's and 1950's. Since then, transposons have been shown to make up a large percentage of eukaryotic genomes, including close to half of the human genome, but have been dismissed as simply "junk DNA." Recently, the importance of keeping transposons tightly regulated within the cellular environment has begun to be appreciated; the mechanisms to accomplish this have been studied and the current understanding of pathways governing transposon regulation is discussed within this dissertation. However, recent work presented within the scope of this dissertation in Drosophila melanogaster revealed a previously unknown function for condensin complexes in transposable element regulation. These studies provide a link between pathways governing chromosome pairing and transposon regulation. The potential interplay between these two pathways is intriguing and until now, largely unexplored.Aside from how transposons themselves are regulated, studies into potential roles they may play in the regulation of other protein coding genes within the cell may provide clues into the functionality of these elements within our genome. As a specific example, BRCA1 has a high density of retrotransposon sequences within its primary transcript, and studies of BRCA1 regulation presented within this dissertation has led to the development of a model for a novel gene regulatory mechanism occurring in human cells involving retrotransposons. This mechanism may provide direct relevance to cancer etiology, as retrotransposons have long been known to be misregulated in cancer.As a sum, the work presented within this dissertation extends our knowledge of how transposons are regulated and provides some of the first evidence for their functionality in gene regulatory pathways within human cells.