Zugl.: Diplomarbeit. / Literaturverz. S. 131 - 135.

Thesis (Ph. D.)--Open University. BLDSC no. DX79221. / Consultation copy in 2 volumes.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 154-166). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 74-85).

Thesis (M.A.M.C.)--University of Florida, 2004. / Title from title page of source document. Document formatted into pages; contains 202 pages. Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Rhode Island, 2003. / Typescript. Includes bibliographical references (leaves 109-123).

Brown adipose tissue (BAT) is a unique organ in existence in mammals. It can induce non-shivering thermogenesis to control body temperature and energy balance through the expression of uncoupling protein 1 (UCP1). In our study, we aimed to evaluate the prevalence of BAT, as detected by fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography combined computer tomography (PET/CT), in a Hong Kong Chinese population. We also assessed the influence of age and sex to BAT in Hong Kong Chinese population. We also determined the factors associated with it, in particular, its relationship with overweight and other metabolic disorders such as diabetes mellitus. We analyzed 1765 consecutive 18F-FDG PET-CT scans of 1442 Chinese for the presence of BAT. Comparison of the variables between positive and negative BAT scans was performed using Student’s t-test. The association between maximum value of standardized uptake value (SUVmax) and variables were explored by Spearman correlation. The predictors of observed BAT were analyzed by multiple logistic regression to determine the significant predictors of positive BAT. The relationship between the monthly numbers of subjects with BAT and the respective mean monthly outdoor temperature was evaluated by Pearson’s correlation co-efficient. P < 0.05 was considered to be statistically significant. Brown adipose tissue was detected in 66 out of 1442 subjects (4.6%). BAT was significantly more commonly found in younger (43.7±13.5 years old vs. 61.4±14.2 years old, P<0.001) and female (59% vs. 46%, P<0.05) subjects. BAT also existed more frequently in subjects with lower body mass index (BMI) (21.2±3.1 kg/m2 vs. 22.4±3.7 kg/m2, P<0.01) and lower blood glucose level (5.9±0.9 mmol/L vs. 6.4±1.6 mmol/L, P<0.01). Also, BAT was detected only in subjects with no history of diabetes meallitus (DM) (0 vs. 10%, P<0.01). Moreover, lower outdoor temperature (21.6±4.6。C vs. 23.4±4.7。C, P<0.005) resulted in higher prevalence of detected BAT. In the multiple logistic regression test, age and mean monthly temperatures were the significant independent predictors of the presence of BAT (P< 0.001 and P=0.001). Age was also significantly correlated to SUVmax (P< 0.001). The monthly prevalence of positive BAT correlated negatively with mean monthly temperature by Pearson’s correlation (r = -0.79; P<0.01). To summarize, BAT was more commonly found in young, female subjects with lower BMI and blood glucose levels, and non-diabetes subjects. Age was the most important factor associated with the prevalence of BAT in humans. Lower outdoor temperature in winter can increase the prevalence of BAT even in Hong Kong’s sub-tropical climates. Also, there was an association of BAT with normal BMI (<=23) and lower blood sugar levels supporting the notion that BAT may potentially be a therapeutic target for obesity and diabetes. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

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The processing of sensory signals is an important, yet complex task in which a system must extract behaviorally relevant stimulus patterns from a vast array of sensory cues. When a neuron within a major sensory area is presented with a stimulus, one of the important characteristics used to distinguish between types of input is frequency. Often sensory neurons are tuned to narrow stimulus frequency ranges and are thus charged with the processing of subtypes of sensory signals. The weakly electric fish Apteronotus lepthorhynchus senses it's environment through modulations of a self-generated electric field. Two main types of sensory signals can be distinguished based on their frequency patterns. Prey stimuli cause low frequency perturbations of the electric field, while communication signals often result in high frequency signals. Pyramidal neurons in the electrosensory lateral line lobe (ELL) encode the low frequency signals with bursts, while the high frequency signals are relayed with single spikes. This thesis describes how a pyramidal neuron's response patterns can be tuned to specific frequencies by the expression of distinct classes of potassium channels. / I have cloned 3 small conductance (SK) calcium activated potassium channels from cDNA libraries created from the brain of Apteronotus. I have subsequently localized the AptSK channels throughout the brain using both in situ hybridization (AptSK1, 2 & 3) and immunohistochemical (AptSK1 & 2) techniques. The 3 channels showed distinct expression patterns, with the AptSK1 & 2 channels showing a partially overlapping expression pattern, while AptSK3 appears to be expressed in unique areas of the brain. In the ELL AptSK1 & 2 show a partially overlapping expression pattern, appearing in similar pyramidal neurons. However, their distribution within individual cell is unique, with AptSK1 showing a dendritic localization, while AptSK2 is primarily somatic. We have demonstrated that the unique expression pattern of the somatic AptSK2 channel in the ELL coincides with the functional SK currents evaluated through in vitro electrophysiology. Further we have shown that neurons that encode low frequencies do not possess functional SK channels. It thus appears that the presence of the AptSK2 channel subtype can predispose a neuron to respond to specific types of sensory signals. / In an attempt to evaluate if second messengers could modify the AptSK control of frequency tuning I investigated the consequences of muscarinic acetylcholine receptor (mAChR) activation on a pyramidal neurons response patterns. While it had been shown in vivo that mAChR activation increased a pyramidal neuron's response to low frequencies, I have found that this was not due to a decrease in AptSK current, but rather appears to be the result of a down-regulation of an A-type potassium channel. / Taken together the studies that comprise this thesis show how the selective expression of a single potassium channel subtype can control a sensory neurons response to specific environmental cues. The secondary modulation of the A-type current highlights the potential for a second messenger to control a neuron's sensory response through the down-regulation of constitutively expressed potassium current.

Members of voltage-gated potassium channel subfamily 3 (Kv3) have been extensively demonstrated to play a significant role in facilitating function of "fast-firing" neurons in the central nervous system. Kv3.1 and Kv3.3 channels, members of Kv3 channel subfamily, have different distribution profiles on the regional level of brain and on the subcellular level of neurons in mammals and in weakly electric fish, according to mRNA hybridizations in situ and immunohistochemical analysis. In mammals, Kv3.1 channels are expressed in soma, axon and proximal dendrites as well as presynaptic membrane of "fast-firing" neurons. In weakly electric fish (Apteronotus), Kv3.1 channels are distributed in the soma, in the basilar dendrites and in the proximal apical dendrites of pyramidal neurons; on the other hand, Kv3.3 channels are expressed in a larger region: soma, basilar dendrites and entire apical dendrites of these cells. Mechanisms underlying differential subcellular distribution of Kv3.1 and Kv3.3 channels in the apical dendritic compartment of pyramidal neurons are unknown. In order to identify peptide sequences responsible for the differential subcellular localization, I have used Semliki Forest virus as a modified viral expression system (PDE) in vivo to study dendritic targeting mechanisms in the pyramidal neurons of electrosensory lateral line lobe (ELL), where the primary processing for afferent input occurs in the apteronotid electrosensory system.