The Role of the Sympathetic Nervous System in the Hypothermic Effect of d-Fenfluramine

Experiments in this dissertation were conducted to characterize the effects of d-fenfluramine on body temperature and the mechanisms by which d-fenfluramine alter body temperature. The experiments were conducted in conscious male Sprague-Dawley rats. Body temperature was measured in all animals using telemetry. The results of the experiments indicated that d-fenfluramine altered body temperature in animals kept 28, 22, 16 and 4 degrees Centigrade. D-fenfluramine produced hyperthermia in animals kept at 28 degrees Centigrade and varying degrees hypothermia at normal and cooler ambient temperatures. Further experiments were conducted to explore the effects of d-fenfluramine on brown adipose tissue (BAT) thermogenesis, cutaneous vascular tone and whole body oxygen consumption. In animals kept at 22 and 4 degrees Centigrade, we found that d-fenfluramine activated BAT, as indicated by a decrease in BAT norepinephrine content, to the same magnitude. Thus, the hypothermia seen at normal and cooler ambient temperature was not due to lack of BAT activation. Also, activation of BAT by d-fenfluramine was mediated through the sympathetic nervous system and through release of central serotonin, since ganglionic blocker pentolinium and serotonin reuptake inhibitor fluoxetine blocked d-fenfluramine-mediated BAT activation. In animals kept at 16 degrees Centigrade, d-fenfluramine increased tail-skin temperature (Tsk), an index of cutaneous vascular tone, indicating that d-fenfluramine produced cutaneous vasodilation. d-fenfluramine-induced increase in Tsk was mediated through withdrawal of the sympathetic vasoconstrictor tone to the tail, since pentolinium blocks this effect. In animals kept at 28 degrees Centigrade, d-fenfluramine produced a decrease in Tsk, indicating vasoconstriction. The effects of d-fenfluramine on the Tsk were mediated through release of serotonin, since fluoxetine blocked these effects. D-fenfluramine increased whole body oxygen consumption, an index of metabolic activity and the increase was due to BAT activation, since pentolinium prevented the increase. Thus, although d-fenfluramine increased metabolic activity through BAT activation, the increase was insufficient to make up for the heat loss produced by cutaneous vasodilation and thus produces hypothermia. The hyperthermia seen at 28oC is due to activation of BAT and the subsequent inability of the animal to lose the excess heat due to cutaneous vasoconstriction produced by d-fenfluramine at 28 degrees Centigrade

Initiation of CME event observed on November 3, 2010: Multi-wavelength Perspective

One of the major unsolved problems in Solar Physics is that of CME initiation. In this paper, we have studied the initiation of a flare associated CME which occurred on 2010 November 03 using multi-wavelength observations recorded by Atmospheric Imaging Assembly (AIA) on board Solar Dynamics Observatory (SDO) and Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI). We report an observation of an inflow structure initially in 304~{\AA} and in 1600~{\AA} images, a few seconds later. This inflow strucure was detected as one of the legs of the CME. We also observed a non-thermal compact source concurrent and near co-spatial with the brightening and movement of the inflow structure. The appearance of this compact non-thermal source, brightening and movement of the inflow structure and the subsequent outward movement of the CME structure in the corona led us to conclude that the CME initiation was caused by magnetic reconnection.Comment: 17 pages, 9 figures, Accepted for Publication in The Astrophysical Journa

Stochasticity of gene products from transcriptional pulsing

Transcriptional pulsing has been observed in both prokaryotes and eukaryotes and plays a crucial role in cell-to-cell variability of protein and mRNA numbers. An important issue is how the time constants associated with episodes of transcriptional bursting and mRNA and protein degradation rates lead to different cellular mRNA and protein distributions, starting from the transient regime leading to the steady state. We address this by deriving and then investigating the exact time-dependent solution of the master equation for a transcriptional pulsing model of mRNA distributions. We find a plethora of results. We show that, among others, bimodal and long-tailed (power-law) distributions occur in the steady state as the rate constants are varied over biologically significant time scales. Since steady state may not be reached experimentally we present results for the time evolution of the distributions. Because cellular behavior is determined by proteins, we also investigate the effect of the different mRNA distributions on the corresponding protein distributions using numerical simulations