Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

The hepatitis delta virus (HDV), composed of ~1,700nt, is the smallest circular RNA pathogen known to infect humans. Understanding the mode of replication of HDV implies on investigating the host proteins that bind to its genome. The polypyrimidine tract-binding protein-associated splicing factor (PSF), an HDV interacting protein, was found to interact with the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), and to facilitate the interaction of RNA transcripts with the CTD of RNAPII. Both PSF and RNAPII were found to interact with both polarities of the terminal stem loop domains of HDV RNA, which possess RNA promoter activity in vitro. Furthermore, PSF and RNAPII were found to simultaneously interact with HDV RNA in vitro. Together, the above experiments suggest that PSF acts as a transcription factor during HDV RNA replication by interacting with both the CTD of RNAPII and HDV RNA simultaneously. PSF knockdown experiments were performed to indicate that PSF is required for HDV RNA accumulation. Mutagenesis experiments of PSF revealed that HDV RNA accumulation might require the N terminal domain, and the RNA recognition motifs RRM1 and RRM2. I propose that the RRM1 and RRM2 domains might interact with HDV RNA, while the N-terminal domain might interact with the CTD of RNAPII for HDV RNA accumulation. Together, the above experiments provide a better understanding of how an RNA promoter might be recognized by RNAPII.

The field of biological acoustics has witnessed a steady increase in the research into overtone singing, or “throat-singing,” in which a singer utilizes resonance throughout the vocal tract to sing melodies with the overtones created by a vocal drone. Recent research has explored both how a singer vocalizes in order to obtain rich harmonics from a vocal drone, as well as how further manipulations of the vocal apparatus function to filter and amplify selected harmonics. In the field of phonetics, vowel production is quantified by measuring the frequencies of vocal tract resonances, or formants, which a speaker manipulates to voice a particular vowel. Thus, an investigation of throat singing is closely linked to human speech production. Formants are usually detected in vowel spectra obtained using Fast Fourier Transform algorithms (FFTs). An alternative method that provides much higher frequency resolution is external excitation of the vocal tract and measurement of the pressure response signal at the mouth’s opening, which can be used to calculate the acoustic impedance spectrum. We demonstrate the use of such an “acoustic impedance meter” to measure the formant frequencies of common vowels as well as the oscillatory modes of simple resonant pipe systems. The impedance meter accurately measures fundamental pipe modes and a variety of formant frequencies with an uncertainty of 1 Hz. Finally, we assess how the impedance meter may be used to measure the unique resonances achieved by qualified throat singers.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

The hepatitis delta virus (HDV), composed of ~1,700nt, is the smallest circular RNA pathogen known to infect humans. Understanding the mode of replication of HDV implies on investigating the host proteins that bind to its genome. The polypyrimidine tract-binding protein-associated splicing factor (PSF), an HDV interacting protein, was found to interact with the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), and to facilitate the interaction of RNA transcripts with the CTD of RNAPII. Both PSF and RNAPII were found to interact with both polarities of the terminal stem loop domains of HDV RNA, which possess RNA promoter activity in vitro. Furthermore, PSF and RNAPII were found to simultaneously interact with HDV RNA in vitro. Together, the above experiments suggest that PSF acts as a transcription factor during HDV RNA replication by interacting with both the CTD of RNAPII and HDV RNA simultaneously. PSF knockdown experiments were performed to indicate that PSF is required for HDV RNA accumulation. Mutagenesis experiments of PSF revealed that HDV RNA accumulation might require the N terminal domain, and the RNA recognition motifs RRM1 and RRM2. I propose that the RRM1 and RRM2 domains might interact with HDV RNA, while the N-terminal domain might interact with the CTD of RNAPII for HDV RNA accumulation. Together, the above experiments provide a better understanding of how an RNA promoter might be recognized by RNAPII.

Vagal and spinal sensory innervation is responsible for the regulation of neurogenic inflammation in the airways. Neurogenic inflammation is the result of the activation of sensory nerve endings by stimulant and induced through axon reflex to release neuropeptides from sensory nerve endings. These neuropitides are tachykinins, including substance P, neurokinin A and neuronkinin B. Tachykinin-1 (NK-1) receptors are mainly involved in neurogenic inflammation in the airway. It is found that 6-hydroxydopamine (6-OHDA) acts as a stimulant of sensory neurons that produces inflammation in the rat trachea. The magnitude of plasma leakage was expressed by the area density (%) of India ink-labeled blood vessels in tissue whole mounts. The present study found that area density of India ink-labeled blood vessel were 36.5%, 29.5%, 27.7%, 28.2%, 19.2%, 15.5% in the rat larynx, trachea, left bronchus, right bronchus, upper esophagus and distal esophagus after i.v. injection of 6-OHDA (100 mg /Kg), respectively. 6-OHDA could stimulate sensory neurons by free radicals that produced by non-enzymatic oxidation. NK-1 receptor antagonist can inhibit plasma leakage in airways. This study also tested the effect of a free radical scavenger. Rats are pretreated with a full dose (2.25 g/kg, i.v.) or lower doses of dimethylthiourea (DMTU) for a period of 15 min. We found that pretreatment with a full dose of DMTU could inhibit inflammatory plasma leakage induced by 6-OHDA, that was 4.8%, 1.6%, 1.1%, 2.4%, 0.4% and 1.0% in the rat larynx, trachea, left bronchus, right bronchus, upper esophagus and distal esophagus, respectively. It is suggested hydroxyl radicals mediated the inflammatory response in the respiratory tract and esophagus. DMTU dose-dependently decreased 6-OHDA-induced plasma leakage in the rat respiratory tract and esophagus. One sixth dose was effective in inhibition in esophagus. 6-OHDA-induced inflammation in the left and right bronchus could be reduced with 2/3 dose of DMTU. A full dose of DMTU (2.25g/Kg) was needed to inhibit inflammation in the larynx and trachea. It is concluded that sensitivity to 6-OHDA was different in the different part of lower airways and esophagus.

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophagus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents. Each wall was divided into many small regions so that the histologic and radiosensitive variations of the tissues across the wall could be distinguished. The characteristic parameters were determined based on the newest information available in the literature. Each of these sections except the stomach was subdivided into multiple subsections to include the spatiotemporal variations in the shape and characteristic parameters. This new GIT was integrated into an anthropomorphic phantom representing both an adult male and a larger-than-average adult female. The current phantom contains 14 different types of tissue. This phantom was coupled with the MCNP 4C Monte Carlo simulation package. The initial design and coding of the phantom and the Monte Carlo treatment employed in this study were validated using the results obtained by Cristy and Eckerman (1987). The code was used for calculating specific absorbed fractions (SAFs) in various organs and radiosensitive tissues from uniformly distributed sources of fifteen monoenergetic photons and electrons, 10 keV - 4 MeV, in the lumenal contents of the five sections of the GIT. The present studies showed that the average photon SAFs to the walls were significantly different from that to the radiosensitive cells (stem cells) for the energies below 50 keV. Above 50 keV, the photon SAFs were found to be almost constant across the walls. The electron SAF at the depth of the stem cells was a small fraction of the SAF routinely estimated at the contents-mucus interface. Electron studies showed that the “self-dose” for the energies below 300 keV and the “cross-dose” below 2 MeV were only from bremsstrahlung and fluorescent radiations at the depth of the stem cells and were not important.

Thesis (Ph. D.)--University of Nevada, Reno, 2002. / Includes bibliographical references. Online version available on the World Wide Web.

No description available.

Poster presentation / Soc 397a / 2015 Poverty in Tucson Field Workshop