Established anatomical tract-tracing techniques have been used to examine the connectional anatomy of the non-cortically and cortically projecting medial geniculate in the neurologically primitive marsupial mammal, Monodelphis domestica. / The results suggest three primary conclusions. First, the medial geniculate body of Monodelphis is divisible into two populations of neurons--a rostral population projecting to neocortex and a caudal population projecting to non-cordical nuclei, with very few neurons projecting to both. Second, although both the rostral and caudal medial geniculate receive ascending projections from the inferior colliculus and other brainstem auditory as well as non-auditory nuclei, caudal medial geniculate receives a greater number and greater relative proportion of afferents from brainstem nuclei that have been shown to largely contribute to the non-lemniscal pathway through the medial and dorsal divisions of the medial geniculate in placental mammals. Inversely, rostral medial geniculate receives a greater number and relative proportion of its afferents from brainstem nuclei that have been shown to largely contribute to the lemniscal pathway through the ventral division. Thirdly, although both rostral and caudal medial geniculate receive substantial axonal terminations from descending corticothalamic fibers, rostral medial geniculate receives cortical input in a way usually seen in placental dorsal thalamic sensory nuclei, while caudal medial geniculate receives cortical input in a way usually seen in the medial division of the medial geniculate in placentals; or perhaps even more similar to the neocortical afferents that terminate in brainstem nuclei such as the inferior colliculus. / Source: Dissertation Abstracts International, Volume: 56-05, Section: B, page: 2491. / Major Professor: R. B. Masterton. / Thesis (Ph.D.)--The Florida State University, 1995.

The purpose of this study was to elucidate the control process for single-joint movements by examining behaviors of preprogrammed and on-line modulated muscle activation patterns that emerged in different task situations. Twelve subjects performed 35$\sp\circ$ and 70$\sp\circ$ elbow extension movements at two velocities with unstable external loads. / For each response, EMG activities of the triceps brachii and biceps brachii were acquired and digitized. The digitized EMG activities were used to calculate multiple EMG variables. Significant multivariate ANOVAs on overall dependent variables were followed by univariate ANOVAs on individual EMG variables, which suggested that only the agonist area for the first 50 ms of movement (Ago50) could be identified as a preprogrammed muscle activity. While external loads did not affect Ago50, velocity requirements and movement amplitudes had significant effects on Ago50, implying that knowledge about initial task constraints is incorporated into preprogramming of motor commands. / However, analyses on other EMG variables, including the first 50 ms of antagonist activity, agonist and antagonist areas after the first 50 ms of movement, their peak amplitudes, and times to reach the peak amplitudes, suggested that these variables could be identified as on-line modulated muscle activation patterns. Unlike the Ago50, they were sensitive to unexpectedly altered external loads, implying that the control system can utilize current sensory input in programming these muscle activation patterns. / Observed patterns of EMG variables suggest that the movement control process involves both preprogramming and on-line modulation of motor commands. Although the control system must preprogram some of the controlling factors before it can initiate a specified movement, the preprogrammed motor commands are not key determinants of the final movement outcome. Instead, the accuracy of the final movement outcome will be determined by the precision of both preprogrammed and on-line modulated controlling factors. Therefore, the control system has to operate continuously during the movement control process utilizing both its predictive ability and current sensory input as the basis for achieving a specified movement goal. / Source: Dissertation Abstracts International, Volume: 57-03, Section: B, page: 1642. / Major Professor: Tonya Toole. / Thesis (Ph.D.)--The Florida State University, 1996.

Light microscopic immunocytochemistry (ICC) of the central nucleus (CA) of the rat amygdaloid complex revealed two populations of corticotropin releasing factor (CRF) immunoreactive (IR) neuronal perikarya and terminals. Perikarya were isolated within the centrolateral (CL) subdivision of the CA (76.6% of all CRF-IR perikarya in the CA) and the centromedial subdivision of the CA (23.4% of total). CRF-IR fibers were occasionally observed within the stria terminals (ST) while a dense population of CRF-IR terminals was located in the central lateral capsular (CLC) subdivision of CA. In the CLC, CRF-IR terminals were observed to gather around clear circular areas suggesting an association with immunonegative neurons. Tyrosine hydroxylase (TH) IR in the CA was restricted to terminals. These terminals were virtually absent from the CLC, but densely accumulated in the CL where the greatest number of CRF-IR cell bodies were located. In the CL and CM, TH-IR terminals were observed in close association with clear areas that appeared to be unstained neurons. Double ICC for CRF and TH revealed that many of the TH-IR terminals were closely associated with CRF-IR neurons suggesting that synaptic contact might be present Electron microscopic ICC of the CA revealed that CRF-IR neuronal processes were spineless and were contacted by many asymmetric axodendritic synapses which occasionally contained dense cored vesicles while CRF-IR neurons were contacted by numerous mostly symmetric terminals. In the CLC, CRF-IR terminals were observed making numerous synaptic contact with immunonegative structures. Many of these terminals contained clear round vesicles of 50nm diameter and occasional dense cored vesicles that were approximately 100nm in diameter. Double EM ICC for CRF and TH revealed TH-IR terminals making both symmetric and asymmetric synaptic contacts with CRF-IR perikarya and denerites. TH-IR terminals contained 50nm clear round vesicles and 100 nm dense cored vesicles The origin or significance of intracentral amygdaloid CRF-IR connections could not be determined in the present study. However, through interconnections with several brainstem autonomic centers as well as the A10 and A9 mesencephalic dopaminergic cell groups, it is possible that the TH to CRF connections described in this work play an important role in directing autonomic responses to stress / acase@tulane.edu

Accurate identification of prognostic markers in primary breast cancer is critical for selecting the most beneficial mode of therapy for the affected patients. The estrogen receptor (ER) is a major prognostic marker, indicating the estrogen-responsive nature of breast tumors and the likelihood of response to hormonal therapy. Estrogen receptor variants may possess outlaw functions, acting in a dominant-positive (transcriptionally active in the absence of estrogen) or dominant-negative (transcriptionally inactive, while inhibiting the function of wild-type ER) manner. Developing a strong correlation between particular ER variants and altered estrogen-responsiveness suggests that over-expression of these ER variants or an altered expression ratio of these variants to the wild-type ER may be an important biologic event leading to the formation of hormone-independent, antiestrogen-resistant breast cancer Using a variety of approaches including RNase protection analysis and RT-PCR followed by cloning and sequencing, variant ER mRNAs with complete deletions of exons 5 and 7, in addition to the wild-type ER transcript, have been identified in the ER-negative BT-20 and ER-positive MCF-7 breast tumor cell lines. We have also been able to identify these two variant ER transcripts in a number of breast tumor cell lines both ER-positive and ER-negative. It appears that the exon 5 deletion variant $(\Delta 5)$ is expressed at higher levels than the exon 7 deletion variant $(\Delta 7)$ in each cell line, and the ratio of expression of variant to wild-type ER transcript differed among the cell lines examined. Immunoprecipitation of ER followed by Western blot analysis revealed a truncated receptor in the BT-20 cell line that is the expected size of the purported $\Delta 5$ variant ER protein and which possesses constitutive transcriptional regulatory activity in a yeast expression system. RNase protection analysis also demonstrated a variation in the levels of expression of $\Delta 5$ variant transcripts among stocks of MCF-7 cell lines obtained from different sources. Perhaps more importantly, a preliminary study has suggested that the expression of the $\Delta 5$ variant is modulated in culture by the presence or absence of estradiol / acase@tulane.edu

Melatonin, the hormonal product of the pineal gland, has been shown to inhibit the development of mammary tumors in vivo and the proliferation of MCF-7 cells in vitro by mechanisms not yet identified. Previous studies have demonstrated that only human breast cancer cells which express estrogen receptor (ER) are responsive to the antimitogenic effects of melatonin, suggesting a link between the effects of melatonin and the estrogen-response pathway. MCF-7 human breast cancer cells, which are ER-positive and responsive to the mitogenic actions of estrogen, were used to examine the possible association between the antiproliferative activity of melatonin and its ability to modulate the estrogen-response pathway at the level of ER expression. In order to determine the mechanism(s) by which melatonin regulates ER expression in MCF-7 cells, the relationship between ER protein expression, estrogen binding activity, steady-state levels of ER mRNA, the level of ER gene transcription, and the stability of the ER transcript were examined in response to melatonin Physiologic concentrations of melatonin significantly decreased estrogen binding activity, expression of immunoreactive ER protein, and steady-state levels of ER mRNA in a dose-specific and time-dependent manner in both complete and estrogen-depleted media. However, melatonin did not alter receptor affinity and was unable to compete with estrogen for binding to the ER. Studies in a yeast transcriptional assay system confirmed that melatonin does not directly bind to the ER to modulate ER expression. The decreased expression of ER protein in response to melatonin appears to be directly related to both suppressed ER gene transcription and decreased half-life of the ER message. This regulation is independent of the synthesis of new proteins since cycloheximide did not block the melatonin-induced decrease in ER mRNA. The expression of several estrogen-induced genes were differentially regulated by melatonin, suggestive of the interplay of early versus late events in the action of melatonin. Thus, it appears that the antiproliferative actions of melatonin may be mediated, at least in part, through the suppression of the estrogen-response pathway of MCF-7 cells / acase@tulane.edu

No description available.

The study of variation in arachnid genitalic structures has contributed to the fields of systematics and sexual selection. Simon (1892--1903) in his Histoire Naturelle des Araignees first divided the ecribellate higher spiders into two groups, the Haplogynae and Entelegynae, using reproductive morphology. Spider genitalia have been used as a taxonomic tool for distinguishing between taxa because of their species-specific morphological variation. Variation in spider genitalic morphology has inspired evolutionary biologists to test mechanisms of sexual selection by which the variation could evolve, ranging from Fisherian run-away selection, chase-away selection, and sperm competition. The Tetragnathidae are particularly interesting for a comparison between haplogyne and entelegyne reproductive morphologies. Within this entelegyne family, a reversal to haplogyny has occurred. Fifteen representative members of this family and four outgroup taxa were examined with scanning and transmission electron microscopy in order to describe the fine structure of spermathecae, including the distribution and density of spermathecal gland pores. While the function(s) of the glandular secretion are unknown, the distribution and density of spermathecal gland pores is discussed with regard to possible functions of the glandular secretion. The potential influence of spermathecal gland secretions on mating behavior and sperm competition is considered. Sperm release patterns have been examined in entelegynes, but previously were not available for haplogynes. The relationship between copulation duration and sperm release was determined in Tetragnatha versicolor, the first examination of sperm release patterns in any haplogyne spider. In this species, copulation duration is not proportional to sperm release. To examine the relative influence of spermathecal morphology and numerical sperm competition on paternity, sperm release and paternity was assessed in the entelegyne Nephila clavipes and the haplogyne Tetragnatha versicolor. The data clearly support differential sperm release between males as the cause of previously reported first-male advantage in Nephila clavipes and the mixed paternity found for N. clavipes and Tetragnatha versicolor in this study. The natural history, mating behavior, and sperm release were determined for a previously unstudied tetragnathid species, Glenognatha emertoni . This is the second examination of haplogyne sperm release behavior as well as the first description of an unusual escape behavior.

A complex set of developmental events transform early primordia within endocardial cushions into the atrioventricular (AV) valves and septa of the mature heart. Endocardial cushions are composed of an inner endocardial layer, and outer myocardial layer, and an acellular extracellular matrix rich layer separating these two layers. A subset of endocardial cells within cushions transform into mesenchymal cells that migrate into the extracellular matrix and differentiate into mature valve and septum tissue. This cell transformation process coupled with asymmetrical cell proliferation within endocardial cushions remodels simple early endocardial cushions into elongated valves. Investigation into molecular mechanisms involved in valve and septum morphogenesis centered on a family of growth factors, called Wnts, due to previous reports showing involvement of this growth factor family in similar developmental processes. Expression analysis of Wnt growth factors, Wnt receptors, and soluble Wnt inhibitors was performed in search of Wnt signaling components with restricted expression in AV endocardial cushions. Initial RT-PCR analysis demonstrated expression of several Wnts (Wnt-5a, Wnt-6, Wnt-9a, Wnt-10a and Wnt-11), Wnt receptors (Fz-1, Fz-3, Fz-4, and Fz-6) and the soluble Wnt antagonist Frzb in early endocardial cushions. Spatial and temporal expression analysis revealed restricted endocardial cushion expression of Wnt-9a and Frzb. Wnt-9a is expressed in the endocardial cell layer while Frzb is expressed in the endocardium and transformed mesenchyme of AV endocardial cushions. Overexpression of Wnt-9a in endocardial cushions increases cell proliferation resulting in enlarged hypercellular endocardial cushions. Overexpression of a truncated mutant form of Wnt-9a, which acts in a dominant negative manner, increases programmed cell death in endocardial cushions. Overexpression of Wnt-9a also induces β-catenin responsive transcription in AV canals consistent with Wnt-9a signaling in a canonical Wnt/β-catenin pathway. Wnt-9a induced increases in cell proliferation are inhibited by overexpression of Frzb. Spatial expression patterns suggest that Frzb delineates a zone of Wnt-9a induced cell proliferation near the endocardial cell layer to promote endocardial cushion outgrowth and remodeling into mature valve leaflets.

Numerous studies in experimental animals have emphasized the importance of tachykinin peptides in hypothalamic function. There is however, little information on the location of these peptides in the human brain. In the first study, in situ hybridization was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) gene transcripts. The distribution of neurons containing tachykinin mRNAs was found to be distinct and complementary: SP was the predominant tachykinin in the striatum, posterior hypothalamus and intermediate, ventromedial and mammillary nuclei; there were more NKB mRNA containing neurons than SP neurons in the magnocellular basal forebrain, the bed nucleus, and the preoptic/anterior hypothalamic regions. Comparable numbers of neurons expressing both mRNAs were identified in the infundibular nucleus and amygdala. Because numerous neurons containing NKB mRNAs were identified in the nucleus basalis of Meynert, it was next determined if NKB mRNA and choline acetyltransferase (ChAT) mRNAs are colocalized in this region. It was found that approximately 30% of the cholinergic neurons in the nucleus basalis also expressed NKB gene transcripts. This is the first identification of peptide colocalization in a significant population of magnocellular cholinergic neurons in the human basal forebrain. The nucleus basalis of Meynert plays an important role in higher brain functions in humans. There is considerable evidence suggesting that SP and gonadotropin releasing hormone (GnRH) neurons are anatomically and functionally connected in the human brain. In this study, double in situ hybridization with 35S-labeled SP receptor (SPR) and digoxigenin-labeled GnRH riboprobes was used to determine if GnRH neurons contain SPR mRNAs. The radiolabeled GnRH riboprobe hybridized with scattered neurons in the preoptic-septal regions and medial basal hypothalamus. A digoxigenin-labeled GnRH probe labeled cells in the medial basal hypothalamus, the primate control center for reproduction. SPR mRNA was identified in numerous magnocellular basal forebrain neurons, however, GnRH neurons containing SPR mRNAs were not identified. Although the possibility that SPR mRNA may be present in these cells but below the level of detection remains, present data suggests that a link between SP and GnRH neurons does not exist in the human brain.

A model of the human head and neck that incorporates active and passive muscles is presented for use in the analysis of non-impact loading in high "g" environments. The inclusion of the active muscles is shown to improve the accuracy of the model response to impulse loading conditions, especially during the interval that begins approximately 120 ms after the application of the impulse. The active muscles have the capability of activating partially and in different combinations. The parameters defining the force-length and force-velocity relationships used for the active muscles are based on recent experimental data for neck muscles, including: muscle length, sarcomere length, and physiological cross-sectional area. The parameters, which fall within a large range of input selections, are applied to the fifteen muscle pairs of the neck. The model is implemented in MADYMO using lumped parameters and Hill muscles. A comparison of simulation results with experimental data, generated by the Naval Biodynamics Laboratory, shows excellent agreement for a flexion/rebound 15 g impulsive load and a 7 g lateral load. A model incorporating the head and neck with active muscles is implemented with a body of a 50th percentile male anthropomorphic test device. This model is subjected to the 15 g flexion impulsive load and also shows excellent agreement with the experimental data.