Effects of Kisspeptin1 on Electrical Activity of an Extrahypothalamic Population of Gonadotropin-Releasing Hormone Neurons in Medaka (Oryzias latipes)

Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca2+/high Mg2+ solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its regulation of an extrahypothalamic population of GnRH neurons involved in multiple neuromodulatory functions

System Dynamics Modeling for Traumatic Brain Injury: Mini-review of Applications

Traumatic brain injury (TBI) is a highly complex phenomenon involving a cascade of disruptions across biomechanical, neurochemical, neurological, cognitive, emotional, and social systems. Researchers and clinicians urgently need a rigorous conceptualization of brain injury that encompasses nonlinear and mutually causal relations among the factors involved, as well as sources of individual variation in recovery trajectories. System dynamics, an approach from systems science, has been used for decades in fields such as management and ecology to model nonlinear feedback dynamics in complex systems. In this mini-review, we summarize some recent uses of this approach to better understand acute injury mechanisms, recovery dynamics, and care delivery for TBI. We conclude that diagram-based approaches like causal-loop diagramming have the potential to support the development of a shared paradigm of TBI that incorporates social support aspects of recovery. When developed using adequate data from large-scale studies, simulation modeling presents opportunities for improving individualized treatment and care delivery

Photoperiodic requirements for timing onset and duration of the breeding season of the ewe: Synchronization of an endogenous rhythm of reproduction

A study was conducted to test the hypothesis that different portions of the annual photoperiodic cycle play different roles in timing the breeding season of the ewe, Ovis aries , an animal in which an endogenous rhythm generates the seasonal reproductive transitions. Adult female sheep were pinealectomized to disrupt transduction of photoperiodic cues at 4 times of the year (summer and winter solstices, vernal and autumnal equinoxes), and the effects on seasonal reproductive neuroendocrine activity were evaluated. Time of pinealectomy greatly influenced the subsequent seasonal reproductive cycle such that the following inferences are possible. Lengthening days between the winter and summer solstices synchronize reproductive onset to the appropriate time of year. The relatively long days around the summer solstice act to suppress reproductive activity and forestall the start of the breeding season until late summer/early autumn. The shortening days between the summer solstice and autumnal equinox maintain a normal intensity and duration of reproductive neuroendocrine induction during the impending breeding season. However, the shortening days between the autumnal equinox and winter solstice (i.e., after breeding season onset) do not appear to play a critical role in maintaining the breeding season of that year, but may provide important cues for timing the breeding season of the following year.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47092/1/359_2004_Article_BF00187330.pd

X-Atlas: An Online Archive of Chandra's Stellar High Energy Transmission Gratings Observations

The high-resolution X-ray spectroscopy made possible by the 1999 deployment of the Chandra X-ray Observatory has revolutionized our understanding of stellar X-ray emission. Many puzzles remain, though, particularly regarding the mechanisms of X-ray emission from OB stars. Although numerous individual stars have been observed in high-resolution, realizing the full scientific potential of these observations will necessitate studying the high-resolution Chandra dataset as a whole. To facilitate the rapid comparison and characterization of stellar spectra, we have compiled a uniformly processed database of all stars observed with the Chandra High Energy Transmission Grating (HETG). This database, known as X-Atlas, is accessible through a web interface with searching, data retrieval, and interactive plotting capabilities. For each target, X-Atlas also features predictions of the low-resolution ACIS spectra convolved from the HETG data for comparison with stellar sources in archival ACIS images. Preliminary analyses of the hardness ratios, quantiles, and spectral fits derived from the predicted ACIS spectra reveal systematic differences between the high-mass and low-mass stars in the atlas and offer evidence for at least two distinct classes of high-mass stars. A high degree of X-ray variability is also seen in both high and low-mass stars, including Capella, long thought to exhibit minimal variability. X-Atlas contains over 130 observations of approximately 25 high-mass stars and 40 low-mass stars and will be updated as additional stellar HETG observations become public. The atlas has recently expanded to non-stellar point sources, and Low Energy Transmission Grating (LETG) observations are currently being added as well

Parent-clinician communication intervention during end-of-life decision making for children with incurable cancer.

Background: In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents\u27 rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child\u27s clinicians in time to be of use in the family\u27s care. Methods: Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life communication with their child\u27s clinicians. They completed the questionnaire again two to three weeks later and responded to three open-ended questions to assess the benefit:risk ratio of their study participation three months after the intervention. Clinicians received the interview data within hours of the parent interview and evaluated the usefulness of the information three weeks later. Results: All preestablished intervention feasibility criteria were met; 77.3% of families consented; and in 100% of interventions, information was successfully provided individually to 3 to 11 clinicians per child before the child died. No harm was reported by parents as a result of participating; satisfaction and other benefits were reported. Clinicians reported moderate to strong satisfaction with the intervention. Conclusion: The communication intervention was feasible within hours of decision making, was acceptable and beneficial without harm to participating parents, and was acceptable and useful to clinicians in their care of families

Proceedings from the National Cancer Institute’s Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and treatment of relapse after allogeneic transplantation

AbstractIn the Second Annual National Cancer Institute’s Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the first relapse workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies to prevent relapse after transplantation, for example, recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction before DLI, combination of targeted agents with DLI, and considerations in use of second transplantations. Dr. Porter addressed strategies to enhance T cell function, including ex vivo activated T cells and T cell engineering, and immunomodulatory approaches to enhance T cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways

Prospectus, April 1, 1987

https://spark.parkland.edu/prospectus_1987/1010/thumbnail.jp

Does Seasonal Reproductive State Affect the Neuroendocrine Response of the Ewe to a Long-Day Pattern of Melatonin?

This study examined whether or not the reproductive response of female sheep to photoperiod varies with seasonal reproductive state. The specific objective was to test the hypothesis that the reproductive response to a long-day pattern of melatonin varies with the reproductive state of the ewe. The response examined was the synchronization of reproductive neuroendocrine induction (rise in serum luteinizing hormone, or LH) following nocturnal infusion of melatonin into pinealectomized ewes for 35 consecutive nights. This infusion restored a pattern of circulating melatonin similar to that in pineal-intact ewes maintained in a long photoperiod (LD 16:8). The ewes had been pinealectomized and without melatonin replacement for 16-25 months prior to the study. They were in differing reproductive states at the start of the infusion, as their endogenous reproductive rhythm had become desynchronized among individuals and with respect to time of year. Noninfused pinealectomized ewes served as controls. Regardless of the reproductive state at the start of the 35-day infusion of the long-day pattern of melatonin, all treated ewes exhibited the same reproductive neuroendocrine response after the infusion was ended. This consisted of a synchronized rise in LH some 6-8 weeks after the infusion was terminated, the maintenance of a high level of serum LH for some 15 weeks, and a subsequent precipitous fall in LH to a very low level. These results provide evidence that a long-day pattern of melatonin can synchronize reproductive neuroendocrine induction in the ewe, regardless of reproductive condition, and thus do not support the hypothesis that this response differs with seasonal reproductive state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66625/2/10.1177_074873049200700101.pd