Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion

Factors modulating the secretion of thyrotropin and other hormones of the thyroid axis.

The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs

The mapping between transformed reaction time costs and models of processing in aging and cognition.

Older adults tend to have slower response times (RTs) than younger adults on cognitive tasks. This makes the examination of domain-specific deficits in aging difficult, as differences between conditions in raw RTs (RT costs) typically increase with slower average RTs. Here, we examine the mapping between 2 established approaches to dealing with this confound in the literature. The first is to use transformed RT costs, with the z-score and proportional transforms both being commonly used. The second is to use mathematical models of choice RT behavior, such as the drift-diffusion model (Ratcliff, 1978). We simulated data for younger and older adults from the drift-diffusion model under 4 scenarios: (a) a domain specific deficit, (b) general slowing, (c) strategic slowing, and (d) a slowing of nondecision processes. In each scenario we varied the size of the difference between younger and older adults in the model parameters, and examined corresponding effect sizes and Type I error rates in the raw and transformed RT costs. The z-score transformation provided better control of Type I error rates than the raw or proportional costs, though did not fully control for differences in the general slowing and strategic slowing scenarios. We recommend that RT analyses are ideally supplemented by analyses of error rates where possible, as these may help to identify the presence of confounds. To facilitate this, it would be beneficial to include conditions that elicit below ceiling accuracy in tasks

The reliability paradox: Why robust cognitive tasks do not produce reliable individual differences.

Individual differences in cognitive paradigms are increasingly employed to relate cognition to brain structure, chemistry, and function. However, such efforts are often unfruitful, even with the most well established tasks. Here we offer an explanation for failures in the application of robust cognitive paradigms to the study of individual differences. Experimental effects become well established – and thus those tasks become popular – when between-subject variability is low. However, low between-subject variability causes low reliability for individual differences, destroying replicable correlations with other factors and potentially undermining published conclusions drawn from correlational relationships. Though these statistical issues have a long history in psychology, they are widely overlooked in cognitive psychology and neuroscience today. In three studies, we assessed test-retest reliability of seven classic tasks: Eriksen Flanker, Stroop, stop-signal, go/no-go, Posner cueing, Navon, and Spatial-Numerical Association of Response Code (SNARC). Reliabilities ranged from 0 to .82, being surprisingly low for most tasks given their common use. As we predicted, this emerged from low variance between individuals rather than high measurement variance. In other words, the very reason such tasks produce robust and easily replicable experimental effects – low between-participant variability – makes their use as correlational tools problematic. We demonstrate that taking such reliability estimates into account has the potential to qualitatively change theoretical conclusions. The implications of our findings are that well-established approaches in experimental psychology and neuropsychology may not directly translate to the study of individual differences in brain structure, chemistry, and function, and alternative metrics may be required

Superfluid Spin-down, with Random Unpinning of the Vortices

The so-called ``creeping'' motion of the pinned vortices in a rotating superfluid involves ``random unpinning'' and ``vortex motion'' as two physically separate processes. We argue that such a creeping motion of the vortices need not be (biased) in the direction of an existing radial Magnus force, nor should a constant microscopic radial velocity be assigned to the vortex motion, in contradiction with the basic assumptions of the ``vortex creep'' model. We point out internal inconsistencies in the predictions of this model which arise due to this unjustified foundation that ignores the role of the actual torque on the superfluid. The proper spin-down rate of a pinned superfluid is then calculated and turns out to be much less than that suggested in the vortex creep model, hence being of even less observational significance for its possible application in explaining the post-glitch relaxations of the radio pulsars.Comment: To be published in J. Low Temp. Phys., Vol. 139, May 2005 [Eqs 11, 15-17 here, have been revised and, may be substituted for the corresponding ones in that paper

Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)

Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurückkehrten. Die Antigenaktivitäten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-Stämme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die Antigenität wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun Stämme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen für die Antikörperbestimmung mit diesen Antigenen zur Verfügung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen für den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen Stämmen dieser Leishmaniaart erhebliche Unterschiede in der Antigenaktivität. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der Antigenaktivität erkannt werden. Für den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition für die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie

Low and variable correlation between reaction time costs and accuracy costs explained by accumulation models: Meta-analysis and simulations.

The underpinning assumption of much research on cognitive individual differences (or group differences) is that task performance indexes cognitive ability in that domain. In many tasks performance is measured by differences (costs) between conditions, which are widely assumed to index a psychological process of interest rather than extraneous factors such as speed–accuracy trade-offs (e.g., Stroop, implicit association task, lexical decision, antisaccade, Simon, Navon, flanker, and task switching). Relatedly, reaction time (RT) costs or error costs are interpreted similarly and used interchangeably in the literature. All of this assumes a strong correlation between RT-costs and error-costs from the same psychological effect. We conducted a meta-analysis to test this, with 114 effects across a range of well-known tasks. Counterintuitively, we found a general pattern of weak, and often no, association between RT and error costs (mean r = .17, range −.45 to .78). This general problem is accounted for by the theoretical framework of evidence accumulation models, which capture individual differences in (at least) 2 distinct ways. Differences affecting accumulation rate produce positive correlation. But this is cancelled out if individuals also differ in response threshold, which produces negative correlations. In the models, subtractions between conditions do not isolate processing costs from caution. To demonstrate the explanatory power of synthesizing the traditional subtraction method within a broader decision model framework, we confirm 2 predictions with new data. Thus, using error costs or RT costs is more than a pragmatic choice; the decision carries theoretical consequence that can be understood through the accumulation model framework

Slow and steady? Strategic adjustments in response caution are moderately reliable and correlate across tasks.

Speed-accuracy trade-offs are often considered a confound in speeded choice tasks, but individual differences in strategy have been linked to personality and brain structure. We ask whether strategic adjustments in response caution are reliable, and whether they correlate across tasks and with impulsivity traits. In Study 1, participants performed Eriksen flanker and Stroop tasks in two sessions four weeks apart. We manipulated response caution by emphasising speed or accuracy. We fit the diffusion model for conflict tasks and correlated the change in boundary (accuracy – speed) across session and task. We observed moderate test-retest reliability, and medium to large correlations across tasks. We replicated this between-task correlation in Study 2 using flanker and perceptual decision tasks. We found no consistent correlations with impulsivity. Though moderate reliability poses a challenge for researchers interested in stable traits, consistent correlation between tasks indicates there are meaningful individual differences in the speed-accuracy trade-off

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

AMSA Conference Indigenous Workshop Summary

This report summarises a two-day Indigenous Workshop at the 2022 Australian Marine Sciences Association Conference. The workshop was the seventh to be supported by the National Environmental Science Program and the most significant to date in terms of Indigenous leadership and attendance. Indigenous participants from 45 language groups joined others from government, research and non-profit agencies. Indigenous organisations expressed a clear desire to work with government and research agencies to enable effective co-development of research, and to establish a nationally coordinated approach to Indigenous-led research and monitoring. The two-day Indigenous workshop brought together Indigenous leaders and community members from across the nation. This was a rare occasion for Indigenous Australians to come together and provide input into two important focal areas. 1. Collaborate and strategise on the research priorities, opportunities and constraints for Indigenous participation and leadership in environmental research in Australia’s marine and coastal regions. 2. Discuss the need for a National Indigenous Environmental Research Network (NIERN)