Glucocorticoid Regulation of Stress-Induced Mineralocorticoid Receptor Gene Transcription in Vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73787/1/j.1749-6632.1994.tb39292.x.pd

Contribution of the Ventral Subiculum to Inhibitory Regulation of the Hypothalamo-Pituitary-Adrenocortical Axis

Anatomical studies indicate that the ventral subiculum is in a prime position to mediate hippocampal inhibition of the hypothalamo-pituitary-adrenocortical (HPA) axis. The present study evaluated this hypothesis by assessing HPA function following ibotenic acid lesion of the ventral subiculum region. Rats with lesions of the ventral subiculum (vSUB) or ventral hippocampus (vHIPPO) did not show changes in basal corticosterone (CORT) secretion at either circadian peak or nadir time points when compared to sham-lesion rats (SHAM) or unoperated controls. However, rats with vSUB lesions exhibited a prolonged glucocorticoid stress response relative to all other groups. Baseline CRH mRNA levels were significantly increased in the medial parvocellular paraventricular nucleus (PVN) of the vSUB group relative to controls. CRH mRNA differences were particularly pronounced at caudal levels of the nucleus, suggesting topographic organization of vSUB interactions with PVN neurons. Notably, the vHIPPO group, which received large lesions of ventral CA1, CA3 and dentate gyrus without significant subicular damage, showed no change in stress-induced CORT secretion, suggesting that the ventral subiculum proper is principally responsible for ventral hippocampal actions on the HPA stress response. No differences in medial parvocellular PVN AVP mRNA expression were seen in either the vSUB or vHIPPO groups. The results indicate a specific inhibitory action of the ventral subiculum on HPA activation. The increase in CRH biosynthesis and stress-induced CORT secretion in the absence of changes in baseline CORT secretion or AVP mRNA expression suggests that the inhibitory actions of ventral subicular neurons affect the response capacity of the HPA axis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74632/1/j.1365-2826.1995.tb00784.x.pd

Measuring the mixing efficiency in a simple model of stirring:some analytical results and a quantitative study via Frequency Map Analysis

We prove the existence of invariant curves for a $T$--periodic Hamiltonian system which models a fluid stirring in a cylindrical tank, when $T$ is small and the assigned stirring protocol is piecewise constant. Furthermore, using the Numerical Analysis of the Fundamental Frequency of Laskar, we investigate numerically the break down of invariant curves as $T$ increases and we give a quantitative estimate of the efficiency of the mixing.Comment: 10 figure

Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder

Background: Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. Methods: We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. Results: Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. Conclusions: Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD

Inflation from R^2 gravity: a new approach using nonlinear electrodynamics

We discuss another approach regarding the inflation from the R^2 theory of gravity originally proposed by Starobinski. A non-singular early cosmology is proposed, where, adding a nonlinear electrodynamics Lagrangian to the high-order action, a bouncing is present and a power-law inflation is obtained. In the model the Ricci scalar works like an inflaton field.Comment: Definitive version to be published in Astroparticle Physics during 2011, 9 page

Natural age dispersion arising from the analysis of broken crystals, part II. Practical application to apatite (U-Th)/He thermochronometry

We describe a new numerical inversion approach to deriving thermal history information from a range of naturally dispersed single grain apatite (U-Th)/He ages. The approach explicitly exploits the information about the shape of the 4He diffusion profile within individual grains that is inherent in the pattern of dispersion that arises from the common and routine practice of analysing broken crystals. Additional dispersion arising from differences in grain size and in U and Th concentration of grains, and the resultant changes to helium diffusivity caused by differential accumulation and annealing of radiation damage, is explicitly included. In this approach we calculate the ingrowth and loss, due to both thermal diffusion and the effects of α-ejection, of helium over time using a finite cylinder geometry. Broken grains are treated explicitly as fragments of an initially larger crystal. The initial grain lengths, L0, can be treated as unknown parameters to be estimated, although this is computationally demanding. A practical solution to the problem of solving for the unknown initial grain lengths is to simply apply a constant and sufficiently long L0 value to each fragment. We found that a good value for L0 was given by the maximum fragment length plus two times the maximum radius of a given set of fragments. Currently whole crystals and fragments with one termination are taken into account. A set of numerical experiments using synthetic fragment ages generated for increasingly complex thermal histories, and including realistic amounts of random noise (5-15%), are presented and show that useful thermal history information can be extracted from datasets showing very large dispersion. These include experiments where dispersion arises only from fragmentation of a single grain (length 400μm and radius 75μm, c. 6-50% dispersion), including the effects of grain size variation (for spherical equivalent grain radii between 74-122 μm, c. 10-70% dispersion) and the combined effects of fragmentation, grain size and radiation damage (for eU between 5-150 ppm, c.10-107% dispersion). Additionally we show that if the spherical equivalent radius of a broken grain is used as a measure of the effective diffusion domain for thermal history inversions then this will likely lead to erroneous thermal histories being obtained in many cases. The viability of the new technique is demonstrated for a real data set of 25 single grain (U-Th)/He apatite ages obtained for a gabbro sample from the BK-1 (Bierkraal) borehole drilled through the Bushveld Complex in South Africa. The inversion produces a well constrained thermal history consistent with both the (U-Th)/He data and available fission track analysis data. The advantage of the new approach is that it can explicitly accommodate all the details of conventional schemes, such as the effects of temporally variable diffusivity, zonation of U and Th and arbitrary grain size variations, and it works equally effectively for whole or broken crystals, and for the most common situation where a mixture of both are analysed. For the routine application of the apatite (U-Th)/He thermochronometry technique with samples where whole apatite grains are rare our experiments indicate that 15-20 single grain analyses are typically required to characterise the age dispersion pattern of a sample. The experiments also suggest that picking very short crystal fragments as well as long fragments, or even deliberately breaking long crystals to maximise the age dispersion in some cases, would ensure the best constraints on the thermal history models. The inversion strategy described in this paper is likely also directly applicable to other thermochronometers, such as the apatite, rutile and titanite U-Pb systems, where the diffusion domain is approximated by the physical grain size

Microcomputer-based three-dimensional reconstruction of in situ hybridization autoradiographs

A number of software routines were written for the public domain Macintosh-based video-densitometry program, Image, to facilitate in situ hybridization analysis. These routines utilize fiducial marks drilled in unused portions of the brain to rotate high-magnification images of individual sections so that they may be placed in register. The regions of interest within the registered sections are outlined and intermediate sections interpolated to produce a data set representing a three-dimensional volume. This shell is then filled with the original density data obtained with one or more in situ hybridization probes. The final object can be viewed in various degrees of translucency and examined from different angles or computationally resectioned to yield new information concerning activity changes within the region and relationships between reactive sites. These static images can be collected and rapidly displayed as a movie. These routines have been used in this paper to display the differential hybridization of three different mRNA probes in the hypothalamic paraventricular nucleus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29154/1/0000198.pd

Emotion, deliberation, and the skill model of virtuous agency

A recent skeptical challenge denies deliberation is essential to virtuous agency: what looks like genuine deliberation is just a post hoc rationalization of a decision already made by automatic mechanisms (Haidt 2001; Doris 2015). Annas’s account of virtue seems well-equipped to respond: by modeling virtue on skills, she can agree that virtuous actions are deliberation-free while insisting that their development requires significant thought. But Annas’s proposal is flawed: it over-intellectualizes deliberation’s developmental role and under-intellectualizes its significance once virtue is acquired. Doing better requires paying attention to a distinctive form of anxiety—one that functions to engage deliberation in the face of decisions that automatic mechanisms alone cannot resolve

Selective forebrain fiber tract lesions implicate ventral hippocampal structures in tonic regulation of paraventricular nucleus corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression

The hippocampus appears to be involved in tonic regulation of the hypothalamo-pituitary-adrenocortical axis via interactions with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular nucleus (PVN). To further investigate the anatomical basis of such interactions, lesions were made to forebrain fiber tracts in position to communicate inhibitory information from the hippocampus to the PVN. Total fimbria-fornix transections (TFF) and lateral fimbria-fornix lesions (LFF) both significantly increased CRH mRNA levels in the medial parvocellular PVN, as assayed by semi-quantitative in situ hybridization histochemistry. Medial fimbria-fornix lesions or section of the medial corticohypothalamic tracts (MCHT) did not influence CRH mRNA levels. The LFF group showed increases in both AVP mRNA and ACTH secretion, whereas no other lesion was effective in this regard. The results suggest: (1) hippocampal efferents confering tonic inhibition of the HPA axis probably originate in regions contributing to the lateral extent of the fornix, representing structures in the ventral subiculum and ventral extent of CA1: (2) projections from the hippocampus to the medial basal hypothalamus (travelling in the MCHT) are unlikely to affect HPA function: (3) hippocampus may influence the PVN CRH/AVP neuron at multiple levels, in that LFF and TFF lesions have differential effects on PVN AVP mRNA levels and ACTH secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29793/1/0000135.pd

The High Resolution X-ray Spectrum of SS 433 using the Chandra HETGS

We present observations of SS 433 using the Chandra High Energy Transmission Grating Spectrometer. Many emission lines of highly ionized elements are detected with the relativistic blue and red Doppler shifts. The lines are measurably broadened to 1700 km/s (FWHM) and the widths do not depend significantly on the characteristic emission temperature, suggesting that the emission occurs in a freely expanding region of constant collimation with opening angle of 1.23 +/- 0.06 deg. The blue shifts of lines from low temperature gas are the same as those of high temperature gas within our uncertainties, again indicating that the hottest gas we observe to emit emission lines is already at terminal velocity. Fits to the emission line fluxes give a range of temperatures in the jet from 5e6 to 1e8 K. We derive the emission measure as a function of temperature for a four component model that fits the line flux data. Using the density sensitive Si XIII triplet, the characteristic electron density is 1e14 cm^{-3}, where the gas temperature is about 1.3e7 K. Based on an adiabatic expansion model of the jet, the electron densities drop from ~2e15 to 4e13 cm^{-3} at distances of 2e10 to 2e11 cm from the apex of the jet cone. The jet mass outflow rate is 1.5e-7 Msun / yr. The kinetic power is 3.2e38 erg/s, which is x1000 larger than the unabsorbed 2-10 keV X-ray luminosity. The bremsstrahlung emission associated with the lines can account for the entire continuum; we see no direct evidence for an accretion disk. The image from zeroth order shows extended emission at a scale of ~2", aligned in the general direction of the radio jets.Comment: 28 pages, 12 figures (1, 4, 5, and 6 are color), to appear in the Astrophysical Journa