Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine

Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion-induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation.     

Temperature,water, and PAR influences on predicted and measured productivity of Agave deserti at various elevations

Summary To measure productivity of Agave deserti over its elevational range in the northwestern Sonoran Desert, leaf unfolding from its basal rosette was monitored on groups of 10 plants at 13 sites. Based on data from an intermediate elevation (840 m), leaf unfolding proved to be highly correlated (r ²=0.88) with an environmental productivity index (EPI) formed as the product of indices for water status, temperature, and photosynthetically active radiation (PAR); each of these latter indices indicated the fraction of maximum net CO₂ uptake expected for that parameter based on laboratory measurements of gas exchange and field microclimatic data. At 840 m, the main environmental variable influencing leaf unfolding for A. deserti over a 2-y period was soil water potential. On steep slopes, however, leaf unfolding during the winter ranged from 0.7 leaves per 10 plants for north-facing slopes to 7.3 for south-facing slopes, reflecting the importance of PAR. Summer and winter rainfall increased 3-fold from elevations of 300 m to 1,200 m. Temperatures were more optimal for net CO₂ uptake at high elevations in the summer and at low elevations in the winter. Hence EPI increased with elevation in the summer but was maximal at an intermediate elevation in the winter. Moreover, measured leaf unfolding in both the summer and the winter closely followed the changes in EPI with elevation, indicating that productivity could be closely predicted for A. deserti based on physiological CO₂ responses and changes in environmental conditions with elevation.     

Ozone increases the permeability of isolated pea chloroplasts

The effect of short-term exposure of chloroplasts isolated from the leaves of Pisum sativum to high concentrations of ozone was examined. The inhibitory effect of O₃ on endogenous photophosphorylation was apparently related to an increased permeability of the chloroplast limiting membranes induced by ozone exposure. A 5 min treatment with 50 ppm O₃ reduced the reflection coefficient of meso-erythritol from 0.84 to 0.58 and that of glycerol from 0.26 to 0.03. Such decreases in reflection coefficients indicate that ozone caused a marked increase in the permeability of the limiting membranes of the chloroplasts, which may result from an oxidation of membrane lipids. The decrease in the reflection coefficient of meso-erythritol was proportional both to ozone concentration (up to 30 ppm for 5 min of bubbling) and to time (up to 5 min at 30 ppm). Extrapolating these results to lower concentrations and longer times, ozone injury should be possible for a 2 hr exposure of plants to 0.3 ppm ozone, as is indeed the case.     

Cannabinoid Receptor Activation Differentially Regulates the Various Adenylyl Cyclase Isozymes

Abstract: Two cannabinoid receptors belonging to the superfamily of G protein-coupled membrane receptors have been identified and cloned: the neuronal cannabinoid receptor (CB1) and the peripheral cannabinoid receptor (CB2). They have been shown to couple directly to the G_i/o subclass of G proteins and to mediate inhibition of adenylyl cyclase upon binding of a cannabinoid agonist. In several cases, however, cannabinoids have been reported to stimulate adenylyl cyclase activity, although the mechanism by which they did so was unclear. With the cloning of nine adenylyl cyclase isozymes with various properties, including different sensitivities to α_s, α_i/o, and βγ subunits, it became important to assess the signaling pattern mediated by each cannabinoid receptor via the different adenylyl cyclase isozymes. In this work, we present the results of cotransfection experiments between the two types of cannabinoid receptors and the nine adenylyl cyclase isoforms. We found that independently of the method used to stimulate specific adenylyl cyclase isozymes (e.g., ionomycin, forskolin, constitutively active α_s, thyroid-stimulating hormone receptor activation), activation of the cannabinoid receptors CB1 and CB2 inhibited the activity of adenylyl cyclase types I, V, VI, and VIII, whereas types II, IV, and VII were stimulated by cannabinoid receptor activation. The inhibition of adenylyl cyclase type III by cannabinoids was observed only when forskolin was used as stimulant. The activity of adenylyl cyclase type IX was inhibited only marginally by cannabinoids.     

Fast atom bombardment and tandem mass spectrometry for structure determination of steroid and flavonoid glycosides

The combination of fast atom bombardment (FAB) and tandem mass spectrometry (MS-MS) was tested for its applicability to generate useful structural information for steroid and flavonoid glycosides. The following compounds were investigated: quercetin, myricitrin, apigetrin, fraxin, rutin, neohesperidin, hesperidin, naringin, apiin, cymarin, digoxin, digitoxin, xanthorhamnin, and frangulin. Upon FAB, the sample molecules are desorbed as (M + H)+, (M - H)-, or as (M + Na)+ or (M + K)+. Collisional activation of (M + H)+ or (M - H)- ions in the MS-MS experiment leads to sequential losses of glycoside moieties in a manner which permits the sequence of glycosides to be established. Some glycosides occur as mixtures of homologs. Proper interpretation of the MS-MS or collisional activation decomposition spectra often allows the homology to be located. In addition to the simple and highly selective fragmentations observed in this combined experiment, FAB and MS-MS also remove interference caused by the ubiquitous matrix ions which are desorbed by FAB.     

Dynamics of thyroid diseases and thyroid‐axis gland masses

Thyroid disorders are common and often require lifelong hormone replacement. Treating thyroid disorders involves a fascinating and troublesome delay, in which it takes many weeks for serum thyroid‐stimulating hormone (TSH) concentration to normalize after thyroid hormones return to normal. This delay challenges attempts to stabilize thyroid hormones in millions of patients. Despite its importance, the physiological mechanism for the delay is unclear. Here, we present data on hormone delays from Israeli medical records spanning 46 million life‐years and develop a mathematical model for dynamic compensation in the thyroid axis, which explains the delays. The delays are due to a feedback mechanism in which peripheral thyroid hormones and TSH control the growth of the thyroid and pituitary glands; enlarged or atrophied glands take many weeks to recover upon treatment due to the slow turnover of the tissues. The model explains why thyroid disorders such as Hashimoto''s thyroiditis and Graves'' disease have both subclinical and clinical states and explains the complex inverse relation between TSH and thyroid hormones. The present model may guide approaches to dynamically adjust the treatment of thyroid disorders.