http://www.jbc.org/content/262/19/9412.full.pdf

Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)

Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, less than 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity

The Oriental white-backed vulture (OWBV; Gyps bengalensis) was once one of the most common raptors in the Indian subcontinent A population decline of >95%, starting in the 1990s, was first noted at Keoladeo National Park, India Since then, catastrophic declines, also involving Gyps indicus and Gyps tenuirostris, have continued to be reported across the subcontinent Consequently these vultures are now listed as critically endangered by BirdLife International In 2000, the Peregrine Fund initiated its Asian Vulture Crisis Project with the Ornithological Society of Pakistan, establishing study sites at 16 OWBV colonies in the Kasur, Khanewal and Muzaffargarh-Layyah Districts of Pakistan to measure mortality at over 2,400 active nest sites Between 2000 and 2003, high annual adult and subadult mortality (5-86%) and resulting population declines (34-95%) (ref 5 and MG, manuscript in preparation) were associated with renal failure and visceral gout Here, we provide results that directly correlate residues of the anti-inflammatory drug diclofenac with renal failure Diclofenac residues and renal disease were reproduced experimentally in OWBVs by direct oral exposure and through feeding vultures diclofenac-treated livestock We propose that residues of veterinary diclofenac are responsible for the OWBV decline

http://www.globalraptors.org/grin/researchers/uploads/200/oaks_et_al_2004.pdf

Diclofenac residues as the cause of vulture population decline in Pakistan

Molecular and cellular biology of cholinesterases

In this study, the authors show that microglia play an important role in the propagation of pathogenic tau protein. In addition, the authors find that spread of the tau protein occurs via exosome secretion from these microglial cells.

Depletion of microglia and inhibition of exosome synthesis halt tau propagation

A new and rapid colorimetric determination of acetylcholinesterase activity.

—The total AChE of brain can be readily extracted into aqueous Triton X-100. By column chromatography of these extracts a preparation was obtained at least six times as active as the original material and in yields of 60-80 per cent of the original amounts. The molecular weight of this material was estimated to be over 200,000. When brain tissue was treated with venom or bacterial protease, a water-soluble AChE was obtained with an overall purification of 150-fold. The most active preparation of AChE hydrolysed 880 μ-moles of acetylthiocholine/hr/mg of protein. The molecular weight of this preparation was estimated to be about 100,000. The enzyme which was extracted by Triton X-100 is probably the precursor of the more water-soluble enzyme that can be prepared from brain tissue by treatment with venom or protease.

Triton solubilized acetylcholinesterase of brain

The extent of psychotropic drug use was evaluated in California's institutionalized developmentally disabled population (N = 6,450). Mean psychotropic drug use was 35.4% for the entire population (range = 13.7% to 63.6% across institutions), with antipsychotic drug use at 26.8% (range = 11.0% to 59.6%). Psychotropic drug use was positively associated with aggression, IQ, depression, and self-injurious behavior, ps less than .0001; it was inversely associated with cerebral palsy and epilepsy. When the influence of demographic and behavioral factors was controlled, significant institutional differences in drug use remained. Language: en

Prevalence and prediction of psychotropic drug use in California developmental centers.

There have been numerous anecdotal and clinical reports of persons suffering asthmatic attacks of significant seventy in response to stimuli which seemingly are not, in themselves, allergenic. The first experimental study of the phenomenon was contributed by Dekker, Pelser and Groen, ' who studied the classical conditioning of asthma attacks in two human subjects. These two asthmatics had skin sensitivities to house dust extract and grass pollen. They were subjected to inhalated exposures of these allergens. After a series of such experiences they experienced attacks after inhalation of the neutral solvent used to deliver the allergens, oxygen delivered through the glass mouthpiece, even though it was not connected to the inhalation apparatus. Their work showed not only fast conditioning of the asthmatic attack, but also tenacious retention, i.e., lack of rapid extinction. The goal of our research program is to develop an animal model of a general phenomenon related to immediate hypersensitivity and then to explore its usefulness in studying the role of classical (Pavlovian) conditioning in allergic disease. The animal we have selected is the guinea pig. Indeed, the idea of using the guinea pig as a subject in classical conditioning of allergic responses seems to have originated with Noelpp and Noelpp-Eschenhagen. They conditioned asthma-like breathing attacks in guinea pigs by exposing them simultaneously to a sound stimulus and an aerosol of an allergen. Using blood (plasma) histamine levels as our dependent variable, we have demonstrated clear conditioning of an odor stimulus when paired with bovine serum albumin (BSA) in BSA-sensitized guinea pigs. The experiments presented in this report deal with two important aspects of conditioning. The first considers the role that mild stress plays in conditioning of the histamine response. The second investigates extinction of the response.

Behaviorally conditioned histamine release. Prior stress and conditionability and extinction of the response.

Territorial cichlids were presented for 30 min with a conspecific male intruder (contained in a clear glass tube). Eight hr prior, 2 groups were administered alcohol (0.15 or 0.30 percent in the aquaria water). A third group served as a control. Three responses were recorded to allow analysis of topographic changes in behavior as well as changes in absolute levels. During the habituation phase, the normal group showed a sequence of long displays, followed by shorter ones as the frequency of attacks increased. The occurrence of threat which gradually gives way to attack is characteristic of the agonistic behavior of this species. In contrast to the controls, the 0.15 percent group was hyperaggressive, while the 0.30 percent group was hypoaggressive. Furthermore, the patterning of responses were abnormal. The 0.15 percent group gave abbreviated threats and more attacks (interpreted as a tendency to attack without warning); whereas, the 0.30 percent group gave many long threat displays, but few attacks. A stimulus specificity test provided strong evidence that the waning found during the initial phase was habituation.

George L. Ellman

Papers

A new and rapid colorimetric determination of acetylcholinesterase activity.

Triton solubilized acetylcholinesterase of brain

Prevalence and prediction of psychotropic drug use in California developmental centers.

Behaviorally conditioned histamine release. Prior stress and conditionability and extinction of the response.

Alcohol, habituation and the patterning of aggressive responses in a cichlid fish.