Seven new aminosterols related to squalamine (8) were isolated from the liver of the dogfish shark Squalus acanthias. Their structures (1-7) were determined using spectroscopic methods, including 2D NMR and HRFABMS. These aminosterols possess a relatively invariant cholestane skeleton with a trans AB ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated. The structure of the lone spermine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5alpha,7alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate. Some members of this family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

The effects of calorie restrictior~ on net protein utilization (N.P.U.) were studied with proteins of different nutritional value. When protein intake remained constant, reduction in the intake from 32 to 16 kcal per day resulted in a rapid decline in N.P.U. values. Increases in body weight were directly proportional to calorie intake per %g0J3 body weight. Even under conditions of marked caloric restriction, only 70-75y0 of the ingested protein was used for energy purposes, the rest evidently being used in essential anabolic activities. Studies on carcass co~npositicrn showed that animals on restricted calorie intakes tried to adapt through shifts in metabolism, arid utilized fat in preference to protein for caloric requirements. KN-4 metabolism in liver and muscle was influenced by energy and rotein intakes.i d e n the percentage of calories from protein remained constant, K.P.U. values were not markedly altered until the calorie intake reached the maintenance energy requirement s f 150 kcal per kg0.73 body weight. Below this point, N.P.U. values dropped sharply, the rate of decrease being greater for proteins of higher nutritive value. Differences in the nutritive value of proteins, as shown by their ability to satisfy protein requiremetats in protein-depleted rats, still existed even a t restricted intakes of calories.Wational Research Council of Canada Postdoctorate Fellow (196M6). I'erlnanent address:

The energy loss of silver ions in metallic gadolinium foil at low velocities (2.7 -4.3)vo, where vp is the Bohr velocity, was measured with the Doppler shift technique. The results are about 20/p smaller than the predictions of a semiempirical formulation [

No abstract

Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type specific molecular responses of cortical upper motor neurons in a preclinical ALS model. Using two bacTRAP mouse lines that label distinct vulnerable or resilient projection neuron populations in motor cortex, we show that the regulation of oxidative phosphorylation (Oxphos) pathways is a common response in both cell types. However, differences in the baseline expression of genes involved in Oxphos and the handling of reactive oxygen species likely lead to the selective degeneration of the vulnerable cells. These results provide a framework to identify cell type-specific processes in neurodegenerative disease.