Structure of the LDL receptor extracellular domain at endosomal pH

The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH < 6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, beta propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the beta propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the beta propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release.     

Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease

We identified axonal defects in mouse models of Alzheimer's disease that preceded known disease-related pathology by more than a year; we observed similar axonal defects in the early stages of Alzheimer's disease in humans. Axonal defects consisted of swellings that accumulated abnormal amounts of microtubule-associated and molecular motor proteins, organelles, and vesicles. Impairing axonal transport by reducing the dosage of a kinesin molecular motor protein enhanced the frequency of axonal defects and increased amyloid-beta peptide levels and amyloid deposition. Reductions in microtubule-dependent transport may stimulate proteolytic processing of beta-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease.     

Lesch-Nyhan syndrome: rapid detection of heterozygotes by use of hair follicles

A method is described which permits rapid phenotypic diagnosis of the Lesch-Nyhan heterozygote by direct assay of hypoxanthine guanine phosphori-bosyltransferase activity in single hair follicles obtained from the scalp.     

Tremor and involuntary movements in monkeys: effect of L-dopa and of a dopamine receptor stimulating agent

Either L-dopa, in combination with 1-alpha-methyldopa hydrazine (MK-486), or 1-(2'-pyrimidyl)-4-piperonylpiperazine, an agent that stimulates dopamine receptors, relieves surgically induced tremor in monkeys and concomitantly evokes involuntary movements. These results indicate that tremor and involuntary movements are associated with a common mechanism and that the activity of the dopamine receptors is involved in the regulation of these dysfunctions.     

Narcotic tolerance and dependence: lack of relationship with serotonin turnover in the brain

Serotonin turnover was measured in mouse brain by means of the conversion of radioactivity from labeled tryptophan into serotonin. Animals with a high degree of tolerance to and physical dependence on morphine did not differ from control mice.     

Lungfish Neoceratodus forsteri: activities of ornithine-urea cycle and enzymes

The level of activity of the ornithine-urea cycle is low in the liver of the permanently aquatic Australian lungfish. The rate of incorporation of (14)C-bicarbonate into urea by liver slices was only 100th of that previously observed in the estivating African lungfish Protopterus dolloi. The activities of enzymes of the ornithine-urea cycle were similarly reduced. The low activity of this cycle in Neoceratodus is consistent with its exclusively aquatic nature.     

The effect of nitrate and organic matter upon mobility of selenium in groundwater and in a water treatment process

Kesterson Reservoir in Merced County, California was formerly used as a storage and evaporation facility for Se-contaminated agricultural drain water. Very little Se entered the shallow aquifer below the ponds with percolating pond water. With few localized exceptions, most of the Se was removed from the water and retained in the first decimeter of soil, which was rich in decaying organic matter. Where it was present in groundwater, Se was nearly always associated with nitrate. Nitrate induces mildly oxidizing conditions (Eh ≈ 350 mV) and inhibits microbial fixation of Se. In the absence of nitrate, relatively reducing conditions prevail in the groundwater (Eh ≈ -50 mV), and Se is quickly removed. Selenate follows oxygen and nitrate in the order that soil microbes utilize electron acceptors. The process of Se removal from water by soil was reproduced in the laboratory, and the effect of nitrate was confirmed. This natural process might be applied to water treatment for Se removal. The deep water ecosystem at Kesterson Reservoir was highly productive. Vegetation growing in water treatment ponds should supply enough organic matter to maintain anaerobic conditions in the sediment. This process, including algae culture, was operated in an outdoor 79 cm column for 100 days. At percolation rates of 15 and 30 m yr^?1 Se removal averaged 94%, with an additional 2% converted to volatile compounds.     

Influences of recovery from clear-cut, climate variability, and thinning on the carbon balance of a young ponderosa pine plantation

From 1999 to 2002, the variations in carbon flux due to management practices (shrub removal, thinning) and climate variability were observed in a young ponderosa pine forest originated from clear-cutting and plantation in 1990. These measurements were done at the Blodgett Forest Ameriflux site located in the Sierra Nevada Mountains of California. Thinning in spring 2000 decreased the leaf area index (LAI) by 34% and added 496 g C m⁻² of wood and leaf debris at the soil surface. Total ecosystem respiration was not significantly affected by thinning (1261 g C m⁻² in 1999 and 1273 g C m⁻² in 2000), while canopy photosynthesis decreased by 202 g C m⁻². As a result the ecosystem shifted from a net sink of CO₂ in 1999 (−201 g C m⁻²) to a small net source in 2000 (13 g C m⁻²). Woody and leaf debris resulting from thinning only accounted for maximum 1% and 7% of the total respiration flux, respectively. Thinning did not affect the relative proportion of the different components of respiration to an observable degree. Low soil water availability in summer 2001 and 2002 decreased the proportion of soil respiration to the total respiration. It also imposed limitations on canopy photosynthesis: as a result the ecosystem shifted from a sink to a source of carbon 1 month earlier than in a wetter year (1999). The leaf area index and biomass of the stand increased rapidly after the thinning. The ecosystem was again a sink of carbon in 2001 (−97 g C m⁻²) and 2002 (−172 g C m⁻²). The net carbon uptake outside the traditionally-defined growing season can be important in this ecosystem (NEE = −50 g C m⁻² in 2000), but interannual variations are significant due to differences in winter temperatures.