The deposition of the β amyloid peptide in neuritic plaques and cerebral blood vessels is a hallmark of Alzheimer's disease (AD) pathology. The major component of the amyloid deposit is a 4.2-kDa ...polypeptide termed amyloid β-protein of 39–43 residues, which is derived from processing of a larger amyloid precursor protein (APP). It is hypothesized that a chymotrypsin-like enzyme is involved in the processing of APP.
We have discovered a new serine protease from the AD brain by polymerase chain reaction amplification of DNA sequences representing active site homologous regions of chymotrypsin-like enzymes. A cDNA clone was identified as one out of one million that encodes Zyme, a serine protease. Messenger RNA encoding Zyme can be detected in some mammalian species but not in mice, rats, or hamster. Zyme is expressed predominantly in brain, kidney, and salivary gland. Zyme mRNA cannot be detected in fetal brain but is seen in adult brain. The Zyme gene maps to chromosome 19q13.3, a region which shows genetic linkage with late onset familial Alzheimer's disease.
When Zyme cDNA is co-expressed with the APP cDNA in 293 (human embryonic kidney) cells, amyloidogenic fragments are detected using C-terminal antibody to APP. These co-transfected cells release an abundance of truncated amyloid β-protein peptide and shows a reduction of residues 17–42 of Aβ (P3) peptide. Zyme is immunolocalized to perivascular cells in monkey cortex and the AD brain. In addition, Zyme is localized to microglial cells in our AD brain sample. The amyloidogenic potential and localization in brain may indicate a role for this protease in amyloid precursor processing and AD.
Although most Americans prize their national parks, Alaskans tend to be ambivalent. Much of the state is wild, population densities are low, and a strong frontier ethic persists. The reaction of ...Alaskans to creation of millions of acres of national parks and monuments from 1917-1925 and later is examined. The conflict began during the gold rush, which marked a huge influx of people hungry for adventure and riches. Those who stayed were independent and believed Alaska was theirs to develop as they saw fit. This attitude was reinforced by the loss of the frontier and excessive exploitation of natural resources elsewhere. Lower 48 enthusiasm for establishing federal reserves was resisted by Alaskans not accustomed to restrictions on what they could do. They also viewed it as a crime against development and advancement. Early NPS leaders were instrumental in pressing for preservation of major park and monument areas. Meager budgets and staff made park management difficult. After World War II, tourism to Alaska increased, putting pressure on NPS to adequately manage its Alaskan lands, but leading ultimately to funding and staff to manage parks.
Chemical and microbial degradation of the nematicides-insecticides aldicarb and ethoprop has been studied extensively in both laboratory and field studies. These studies show that temperature is the ...most important variable affecting the degradation rate of aldicarb and its carbamate metabolites in surface soils. Temperature and organic matter appear to be the most important variables affecting degradation rates of ethoprop in soils under normal agricultural conditions, with organic matter being inversely related to degradation, presumably due to increased binding to soil particles. Soil moisture may be important under some conditions for both compounds, with degradation reduced in low-moisture soils. The rate of degradation of aldicarb residues (aldicarb + aldicarb sulfoxide + aldicarb sulfone) does not seem to be significantly affected by depth from soil surface, except that aldicarb residues degrade more slowly in acidic, coarse sand subsoils. Degradation of ethoprop also continues in subsurface soils, although field data are limited due to its lower mobility. Both compounds degrade in groundwater. Because microbial activity decreases with depth below soil surface, chemical processes are important components of the degradation of both aldicarb residues and ethoprop. For aldicarb, transformation to carbamate oxides in surface soils is primarily microbial, while degradation to non-carbamate compounds appears to be primarily the result of soil-catalyzed hydrolysis throughout the soil profile. For ethoprop, both chemical and microbial catalyzed hydrolysis are important in surface soils, with chemical hydrolysis becoming more important with increasing depth.
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