Global properties of the mapping between local amino acid sequence and local structure in proteins.

Local protein structure prediction efforts have consistently failed to exceed approximately 70% accuracy. We characterize the degeneracy of the mapping from local sequence to local structure responsible for this failure by investigating the extent to which similar sequence segments found in different proteins adopt similar three-dimensional structures. Sequence segments 3-15 residues in length from 154 different protein families are partitioned into neighborhoods containing segments with similar sequences using cluster analysis. The consistency of the sequence-to-structure mapping is assessed by comparing the local structures adopted by sequence segments in the same neighborhood in proteins of known structure. In the 154 families, 45% and 28% of the positions occur in neighborhoods in which one and two local structures predominate, respectively. The sequence patterns that characterize the neighborhoods in the first class probably include virtually all of the short sequence motifs in proteins that consistently occur in a particular local structure. These patterns, many of which occur in transitions between secondary structural elements, are an interesting combination of previously studied and novel motifs. The identification of sequence patterns that consistently occur in one or a small number of local structures in proteins should contribute to the prediction of protein structure from sequence.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

Fixing America's School Lunch Program: Local Issues, National Challenges, and Global Perspectives on Possible Solutions

The National School Lunch Program (NSLP) has undergone profound changes since its establishment in the 1930s with a primary goal of feeding undernourished school children. Today, the program is under scrutiny for its negative impact on student health and environmental unsustainability. This project investigates the origins of the NSLP, the current status of the program, and opportunities for reform. In view of the program's deficiencies, much can be learned by studying other relevant models for school lunch, such as those used in Italy and France. While recognizing the political realities and budgetary constraints public schools currently confront, the Business Plan applies these lessons in its proposals for rethinking the school lunch program at one Denver public school.

The cognitive mobilization index: crises and political generations

This article shows how the cognitive mobilization index, designed for use in observing potential political participation, can be used as an indicator of the political climate that a particular society is going through. Following a discussion of the theoretical elaborations (and their working definitions) of the concept of cognitive mobilization, a longitudinal study of various European countries is used to consider the question of how political crises influence cognitive mobilization indexes and what effects they have on the political socialization process among the youngest cohorts.

Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages

Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.

William Lambarde and local government: his "Ephemeris" and twenty-nine charges to juries and commissions.

Mode of access: Internet.

Molybdenum; its ores and their concentration, with a discussion of markets, prices, and uses,

"Tabulation of molybdenite and of wulfenite occurrences in the United States": p. 86-90.

Integrating bicycle and pedestrian considerations into state and local transportation planning, design, and operations. National Bicycling and Walking Study. Case study no. 21.

Federal Highway Administration, Washington, D.C.