Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. © 2009 Elsevier Ltd. All rights reserved

Adiabatic population transfer via multiple intermediate states

This paper discusses a generalization of stimulated Raman adiabatic passage (STIRAP) in which the single intermediate state is replaced by $N$ intermediate states. Each of these states is connected to the initial state \state{i} with a coupling proportional to the pump pulse and to the final state \state{f} with a coupling proportional to the Stokes pulse, thus forming a parallel multi-$\Lambda$ system. It is shown that the dark (trapped) state exists only when the ratio between each pump coupling and the respective Stokes coupling is the same for all intermediate states. We derive the conditions for existence of a more general adiabatic-transfer state which includes transient contributions from the intermediate states but still transfers the population from state \state{i} to state \state{f} in the adiabatic limit. We present various numerical examples for success and failure of multi-$\Lambda$ STIRAP which illustrate the analytic predictions. Our results suggest that in the general case of arbitrary couplings, it is most appropriate to tune the pump and Stokes lasers either just below or just above all intermediate states.Comment: 14 pages, two-column revtex style, 10 figure

Methods for Assessing Child and Family Outcomes in Early Childhood Special Education Programs

Although many concerns have been raised about methods of assessing outcomes in early childhood special education programs, professionals in the field are nevertheless faced with the need to select appropriate instruments for evaluating child and family outcomes as the result of intervention. A conference to address the current assessment needs of professionals was convened. This paper summarizes this conference, in which five prominent individuals in the field of early childhood special education gave specific recommendations for one child and one family outcome measure which would be applicable to a range of handicapped children between birth and age 5 being served in typical early intervention programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68510/2/10.1177_027112148600600202.pd

Entry State Distributions of Discrete Yrast Transitions in Heavy Ion Induced Fusion Reactions

Gamma rays emitted during yrast transitions from compound nuclei are detected with a 4..pi.. multielement gamma ray detector system. Both total pulse height (H) and coincidence fold data (k) are obtained for each event. Results presented include entry state distribution states, k and H projections for some of these distributions, and k and H as a function of spin of the yrast transition. 5 figs. (DWL

Within-group behavioral variation promotes biased task performance and the emergence of a defensive caste in a social spider

The social spider Anelosimus studiosus exhibits a behavioral polymorphism where colony members express either a passive, tolerant behavioral tendency (social) or an aggressive, intolerant behavioral tendency (asocial). Here we test whether asocial individuals act as colony defenders by deflecting the suite of foreign (i.e., heterospecific) spider species that commonly exploit multi-female colonies. We (1) determined whether the phenotypic composition of colonies is associated with foreign spider abundance, (2) tested whether heterospecific spider abundance and diversity affect colony survival in the field, and (3) performed staged encounters between groups of A. studiosus and their colony-level predator Agelenopsis emertoni (A. emertoni)to determine whether asocial females exhibit more defensive behavior. We found that larger colonies harbor more foreign spiders, and the number of asocial colony members was negatively associated with foreign spider abundance. Additionally, colony persistence was negatively associated with the abundance and diversity of foreign spiders within colonies. In encounters with a colony-level predator, asocial females were more likely to exhibit escalatory behavior, and this might explain the negative association between the frequency of asocial females and the presence of foreign spider associates. Together, our results indicate that foreign spiders are detrimental to colony survival, and that asocial females play a defensive role in multi-female colonies

Effects of Brood Pheromone Modulated Brood Rearing Behaviors on Honey Bee (Apis mellifera L.) Colony Growth

A hallmark of eusociality is cooperative brood care. In most social insect systems brood rearing labor is divided between individuals working in the nest tending the queen and larvae, and foragers collecting food outside the nest. To place brood rearing division of labor within an evolutionary context, it is necessary to understand relationships between individuals in the nest engaged in brood care and colony growth in the honey bee. Here we examined responses of the queen, queen-worker interactions, and nursing behaviors to an increase in the brood rearing stimulus environment using brood pheromone. Colony pairs were derived from a single source and were headed by open-mated sister queens, for a total of four colony pairs. One colony of a pair was treated with 336 µg of brood pheromone, and the other a blank control. Queens in the brood pheromone treated colonies laid significantly more eggs, were fed longer, and were less idle compared to controls. Workers spent significantly more time cleaning cells in pheromone treatments. Increasing the brood rearing stimulus environment with the addition of brood pheromone significantly increased the tempo of brood rearing behaviors by bees working in the nest resulting in a significantly greater amount of brood reared

Team sports performance analysed through the lens of social network theory: implications for research and practice

This paper discusses how social network analyses and graph theory can be implemented in team sports performance analyses to evaluate individual (micro) and collective (macro) performance data, and how to use this information for designing practice tasks. Moreover, we briefly outline possible limitations of social network studies and provide suggestions for future research. Instead of cataloguing discrete events or player actions, it has been argued that researchers need to consider the synergistic interpersonal processes emerging between teammates in competitive performance environments. Theoretical assumptions on team coordination prompted the emergence of innovative, theoretically-driven methods for assessing collective team sport behaviours. Here, we contribute to this theoretical and practical debate by conceptualising sports teams as complex social networks. From this perspective, players are viewed as network nodes, connected through relevant information variables (e.g., a ball passing action), sustaining complex patterns of interaction between teammates (e.g., a ball passing network). Specialized tools and metrics related to graph theory could be applied to evaluate structural and topological properties of interpersonal interactions of teammates, complementing more traditional analysis methods. This innovative methodology moves beyond use of common notation analysis methods, providing a richer understanding of the complexity of interpersonal interactions sustaining collective team sports performance. The proposed approach provides practical applications for coaches, performance analysts, practitioners and researchers by establishing social network analyses as a useful approach for capturing the emergent properties of interactions between players in sports teams

Eukaryotic Cells Producing Ribosomes Deficient in Rpl1 Are Hypersensitive to Defects in the Ubiquitin-Proteasome System

It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.United States. National Institutes of Health (GM25532)United States. National Institutes of Health (ARRAGM25532-S1)United States. National Institutes of Health (GM085177)United States. National Institutes of Health (CAI-3330)Natural Sciences and Engineering Research Council of Canada (NSERC