Do ants make direct comparisons?

Many individual decisions are informed by direct comparison of the alternatives. In collective decisions, however, only certain group members may have the opportunity to compare options. Emigrating ant colonies (Temnothorax albipennis) show sophisticated nest-site choice, selecting superior sites even when they are nine times further away than the alternative. How do they do this? We used radio-frequency identification-tagged ants to monitor individual behaviour. Here we show for the first time that switching between nests during the decision process can influence nest choice without requiring direct comparison of nests. Ants finding the poor nest were likely to switch and find the good nest, whereas ants finding the good nest were more likely to stay committed to that nest. When ants switched quickly between the two nests, colonies chose the good nest. Switching by ants that had the opportunity to compare nests had little effect on nest choice. We suggest a new mechanism of collective nest choice: individuals respond to nest quality by the decision either to commit or to seek alternatives. Previously proposed mechanisms, recruitment latency and nest comparison, can be explained as side effects of this simple rule. Colony-level comparison and choice can emerge, without direct comparison by individuals.     

Stable and Unstable Malaria Hotspots in Longitudinal Cohort Studies in Kenya

Background

Infectious diseases often demonstrate heterogeneity of transmission among host populations. This heterogeneity reduces the efficacy of control strategies, but also implies that focusing control strategies on “hotspots” of transmission could be highly effective.

Methods and Findings

In order to identify hotspots of malaria transmission, we analysed longitudinal data on febrile malaria episodes, asymptomatic parasitaemia, and antibody titres over 12 y from 256 homesteads in three study areas in Kilifi District on the Kenyan coast. We examined heterogeneity by homestead, and identified groups of homesteads that formed hotspots using a spatial scan statistic. Two types of statistically significant hotspots were detected; stable hotspots of asymptomatic parasitaemia and unstable hotspots of febrile malaria. The stable hotspots were associated with higher average AMA-1 antibody titres than the unstable clusters (optical density [OD] = 1.24, 95% confidence interval [CI] 1.02–1.47 versus OD = 1.1, 95% CI 0.88–1.33) and lower mean ages of febrile malaria episodes (5.8 y, 95% CI 5.6–6.0 versus 5.91 y, 95% CI 5.7–6.1). A falling gradient of febrile malaria incidence was identified in the penumbrae of both hotspots. Hotspots were associated with AMA-1 titres, but not seroconversion rates. In order to target control measures, homesteads at risk of febrile malaria could be predicted by identifying the 20% of homesteads that experienced an episode of febrile malaria during one month in the dry season. That 20% subsequently experienced 65% of all febrile malaria episodes during the following year. A definition based on remote sensing data was 81% sensitive and 63% specific for the stable hotspots of asymptomatic malaria.

Conclusions

Hotspots of asymptomatic parasitaemia are stable over time, but hotspots of febrile malaria are unstable. This finding may be because immunity offsets the high rate of febrile malaria that might otherwise result in stable hotspots, whereas unstable hotspots necessarily affect a population with less prior exposure to malaria. Please see later in the article for the Editors'' Summary     

Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition

AKT1 ({"type":"entrez-protein","attrs":{"text":"NP_005154.2","term_id":"62241011","term_text":"NP_005154.2"}}NP_005154.2) is a member of the serine/threonine AGC protein kinase family involved in cellular metabolism, growth, proliferation and survival. The three human AKT isozymes are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. Dysregulation of the AKT pathway has been identified in multiple human cancers. Several clinical trials are in progress to test the efficacy of AKT pathway inhibitors in treating cancer. Recently, a series of AKT isozyme-selective allosteric inhibitors have been reported. They require the presence of both the pleckstrin-homology (PH) and kinase domains of AKT, but their binding mode has not yet been elucidated. We present here a 2.7 Å resolution co-crystal structure of human AKT1 containing both the PH and kinase domains with a selective allosteric inhibitor bound in the interface. The structure reveals the interactions between the PH and kinase domains, as well as the critical amino residues that mediate binding of the inhibitor to AKT1. Our work also reveals an intricate balance in the enzymatic regulation of AKT, where the PH domain appears to lock the kinase in an inactive conformation and the kinase domain disrupts the phospholipid binding site of the PH domain. This information advances our knowledge in AKT1 structure and regulation, thereby providing a structural foundation for interpreting the effects of different classes of AKT inhibitors and designing selective ones.     

How pure is your thiosialoside? A reinvestigation into the HPLC purification of thioglycosides of N-acetylneuraminic acid

The synthesis of thiosialosides as potential biological probes for investigations involving the use of sialic acid-recognising proteins has been reinvestigated. It has been found that the most efficient method for the preparation of thiosialosides free from any 2,3-didehydro sialic acid contaminants involves an intermediate HPLC purification of thiosialosides as their methyl esters. Subsequent methyl ester hydrolysis provides thiosialosides (eg. 6 and 14) which are suitable for studies involving the use of sialic acid-recognising proteins.     

Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells

Caveolae, specialized flask-shaped lipid rafts on the cell surface, are composed of cholesterol, sphingolipids, and structural proteins termed caveolins; functionally, these plasma membrane microdomains have been implicated in signal transduction and transmembrane transport. In the present study, we examined the role of caveolin-1 in multiple myeloma cells. We show for the first time that caveolin-1, which is usually absent in blood cells, is expressed in multiple myeloma cells. Analysis of myeloma cell-derived plasma membrane fractions shows that caveolin-1 is co-localized with interleukin-6 receptor signal transducing chain gp130 and with insulin-like growth factor-I receptor. Cholesterol depletion by beta-cyclodextrin results in the loss of caveola structure in myeloma cells, as shown by transmission electron microscopy, and loss of caveolin-1 function. Interleukin-6 and insulin-like growth factor-I, growth and survival factors in multiple myeloma, induce caveolin-1 phosphorylation, which is abrogated by pre-treatment with beta-cyclodextrin. Importantly, inhibition of caveolin-1 phosphorylation blocks both interleukin-6-induced protein complex formation with caveolin-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. beta-Cyclodextrin also blocks insulin-like growth factor-I-induced tyrosine phosphorylation of insulin-responsive substrate-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. Therefore, cholesterol depletion by beta-cyclodextrin abrogates both interleukin-6- and insulin-like growth factor-I-triggered multiple myeloma cell survival via negative regulation of caveolin-1. Taken together, this study identifies caveolin-1 and other structural membrane components as potential new therapeutic targets in multiple myeloma.     

Expression of a novel chitinase by the fungal endophyte in Poa ampla

Many wild and cultivated cool-season grass species are naturally infected with fungal endophytes of the genera Neotyphodium and Epichlo?. These associations generally are considered mutualistic with the plants benefiting from reduced herbivory and the fungi benefiting from nutrients supplied by the plants. The fungi secrete proteins that might have a role in the interspecies symbiosis. In the interaction between Poa ampla Merr. and the endophyte Neotyphodium sp., a fungal chitinase was detected in the apoplastic protein fraction. The chitinase was also the major protein secreted in culture. Sequence analysis of the chitinase revealed it has a low level of amino acid sequence identity to other fungal chitinases and one of the conserved active site residues is altered. DNA gel-blot analysis indicated the chitinase was encoded by a single gene. Expression of similar chitinases also was detected in endophyte-infected tall fescue (Festuca arundinacea Schreb.), perennial ryegrass (Lolium perenne L.) and Chewings fescue (Festuca rubra L. subsp. fallax [Thuill] Nyman). This is the first report of an endophyte chitinase expressed in the infected host grass. As a secreted hydrolytic enzyme, the chitinase might have roles in the nutrition, growth or defense of the endophyte.     

Post-embryonic development of cuticular caps of campaniform sensilla of the cockroach leg: potential implications in scaling force detection

All animals generate progressively larger forces as they increase in size and mass. Their abilities to detect these forces must be similarly adjusted. In insects, campaniform sensilla monitor strains in the exoskeleton and provide information about forces acting upon the legs. Each sensory neuron possesses a dendrite that inserts into a cuticular cap in the exoskeleton. The cap is the site of mechanotransduction. We measured the sizes and numbers of receptor caps on the cockroach hindleg at different developmental stages. Our goal was to identify morphological features that could be correlated with the range of forces that must be detected. As cockroaches increase in size through successive molts, the number of cuticular caps in each group increases. The tibial group, for example, has two sensilla in first instar animals and 10-12 in the adult. There is also an increase in the range of cap sizes within each group. Observations of animals and their molted exoskeletons suggest that this increase occurs as the caps of existing receptors increase in size and smaller ones are added with each molt. These changes may be important in increasing the range of forces the receptors can signal while retaining sensitivity to low levels of force.