Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity

The development of multicomponent biotherapeutic carriers is an important challenge in the field of drug delivery, particularly in the area of protein-based vaccines. While the delivery of protein antigens to antigen presenting cells (APCs) is crucial for this type of vaccination, the incorporation of additional adjuvants may be just as important in order to generate more potent immune responses. This article presents the synthesis and biological evaluation of carrier particles that both deliver a protein payload to APCs and display receptor ligands for the enhancement of APC immunostimulation. Particles displaying CpG oligonucleotide ligands for Toll-like receptor 9 were synthesized. The addition of CpG DNA to the particles led to a 45-fold increase in the secretion of interleukin-12, a cytokine that aids in T-cell activation, and a significant increase in the expression of costimulatory molecules by APCs. Moreover, vaccination with particles containing both ovalbumin (OVA) and CpG DNA induced a superior OVA-specific CD8 T-cell response in vivo, as measured by increased OVA-specific CD8 T-cell proliferation, secretion of the proinflammatory cytokine IFN-gamma, and the induction of OVA-specific cytotoxicity.     

Lethal combat and sex ratio evolution in a parasitoid wasp

Sex allocation theory provides excellent opportunities for testinghow behavior and life histories are adjusted in response toenvironmental variation. One of the most successful areas fromthis respect is Hamilton's local mate competition theory. Aspredicted by theory, a large number of animal species have beenshown to adjust their offspring sex ratios (proportion male)conditionally, laying less female-biased sex ratios as the numberof females that lay eggs on a patch increases. However, recentstudies have shown that this predicted pattern is not followedby 2 parasitoid species in the genus Melittobia, which alwaysproduce extremely female-biased sex ratios. A possible explanationfor this is that males fight fatally and that males producedby the first female to lay eggs on a patch have a competitiveadvantage over later emerging males. This scenario would negatethe advantage of later females producing a less female-biasedsex ratio. Here we examine fatal fighting and sex ratio evolutionin another species, Melittobia acasta. We show that femalesof this species also fail to adjust their offspring sex ratioin response to the number of females laying eggs on a patch.We then show that although earlier emerging males do have anadvantage in winning fights, this advantage 1) can be reducedby an interaction with body size, with larger males more likelyto win fights and 2) only holds for a brief period around thetime at which the younger males emerge from their pupae. Thissuggests that lethal male combat cannot fully explain the lackof sex ratio shift observed in Melittobia species. We discussalternative explanations.     

How partnerships end in guillemots Uria aalge: chance events, adaptive change, or forced divorce?

Divorce in socially monogamous species can result from differentmechanisms, for example, chance events, active desertion ofthe partner, or the intrusion of a third individual oustingthe partner. We compared the predictions associated with suchmechanisms with data from common guillemots (Uria aalge) breedingon the Isle of May, Scotland. The data cover the years 1982–2005and show a yearly divorce rate of 10.2%. In most divorces (86%),one of the original partners moved to another breeding site,whereas the other bird stayed and bred with a new partner. Onaverage, movers had a significantly lower breeding success afterdivorce, stayers were largely unaffected, whereas the incomingbirds benefited significantly from the change. This patternfits best the predictions of the "forced-divorce" hypothesis,suggesting that many divorces were caused by incoming birdsrather than the original partners or chance events. Althoughwe are unable to document the precise behavioral sequence thatled to divorces, our interpretation is supported by observationsof frequent fights over breeding-site ownership. Our data alsoindicate within-population diversity of divorce mechanisms:some divorces were apparently accidental, others desertion ofpartners and sites if the latter were of low quality. Our studyfinally illustrates that a negative correlation between breedingsuccess and probability of divorce (which our data show) neednot indicate the adaptiveness of divorce for the original partners.Because such a connection has often been made, adaptive divorcemay in general be less common than usually assumed.     

People as Ecological Participants in Ecological Restoration

In 1987, Bradshaw proposed that ecological restoration is the ultimate “acid test” of our understanding the functioning of ecosystems ( Bradshaw 1987 ). Although this concept is widely supported academically, how it can be applied by restoration practitioners is still unclear. This is an issue not limited to Bradshaw’s acid test, but moreover, reflects a general difficulty associated with the polarization between conceptual restoration (restoration ecology) and practical restoration (ecological restoration), where each has functioned to certain degree in isolation of the other. Outside of the more obvious pragmatic reasons for the relative independence between ecological restoration and restoration ecology, we propose that a more contentious explanation is that the approach taken toward understanding ecosystem development in restoration ecology is tangential to what actually takes place in ecological restoration. Current paradigms assume that the process of ecosystem development in restoration should follow the developmental trajectories suggested by classical ecological succession models. However, unlike these models, ecosystem development in restoration is, at least initially, largely manipulated by people, rather than by abiotic and biotic forces alone. There has been little research undertaken to explore how restoration activities impact upon or add to the extant ecological processes operating within a restoration site. Consequently, ecological restoration may not be so much an acid test of our understanding the functioning of ecosystems, but rather, an acid test of our understanding mutually beneficial interactions between humans and ecosystems.     

Validation of instrumentation to monitor dynamic performance of olympic weightlifters

The purpose of this study was to validate the accuracy and reliability of the Weightlifting Video Overlay System (WVOS) used by coaches and sport biomechanists at the United States Olympic Training Center. Static trials with the bar set at specific positions and dynamic trials of a power snatch were performed. Static and dynamic values obtained by the WVOS were compared with values obtained by tape measure and standard video kinematic analysis. Coordinate positions (horizontal [X] and vertical [Y]) were compared on both ends (left and right) of the bar. Absolute technical error of measurement between WVOS and kinematic values were calculated (0.97 cm [left X], 0.98 cm [right X], 0.88 cm [left Y], and 0.53 cm [right Y]) for the static data. Pearson correlations for all dynamic trials exceeded r = 0.88. The greatest discrepancies between the 2 measuring systems were found to occur when there was twisting of the bar during the performance. This error was probably due to the location on the bar where the coordinates were measured. The WVOS appears to provide accurate position information when compared with standard kinematics; however, care must be taken in evaluating position measurements if there is a significant amount of twisting in the movement. The WVOS appears to be reliable and valid within reasonable error limits for the determination of weightlifting movement technique.     

Reliability and detecting change following short-term creatine supplementation: comparison of two-component body composition methods

The purpose of the present study was twofold: firstly, to assess the reliability of various body composition methods, and secondly, to determine the ability of the methods to estimate changes in fat-free mass (FFM) following creatine (Cr) supplementation. Fifty-five healthy male athletes (weight 78.3 +/- 10.3 kg, age 21 +/- 1 years) gave informed consent to participate in this study. Subjects' FFM was estimated by hydrostatic weighing (HW), air-displacement plethysmography (ADP), bioelectrical impedance analysis (BIA), near-infrared spectroscopy (NIR), and anthropometric measurements (ANTHRO). Measurements were taken on 2 occasions separated by 7 days to assess the reliability of the methods. Following this, 30 subjects returned to the laboratory for an additional test day following 7 days of Cr supplementation (20 g.d(-1) Cr + 140 g.d(-1) dextrose) to assess each method's ability to detect acute changes in FFM. In terms of reliability, we found excellent test-retest correlations for all 5 methods, ranging from 0.983 to 0.998 (p < 0.001). The mean biases for the 5 methods were close to 0 (range -0.1 to 0.3 kg) and their 95% limits of agreement (LOAs) were within acceptable limits (HW = -1.1 to 1.7 kg; ADP = -1.1 to 1.2 kg; BIA = -1.0 to 1.0 kg; NIR = -1.4 to 1.4 kg); however, the 95% LOAs were slightly wider for ANTHRO (-2.4 to 2.6 kg). Following Cr supplementation there was a significant increase in body mass (from 77.9 +/- 10.1 kg to 78.9 +/- 10.3 kg, p = 0.000). In addition, all 5 body composition techniques detected the change in FFM to a similar degree (mean change: HW = 0.9 +/- 0.6 kg; ADP = 0.9 +/- 0.6 kg; BIA = 0.9 +/- 0.6 kg; NIR = 0.8 +/- 0.5 kg; ANTHRO = 1.0 +/- 0.7 kg; intraclass correlation coefficient = 0.962). We conclude that between-day differences in FFM estimation were within acceptable limits, with the possible exception of ANTHRO. In addition, all 5 methods provided similar measures of FFM change during acute Cr supplementation.     

Gene microarray analysis using angular distribution decomposition.

Clustering techniques have been widely used in the analysis of microarray data to group genes with similar expression profiles. The similarity of expression profiles and hence the results of clustering greatly depend on how the data has been transformed. We present a method that uses the relative expression changes between pairs of conditions and an angular transformation to define the similarity of gene expression patterns. The pairwise comparisons of experimental conditions can be chosen to reflect the purpose of clustering allowing control the definition of similarity between genes. A variational Bayes mixture modeling approach is then used to find clusters within the transformed data. The purpose of microarray data analysis is often to locate groups genes showing particular patterns of expression change and within these groups to locate specific target genes that may warrant further experimental investigation. We show that the angular transformation maps data to a representation from which information, in terms of relative regulation changes, can be automatically mined. This information can be then be used to understand the "features" of expression change important to different clusters allowing potentially interesting clusters to be easily located. Finally, we show how the genes within a cluster can be visualized in terms of their expression pattern and intensity change, allowing potential target genes to be highlighted within the clusters of interest.