A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Dissecting the Genetic Architecture of Host–Pathogen Specificity

International audienc

Gelotophobia and the challenges of implementing laughter into virtual agents interactions

This study investigated which features of AVATAR laughter are perceived threatening for individuals with a fear of being laughed at (gelotophobia), and individuals with no gelotophobia. Laughter samples were systematically varied (e.g., intensity, laughter pitch, and energy for the voice, intensity of facial actions of the face) in three modalities: animated facial expressions, synthesized auditory laughter vocalizations, and motion capture generated puppets displaying laughter body movements. In the online study 123 adults completed, the GELOPH (Ruch and Proyer, 2008a,b) and rated randomly presented videos of the three modalities for how malicious, how friendly, how real the laughter was (0 not at all to 8 extremely). Additionally, an open question asked which markers led to the perception of friendliness/maliciousness. The current study identified features in all modalities of laughter stimuli that were perceived as malicious in general, and some that were gelotophobia specific. For facial expressions of AVATARS, medium intensity laughs triggered highest maliciousness in the gelotophobes. In the auditory stimuli, the fundamental frequency modulations and the variation in intensity were indicative of maliciousness. In the body, backwards and forward movements and rocking vs. jerking movements distinguished the most malicious from the least malicious laugh. From the open answers, the shape and appearance of the lips curling induced feelings that the expression was malicious for non-gelotophobes and that the movement round the eyes, elicited the face to appear as friendly. This was opposite for gelotophobes. Gelotophobia savvy AVATARS should be of high intensity, containing lip and eye movements and be fast, non-repetitive voiced vocalization, variable and of short duration. It should not contain any features that indicate a down-regulation in the voice or body, or indicate voluntary/cognitive modulation.the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no. 270780 (ILHAIRE project)

Genes That Influence Swarming Motility and Biofilm Formation in Variovorax paradoxus EPS

Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces.We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR.The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant.The data presented here point to complex regulation of these surface behaviors

Genetic analysis of the capsule polysaccharide (K antigen) and exopolysaccharide genes in pandemic Vibrio parahaemolyticus O3:K6

<p>Abstract</p> <p>Background</p> <p>Pandemic <it>Vibrio parahaemolyticus </it>has undergone rapid changes in both K- and O-antigens, making detection of outbreaks more difficult. In order to understand these rapid changes, the genetic regions encoding these antigens must be examined. In <it>Vibrio cholerae </it>and <it>Vibrio vulnificus</it>, both O-antigen and capsular polysaccharides are encoded in a single region on the large chromosome; a similar arrangement in pandemic <it>V. parahaemolyticus </it>would help explain the rapid serotype changes. However, previous reports on "capsule" genes are controversial. Therefore, we set out to clarify and characterize these regions in pandemic <it>V. parahaemolyticus </it>O3:K6 by gene deletion using a chitin based transformation strategy.</p> <p>Results</p> <p>We generated different deletion mutants of putative polysaccharide genes and examined the mutants by immuno-blots with O and K specific antisera. Our results showed that O- and K-antigen genes are separated in <it>V. parahaemolyticus </it>O3:K6; the region encoding both O-antigen and capsule biosynthesis in other vibrios, i.e. genes between <it>gmhD </it>and <it>rjg</it>, determines the K6-antigen but not the O3-antigen in <it>V. parahaemolyticus</it>. The previously identified "capsule genes" on the smaller chromosome were related to exopolysaccharide synthesis, not K-antigen.</p> <p>Conclusion</p> <p>Understanding of the genetic basis of O- and K-antigens is critical to understanding the rapid changes in these polysaccharides seen in pandemic <it>V. parahaemolyticus. </it>This report confirms the genetic location of K-antigen synthesis in <it>V. parahaemolyticus </it>O3:K6 allowing us to focus future studies of the evolution of serotypes to this region.</p

Spatial Patterns in Herbivory on a Coral Reef Are Influenced by Structural Complexity but Not by Algal Traits

Background: Patterns of herbivory can alter the spatial structure of ecosystems, with important consequences for ecosystem functions and biodiversity. While the factors that drive spatial patterns in herbivory in terrestrial systems are well established, comparatively less is known about what influences the distribution of herbivory in coral reefs. Methodology and Principal Findings: We quantified spatial patterns of macroalgal consumption in a cross-section of Ningaloo Reef (Western Australia). We used a combination of descriptive and experimental approaches to assess the influence of multiple macroalgal traits and structural complexity in establishing the observed spatial patterns in macroalgal herbivory, and to identify potential feedback mechanisms between herbivory and macroalgal nutritional quality. Spatial patterns in macroalgal consumption were best explained by differences in structural complexity among habitats. The biomass of herbivorous fish, and rates of herbivory were always greater in the structurally-complex coral-dominated outer reef and reef flat habitats, which were also characterised by high biomass of herbivorous fish, low cover and biomass of macroalgae and the presence of unpalatable algae species. Macroalgal consumption decreased to undetectable levels within 75 m of structurally-complex reef habitat, and algae were most abundant in the structurally-simple lagoon habitats, which were also characterised by the presence of the most palatable algae species. In contrast to terrestrial ecosystems, herbivory patterns were not influenced by the distribution, productivity or nutritional quality of resources (macroalgae), and we found no evidence of a positive feedback between macroalgal consumption and the nitrogen content of algae. Significance: This study highlights the importance of seascape-scale patterns in structural complexity in determining spatial patterns of macroalgal consumption by fish. Given the importance of herbivory in maintaining the ability of coral reefs to reorganise and retain ecosystem functions following disturbance, structural complexity emerges as a critical feature that is essential for the healthy functioning of these ecosystems

The N–Terminal Tail of hERG Contains an Amphipathic α–Helix That Regulates Channel Deactivation

The cytoplasmic N–terminal domain of the human ether–a–go–go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N–terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N–terminal 135 residues of hERG contains a previously described Per–Arnt–Sim (PAS) domain (residues 26–135) as well as an amphipathic α–helix (residues 13–23) and an initial unstructured segment (residues 2–9). Deletion of residues 2–25, only the unstructured segment (residues 2–9) or replacement of the α–helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α–helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N–terminal α–helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel

Endophyte Microbiome Diversity in Micropropagated Atriplex canescens and Atriplex torreyi var griffithsii

Microbial diversity associated with micropropagated Atriplex species was assessed using microscopy, isolate culturing, and sequencing. Light, electron, and confocal microscopy revealed microbial cells in aseptically regenerated leaves and roots. Clone libraries and tag-encoded FLX amplicon pyrosequencing (TEFAP) analysis amplified sequences from callus homologous to diverse fungal and bacterial taxa. Culturing isolated some seed borne endophyte taxa which could be readily propagated apart from the host. Microbial cells were observed within biofilm-like residues associated with plant cell surfaces and intercellular spaces. Various universal primers amplified both plant and microbial sequences, with different primers revealing different patterns of fungal diversity. Bacterial and fungal TEFAP followed by alignment with sequences from curated databases revealed 7 bacterial and 17 ascomycete taxa in A. canescens, and 5 bacterial taxa in A. torreyi. Additional diversity was observed among isolates and clone libraries. Micropropagated Atriplex retains a complex, intimately associated microbiome which includes diverse strains well poised to interact in manners that influence host physiology. Microbiome analysis was facilitated by high throughput sequencing methods, but primer biases continue to limit recovery of diverse sequences from even moderately complex communities