Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor.

Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8(+) T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8(+) T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8(+) T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety.This work was supported by grants from the Wellcome Trust and the Medical Research Council. GLS is a Wellcome Trust Principal Research Fellow.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/imm.1242

Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection

The Schro¨\ddot{o}dinger-Poisson equations as the large-N limit of the Newtonian N-body system: applications to the large scale dark matter dynamics

In this paper it is argued how the dynamics of the classical Newtonian N-body system can be described in terms of the Schr$\ddot{o}$dinger-Poisson equations in the large $N$ limit. This result is based on the stochastic quantization introduced by Nelson, and on the Calogero conjecture. According to the Calogero conjecture, the emerging effective Planck constant is computed in terms of the parameters of the N-body system as $\hbar \sim M^{5/3} G^{1/2} (N/)^{1/6}$, where is $G$ the gravitational constant, $N$ and $M$ are the number and the mass of the bodies, and $$ is their average density. The relevance of this result in the context of large scale structure formation is discussed. In particular, this finding gives a further argument in support of the validity of the Schr$\ddot{o}$dinger method as numerical double of the N-body simulations of dark matter dynamics at large cosmological scales.Comment: Accepted for publication in the Euro. Phys. J.

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Importance of Achromatic Contrast in Short-Range Fruit Foraging of Primates

Trichromatic primates have a ‘red-green’ chromatic channel in addition to luminance and ‘blue-yellow’ channels. It has been argued that the red-green channel evolved in primates as an adaptation for detecting reddish or yellowish objects, such as ripe fruits, against a background of foliage. However, foraging advantages to trichromatic primates remain unverified by behavioral observation of primates in their natural habitats. New World monkeys (platyrrhines) are an excellent model for this evaluation because of the highly polymorphic nature of their color vision due to allelic variation of the L-M opsin gene on the X chromosome. In this study we carried out field observations of a group of wild, frugivorous black-handed spider monkeys (Ateles geoffroyi frontatus, Gray 1842, Platyrrhini), consisting of both dichromats (n = 12) and trichromats (n = 9) in Santa Rosa National Park, Costa Rica. We determined the color vision types of individuals in this group by genotyping their L-M opsin and measured foraging efficiency of each individual for fruits located at a grasping distance. Contrary to the predicted advantage for trichromats, there was no significant difference between dichromats and trichromats in foraging efficiency and we found that the luminance contrast was the main determinant of the variation of foraging efficiency among red-green, blue-yellow and luminance contrasts. Our results suggest that luminance contrast can serve as an important cue in short-range foraging attempts despite other sensory cues that could be available. Additionally, the advantage of red-green color vision in primates may not be as salient as previously thought and needs to be evaluated in further field observations

Stochastic and Regulatory Role of Chromatin Silencing in Genomic Response to Environmental Changes

Phenotypic diversity and fidelity can be balanced by controlling stochastic molecular mechanisms. Epigenetic silencing is one that has a critical role in stress response. Here we show that in yeast, incomplete silencing increases stochastic noise in gene expression, probably owing to unstable chromatin structure. Telomere position effect is suggested as one mechanism. Expression diversity in a population achieved in this way may render a subset of cells to readily respond to various acute stresses. By contrast, strong silencing tends to suppress noisy expression of genes, in particular those involved in life cycle control. In this regime, chromatin may act as a noise filter for precisely regulated responses to environmental signals that induce huge phenotypic changes such as a cell fate transition. These results propose modulation of chromatin stability as an important determinant of environmental adaptation and cellular differentiation

Nurse-patient interaction and communication: a systematic literature review

Aim: The purpose of this review is to describe the use and definitions of the concepts of nurse-patient interaction and nurse-patient communication in nursing literature. Furthermore, empirical findings of nurse-patient communication research will be presented, and applied theories will be shown. Method: An integrative literature search was executed. The total number of relevant citations found was 97. The search results were reviewed, and key points were extracted in a standardized form. Extracts were then qualitatively summarized according to relevant aspects and categories for the review. Results: The relation of interaction and communication is not clearly defined in nursing literature. Often the terms are used interchangeably or synonymously, and a clear theoretical definition is avoided or rather implicit. Symbolic interactionism and classic sender-receiver models were by far the most referred to models. Compared to the use of theories of adjacent sciences, the use of original nursing theories related to communication is rather infrequent. The articles that try to clarify the relation of both concepts see communication as a special or subtype of interaction. Conclusion: The included citations all conclude that communication skills can be learned to a certain degree. Involvement of patients and their role in communication often is neglected by authors. Considering the mutual nature of communication, patients’ share in conversation should be taken more into consideration than it has been until now. Nursing science has to integrate its own theories of nursing care with theories of communication and interaction from other scientific disciplines like sociology