Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity

Item does not contain fulltextIt is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response

Ordering and finite-size effects in the dynamics of one-dimensional transient patterns

We introduce and analyze a general one-dimensional model for the description of transient patterns which occur in the evolution between two spatially homogeneous states. This phenomenon occurs, for example, during the Freedericksz transition in nematic liquid crystals.The dynamics leads to the emergence of finite domains which are locally periodic and independent of each other. This picture is substantiated by a finite-size scaling law for the structure factor. The mechanism of evolution towards the final homogeneous state is by local roll destruction and associated reduction of local wavenumber. The scaling law breaks down for systems of size comparable to the size of the locally periodic domains. For systems of this size or smaller, an apparent nonlinear selection of a global wavelength holds, giving rise to long lived periodic configurations which do not occur for large systems. We also make explicit the unsuitability of a description of transient pattern dynamics in terms of a few Fourier mode amplitudes, even for small systems with a few linearly unstable modes.Comment: 18 pages (REVTEX) + 10 postscript figures appende

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Automated Analysis in Feature Modelling and Product Configuration

The automated analysis of feature models is one of the thriving topics of research in the software product line and variability management communities that has attracted more attention in the last years. A recent literature review reported that more than 30 analysis operations have been identi ed and di erent analysis mechanisms have been proposed. Product con guration is a well established research eld with more than 30 years of successful applications in di erent industrial domains. Our hypothesis, that is not really new, is that these two independent areas of research have interesting synergies that have not been fully explored. To try to explore the potential synergies systematically, in this paper we provide a rapid review to bring together these previously disparate streams of work. We de ne a set of research questions and give a preliminary answer to some of them. We conclude that there are many research opportunities in the synergy of these independent areas.Ministerio de Ciencia e Innovación TIN2009- 07366Junta de Andalucía TIC-590

Genetic, abiotic and social influences on sex differentiation in cichlid fishes and the evolution of sequential hermaphroditism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73799/1/j.1467-2979.2005.00184.x.pd

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness