SUMMARY Innate signals underlying the differentiation of tolerogenic dendritic cells (DC) remain ill defined. Here we show that TLR6 associated with TLR2 uniquely induces IL-10 producing DC and type-1 regulatory T cells. In contrast TLR1 associated with TLR2 promotes differentiation of IL-12p40 producing DC and inflammatory IFN-γ+ T cells. These distinct functional properties are supported by opposite patterns of JNK and p38 MAP kinase activation. The Y. pestis virulence factor LcrV, interestingly, hijacks the TLR2/6 pathway to promote IL-10 and block protective inflammatory responses. These results provide an explanation as to why TLR2 can mediate pro- and anti-inflammatory immune responses and place TLR6 as a distinct TLR receptor driving regulatory IL-10 responses. These findings have also important implications in infectious and inflammatory disease pathogenesis.
This article documents how biomedical researchers in the United Kingdom understand and enact the idea of “openness.” This is of particular interest to researchers and science policy worldwide in view of the recent adoption of pioneering policies on Open Science and Open Access by the U.K. government—policies whose impact on and implications for research practice are in need of urgent evaluation, so as to decide on their eventual implementation elsewhere. This study is based on 22 in-depth interviews with U.K. researchers in systems biology, synthetic biology, and bioinformatics, which were conducted between September 2013 and February 2014. Through an analysis of the interview transcripts, we identify seven core themes that characterize researchers’ understanding of openness in science and nine factors that shape the practice of openness in research. Our findings highlight the implications that Open Science policies can have for research processes and outcomes and provide recommendations for enhancing their content, effectiveness, and implementation.
Open Science policies encourage researchers to disclose a wide range of outputs from their work, thus codifying openness as a specific set of research practices and guidelines that can be interpreted and applied consistently across disciplines and geographical settings. In this paper, we argue that this “one-size-fits-all” view of openness sidesteps key questions about the forms, implications, and goals of openness for research practice. We propose instead to interpret openness as a dynamic and highly situated mode of valuing the research process and its outputs, which encompasses economic as well as scientific, cultural, political, ethical, and social considerations. This interpretation creates a critical space for moving beyond the economic definitions of value embedded in the contemporary biosciences landscape and Open Science policies, and examining the diversity of interests and commitments that affect research practices in the life sciences. To illustrate these claims, we use three case studies that highlight the challenges surrounding decisions about how––and how best––to make things open. These cases, drawn from ethnographic engagement with Open Science debates and semistructured interviews carried out with UK-based biologists and bioinformaticians between 2013 and 2014, show how the enactment of openness reveals judgments about what constitutes a legitimate intellectual contribution, for whom, and with what implications.
This ethnographic study, based on fieldwork at the Computational and Systems Medicine laboratory at Imperial College London, shows how researchers in the field of metabolomicsthe post-genomic study of the molecules and processes that make up metabolism -enact and coproduce complex views of biology with multivariate statistics. From this data-driven science, metabolism emerges as a multiple, informational and statistical object, which is both produced by and also necessitates particular forms of data production and analysis. Multivariate statistics emerge as 'natural' and 'correct' ways of engaging with a metabolism that is made up of many variables. In this sense, multivariate statistics allow researchers to engage with and conceptualize metabolism, and also disease and processes of life, as complex entities. Consequently, this article builds on studies of scientific practice and visualization to examine data as material objects rather than black-boxed representations. Data practices are not merely the technological components of experimentation, but are simultaneously technologies and methods and are intertwined with ways of seeing and enacting the biological world. Ultimately, this article questions the increasing invocation and role of complexity within biology, suggesting that discourses of complexity are often imbued with reductionist and determinist ways of thinking about biology, as scientists engage with complexity in calculated and controlled, but also limited, ways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.