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Salmonella profits from immunometabolism Extensive metabolic rewiring occurs in various immune cells during the course of infection. Whether these changes can be exploited by intracellular pathogens remains an open question. Rosenberg et al. report that infection with Salmonella enterica serovar Typhimurium ( S. Tm) induces the accumulation of the metabolite succinate in macrophages (see the Perspective by Lynch and Lesser). This key intermediate in the citric acid cycle activates virulence genes in S. Tm, leading to microbial resistance. Moreover, the active transport of succinate through the C4-dicarboxylate transporter DcuB is required for S. Tm virulence and survival within macrophages. Sensing of citric acid cycle intermediates may more generally serve as a cue to initiate the resistance programs of intracellular pathogens. Science , this issue p. 400 ; see also p. 344

SummaryEncounters between host cells and intracellular bacterial pathogens lead to complex phenotypes that determine the outcome of infection. Single-cell RNA-sequencing (scRNA-seq) are increasingly used to study the host factors underlying diverse cellular phenotypes. But current approaches do not permit the simultaneous unbiased study of both host and bacterial factors during infection. Here, we developed scPAIR-seq, an approach to analyze both host and pathogen factors during infection by combining multiplex-tagged mutant bacterial library with scRNA-seq to identify mutant-specific changes in host transcriptomes. We applied scPAIR-seq to macrophages infected with a library of Salmonella Typhimurium secretion system effector mutants. We developed a pipeline to independently analyze redundancy between effectors and mutant-specific unique fingerprints, and mapped the global virulence network of each individual effector by its impact on host immune pathways. ScPAIR-seq is a powerful tool to untangle bacterial virulence strategies and their complex interplay with host defense strategies that drive infection outcome.

In contrast to science and technology, public policymaking systems lack knowledge about the design and operation of overall social control. Policy sciences contribute to the understanding and improvement of large-scale control systems, especially in their attempt to give rationality to policymaking and decisionmaking activities. The most important implication of policy sciences is that they provide man with the ability to direct and control his future. (RA)

Public policymaking institutions and their operations should be viewed as complex systems, to be analyzed and improved with the help of basic general systems theory ideas and concepts. Possibilities of and needs for changes in the policymaking system can be illustrated by eleven improvement proposals: explicit strategy decisions, explicit learning feedback, better consideration of the future, much analysis, encouragement of creativity and inventions, improvement of one-person-centered decisionmaking, development of policy professionals, development of politicians, establishment of policy sciences as an academic discipline, radical changes in school teaching of civic and current affairs subjects, and explicit and systematic metapolicymaking. (Author)

The main thesis of this paper is that innovative changes in both urban metapolicy and in urban education are needed to meet present and future urban problems. Metapolicy deals with policies on policymaking, including the characteristics of the policymaking system and basic policy frameworks and postures. Unless urban metapolicy is improved, no meaningful improvements are possible in concrete policies on specific issues. Required changes in urban metapolicy include: (1) development of urban policy sciences knowledge; (2) invention of new urban policy tools; (3) explicit strategy determination; (4) new policy-contributing institutions and/or policy research organizations; (5) improvement of urban policymaking personnel; and, (6) advancement of citizen participation. This analysis has important implications for urban educators. On one hand, similar improvements in the urban education policymaking subsystems are needed for better urban educational policies. On the other hand, some radical changes in urban education are needed to meet the needs of better urban metapolicies. These include: (1) education of adults for more active roles in urban policymaking; (2) preparation of children for even more active future roles in urban policymaking; (3) training and retraining of urban policy practitioners for new patterns of urban policymaking; (4) training of new types of urban policy professionals; and (5) development of policy scientists. (Author)

Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Advances in single cell RNA-sequencing (scRNA-seq) allow probing of these immune interactions, such as cell-type compositions, which are then interpreted by deconvolution algorithms using bulk RNA-seq measurements. However, not all aspects of immune surveillance are represented by current algorithms. Here, using scRNA-seq of human peripheral blood cells infected with Salmonella, we develop a deconvolution algorithm for inferring cell-type specific infection responses from bulk measurements. We apply our dynamic deconvolution algorithm to a cohort of healthy individuals challenged ex vivo with Salmonella, and to three cohorts of tuberculosis patients during different stages of disease. We reveal cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and human infection outcomes., Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Here, Avraham and colleagues present a deconvolution algorithm that uses single-cell RNA and bulk RNA sequencing measurements of pathogen-infected cells to predict disease risk outcomes.