The different faces of the macrophage in asthma

PURPOSE OF REVIEW: Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization. RECENT FINDINGS: Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet.Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research. SUMMARY: The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open

Measured potential profile in a quantum anomalous Hall system suggests bulk-dominated current flow

Ideally, quantum anomalous Hall systems should display zero longitudinal resistance. Yet in experimental quantum anomalous Hall systems elevated temperature can make the longitudinal resistance finite, indicating dissipative flow of electrons. Here, we show that the measured potentials at multiple locations within a device at elevated temperature are well-described by solution of Laplace's equation, assuming spatially-uniform conductivity, suggesting non-equilibrium current flows through the two-dimensional bulk. Extrapolation suggests that at even lower temperatures current may still flow primarily through the bulk rather than, as had been assumed, through edge modes. An argument for bulk current flow previously applied to quantum Hall systems supports this picture.Comment: 6 pages, 4 figures, plus supplemental material

Profitable failure: antidepressant drugs and the triumph of flawed experiments

Drawing on an analysis of Irving Kirsch and colleagues? controversial 2008 article in PLoS [Public Library of Science] Medicine on the efficacy of SSRI antidepressant drugs such as Prozac, I examine flaws within the methodologies of randomized controlled trials (RCTs) that have made it difficult for regulators, clinicians and patients to determine the therapeutic value of this class of drug. I then argue, drawing analogies to work by Pierre Bourdieu and Michael Power, that it is the very limitations of RCTs ? their inadequacies in producing reliable evidence of clinical effects ? that help to strengthen assumptions of their superiority as methodological tools. Finally, I suggest that the case of RCTs helps to explore the question of why failure is often useful in consolidating the authority of those who have presided over that failure, and why systems widely recognized to be ineffective tend to assume greater authority at the very moment when people speak of their malfunction

The Elusive Rentier Rich: Piketty's Data Battles and the Power of Absent Evidence

The popularity of Thomas Piketty?s research on wealth inequality has drawn attention to a curious question: why was widening wealth inequality largely neglected by mainstream economists in recent decades? To explore and explain that neglect, I draw on the writing of the early neoclassical economist John Bates Clark, who introduced the notion of the marginal productivity of income distribution at the end of the nineteenth century. I then turn to Piketty?s Capital in order to analyze the salience of marginal productivity theories of income today. I suggest that most of the criticism and praise for Piketty?s research is focused on data that are accessible and measurable, obscuring attention to questions over whether current methods for measuring economic capital are defensible or not. My overarching aim is to explore how ?absent? data in economics as a whole help to reinforce blind spots within mainstream economic theory

Survival processing in times of stress

Recent studies have found that processing information according to an evolutionary relevant (i.e., survival) scenario improves its subsequent memorability, potentially as a result of fitness advantages gained in the ancestral past. So far, research has not revealed much about any proximate mechanisms that might underlie this so-called survival processing advantage in memory. Intriguingly, research has shown that the memorability of stressful situations is enhanced via the release of stress hormones acting on brain regions involved in memory. Since survival situations habitually involve some degree of stress, in the present study, we investigated whether stress serves as a proximate mechanism to promote survival processing. Participants rated words for their relevance to either a survival or a neutral (moving) scenario after they had been exposed to a psychosocial stressor or a no-stress control condition. Surprise retention tests immediately following the rating task revealed that survival processing and acute stress independently boosted memory performance. These results therefore suggest that stress does not serve as a proximate mechanism of the survival processing advantage in memory

Emergence of Anthrax Edema Toxin as a Master Manipulator of Macrophage and B Cell Functions

Anthrax edema toxin (ET), a powerful adenylyl cyclase, is an important virulence factor of Bacillus anthracis. Until recently, only a modest amount of research was performed to understand the role this toxin plays in the organism’s immune evasion strategy. A new wave of studies have begun to elucidate the effects this toxin has on a variety of host cells. While efforts have been made to illuminate the effect ET has on cells of the adaptive immune system, such as T cells, the greatest focus has been on cells of the innate immune system, particularly the macrophage. Here we discuss the immunoevasive activities that ET exerts on macrophages, as well as new research on the effects of this toxin on B cells

The Art of Research: A Divergent/Convergent Framework and Opportunities for Science-Based Approaches

Applying science to the current art of producing engineering and research knowledge has proven difficult, in large part because of its seeming complexity. We posit that the microscopic processes underlying research are not so complex, but instead are iterative and interacting cycles of divergent (generation of ideas) and convergent (testing and selecting of ideas) thinking processes. This reductionist framework coherently organizes a wide range of previously disparate microscopic mechanisms which inhibit these processes. We give examples of such inhibitory mechanisms and discuss how deeper scientific understanding of these mechanisms might lead to dis-inhibitory interventions for individuals, networks and institutional levels

Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes