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"Johnston, Christopher D"
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Open versus closed : personality, identity, and the politics of redistribution
\"Debates over redistribution, social welfare, and market regulation are central to American politics. Why do some of us prefer a large role for government in the economic life of the nation while others prefer a smaller role? In Open Versus Closed, the authors argue that these preferences are not always what they seem. They show how deep-seated personality traits underpinning the culture wars over race and immigration, sexuality, gender roles, and religion influence debates about economics, binding cultural and economic preferences together in unexpected ways. Integrating insights from both psychology and political science - and twenty years of observational and experimental data - the authors reveal the deeper motivations driving attitudes toward government. The book concludes that for the politically engaged these attitudes are not primarily driven by self-interest but by a desire to express the traits and cultural commitments that define their identities\"-- Provided by publisher.
Book
Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer
The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types
1
,
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. Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis
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–
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, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies
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and single-cell RNA sequencing
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to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host–microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling
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, we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion–adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.
Spatial profiling and single-cell RNA sequencing are used to map the spatial distribution of the microbiota within human tumours, revealing how intratumoral microbial communities contribute to tumour heterogeneity and cancer progression.
Journal Article
Biosensor libraries harness large classes of binding domains for construction of allosteric transcriptional regulators
The ability of bacteria to sense specific molecules within their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating such processes have been studied, only a handful have been leveraged for molecular biology applications. To expand the repertoire of biotechnologically relevant sensors we present a strategy for the construction and testing of chimeric TF libraries, based on the fusion of highly soluble periplasmic binding proteins (PBPs) with DNA-binding domains (DBDs). We validate this concept by constructing and functionally testing two unique sense-and-respond regulators for benzoate, an environmentally and industrially relevant metabolite. This work will enable the development of tailored biosensors for novel synthetic regulatory circuits.
Bacterially encoded environmental sensor proteins are potentially a rich source of transcriptional control but only a few have been harnessed for biotechnological applications. Here the authors develop a general strategy for designing custom-made monogenic synthetic sensors and validate the approach by designing two sense-and-respond regulators for benzoate.
Journal Article
Ideological Asymmetries and the Determinants of Politically Motivated Reasoning
A large literature demonstrates that conservatives have greater needs for certainty than liberals. This suggests an asymmetry hypothesis: Conservatives are less open to new information that conflicts with their political identity and, in turn, political accountability will be lower on the right than the left. However, recent work suggests that liberals and conservatives are equally prone to politically motivated reasoning (PMR). The present article confronts this puzzle. First, we identify significant limitations of extant studies evaluating the asymmetry hypothesis and deploy two national survey experiments to address them. Second, we provide the first direct test of the key theoretical claim underpinning the asymmetry hypothesis: epistemic needs for certainty promote PMR. We find little evidence for the asymmetry hypothesis. Importantly, however, we also find no evidence that epistemic needs promote PMR. That is, although conservatives report greater needs for certainty than liberals, these needs are not a major source of political bias.
Journal Article
Restriction-modification mediated barriers to exogenous DNA uptake and incorporation employed by Prevotella intermedia
Prevotella intermedia, a major periodontal pathogen, is increasingly implicated in human respiratory tract and cystic fibrosis lung infections. Nevertheless, the specific mechanisms employed by this pathogen remain only partially characterized and poorly understood, largely due to its total lack of genetic accessibility. Here, using Single Molecule, Real-Time (SMRT) genome and methylome sequencing, bisulfite sequencing, in addition to cloning and restriction analysis, we define the specific genetic barriers to exogenous DNA present in two of the most widespread laboratory strains, P. intermedia ATCC 25611 and P. intermedia Strain 17. We identified and characterized multiple restriction-modification (R-M) systems, some of which are considerably divergent between the two strains. We propose that these R-M systems are the root cause of the P. intermedia transformation barrier. Additionally, we note the presence of conserved Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems in both strains, which could provide a further barrier to exogenous DNA uptake and incorporation. This work will provide a valuable resource during the development of a genetic system for P. intermedia, which will be required for fundamental investigation of this organism's physiology, metabolism, and pathogenesis in human disease.
Journal Article
Economists and Public Opinion
How do citizens view economists, and how do they respond to consensus in the profession? We examine the responsiveness of the American public to information regarding the distribution of opinion among economists on five economic policy issues. We also examine the extent and role of citizens’ trust in economists. We find that trust is tepid and find correspondingly small-to-moderate changes in public opinion when citizens are given information about expert opinion. Indeed, we provide evidence that responsiveness is larger when the consensus is attributed to a generic sample of people than when it is attributed to economists. We also find heterogeneity in responsiveness across issues, such that opinion change is smaller on symbolic policy issues than technical ones. Further, on the former, but not the latter, we find that citizens use judgments of trust in economists in a motivated fashion, to reinforce prior opinions.
Journal Article
The tumour-associated microbiome
The burgeoning field of intratumoural microbiome research has been driven by advances in next-generation sequencing technologies, with compelling evidence on the role of the microbiota in cancer initiation, progression and patient response to treatment. Here, we discuss new concepts of the tumour-associated microbiota and what is needed to advance the translational impact of these findings in gastrointestinal cancers.
Journal Article
Harnessing the microbiome to restore immunotherapy response
Despite the profound clinical success of immune-checkpoint inhibitors, their effectiveness is limited by intrinsic and acquired resistance. Bullman, Zitvogel and colleagues provide their views on two clinical trials modulating the microbiome of immunotherapy-resistant patients with melanoma via transplantation of fecal microbiota from patients who responded to immunotherapy.
Journal Article
On the Ideological Foundations of Supreme Court Legitimacy in the American Public
Conventional wisdom says that individuals' ideological preferences do not influence Supreme Court legitimacy orientations. Most work is based on the assumption that the contemporary Court is objectively conservative in its policymaking, meaning that ideological disagreement should come from liberals and agreement from conservatives. Our nuanced look at the Court's policymaking suggests rational bases for perceiving the Court's contemporary policymaking as conservative, moderate, and even liberal. We argue that subjective ideological disagreement—incongruence between one's ideological preferences and one's perception of the Court's ideological tenor—must be accounted for when explaining legitimacy. Analysis of a national survey shows that subjective ideological disagreement exhibits a potent, deleterious impact on legitimacy. Ideology exhibits sensible connections to legitimacy depending on how people perceive the Court's ideological tenor. Results from a survey experiment support our posited mechanism. Our work has implications for the public's view of the Court as a \"political\" institution.
Journal Article