Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice.

Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR end points, including acellular capillaries and leukocyte infiltration. We hypothesized that IF-mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia. Compared with db/db mice on ad libitum feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number, villi length, and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR5, the TUDCA receptor, was found in the retinal primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a downstream target of TGR5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota toward species producing TUDCA and subsequent retinal protection by TGR5 activation.

Writer-reader contagion of inspiration and related states: Conditional process analyses within a cross-classified writer × reader framework.

A longstanding tradition in the humanities holds that a writer's inspiration is infectious, but this thesis has not been tested. We hypothesized that (a) inspiration is infectious, such that inspired writers are more inspiring to the average reader; (b) contagion is mediated by the insightfulness of the text; and (c) contagion is moderated by readers' openness to experience, such that open readers are more prone to contagion. To test these hypotheses, a sample of 195 student writers, each of whom wrote 1 poem, was crossed with a sample of 220 student readers, who read all poems. Data were available for 36,020 cells of the resulting Writer × Reader matrix. Our analytic approach integrated cross-classified multilevel modeling with conditional process analysis. As hypothesized, writers who were more inspired elicited higher levels of inspiration in the average reader. Inspiration contagion was mediated by the insightfulness and pleasantness of the text and was partially suppressed by originality. Inspiration contagion was moderated by reader openness. Moderated mediation analyses indicated that open readers were prone to contagion because they were tolerant of the originality and sublimity of inspired writing. Additional analyses differentiated contagion of inspiration from contagion of its covariates (awe, positive affect), documented effects of writer inspiration on reader enthrallment (awe, chills), and showed that writer effort is a poor predictor of reader states. The infectiousness of inspiration-through poetry, if not also through scripture and academic writing-suggests that a given instance of inspiration may have far-reaching cultural implications, including dissemination of innovations and ideologies. (PsycINFO Database Record

The scientific study of inspiration in the creative process: challenges and opportunities.

Inspiration is a motivational state that compels individuals to bring ideas into fruition. Creators have long argued that inspiration is important to the creative process, but until recently, scientists have not investigated this claim. In this article, we review challenges to the study of creative inspiration, as well as solutions to these challenges afforded by theoretical and empirical work on inspiration over the past decade. First, we discuss the problem of definitional ambiguity, which has been addressed through an integrative process of construct conceptualization. Second, we discuss the challenge of how to operationalize inspiration. This challenge has been overcome by the development and validation of the Inspiration Scale (IS), which may be used to assess trait or state inspiration. Third, we address ambiguity regarding how inspiration differs from related concepts (creativity, insight, positive affect) by discussing discriminant validity. Next, we discuss the preconception that inspiration is less important than "perspiration" (effort), and we review empirical evidence that inspiration and effort both play important-but different-roles in the creative process. Finally, with many challenges overcome, we argue that the foundation is now set for a new generation of research focused on neural underpinnings. We discuss potential challenges to and opportunities for the neuroscientific study of inspiration. A better understanding of the biological basis of inspiration will illuminate the process through which creative ideas "fire the soul," such that individuals are compelled to transform ideas into products and solutions that may benefit society.