Counter Regulation of Spic by NF-κB and STAT Signaling Controls Inflammation and Iron Metabolism in Macrophages.

Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this "balancing act" remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a "default" Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.

GATA factors promote ER integrity and ß-cell survival and contribute to type 1 diabetes risk.

Pancreatic ß-cell survival remains poorly understood despite decades of research. GATA transcription factors broadly regulate embryogenesis and influence survival of several cell types, but their role in adult ß-cells remains undefined. To investigate the role of GATA factors in adult ß-cells, we derived ß-cell-inducible Gata4- and Gata6-knockout mice, along with whole-body inducible Gata4 knockouts. ß-Cell Gata4 deletion modestly increased the proportion of dying ß-cells in situ with ultrastructural abnormalities suggesting endoplasmic reticulum (ER) stress. Notably, glucose homeostasis was not grossly altered in Gata4- and Gata6-knockout mice, suggesting that GATA factors do not have essential roles in ß-cells. Several ER stress signals were up-regulated in Gata4 and Gata6 knockouts, most notably CHOP, a known regulator of ER stress-induced apoptosis. However, ER stress signals were not elevated to levels observed after acute thapsigargin administration, suggesting that GATA deficiency only caused mild ER stress. Simultaneous deletion of Gata4 and CHOP partially restored ß-cell survival. In contrast, whole-body inducible Gata4 knockouts displayed no evidence of ER stress in other GATA4-enriched tissues, such as heart. Indeed, distinct GATA transcriptional targets were differentially expressed in islets compared with heart. Such ß-cell-specific findings prompted study of a large meta-analysis dataset to investigate single nucleotide polymorphisms harbored within the human GATA4 locus, revealing several variants significantly associated with type 1 diabetes mellitus. We conclude that GATA factors have important but nonessential roles to promote ER integrity and ß-cell survival in a tissue-specific manner and that GATA factors likely contribute to type 1 diabetes mellitus pathogenesis.

Big secrets do not necessarily cause hills to appear steeper.

Slepian, Masicampo, Toosi, and Ambady (Journal of Experimental Psychology: General, 141, 619-624, 2012, Study 1) found that individuals recalling and writing about a big, meaningful secret judged a pictured hill as steeper than did those who recalled and wrote about a small, inconsequential secret (with estimates unrelated to physical effort unaffected). From an embodied cognition perspective, this result was interpreted as suggesting that important secrets weigh people down. Answering to mounting calls for the crucial need of independent direct replications of published findings to ensure the self-correcting nature of our science, we sought to corroborate Slepian et al.'s finding in two extremely high-powered, preregistered studies that were very faithful to all procedural and methodological details of the original study (i.e., same cover story, study title, manipulation, measures, item order, scale anchors, task instructions, sampling frame, population, and statistical analyses). In both samples, we were unsuccessful in replicating the target finding. Although Slepian et al. reported three other studies supporting the secret burdensomeness phenomenon, we advise that these three other findings need to be independently corroborated before the general phenomenon informs theory or health interventions.

ß-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

The existence of adult ß-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that ß-cell progenitors can be activated by ductal ligation-induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional ß-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to ß-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of ß-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified ß-cells from the entire pancreas and observed that ß-cell mass and insulin content are totally unchanged by PDL-induced injury. Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter-driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the ß-cell lineage. Thus, we conclude that ß-cells are not generated in injured adult mouse pancreas.

Humor in romantic contexts: do men participate and women evaluate?

Several lines of research illustrate that humor plays a pivotal role in relationship initiation. The current article applies sexual selection theory to argue that humor production is a fitness indicator, allowing men to transmit information tacitly about their underlying qualities. And whereas prior research has emphasized women's appreciation of humor as a signal of interest, the focus here is on how women evaluate prospective suitors' humorous offerings. Two studies, including an ecologically valid study of online dating advertisements, provided evidence for men's production and women's evaluation of humor in romantic contexts. A third study revealed that women's evaluations of potential mates' humor are predictive of their romantic interest. Moreover, this article shows that preferences for and perceptions of humor are associated with preferences for and perceptions of intelligence and warmth, consistent with the argument that one function of humor is as a fitness indicator that provides information about underlying mate quality.

Are "implicit" attitudes unconscious?

A widespread assumption in recent research on attitudes is that self-reported (explicit) evaluations reflect conscious attitudes, whereas indirectly assessed (implicit) evaluations reflect unconscious attitudes. The present article reviews the available evidence regarding unconscious features of indirectly assessed "implicit" attitudes. Distinguishing between three different aspects of attitudes, we conclude that (a) people sometimes lack conscious awareness of the origin of their attitudes, but that lack of source awareness is not a distinguishing feature of indirectly assessed versus self-reported attitudes, (b) there is no evidence that people lack conscious awareness of indirectly assessed attitudes per se, and (c) there is evidence showing that, under some conditions, indirectly assessed (but not self-reported) attitudes influence other psychological processes outside of conscious awareness. Implications for the concept of "implicit attitudes" are discussed.

Finger-length ratios show evidence of prenatal hormone-transfer between opposite-sex twins.

Finger-length ratio (second to fourth finger; 2D:4D) has been associated with various measures thought to be related to prenatal androgens. In addition, hormone-transfer theory posits that hormones can transfer between twins. We examined 2D:4D in same-sex (SS) and opposite-sex (OS) dizygotic twins to test both propositions. Results show that 2D:4D is masculinized in OS females compared to SS females. This provides strong evidence that 2D:4D is laid down prenatally, and that hormones (likely androgens) can transfer from male to female fetuses. Implications for developmental timeframes for both hormone-transfer and 2D:4D are discussed.

Sexually selective cognition: beauty captures the mind of the beholder.

Across 5 experimental studies, the authors explore selective processing biases for physically attractive others. The findings suggest that (a). both male and female observers selectively attend to physically attractive female targets, (b). limiting the attentional capacity of either gender results in biased frequency estimates of attractive females, (c). although females selectively attend to attractive males, limiting females' attentional capacity does not lead to biased estimates of attractive males, (d). observers of both genders exhibit enhanced recognition memory for attractive females but attenuated recognition for attractive males. Results suggest that different mating-related motives may guide the selective processing of attractive men and women.