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Summary: 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.

Pancreatic β-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 β-cells remains undefined. To investigate the role of GATA factors in adult β-cells, we derived β-cell-inducible Gata4- and Gata6-knockout mice, along with whole-body inducible Gata4 knockouts. β-Cell Gata4 deletion modestly increased the proportion of dying β-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 β-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 β-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 β-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 β-cell survival in a tissue-specific manner and that GATA factors likely contribute to type 1 diabetes mellitus pathogenesis.

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.

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. Think back to the last time you walked across a college campus or down a crowded city street. Did you find yourself looking at some people more than others, and are there some people in particular you could now pick out of a line up? Are the answers to these questions determined merely by random characteristics of the people you passed or are the ways we selectively process others linked to theoretically important constraints on how the mind works? In this article, we report some initial investigations into how biases in social information processing might be linked to fundamental adaptive motivations. Because social environments can be quite complex, selective cognitive attunements can lead to biases in the way people process social information (cf. Haselton & Buss, 2000). For example, a newcomer walking across a large university campus for the first time may be exposed to thousands of unfamiliar strangers. One can imagine that such a person might selectively attend to the most attractive of his or her new schoolmates. Because one’s ability to encode and remember people is influenced by the degree to which one attends to them, this new student might consequently overestimate the proportion of attractive students at that university. This, in turn, might influence the student’s relationship decisions and behavior (Guttentag & Secord, 1983). Functionalist evolutionary theories often posit the existence of adaptively tuned cognitive mechanisms (Klein, Cosmides, Tooby, & Chance, 2002). However, research inspired by such theories has at times fallen short of directly investigating these mechanisms and determining at what stage of information processing they occur (e.g., Kenrick, Neuberg, Zierk, & Krones, 1994). Such research often focuses more directly on overt preferences, judgments, and evaluative outcomes, leaving unexplored the more basic-level cognitive mechanisms assumed to underlie them. In contrast, social cognitive researchers have used rigorous methods to examine these more proximate mechanisms, but have focused less on the role of specific types of stimulus content and on the ultimate motives leading people to selectively process some kinds of social information more than others. The present research merges functionalist and social cognitive perspectives by investigating selective processing biases within the domain of mating. Across five experimental studies, we explore selective cognitive attunements to physically attractive others at different levels of processing. First, we examine whether limiting participants’ attentional capacity might result in biased frequency estimates of attractive targets. Second, we use an eyetracking method to investigate the extent to which observers selectively attend to physically attractive male and female targets. Third, we examine whether observers exhibit recognition memory biases for attractive faces.

The existence of adult β-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that β-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 β-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to β-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of β-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified β-cells from the entire pancreas and observed that β-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 β-cell lineage. Thus, we conclude that β-cells are not generated in injured adult mouse pancreas.