Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Jan 2017
Case ReportsInherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. ⋯ By contrast, the patient's peripheral blood mononuclear cells responded normally to all TLR1/2, TLR2/6, TLR4, TLR7, and TLR8 (R848) agonists tested, and to IL-1β. The death of this child precluded long-term evaluations of the clinical consequences of inherited IRAK-1 deficiency. However, these findings suggest that human IRAK-1 is essential downstream from TLRs but not IL-1Rs in fibroblasts, whereas it plays a redundant role downstream from both TLRs and IL-1Rs in leukocytes.
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2016
Past-focused environmental comparisons promote proenvironmental outcomes for conservatives.
Conservatives appear more skeptical about climate change and global warming and less willing to act against it than liberals. We propose that this unwillingness could result from fundamental differences in conservatives' and liberals' temporal focus. Conservatives tend to focus more on the past than do liberals. ⋯ Past comparisons largely eliminated the political divide that separated liberal and conservative respondents' attitudes toward and behavior regarding climate change, so that across these studies conservatives and liberals were nearly equally likely to fight climate change. This research demonstrates how psychological processes, such as temporal comparison, underlie the prevalent ideological gap in addressing climate change. It opens up a promising avenue to convince conservatives effectively of the need to address climate change and global warming.
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2016
Nicotinic receptors in mouse prefrontal cortex modulate ultraslow fluctuations related to conscious processing.
The prefrontal cortex (PFC) plays an important role in cognitive processes, including access to consciousness. The PFC receives significant cholinergic innervation and nicotinic acetylcholine receptors (nAChRs) contribute greatly to the effects of acetylcholine signaling. Using in vivo two-photon imaging of both awake and anesthetized mice, we recorded spontaneous, ongoing neuronal activity in layer II/III in the PFC of WT mice and mice deleted for different nAChR subunits. ⋯ The β2 subunit is specifically required for synchronized activity patterns. Furthermore, chronic application of mecamylamine, an antagonist of nAChRs, disrupts the generation of ultraslow fluctuations. Our findings provide new insight into the ongoing spontaneous activity in the awake and anesthetized state, and the role of cholinergic neurotransmission in the orchestration of cognitive functions.
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Proc. Natl. Acad. Sci. U.S.A. · Nov 2016
Comparative StudyFor blacks in America, the gap in neighborhood poverty has declined faster than segregation.
Black residential segregation has been declining in the United States. That accomplishment rings hollow, however, if blacks continue to live in much poorer neighborhoods than other Americans. ⋯ Because black-white differences in neighborhood poverty declined much faster than black-white segregation, the neighborhood poverty disadvantage of blacks declined faster than black segregation-a noteworthy finding because the narrowing of the racial gap in neighborhood poverty for blacks has gone largely unnoticed. Further analysis reveals that the narrowing of the gap was produced by change in both the medians and shapes of the distribution of poverty across the neighborhoods where blacks, whites, Hispanics, and Asians reside.