Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2013
Both information and social cohesion determine collective decisions in animal groups.
During consensus decision making, individuals in groups balance personal information (based on their own past experiences) with social information (based on the behavior of other individuals), allowing the group to reach a single collective choice. Previous studies of consensus decision making processes have focused on the informational aspects of behavioral choice, assuming that individuals make choices based solely on their likelihood of being beneficial (e.g., rewarded). However, decisions by both humans and nonhuman animals systematically violate such expectations. ⋯ In addition, we demonstrate how multiple informational dimensions (here color and stripe orientation) are integrated within groups to achieve consensus, even though no individual is explicitly aware of, or has a unique preference for, the consensus option. Balancing of personal information and social cues by individuals in key frontal positions in the group is shown to be essential for such group-level capabilities. Our results demonstrate the importance of integrating informational with other social considerations when explaining the collective capabilities of group-living animals.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2013
B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells.
Although innate immune responses are necessary for the initiation of acquired immune responses and the subsequent successful elimination of pathogens, excessive responses occasionally result in lethal endotoxic shock accompanied by a cytokine storm. B and T lymphocyte attenuator (BTLA), a coinhibitory receptor with similarities to cytotoxic T-lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, is expressed in not only B and T cells but also dendritic cells (DCs) and macrophages (Mϕs). Recently, several studies have reported that BTLA-deficient (BTLA(-/-)) mice show enhanced pathogen clearance compared with WT mice in early phase of infections. ⋯ Moreover, BTLA(-/-) DCs showed enhanced MyD88- and toll/IL-1R domain-containing adaptor inducing IFN (TRIF)-dependent signaling on LPS stimulation, which is associated with impaired accumulation of Src homology 2-containing protein tyrosine phosphatase in lipid rafts. Finally, we found that an agonistic anti-BTLA antibody rescued mice from LPS-induced endotoxic shock, even if the antibody was given to mice that had developed a sign of endotoxic shock. These results suggest that BTLA directly inhibits LPS responses in DCs and Mϕs and that agonistic agents for BTLA might have therapeutic potential for LPS-induced endotoxic shock.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2013
Biography Historical ArticleRita Levi-Montalcini: NGF, the prototypical growth factor.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2013
Biography Historical ArticleRita Levi-Montalcini: Neuroscientist par excellence.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2013
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors.
Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. ⋯ Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.