Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2007
Hemopressin is an inverse agonist of CB1 cannabinoid receptors.
To date, the endogenous ligands described for cannabinoid receptors have been derived from membrane lipids. To identify a peptide ligand for CB(1) cannabinoid receptors, we used the recently described conformation-state sensitive antibodies and screened a panel of endogenous peptides from rodent brain or adipose tissue. This led to the identification of hemopressin (PVNFKFLSH) as a peptide ligand that selectively binds CB(1) cannabinoid receptors. ⋯ Finally, we examine the activity of hemopressin in vivo using different models of pain and find that it exhibits antinociceptive effects when administered by either intrathecal, intraplantar, or oral routes, underscoring hemopressin's therapeutic potential. These results represent a demonstration of a peptide ligand for CB(1) cannabinoid receptors that also exhibits analgesic properties. These findings are likely to have a profound impact on the development of novel therapeutics targeting CB(1) receptors.
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Proc. Natl. Acad. Sci. U.S.A. · Nov 2007
Selective changes of resting-state networks in individuals at risk for Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. ⋯ The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation.
UV radiation (UVR) is a complete carcinogen that elicits a constellation of pathological events, including direct DNA damage, generation of reactive oxidants that peroxidize lipids and damage other cellular components, initiation of inflammation, and suppression of the immune response. Recent dramatic increases in the incidence of nonmelanoma skin cancers are largely attributable to higher exposure of an aging population to UVR. Therefore, the development of cellular strategies for intrinsic protection of the skin against the deleterious effects of UVR is imperative. ⋯ Topical application of sulforaphane-rich extracts of 3-day-old broccoli sprouts up-regulated phase 2 enzymes in the mouse and human skin, protected against UVR-induced inflammation and edema in mice, and reduced susceptibility to erythema arising from narrow-band 311-nm UVR in humans. In six human subjects (three males and three females, 28-53 years of age), the mean reduction in erythema across six doses of UVR (300-800 mJ/cm(2) in 100 mJ/cm(2) increments) was 37.7% (range 8.37-78.1%; P = 0.025). This protection against a carcinogen in humans is catalytic and long lasting.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
Gossip as an alternative for direct observation in games of indirect reciprocity.
Communication about social topics is abundant in human societies, and many functions have been attributed to such gossiping. One of these proposed functions is the management of reputations. Reputation by itself has been shown to have a strong influence on cooperation dynamics in games of indirect reciprocity, and this notion helps to explain the observed high level of cooperation in humans. ⋯ We show that gossip has a strong influence on the resulting behavior even when participants have access to the original information (i.e., direct observation) as well as gossip about the same information. Thus, it is evident that gossip has a strong manipulative potential. Furthermore, gossip about cooperative individuals is more positive than gossip about uncooperative individuals, gossip comments transmit social information successfully, and cooperation levels are higher when people encounter positive compared with negative gossip.