Reciprocity and the tragedies of maintaining and providing the commons

Social cooperation often requires collectively beneficial but individually costly restraint to maintain a public good, or it needs costly generosity to create one. Status quo effects predict that maintaining a public good is easier than providing a new one. Here, we show experimentally and with simulations that even under identical incentives, low levels of cooperation (the ‘tragedy of the commons’) are systematically more likely in maintenance than provision. Across three series of experiments, we find that strong and weak positive reciprocity, known to be fundamental tendencies underpinning human cooperation, are substantially diminished under maintenance compared with provision. As we show in a fourth experiment, the opposite holds for negative reciprocity (‘punishment’). Our findings suggest that incentives to avoid the ‘tragedy of the commons’ need to contend with dilemma specific reciprocity

In Silico Improvement of beta(3)-Peptide Inhibitors of p53 center dot hDM2 and p53 center dot hDMX

There is great interest in molecules capable of inhibiting the interactions between p53 and its negative regulators hDM2 and hDMX, as these molecules have validated potential against cancers in which one or both oncoproteins are overexpressed. We reported previously that appropriately substituted β(3)-peptides inhibit these interactions and, more recently, that minimally cationic β(3)-peptides are sufficiently cell permeable to upregulate p53-dependent genes in live cells. These observations, coupled with the known stability of β-peptides in a cellular environment, and the recently reported structures of hDM2 and hDMX, motivated us to exploit computational modeling to identify β-peptides with improved potency and/or selectivity. This exercise successfully identified a new β(3)-peptide, β53-16, that possesses the highly desirable attribute of high affinity for both hDM2 as well as hDMX and identifies the 3,4-dichlorophenyl moiety as a novel determinant of hDMX affinity. [Image: see text

Bridged beta(3)-Peptide Inhibitors of p53-hDM2 Complexation: Correlation between Affinity and Cell Permeability

β-peptides possess several features that are desirable in peptidomimetics; they are easily synthesized, fold into stable secondary structures in physiologic buffers, and resist proteolysis. They can also bind to a diverse array of proteins to inhibit their interactions with α–helical ligands. β–peptides are not usually cell permeable, however, and this feature limits their utility as research tools and potential therapeutics. Appending an Arg(8) sequence to a β–peptide improves uptake but adds considerable mass. We reported that embedding a small cationic patch within a PPII, α– or β–peptide helix improves uptake without the addition of significant mass. In another mass-neutral strategy, Verdine, Walensky, and others have reported that insertion of a hydrocarbon bridge between the i and i+4 positions of an α–helix also increases cell uptake. Here we describe a series of β–peptides containing diether and hydrocarbon bridges and compare them on the basis of cell uptake and localization, affinities for hDM2, and 14-helix structure. Our results highlight the relative merits of cationic patch and hydrophobic bridge strategies for improving β–peptide uptake and identify a surprising correlation between uptake efficiency and hDM2 affinity

Crystal structure of (1S,2R,4S)-2-bromomethyl-1-azabicyclo[2.2.2]·octan-5-one, C8H12BrNO

[no abstract

Analysis of Nocturnal op. 70 by Benjamin Britten

Nocturnal op. 70 is one of the most important large-scale works written for guitar in the twentieth century. Brief biographical data and some background information on Nocturnal show how it exemplifies Britten's compositional approach. The focus of the analysis is on three structural aspects: the rhythmic, the intervallic, and the aspect of underlying pitch patterns. The rhythmic analysis discusses the distortion of rhythmic patterns by the use of compression, expansion, elisions, syncopation, and rhythmic dissonance. The pitch set analysis discusses the intervallic character of the work, identifying and correlating set types as they form networks of relationship. The reductive analysis discusses the underlying connections of focal pitches in the linear material of Nocturnal. The conclusion then correlates the results of the preceding analyses, discussing the large-scale unfolding of the form in Nocturnal

Crystal structure of (1S,2R,4S,5S)-5-ethynyl-2-hydroxymethyl-1-azabicyclo[2.2.2]octane, (HC2)(HOCH2)C7H11N)

[no abstract

Crystal structure of (1S,2R,5R,6R)-2-methoxy-6-(16-nitrophenylethynyl)-1-azabicyclo[3.2.2]nonane, C17H20N2O3

[no abstract

Imaging of a beta-peptide distribution in whole-body mice sections by MALDI mass spectrometry

Markus Stoeckli, Dieter Staab, Alain Schweitzer, James Gardiner and Dieter Seebac