Reasons to strike first.

De Dreu and Gross predict that attackers will have more difficulty winning conflicts than defenders. As their analysis is presumed to capture the dynamics of decentralized conflict, we consider how their framework compares with ethnographic evidence from small-scale societies, as well as chimpanzee patterns of intergroup conflict. In these contexts, attackers have significantly more success in conflict than predicted by De Dreu and Gross's model. We discuss the possible reasons for this disparity.

Aggressive Mimicry and the Evolution of the Human Cognitive Niche.

The evolutionary origins of deception and its functional role in our species is a major focus of research in the science of human origins. Several hypotheses have been proposed for its evolution, often packaged under either the Social Brain Hypothesis, which emphasizes the role that the evolution of our social systems may have played in scaffolding our cognitive traits, and the Foraging Brain Hypothesis, which emphasizes how changes in the human dietary niche were met with subsequent changes in cognition to facilitate foraging of difficult-to-acquire foods. Despite substantive overlap, these hypotheses are often presented as competing schools of thought, and there have been few explicitly proposed theoretical links unifying the two. Utilizing cross-cultural data gathered from the Human Relations Area Files (HRAF), we identify numerous (n = 357) examples of the application of deception toward prey across 145 cultures. By comparing similar behaviors in nonhuman animals that utilize a hunting strategy known as aggressive mimicry, we suggest a potential pathway through which the evolution of deception may have taken place. Rather than deception evolving as a tactic for deceiving conspecifics, we suggest social applications of deception in humans could have evolved from an original context of directing these behaviors toward prey. We discuss this framework with regard to the evolution of other mental traits, including language, Theory of Mind, and empathy.

Norm violations and punishments across human societies.

Punishments for norm violations are hypothesised to be a crucial component of the maintenance of cooperation in humans but are rarely studied from a comparative perspective. We investigated the degree to which punishment systems were correlated with socioecology and cultural history. We took data from the Standard Cross-Cultural Sample database and coded ethnographic documents from a sample of 131 largely non-industrial societies. We recorded whether punishment for norm violations concerned adultery, religion, food, rape or war cowardice and whether sanctions were reputational, physical, material or execution. We used Bayesian phylogenetic regression modelling to test for culture-level covariation. We found little evidence of phylogenetic signals in evidence for punishment types, suggesting that punishment systems change relatively quickly over cultural evolutionary history. We found evidence that reputational punishment was associated with egalitarianism and the absence of food storage; material punishment was associated with the presence of food storage; physical punishment was moderately associated with greater dependence on hunting; and execution punishment was moderately associated with social stratification. Taken together, our results suggest that the role and kind of punishment vary both by the severity of the norm violation, but also by the specific socio-economic system of the society.

Supernatural explanations across 114 societies are more common for natural than social phenomena.

Humans across the globe use supernatural beliefs to explain the world around them. This article explores whether cultural groups invoke the supernatural more to explain natural phenomena (for example, storms, disease outbreaks) or social phenomena (for example, murder, warfare). Quantitative analysis of ethnographic text across 114 geographically and culturally diverse societies found that supernatural explanations are more prevalent for natural than for social phenomena, consistent with theories that ground the origin of religious belief in a human tendency to perceive intent and agency in the natural world. Despite the dominance of supernatural explanations of natural phenomena, supernatural explanations of social phenomena were especially prevalent in urbanized societies with more socially complex and anonymous groups. Our results show how people use supernatural beliefs as explanatory tools in non-industrial societies, and how these applications vary across small-scale communities versus large and urbanized groups.

Disguises and the Origins of Clothing.

Thermoregulation is often thought to be a key motivating factor behind the origins of clothing. Less attention has been given, however, to the production and use of clothing across traditional societies in contexts outside of thermoregulatory needs. Here I investigate the use of disguises, modesty coverings, and body armor among the 10 hunter-gatherer societies in the Probability Sample Files (PSF) within the Human Relations Area Files (HRAF) World Cultures database, with a particular focus on disguise cases and how they compare with strategies of deception across other taxa. The employment of disguises-defined as altering one's appearance for purposes of deceiving conspecifics or other animals-is noted for eight of the 10 societies, with their use occurring in contexts of hunting, religious or cult practices, and war or interpersonal violence. Most hunter-gatherer disguises demonstrated clear similarities to cases of visual deception found in other species, with the majority of examples fitting categories of animal mimicry, masquerading as plants, disruptive coloration (camouflage), or background matching (camouflage), while disguises unique to humans involved the impersonation of culture-specific "spirit-beings." Clothing for modesty purposes (nine societies) and body armor (six societies) are also noted. I propose that strategic initiatives by individuals or groups to disguise or conceal themselves represents one possible initial pathway to the cultural evolution of clothing. There are likely multiple potential (nonexclusive) social and functional pathways to the emergence of clothing outside of thermoregulatory needs.

Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)amino)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation.

Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity.

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED(50) of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

Discovery and optimization of a novel series of N-arylamide oxadiazoles as potent, highly selective and orally bioavailable cannabinoid receptor 2 (CB2) agonists.

The CB2 receptor is an attractive therapeutic target for analgesic and anti-inflammatory agents. Herein we describe the discovery of a novel class of oxadiazole derivatives from which potent and selective CB2 agonist leads were developed. Initial hit 7 was identified from a cannabinoid target-biased library generated by virtual screening of sample collections using a pharmacophore model in combination with a series of physicochemical filters. 7 was demonstrated to be a selective CB2 agonist (CB2 EC50 = 93 nM, Emax = 98%, CB1 EC50 > 10 microM). However, this compound exhibited poor solubility and relatively high clearance in rat, resulting in low oral bioavailability. In this paper, we report detailed SAR studies on 7 en route toward improving potency, physicochemical properties, and solubility. This effort resulted in identification of 63 that is a potent and selective agonist at CB2 (EC50 = 2 nM, Emax = 110%) with excellent pharmacokinetic properties.

Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR.

4-Amino-5,6-biaryl-furo[2,3-d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity.