In the version of this article initially published, the fourth image in Figure 4b was a duplication of the third image. The error has been corrected in the HTML and PDF versions of the article.nature medicine volume 16 | number 11 | november 2010 1341 e r r ata

MicroRNAs (miRNAs) are endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes. Although no miRNA has been reported to play an important role in the regulation of fracture healing, several miRNAs control key elements in tissue repair processes such as inflammation, hypoxia response, angiogenesis, stem cell differentiation, osteogenesis, and chondrogenesis. We compared the plasma concentrations of 134 miRNAs in 4 patients with trochanteric fractures and 4 healthy controls (HCs), and the levels of six miRNAs were dysregulated. Among these miRNAs, miR-92a levels were significantly decreased 24 hours after fracture, compared to HCs. In patients with a trochanteric fracture or a lumbar compression fracture, the plasma concentrations of miR-92a were lower on days 7 and 14, but had recovered on day 21 after the surgery or injury. To determine whether systemic downregulation of miR-92a can modulate fracture healing, we administered antimir-92a, designed using locked nucleic acid technology to inhibit miR-92a, to mice with a femoral fracture. Systemic administration of antimir-92a twice a week increased the callus volume and enhanced fracture healing. Enhancement of fracture healing was also observed after local administration of antimir-92a. Neovascularization was increased in mice treated with antimir-92a. These results suggest that plasma miR-92a plays a crucial role in bone fracture healing in human and that inhibition of miR-92a enhances fracture healing through angiogenesis and has therapeutic potential for bone repair.

Game theory has been extensively applied to help explain how cooperative behaviour is promoted in human and animal societies. How do humans and animals establish reciprocity when confronting a social dilemma? In 2006, Nowak theoretically proved that numerous mechanisms and models for evolving cooperative behaviour reported over the last few decades can be distilled into five reciprocity mechanisms (rules). Additionally, universal scaling parameters were proposed to measure two different types of dilemmas, namely, the gamble-intending dilemma (GID) and risk-averting dilemma (RAD). In this work, by drawing a RAD–GID phase-plane diagram for pair-wise games, we prove that these five rules are indeed quite different for the resolution (relaxation) of the two dilemmas. These diagrams also demonstrate whether and when game-class change (resolution of a dilemma) occurs, thus implying how defectors can be eliminated.

What do corruption, resource overexploitation, climate inaction, vaccine hesitancy, traffic congestion, and even cancer metastasis have in common? All these socioeconomic and sociobiological phenomena are known as social dilemmas because they embody in one form or another a fundamental conflict between immediate self-interest and long-term collective interest. A shortcut to the resolution of social dilemmas has thus far been reserved solely for highly stylised cases reducible to dyadic games (e.g., the Prisoner’s Dilemma), whose nature and outcome coalesce in the concept of dilemma strength. We show that a social efficiency deficit, measuring an actor’s potential gain in utility or fitness by switching from an evolutionary equilibrium to a social optimum, generalises dilemma strength irrespective of the underlying social dilemma’s complexity. We progressively build from the simplicity of dyadic games for which the social efficiency deficit and dilemma strength are mathematical duals, to the complexity of carcinogenesis and a vaccination dilemma for which only the social efficiency deficit is numerically calculable. The results send a clear message to policymakers to enact measures that increase the social efficiency deficit until the strain between what is and what could be incentivises society to switch to a more desirable state.