MiR-29 coordinates age-dependent plasticity brakes in the adult visual cortex

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular “brakes” limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR‐29a expression in the visual cortex dramatically increases with age, but it is not experience‐dependent. Precocious high levels of miR‐29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR‐29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR‐29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR‐29a is a regulator of the plasticity brakes promoting age‐dependent stabilization of visual cortical connections

Unifying a profession and a health care system: Building the case for a “one pharmacy” global community

The rational use of medicines to achieve better patient outcomes is a global concern. This need has pressured the practice of pharmacy to move away from focusing only on dispensing of the drug product towards the patient's appropriate utilization of the medicine. PharmAlliance, a unique partnership among three leading schools of pharmacy at the University of North Carolina at Chapel Hill (United States), Monash University (Australia), and University College London (United Kingdom), convened a Global Summit of Pharmacy Practice Innovation in November 2017 to bring together the leaders of the professional associations of the three countries to dialogue about how to lead the identified changes. A framework of “One Pharmacy Community” resulted from the discussions and was conceptualized from the overarching theme of the Summit. Recognizing and articulating these similarities into a One Pharmacy Community framework enables the development of a consistent global nomenclature of pharmacy services. The four pillars that resulted from the conversation are education, research, practice, and collaboration. Each of these are essential and dependent on the other in order to enable pharmacy practice to meet the global requirements of patient-focused health care design and delivery. This article describes the framework and each of the pillars

MiR-29 coordinates age-dependent plasticity brakes in the adult visual cortex

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular “brakes” limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR-29a is a regulator of the plasticity brakes promoting age-dependent stabilization of visual cortical connections

Simulated annealing for constrained global optimization

Hide-and-Seek is a powerful yet simple and easily implemented continuous simulated annealing algorithm for finding the maximum of a continuous function over an arbitrary closed, bounded and full-dimensional body. The function may be nondifferentiable and the feasible region may be nonconvex or even disconnected. The algorithm begins with any feasible interior point. In each iteration it generates a candidate successor point by generating a uniformly distributed point along a direction chosen at random from the current iteration point. In contrast to the discrete case, a single step of this algorithm may generate any point in the feasible region as a candidate point. The candidate point is then accepted as the next iteration point according to the Metropolis criterion parametrized by an adaptive cooling schedule. Again in contrast to discrete simulated annealing, the sequence of iteration points converges in probability to a global optimum regardless of how rapidly the temperatures converge to zero. Empirical comparisons with other algorithms suggest competitive performance by Hide-and-Seek.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44934/1/10898_2005_Article_BF01100688.pd