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Wireless connectivity has traditionally been regarded as an opaque data pipe carrying messages, whose context-dependent meaning and effectiveness have been ignored. Nevertheless, in emerging cyber-physical and autonomous networked systems, acquiring, processing, and sending excessive amounts of distributed real-time data, which ends up being stale or useless to the end user, will cause communication bottlenecks, increased latency, and safety issues. We envision a communication paradigm shift, which makes the Semantics of Information, i.e., the significance and the usefulness of messages with respect to the goal of data exchange, the underpinning of the entire communication process. This entails a goal-oriented unification of information generation, transmission, and usage, by taking into account process dynamics, signal sparsity, data correlation, and semantic information attributes. We apply this structurally new, synergetic approach to a communication scenario where the destination is tasked with real-time source reconstruction for the purpose of remote actuation. Capitalizing on semantics-empowered sampling and communication policies, we show significant reduction in both reconstruction error and cost of actuation error, as well as in the number of uninformative samples generated.