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Another MPO planning organization has developed in the area of western central Florida. Several MPOs there, with governance over eight counties, have developed a greater regional planning committee, the Chairs Coordinating Committee (CCC),[10] composed of the chairs of seven MPOs and the chairs of their appointed advisory committee (or their representatives) in order to coordinate transportation planning for the region, that is compatible with all, as well as addressing the challenges of long range planning for a large and growing region that has overlapping issues among the MPOs or transportation plans that extend throughout the entire area. Often the members of the executive committee of an MPO act interchangeably as the representative to this seven-MPO regional committee. This committee meets less frequently than the participating MPOs.

In addition, ISTEA placed a new requirement on MPOs to conduct "fiscally constrained planning", and ensure that long-range transportation plans and short-term transportation improvement programs were fiscally constrained; in other words, adopted plans and programs can not include more projects than reasonably can be expected to be funded through existing or projected sources of revenues. This new requirement represented a major conceptual shift for many MPOs (and others in the planning community), since the imposition of fiscal discipline on plans now required, not only understanding how much money might be available, but how to prioritize investment needs and make difficult choices among competing needs. Adding to this complexity is the need to plan across transportation modes and develop approaches for multimodal investment prioritization and decision making. It is in this context of greater prominence, funding, and requirements that MPOs function today.

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An annual element is composed of transportation improvement projects contained in an area's transportation improvement program (TIP), which is proposed for implementation during the current year. The annual element is submitted to the U.S. Department of Transportation as part of the required planning process.

In addition to its central role in energy metabolism, the mitochondrion has many other functions essential for cell survival. When stressed, the multifunctional mitochondria are expected to engender multifaceted cell stress with complex physiological consequences. Potential extra-mitochondrial proteostatic burdens imposed by inefficient protein import have been largely overlooked. Accumulating evidence suggests that a diverse range of pathogenic mitochondrial stressors, which do not directly target the core protein import machinery, can reduce cell fitness by disrupting the proteostatic network in the cytosol. The resulting stress, named mitochondrial precursor overaccumulation stress (mPOS), is characterized by the toxic accumulation of unimported mitochondrial proteins in the cytosol. Here, we review our current understanding of how mitochondrial dysfunction can impact the cytosolic proteome and proteostatic signaling. We also discuss the intriguing possibility that the mPOS model may help untangle the cause-effect relationship between mitochondrial dysfunction and cytosolic protein aggregation, which are probably the two most prominent molecular hallmarks of neurodegenerative disease. 17dc91bb1f