A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria

Mitochondria metabolise almost all of the oxygen that we consume, reducing it to water by cytochrome c oxidase (CcO). CcO maximises energy capture into the protonmotive force by pumping protons across the mitochondrial inner membrane. Forty years after the H+/e- stoichiometry was established, a consensus has yet to be reached on the route taken by pumped protons to traverse CcO’s hydrophobic core and on whether bacterial and mitochondrial CcOs operate via the same coupling mechanism. To resolve this, we exploited the unique amenability to mitochondrial DNA mutagenesis of the yeast S. cerevisiae to introduce single point mutations in the hydrophilic pathways of CcO to test function. From ADP/O ratio measurements on preparations of intact mitochondria, we definitely established that the D-channel, and not the H-channel, is the proton pump of the yeast mitochondrial enzyme, supporting an identical coupling mechanism in all forms of the enzyme

Effects of STN and GPi Deep Brain Stimulation on Impulse Control Disorders and Dopamine Dysregulation Syndrome

Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD) and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED), and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement) were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery

A complete network-on-chip emulation framework

Current Systems-On-Chip (SoC) execute applications that demand extensive parallel processing. Networks-On-Chip (NoC) provide a structured way of realizing interconnections on silicon, and obviate the limitations of bus-based solution. NoCs can have regular or ad hoc topologies, and functional validation is essential to assess their correctness and performance. In this paper, we present a flexible emulation environment implemented on an FPGA that is suitable to explore, evaluate and compare a wide range of NoC solutions with a very limited effort. Our experimental results show a speed-up of four orders of magnitude with respect to cycle-accurate HDL simulation, while retaining cycle accuracy. With our emulation framework, designers can explore and optimize a various range of solutions, as well as characterize quickly performance figures.

A Novel Approach for Network on Chip Emulation

Current systems-on-chip execute applications that demand extensive parallel processing. Networks-on-chip (NoC) provide a structured way of realizing interconnections on silicon, and obviate the limitations of bus-based solutions. NoCs can have regular or ad hoc topologies, and functional validation is essential to assess their correctness and performance. In this paper, we present a flexible emulation environment implemented on an FPGA that is suitable to explore, evaluate and compare a wide range of NoC solutions with a very limited effort. Our experimental results show a speed-up of four orders of magnitude with respect to cycle-accurate HDL simulation, while retaining cycle accuracy. With our emulation framework, designers can explore and optimize a range of solutions, as well as characterize quickly performance figures