Feeding behavior is one of the most essential activities in animals, which is tightly regulated by neuroendocrine factors. Drosophila melanogaster short neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY) regulate food intake. Understanding the molecular mechanism of sNPF and NPY signaling is critical to elucidate feeding regulation. Here, we found that minibrain (mnb) and the mammalian ortholog Dyrk1a target genes of sNPF and NPY signaling and regulate food intake in Drosophila melanogaster and mice. In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway. Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake. Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a transgenic mice exhibited decreased FOXO acetylation and increased NPY expression in the hypothalamus, as well as increased food intake. Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.

Vertebrate Pax2 and Pax8 proteins are closely related transcription factors hypothesized to regulate early aspects of inner ear development. In zebrafish and mouse, Pax8 expression is the earliest known marker of otic induction, and Pax2 homologs are expressed at slightly later stages of placodal development. Analysis of compound mutants has not been reported. To facilitate analysis of zebrafish pax8, we completed sequencing of the entire gene, including the 5′ and 3′ UTRs. pax8transcripts undergo complex alternative splicing to generate at least ten distinct isoforms. Two different subclasses of pax8 splice isoforms encode different translation initiation sites. Antisense morpholinos (MOs)were designed to block translation from both start sites, and four additional MOs were designed to target different exon-intron boundaries to block splicing. Injection of MOs, individually and in various combinations,generated similar phenotypes. Otic induction was impaired, and otic vesicles were small. Regional ear markers were expressed correctly, but hair cell production was significantly reduced. This phenotype was strongly enhanced by simultaneously disrupting either of the co-inducers fgf3 or fgf8, or another early regulator, dlx3b, which is thought to act in a parallel pathway. In contrast, the phenotype caused by disrupting foxi1, which is required for pax8 expression, was not enhanced by simultaneously disrupting pax8. Disrupting pax8,pax2a and pax2b did not further impair otic induction relative to loss of pax8 alone. However, the amount of otic tissue gradually decreased in pax8-pax2a-pax2b-deficient embryos such that no otic tissue was detectable by 24 hours post-fertilization. Loss of otic tissue did not correlate with increased cell death, suggesting that otic cells dedifferentiate or redifferentiate as other cell type(s). These data show that pax8 is initially required for normal otic induction, and subsequently pax8, pax2a and pax2b act redundantly to maintain otic fate.

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The formation of the otic placode is a complex process requiring multiple inductive signals. In zebrafish, fgf3 and fgf8, dlx3b and dlx4b, and foxi1 have been identified as the earliest-acting genes in this process. fgf3 and fgf8 are required as inductive signals, whereas dlx3b, dlx4b, and foxi1 appear to act directly within otic primordia. We have investigated potential interactions among these genes. Depletion of either dlx3b and dlx4b or foxi1 leads to a delay of pax2a expression in the otic primordia and reduction of the otic vesicle. Depletion of both foxi1 and dlx3b results in a complete ablation of otic placode formation. A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8, and a weaker interaction among dlx3b, fgf3, and fgf8. Misexpression of foxi1 can induce expression of pax8, an early marker for the otic primordia, in embryos treated with an inhibitor of fibroblast growth factor (FGF) signaling. Conversely, morpholino knockdown of foxi1 blocks ectopic pax8 expression and otic vesicle formation induced by misexpression of fgf3 and/or fgf8. The observed genetic interactions suggest a model in which foxi1 and dlx3b/dlx4b act in independent pathways together with distinct phases of FGF signaling to promote otic placode induction and development. Developmental Dynamics 230:419 -433, 2004.

In this paper, we propose model predictive control methods to reduce the common-mode voltage of three-phase voltage source inverters (VSIs). In the reduced common-mode voltage-model predictive control (RCMV-MPC) methods proposed in this paper, only nonzero voltage vectors are utilized to reduce the common-mode voltage as well as to control the load currents. In addition, two nonzero voltage vectors are selected from the cost function at every sampling period, instead of using only one optimal vector during one sampling period. The two selected nonzero vectors are distributed in one sampling period in such a way as to minimize the error between the measured load current and the reference. Without utilizing the zero vectors, the common-mode voltage controlled by the proposed RCMV-MPC algorithms can be restricted within ±V dc /6. Furthermore, application of the two nonzero vectors with optimal time sharing between them can yield satisfactory load current ripple performance without using the zero vectors. Thus, the proposed RCMV-MPC methods can reduce the common-mode voltage as well as control the load currents with fast transient response and satisfactory load current ripple performance compared with the conventional model predictive control method. Simulation and experimental results are included to verify the effectiveness of the proposed RCMV-MPC methods.Index Terms -Predictive control, common-mode voltage, current control, voltage source inverter. 0885-8993 (c) reference, the current controller evaluates all the predicted current values obtained by the seven possible states to select one optimal switching state with the smallest cost value. Finally, the VSI with the model predictive controller applies the optimal switching state during the entire sampling period of the controller. Because of its simplicity with no requirement of individual PWM blocks as well as its control flexibility, the model predictive control scheme has been employed to control the load currents of power converters other than VSIs, such as multilevel inverters, multiphase inverters, active power filters, and matrix converters [14][15][16][17][18][19][20][21][22][23][24][25][26].This paper proposes two reduced common-mode voltage-model predictive control (RCMV-MPC) methods to reduce the common-mode voltage of three-phase VSIs on the basis of the model predictive control method. In the proposed RCMV-MPC methods, only six nonzero VSI states are considered to perform model predictive control to reduce the common-mode voltage by avoiding the zero vectors. Furthermore, the proposed methods utilize two nonzero voltage states in one sampling period in order to compensate for the reduced number of voltage states, instead of using only one optimal vector during one sampling period as in the conventional method. The two selected active vectors are distributed within the sampling period in such a way as to minimize the squared current errors between the reference and actual future load currents in the proposed methods. Therefore, the common-mode volta...