The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease...The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.展开更多
The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for ea...The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for each DR operation. A recursion symmetry Hungarian method （RSHM）, modified from the Hungarian method, is proposed for generating a DR operation sequence with minimal total travel time, in which symmetry marking is introduced to ensure a feasible solution and recursion is adopted to break the endless loop caused by the symmetry marking. Simulation experiments are conducted to evaluate the cost effectiveness and the performance of the proposed method. Experimental results illustrate that compared to the single-shuttle machine, the dual-shuttle machine can reduce more than 40% of the total travel time of retrieval operations, and the RSHM saves about 5% to 10% of the total travel time of retrieval operations compared to the greedy-based heuristic.展开更多
Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as w...Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82071395)the Natural Science Foundation of Chongqing(Grant Nos.cstc2021ycjh-bgzxm0186,cstc2020jcyj-zdxmX0004,and cstc2021jcyj-bsh0023)the CQMU Program for Youth Innovation in Future Medicine(Grant No.W0044).
文摘The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.
基金The National Natural Science Foundation of China(No.61003158,61272377)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20120092110027)
文摘The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for each DR operation. A recursion symmetry Hungarian method （RSHM）, modified from the Hungarian method, is proposed for generating a DR operation sequence with minimal total travel time, in which symmetry marking is introduced to ensure a feasible solution and recursion is adopted to break the endless loop caused by the symmetry marking. Simulation experiments are conducted to evaluate the cost effectiveness and the performance of the proposed method. Experimental results illustrate that compared to the single-shuttle machine, the dual-shuttle machine can reduce more than 40% of the total travel time of retrieval operations, and the RSHM saves about 5% to 10% of the total travel time of retrieval operations compared to the greedy-based heuristic.
基金supported by a grant from NIH(NINDSgrant number R15NS098389 to KW)
文摘Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.
