Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexit...Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexity of the mammalian nervous system and our inability to visualize DA neurons in vivo restricts the advances in elucidating the molecular mechanisms of PD. Conservation between C. elegans and mammals in genomic, biosynthetic and metabolic pathways as well as the advantages of observing DA neurons morphology in vivo and the ease of transgenic and genetic manipulation make C. elegans an excellent model organism for PD.展开更多
Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the ag...Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal＇ s life-span control machinery, as well as the dauer formation control.展开更多
Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-synuclein transgenic C.elegans was used as the animal model...Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-synuclein transgenic C.elegans was used as the animal model,the toxic effect of MPP^＋ to dopamine（DA）neurons and the lifespan of worms was tested.The worms were feed with OP50 to determine whether ATP increase can rescue the worm from toxicity.ATP level and aberrant protein accumulation were analyzed in the MPP^＋ treated worms with or without OP50 addition.Results We found that MPP^＋ induced DA cell death and worm lethality,which could be prevented by OP50 treatment.OP50 exerted the protective effect by up-regulating ATP level,even though it also induced accumulation ofα-synuclein.Despite the undefined role of protein aggregation to the cell death,our results showed that the toxicity of MPP^＋ was mainly caused by the ATP depletion in theα-synuclein transgenic C.elegans.Conclusion MPP^＋ could induce DA neuronal death and worm lethality inα-synuclein transgenic C.elegans;Compared with the aggregation ofα-synuclein,the major cause of MPP^＋ toxicity appeared due to ATP depletion.展开更多
Diet has been shown to play an important role in human physiology.It is a predominant exogenous factor regulating the composition of gut microbiota,and dietary intervention holds promise for treatment of diseases such...Diet has been shown to play an important role in human physiology.It is a predominant exogenous factor regulating the composition of gut microbiota,and dietary intervention holds promise for treatment of diseases such as obesity,type 2 diabetes,and malnutrition.Furthermore,it was reported that diet has significant effects on physiological processes of C.elegans,including reproduction,fat storage,and aging.To reveal novel signaling pathways responsive to different diets,C.elegans and its bacterial diet were used as an interspecies model system to mimic the interaction between host and gut microbiota.Most signaling pathways identified in C.elegans are highly conserved across different species,including humans.A better understanding of these pathways can,therefore,help to develop interventions for human diseases.In this article,we summarize recent achievements on molecular mechanisms underlying the response of C.elegans to different diets and discuss their relevance to human health.展开更多
WormGUIDES is an open-source dynamic embryonic system designed to facilitate global understanding of cellular decisions in the developing nervous system of the nematode C. elegans. WormGUIDES was designed to allow inv...WormGUIDES is an open-source dynamic embryonic system designed to facilitate global understanding of cellular decisions in the developing nervous system of the nematode C. elegans. WormGUIDES was designed to allow investigation and exploration of the observational results of the C. elegans life cycle from laboratory experiments. In the process of a mechanistic C. elegans model development, some functionalities of WormGUIDES needed to be enhanced to support model validation and verification. In this study, a new way to visualize 3-dimentional vectors within WormGUIDES was investigated and presented. Then, the practical values of this method were demonstrated by visualizing two biologically significant directions (i.e., division orientation and cell polarity) of individual embryonic cells in C. elegans. Lastly, a mathematic approach was designed to illustrate the differences between these two sets of vectors and provide easy indications of the location of these individual cells that have large data discrepancies within the C. elegans embryonic system.展开更多
This paper presents a conception of an exponential observer for a class of linear distributed-parameter systems (DPSs), in which the dynamics are partially unknown. The given distributed-parameter observer ensures asy...This paper presents a conception of an exponential observer for a class of linear distributed-parameter systems (DPSs), in which the dynamics are partially unknown. The given distributed-parameter observer ensures asymptotic state estimator with exponentially decay error, based on the theory of C0-semigroups in a Hilbert space. The theoretical observer developed is applied to a chemical tubular reactor, namely the isothermal Plug-Flow reactor basic dynamical model for which measurements are available at the reactor output only. The process is described by Partial differential equations with unknown initial states. For this application, performance issues are illustrated in a simulation study.展开更多
The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caeno...The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.展开更多
Dimethylsulfoniopropionate(DMSP)is a compound synthesized by marine phytoplankton that contributes to the oceanic sulfur cycle.Interestingly,DMSP has also been found in algal species and several terrestrial plants,for...Dimethylsulfoniopropionate(DMSP)is a compound synthesized by marine phytoplankton that contributes to the oceanic sulfur cycle.Interestingly,DMSP has also been found in algal species and several terrestrial plants,forming part of the global sulfur cycle.However,compared to its role in the marine environment,the impact of DMSP on terrestrial ecosystems remains relatively unexplored.In this study,DMSP was shown to promote longevity and prevent age-associated functional decline in Caenorhabditis elegans(C.elegans),a soil-dwelling organism.DMSP decreased mitochondrial content and improved mitochondrial function in C.elegans at the old stage,which was via enhancing autophagy flux.It was demonstrated that DMSP significantly increased the expression of autophagy and mitophagy genes during aging.Furthermore,DMSP protected against Parkinson’s disease(PD)induced byα-synuclein(α-syn)aggregation via autophagy.Mechanistic studies showed that DMSP directly activated nuclear translocation of the Skinhead-1(SKN-1)transcription factor from the cytoplasm.Moreover,SKN-1 was involved in DMSP-induced autophagy and played a key role in lifespan extension andα-syn clearance in C.elegans.In conclusion,DMSP delays physiological aspects of aging in C.elegans,providing insights into the interplay between the global sulfur cycle and terrestrial organisms.展开更多
The accuracy of the cloud-aerosol lidar with orthogonal polarization (CALIOP), moderate resolution imaging spectroradiometer (MODIS), Multi-Angle Implementation of Atmospheric Correction (MAIAC), and Geostationary Ope...The accuracy of the cloud-aerosol lidar with orthogonal polarization (CALIOP), moderate resolution imaging spectroradiometer (MODIS), Multi-Angle Implementation of Atmospheric Correction (MAIAC), and Geostationary Operational Environmental Satellite (GOES) aerosol optical depth (AOD) products for the Arctic north of 59.75°N was examined by means of 35 aerosol robotic network (AERONET) AOD sites. The assessment for June to October 2006 to 2020 showed MAIAC AOD agreed the best with AERONET AOD;CALIOP AOD differed the strongest from the AERONET AOD. Cross-correlations of CALIOP AOD along the satellite path indicated that AOD-values 40 km up-and-down the path often failed to represent the AERONET AOD-values within ±30 min of the overpass in this region dominated by easterly winds. Typically, CALIOP AOD was lower than AERONET AOD and MAIAC AOD at the sites, especially, at sites with mean AOD below 0.1. Generally, MODIS AOD values exceeded those of MAIAC. Comparison of CALIOP, MAIAC, and MODIS products resampled on a 0.25° × 0.25° grid revealed differences among the products caused by their temporal and spatial resolution, sample habit and size. Typically, the MODIS AOD-product showed the most details in AOD distribution. Despite differences in AOD-values, all products provided similar temporal evolution of elevated and lower AOD.展开更多
文摘Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexity of the mammalian nervous system and our inability to visualize DA neurons in vivo restricts the advances in elucidating the molecular mechanisms of PD. Conservation between C. elegans and mammals in genomic, biosynthetic and metabolic pathways as well as the advantages of observing DA neurons morphology in vivo and the ease of transgenic and genetic manipulation make C. elegans an excellent model organism for PD.
文摘Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal＇ s life-span control machinery, as well as the dauer formation control.
文摘Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-synuclein transgenic C.elegans was used as the animal model,the toxic effect of MPP^＋ to dopamine（DA）neurons and the lifespan of worms was tested.The worms were feed with OP50 to determine whether ATP increase can rescue the worm from toxicity.ATP level and aberrant protein accumulation were analyzed in the MPP^＋ treated worms with or without OP50 addition.Results We found that MPP^＋ induced DA cell death and worm lethality,which could be prevented by OP50 treatment.OP50 exerted the protective effect by up-regulating ATP level,even though it also induced accumulation ofα-synuclein.Despite the undefined role of protein aggregation to the cell death,our results showed that the toxicity of MPP^＋ was mainly caused by the ATP depletion in theα-synuclein transgenic C.elegans.Conclusion MPP^＋ could induce DA neuronal death and worm lethality inα-synuclein transgenic C.elegans;Compared with the aggregation ofα-synuclein,the major cause of MPP^＋ toxicity appeared due to ATP depletion.
文摘Diet has been shown to play an important role in human physiology.It is a predominant exogenous factor regulating the composition of gut microbiota,and dietary intervention holds promise for treatment of diseases such as obesity,type 2 diabetes,and malnutrition.Furthermore,it was reported that diet has significant effects on physiological processes of C.elegans,including reproduction,fat storage,and aging.To reveal novel signaling pathways responsive to different diets,C.elegans and its bacterial diet were used as an interspecies model system to mimic the interaction between host and gut microbiota.Most signaling pathways identified in C.elegans are highly conserved across different species,including humans.A better understanding of these pathways can,therefore,help to develop interventions for human diseases.In this article,we summarize recent achievements on molecular mechanisms underlying the response of C.elegans to different diets and discuss their relevance to human health.
文摘WormGUIDES is an open-source dynamic embryonic system designed to facilitate global understanding of cellular decisions in the developing nervous system of the nematode C. elegans. WormGUIDES was designed to allow investigation and exploration of the observational results of the C. elegans life cycle from laboratory experiments. In the process of a mechanistic C. elegans model development, some functionalities of WormGUIDES needed to be enhanced to support model validation and verification. In this study, a new way to visualize 3-dimentional vectors within WormGUIDES was investigated and presented. Then, the practical values of this method were demonstrated by visualizing two biologically significant directions (i.e., division orientation and cell polarity) of individual embryonic cells in C. elegans. Lastly, a mathematic approach was designed to illustrate the differences between these two sets of vectors and provide easy indications of the location of these individual cells that have large data discrepancies within the C. elegans embryonic system.
文摘This paper presents a conception of an exponential observer for a class of linear distributed-parameter systems (DPSs), in which the dynamics are partially unknown. The given distributed-parameter observer ensures asymptotic state estimator with exponentially decay error, based on the theory of C0-semigroups in a Hilbert space. The theoretical observer developed is applied to a chemical tubular reactor, namely the isothermal Plug-Flow reactor basic dynamical model for which measurements are available at the reactor output only. The process is described by Partial differential equations with unknown initial states. For this application, performance issues are illustrated in a simulation study.
基金the National Key R&D Program of China(2021YFA0805802 to D.C.)the National Natural Science Foundation of China(31971092 and 32171156 to D.C.)Some strains were provided by the Caenorhabditis Genetics Center(CGC),which is funded by NIHOffice of Research Infrastructure Programs(P40 OD010440).
文摘The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.
基金National Key R&D Program of China(2022YFE0113000)Jilin Provincial Development and Reform Commission(2023C038-3)+2 种基金Brain Science and Brain-Like Intelligence Technology Program(2021ZD0203003)Beijing National Laboratory for Molecular Sciences(BNLMS202108)Chinese Academy of Sciences Pioneer Hundred Talents Program.
文摘Dimethylsulfoniopropionate(DMSP)is a compound synthesized by marine phytoplankton that contributes to the oceanic sulfur cycle.Interestingly,DMSP has also been found in algal species and several terrestrial plants,forming part of the global sulfur cycle.However,compared to its role in the marine environment,the impact of DMSP on terrestrial ecosystems remains relatively unexplored.In this study,DMSP was shown to promote longevity and prevent age-associated functional decline in Caenorhabditis elegans(C.elegans),a soil-dwelling organism.DMSP decreased mitochondrial content and improved mitochondrial function in C.elegans at the old stage,which was via enhancing autophagy flux.It was demonstrated that DMSP significantly increased the expression of autophagy and mitophagy genes during aging.Furthermore,DMSP protected against Parkinson’s disease(PD)induced byα-synuclein(α-syn)aggregation via autophagy.Mechanistic studies showed that DMSP directly activated nuclear translocation of the Skinhead-1(SKN-1)transcription factor from the cytoplasm.Moreover,SKN-1 was involved in DMSP-induced autophagy and played a key role in lifespan extension andα-syn clearance in C.elegans.In conclusion,DMSP delays physiological aspects of aging in C.elegans,providing insights into the interplay between the global sulfur cycle and terrestrial organisms.
文摘The accuracy of the cloud-aerosol lidar with orthogonal polarization (CALIOP), moderate resolution imaging spectroradiometer (MODIS), Multi-Angle Implementation of Atmospheric Correction (MAIAC), and Geostationary Operational Environmental Satellite (GOES) aerosol optical depth (AOD) products for the Arctic north of 59.75°N was examined by means of 35 aerosol robotic network (AERONET) AOD sites. The assessment for June to October 2006 to 2020 showed MAIAC AOD agreed the best with AERONET AOD;CALIOP AOD differed the strongest from the AERONET AOD. Cross-correlations of CALIOP AOD along the satellite path indicated that AOD-values 40 km up-and-down the path often failed to represent the AERONET AOD-values within ±30 min of the overpass in this region dominated by easterly winds. Typically, CALIOP AOD was lower than AERONET AOD and MAIAC AOD at the sites, especially, at sites with mean AOD below 0.1. Generally, MODIS AOD values exceeded those of MAIAC. Comparison of CALIOP, MAIAC, and MODIS products resampled on a 0.25° × 0.25° grid revealed differences among the products caused by their temporal and spatial resolution, sample habit and size. Typically, the MODIS AOD-product showed the most details in AOD distribution. Despite differences in AOD-values, all products provided similar temporal evolution of elevated and lower AOD.
