要改变妆容风格,给人焕然一新的感觉,那么你首先改变眼线的画法吧。通过画眼线还可以表达人的气质。比如,把眼线的重点故在下边,也就是下面的眼线比上面的眼线粗时,就显得天真活泼;如果把眼线的重点放在上边并延长,就显得性感妩媚。Styl...要改变妆容风格,给人焕然一新的感觉,那么你首先改变眼线的画法吧。通过画眼线还可以表达人的气质。比如,把眼线的重点故在下边,也就是下面的眼线比上面的眼线粗时,就显得天真活泼;如果把眼线的重点放在上边并延长,就显得性感妩媚。Style 1:性感风微扬长眼线眼睛太圆,有时显得太孩子气,用长眼线来平衡,末梢稍稍上挑,作为点睛之笔,眼神马上变妩媚。How to make-up:展开更多
Objective To examine the important roles of microRNAs (miRNAs) in regulating amphid structure and function, we performed a computational analysis for the genetic loci required for the sensory perception and their po...Objective To examine the important roles of microRNAs (miRNAs) in regulating amphid structure and function, we performed a computational analysis for the genetic loci required for the sensory perception and their possibly corresponding miRNAs in C. elegans. Methods Total 55 genetic loci required for the amphid structure and function were selected. Sequence alignment was combined with E value evaluation to investigate and identify the possible corresponding miRNAs. Results Total 30 genes among the 55 genetic loci selected have their possible corresponding regulatory miRNA(s), and identified genes participate in the regulation of almost all aspects of amphid structure and function. In addition, our data suggest that both the amphid structure and the amphid functions might be regulated by a series of network signaling pathways. Moreover, the distribution of miRNAs along the 3' untranslated region (UTR) of these 30 genes exhibits different patterns. Conclusion We present the possible miRNA-mediated signaling pathways involved in the regulation of chemosensation and thermosensation by controlling the corresponding sensory neuron and interneuron functions. Our work will be useful for better understanding of the miRNA-mediated control of the chemotaxis and thermotaxis in C. elegans.展开更多
Objective To screen and identify genetic loci affecting the active zone formation in C. elegans. Methods A SYD-2::GFP reporter was constructed and used as an active zone marker for forward genetic screen to identify...Objective To screen and identify genetic loci affecting the active zone formation in C. elegans. Methods A SYD-2::GFP reporter was constructed and used as an active zone marker for forward genetic screen to identify genetic loci affecting the active zone formation. Results Eight isolated mutant alleles were characterized from 15,000 haploid genomes. The SYD-2::GFP phenotypes of these mutants are mainly reflected as the changes of number, morphology, distribution of puncta and the gaps appearance. Some mutants also exhibit visible behavioral or physical phenotypes, and aldicarb resistant or sensitive phenotypes. Conclusion These mutants provide the opportunity for further systematic research on the active zone formation and the neurotransmission.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
Due to the large number of ionic liquids (ILs) and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship...Due to the large number of ionic liquids (ILs) and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship (QSAR) has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R^2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.展开更多
Objective To perform the modulation of an assay system for the sensory integration of 2 sensory stimuli that inhibit each other.Methods The assay system for assessing the integrative response to 2 reciprocally-inhibit...Objective To perform the modulation of an assay system for the sensory integration of 2 sensory stimuli that inhibit each other.Methods The assay system for assessing the integrative response to 2 reciprocally-inhibitory sensory stimuli was modulated by changing the metal ion barrier.Moreover,the hen-1,ttx-3 and casy-1 mutants having known defects in integrative response were used to evaluate the modulated assay systems.Based on the examined assay systems,new genes possibly involved in the sensory integration control were identified.Results In the presence of different metal ion barriers and diacetyl,locomotion behaviors,basic movements,pan-neuronal,cholinergic and GABAergic neuronal GFP expressions,neuronal development,structures of sensory neurons and interneurons,and stress response of nematodes in different regions of examined assay systems were normal,and chemotaxis toward different concentrations of diacetyl and avoidance of different concentrations of metal ions were inhibited.In the first group,most of the nematodes moved to diacetyl by crossing the barrier of Fe2+,Zn2+,or Mn2+.In the second group,almost half of the nematodes moved to diacetyl by crossing the barrier of Ag+,Cu2+,Cr2+,or Cd2+.In the third group,only a small number of nematodes moved to diacetyl by crossing the barrier of Pb2+ or Hg2+.Moreover,when nematodes encountered different metal ion barriers during migration toward diacetyl,the percentage of nematodes moving back and then turning and that of nematodes moving straight to diacetyl were very different.With the aid of examined assay systems,it was found that mutations of fsn-1 that encodes a F-box protein,and its target scd-2 that encodes a receptor tyrosine kinase,caused severe defects in integrative response,and the sensory integration defects of fsn-1 mutants were obviously inhibited by scd-2 mutation.Conclusion Based on the nematode behaviors in examined assay systems,3 groups of assay systems were obtained.The first group may be helpful in evaluating or identifying the very subtle deficits in sensory integration,and the third group may be useful for the final confirmation of sensory integration defects of mutants identified in the first or the second group of assay systems.Furthermore,the important association of sensory integration regulation with stabilization or destabilization of synaptic differentiation may exist in C.elegans.展开更多
Objective To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. Methods Fat storage was examined in mutants of genes affecti...Objective To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. Methods Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. Results Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor], daf-7 [encoding a transforming growth factor-β (TGF-β) ligand], and nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nematodes, suggesting that unc-64 functions in parallel with ric-4 in regulating fat storage. Conclusion The plasma membrane-associated SNAREs syntaxin/ unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.展开更多
Objective To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Methods To evaluate the functions of HLB-1 in regulating the organization...Objective To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Methods To evaluate the functions of HLB-1 in regulating the organization and function of neuromuscular junctions, effects of hlb-1 mutation on the synaptic structures were revealed by uncovering the expression patterns of SNB-1 ::GFP and UNC-49:GFP, and pharmacologic assays with aldicarb and levamisole were also used to test the synaptic functions. Further rescue and mosaic analysis confirmed HLB-1's role in regulating the organization and function of neuromuscular junctions. Results Loss of HLB-1 function did not result in defects in neuronal outgrowth or neuronal loss, but caused obvious defects of SNB-1::GFP and UNC-49::GFP puncta localization, suggesting the altered presynaptic and postsynaptic structures. The mutant animals exhibited severe defects in locomotion behaviors and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating the altered presynaptic and postsynaptic functions. Rescue and mosaic analysis experiments suggested that HLB-1 regulated synaptic functions in a cell nonautonomously way. Moreover, HLB- 1 expression was not required for the presynaptic active zone morphology. Genetic evidence further demonstrated that hlb-1 acted in a parallel pathway with syd-2 to regulate the synaptic functions. Conclusion HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.展开更多
Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans). Me...Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans). Methods The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confrm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/ IGF signaling were investigated. Results Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr- 2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not infuence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf- 2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. Conclusion The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.展开更多
Objective To investigate the role of environmental factor—temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. Methods The lifespan, the speed of pharynx pumping, and the inte...Objective To investigate the role of environmental factor—temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. Methods The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. Results Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 oC and 25 oC, while no noticeable increase was found at 15 oC in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 oC and 25 oC, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 oC and 25 oC conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 oC. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 oC. Conclusion The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.展开更多
Six lactic acid bacterial (LAB) strains were isolated from traditionally fermented Xinjiang cheese and evaluated for functional and probiotic properties and potentials as starter cultures. The isolated six LAB strai...Six lactic acid bacterial (LAB) strains were isolated from traditionally fermented Xinjiang cheese and evaluated for functional and probiotic properties and potentials as starter cultures. The isolated six LAB strains com- prised Lactobacillus rhamnosus (one strain), Lactobacillus helveticus (one strain), and Enterococcus hirae (four strains). All of the six strains were tolerant to acidic and bile salt conditions. Among which, the L. rhamnosus R4 strain showed more desirable antimicrobial, auto-aggregation, and hydrophobic activity. In addition, the strain L. rhamnosus R4 exhibited the highest level of free radical scavenging activity (53.78% of 1,1-dipheny1-2-picrylhydrazyl (DPPH) free radicals and 45.79% of hydroxyl radicals). L. rhamnosus R4 also demonstrated cholesterol and triglyceride degrada- tion by 50.97% and 28.92%, respectively. To further examine the health-promoting effects of these LAB strains on host lifespan, Caenorhabditis elegans was used as an in vivo model. Worms fed LAB as a food source had significant differences in lifespan compared to those fed Escherichia coil OP50 (as a negative control). Feeding of L. rhamnosus R4 extended the mean lifespan of C. elegans by up to 36.1% compared to that of the control. The results suggest that the strains isolated from Xinjiang fermented dairy products have high potential as starter cultures in the cheese industry.展开更多
In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvat...In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvate(3-BrPA)treatment.C.elegans was treated with various concentrations of 3-BrPA on nematode growth medium(NGM)plates,and their survival was monitored every 24 h.The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction(qPCR).Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase(HK)genes.The average life span of C.elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group.hxk-1,hxk-2,and hxk-3 were overexpressed after the treatment with 3-BrPA.After successfully interfering hxk-1,hxk-2,and hxk-3,the 50%lethal concentration(LC50)of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control.All the cyp35 genes tested were overexpressed,except cyp-35B3.The induction of cyp-35A1 expression was most obvious.The LC50 values of the mutant strains cyp-35A1,cyp-35A2,cyp-35A4,cyp-35B3,and cyp-35C1 were lower than that of the control.Thus,the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes,and the cyp-35 family plays a key role in the metabolism of 3-BrPA.展开更多
Dietary restriction(DR) is one of the most robust environmental manipulations that not only extend life span but also delay the onset of age-related diseases in almost every species examined. Caenorhabditis elegans pl...Dietary restriction(DR) is one of the most robust environmental manipulations that not only extend life span but also delay the onset of age-related diseases in almost every species examined. Caenorhabditis elegans plays an important role in aging studies due to its simple life cycle, easy genetic manipulations and highly conserved genome. Recent studies have demonstrated that the beneficial effects of DR are mediated by the highly conserved transcription factors and signaling pathways in C. elegans. Here we review recent progress in the methodology and molecular mechanisms of DR using C. elegans as a model, as well as prospects for future research.展开更多
Caenorhabditis elegans (C. elegans) was used as an animal model to study the effect of (-)-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal ...Caenorhabditis elegans (C. elegans) was used as an animal model to study the effect of (-)-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal and oxidative stress. The resultsshowed that (-)-5-hydroxy-equol not only significantly increased the lifespan of C. elegans but also significantly enhancedthe resistance against thermal and oxidative stress at the concentrations of 0.1 mmol/L and 0.2 mmol/L. However, the fecundityof C. elegans was not obviously influenced after being exposed to the same concentrations of (-)-5-hydroxy-equol. Further studieson comparative transcriptome analyses and the lifespan ofdaf-16 (mu86) mutant and daf-2 (e1370) mutant indicated that(-)-5-hydroxy-equol prolonged the lifespan of C. elegans through DAF-2/DAF-16 Insulin/IGF-1 signaling pathway. This isthe first report that (-)-5-hydroxy-equol was able to increase the lifespan and improve the thermal and oxidative stress toleranceof C. elegans.展开更多
The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activ...The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase (SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-l, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/1GF signaling pathway.展开更多
Compared to proteins and RNAs, functional specificities associated with structural variations in fatty acids and lipids have been greatly underexplored. This review describes how our lab naively started to work on lip...Compared to proteins and RNAs, functional specificities associated with structural variations in fatty acids and lipids have been greatly underexplored. This review describes how our lab naively started to work on lipids 14 years ago, and how we have gradually overcome obstacles to address some interesting biological questions by combining genetics with biochemical methods on the nematode Caenorhabditis elegans. Our studies have revealed lipid variants and their metabolic pathways, in specific tissues, impact development and behaviors by regulating specific signaling events. The review also discusses the general research approach, style of lab management, and funding mechanisms that have facilitated the frequent research direction changes in the lab, including the journey into the lipid field.展开更多
文摘要改变妆容风格,给人焕然一新的感觉,那么你首先改变眼线的画法吧。通过画眼线还可以表达人的气质。比如,把眼线的重点故在下边,也就是下面的眼线比上面的眼线粗时,就显得天真活泼;如果把眼线的重点放在上边并延长,就显得性感妩媚。Style 1:性感风微扬长眼线眼睛太圆,有时显得太孩子气,用长眼线来平衡,末梢稍稍上挑,作为点睛之笔,眼神马上变妩媚。How to make-up:
文摘Objective To examine the important roles of microRNAs (miRNAs) in regulating amphid structure and function, we performed a computational analysis for the genetic loci required for the sensory perception and their possibly corresponding miRNAs in C. elegans. Methods Total 55 genetic loci required for the amphid structure and function were selected. Sequence alignment was combined with E value evaluation to investigate and identify the possible corresponding miRNAs. Results Total 30 genes among the 55 genetic loci selected have their possible corresponding regulatory miRNA(s), and identified genes participate in the regulation of almost all aspects of amphid structure and function. In addition, our data suggest that both the amphid structure and the amphid functions might be regulated by a series of network signaling pathways. Moreover, the distribution of miRNAs along the 3' untranslated region (UTR) of these 30 genes exhibits different patterns. Conclusion We present the possible miRNA-mediated signaling pathways involved in the regulation of chemosensation and thermosensation by controlling the corresponding sensory neuron and interneuron functions. Our work will be useful for better understanding of the miRNA-mediated control of the chemotaxis and thermotaxis in C. elegans.
文摘Objective To screen and identify genetic loci affecting the active zone formation in C. elegans. Methods A SYD-2::GFP reporter was constructed and used as an active zone marker for forward genetic screen to identify genetic loci affecting the active zone formation. Results Eight isolated mutant alleles were characterized from 15,000 haploid genomes. The SYD-2::GFP phenotypes of these mutants are mainly reflected as the changes of number, morphology, distribution of puncta and the gaps appearance. Some mutants also exhibit visible behavioral or physical phenotypes, and aldicarb resistant or sensitive phenotypes. Conclusion These mutants provide the opportunity for further systematic research on the active zone formation and the neurotransmission.
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.
基金This work was supported by the National Natural Science Foundation of China (No.21477121), and the Fundamental Research Funds for the Central Universities for the support of this work. The numerical calculations were performed on the super computing system in the Supercomputing Center at the University of Science and Technology of China.
文摘Due to the large number of ionic liquids (ILs) and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship (QSAR) has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R^2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.
基金supported by the National Natural Science Foundation of China (No. 30870810)National Basic Research Program of China (No. 2011CB933404)
文摘Objective To perform the modulation of an assay system for the sensory integration of 2 sensory stimuli that inhibit each other.Methods The assay system for assessing the integrative response to 2 reciprocally-inhibitory sensory stimuli was modulated by changing the metal ion barrier.Moreover,the hen-1,ttx-3 and casy-1 mutants having known defects in integrative response were used to evaluate the modulated assay systems.Based on the examined assay systems,new genes possibly involved in the sensory integration control were identified.Results In the presence of different metal ion barriers and diacetyl,locomotion behaviors,basic movements,pan-neuronal,cholinergic and GABAergic neuronal GFP expressions,neuronal development,structures of sensory neurons and interneurons,and stress response of nematodes in different regions of examined assay systems were normal,and chemotaxis toward different concentrations of diacetyl and avoidance of different concentrations of metal ions were inhibited.In the first group,most of the nematodes moved to diacetyl by crossing the barrier of Fe2+,Zn2+,or Mn2+.In the second group,almost half of the nematodes moved to diacetyl by crossing the barrier of Ag+,Cu2+,Cr2+,or Cd2+.In the third group,only a small number of nematodes moved to diacetyl by crossing the barrier of Pb2+ or Hg2+.Moreover,when nematodes encountered different metal ion barriers during migration toward diacetyl,the percentage of nematodes moving back and then turning and that of nematodes moving straight to diacetyl were very different.With the aid of examined assay systems,it was found that mutations of fsn-1 that encodes a F-box protein,and its target scd-2 that encodes a receptor tyrosine kinase,caused severe defects in integrative response,and the sensory integration defects of fsn-1 mutants were obviously inhibited by scd-2 mutation.Conclusion Based on the nematode behaviors in examined assay systems,3 groups of assay systems were obtained.The first group may be helpful in evaluating or identifying the very subtle deficits in sensory integration,and the third group may be useful for the final confirmation of sensory integration defects of mutants identified in the first or the second group of assay systems.Furthermore,the important association of sensory integration regulation with stabilization or destabilization of synaptic differentiation may exist in C.elegans.
基金supported by the grants from the National Natural Science Foundation of China(No. 30771113, 30870810)the Program for New Century Excellent Talents in University
文摘Objective To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. Methods Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. Results Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor], daf-7 [encoding a transforming growth factor-β (TGF-β) ligand], and nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nematodes, suggesting that unc-64 functions in parallel with ric-4 in regulating fat storage. Conclusion The plasma membrane-associated SNAREs syntaxin/ unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.
基金the National Natural Science Foundation of China (No. 30771113, 30870810)the Program for New Century Excellent Talents in University, Ministry of Education, China
文摘Objective To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Methods To evaluate the functions of HLB-1 in regulating the organization and function of neuromuscular junctions, effects of hlb-1 mutation on the synaptic structures were revealed by uncovering the expression patterns of SNB-1 ::GFP and UNC-49:GFP, and pharmacologic assays with aldicarb and levamisole were also used to test the synaptic functions. Further rescue and mosaic analysis confirmed HLB-1's role in regulating the organization and function of neuromuscular junctions. Results Loss of HLB-1 function did not result in defects in neuronal outgrowth or neuronal loss, but caused obvious defects of SNB-1::GFP and UNC-49::GFP puncta localization, suggesting the altered presynaptic and postsynaptic structures. The mutant animals exhibited severe defects in locomotion behaviors and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating the altered presynaptic and postsynaptic functions. Rescue and mosaic analysis experiments suggested that HLB-1 regulated synaptic functions in a cell nonautonomously way. Moreover, HLB- 1 expression was not required for the presynaptic active zone morphology. Genetic evidence further demonstrated that hlb-1 acted in a parallel pathway with syd-2 to regulate the synaptic functions. Conclusion HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.
基金supported by the National Natural Science Foundation of China (No. 30771113,30870810)the Program for New Century Excellent Talents in University
文摘Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans). Methods The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confrm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/ IGF signaling were investigated. Results Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr- 2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not infuence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf- 2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. Conclusion The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.
基金supported by grants from the National Natural Science Foundation of China (No.30771113, 30870810)the Program for New Century Excellent Talents in Universitythe Innovative Research Program for Undergraduates in China (No. C2007052)
文摘Objective To investigate the role of environmental factor—temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. Methods The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. Results Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 oC and 25 oC, while no noticeable increase was found at 15 oC in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 oC and 25 oC, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 oC and 25 oC conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 oC. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 oC. Conclusion The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.
基金supported by the National Key Technology R&D Program of China(No.2012BAD33B08)the Zhejiang Provincial Natural Science Foundation of China(No.LY12B06006)+1 种基金the Research Program of Education Department of Zhejiang Province(No.Y201122061)the National Natural Science Foundation of China(No.20906060)
文摘Six lactic acid bacterial (LAB) strains were isolated from traditionally fermented Xinjiang cheese and evaluated for functional and probiotic properties and potentials as starter cultures. The isolated six LAB strains com- prised Lactobacillus rhamnosus (one strain), Lactobacillus helveticus (one strain), and Enterococcus hirae (four strains). All of the six strains were tolerant to acidic and bile salt conditions. Among which, the L. rhamnosus R4 strain showed more desirable antimicrobial, auto-aggregation, and hydrophobic activity. In addition, the strain L. rhamnosus R4 exhibited the highest level of free radical scavenging activity (53.78% of 1,1-dipheny1-2-picrylhydrazyl (DPPH) free radicals and 45.79% of hydroxyl radicals). L. rhamnosus R4 also demonstrated cholesterol and triglyceride degrada- tion by 50.97% and 28.92%, respectively. To further examine the health-promoting effects of these LAB strains on host lifespan, Caenorhabditis elegans was used as an in vivo model. Worms fed LAB as a food source had significant differences in lifespan compared to those fed Escherichia coil OP50 (as a negative control). Feeding of L. rhamnosus R4 extended the mean lifespan of C. elegans by up to 36.1% compared to that of the control. The results suggest that the strains isolated from Xinjiang fermented dairy products have high potential as starter cultures in the cheese industry.
基金Project supported by the National Natural Science Foundation of China(Nos.31172174 and 81460677)the Fundamental Research Funds for the Central Universities of China(No.31920170039)the Natural Science Found of Gansu Province(No.18JR3RA283),China
文摘In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvate(3-BrPA)treatment.C.elegans was treated with various concentrations of 3-BrPA on nematode growth medium(NGM)plates,and their survival was monitored every 24 h.The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction(qPCR).Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase(HK)genes.The average life span of C.elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group.hxk-1,hxk-2,and hxk-3 were overexpressed after the treatment with 3-BrPA.After successfully interfering hxk-1,hxk-2,and hxk-3,the 50%lethal concentration(LC50)of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control.All the cyp35 genes tested were overexpressed,except cyp-35B3.The induction of cyp-35A1 expression was most obvious.The LC50 values of the mutant strains cyp-35A1,cyp-35A2,cyp-35A4,cyp-35B3,and cyp-35C1 were lower than that of the control.Thus,the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes,and the cyp-35 family plays a key role in the metabolism of 3-BrPA.
基金supported by grants from the National Natural Science Foundation of China(31471379)Natural Science Foundation for Universities in Jiangsu Province,China(BK2014021506)to Chen Di
文摘Dietary restriction(DR) is one of the most robust environmental manipulations that not only extend life span but also delay the onset of age-related diseases in almost every species examined. Caenorhabditis elegans plays an important role in aging studies due to its simple life cycle, easy genetic manipulations and highly conserved genome. Recent studies have demonstrated that the beneficial effects of DR are mediated by the highly conserved transcription factors and signaling pathways in C. elegans. Here we review recent progress in the methodology and molecular mechanisms of DR using C. elegans as a model, as well as prospects for future research.
基金National Natural Science Foundation of China(Grant No.31170058)the Service Center for Experts and Scholars of Hebei Province(Grant No.CPRC027)
文摘Caenorhabditis elegans (C. elegans) was used as an animal model to study the effect of (-)-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal and oxidative stress. The resultsshowed that (-)-5-hydroxy-equol not only significantly increased the lifespan of C. elegans but also significantly enhancedthe resistance against thermal and oxidative stress at the concentrations of 0.1 mmol/L and 0.2 mmol/L. However, the fecundityof C. elegans was not obviously influenced after being exposed to the same concentrations of (-)-5-hydroxy-equol. Further studieson comparative transcriptome analyses and the lifespan ofdaf-16 (mu86) mutant and daf-2 (e1370) mutant indicated that(-)-5-hydroxy-equol prolonged the lifespan of C. elegans through DAF-2/DAF-16 Insulin/IGF-1 signaling pathway. This isthe first report that (-)-5-hydroxy-equol was able to increase the lifespan and improve the thermal and oxidative stress toleranceof C. elegans.
基金supported by a grant from Woosuk University(2013)
文摘The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase (SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-l, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/1GF signaling pathway.
基金supported by Howard Hughes Medical Institute and National Institute of Health
文摘Compared to proteins and RNAs, functional specificities associated with structural variations in fatty acids and lipids have been greatly underexplored. This review describes how our lab naively started to work on lipids 14 years ago, and how we have gradually overcome obstacles to address some interesting biological questions by combining genetics with biochemical methods on the nematode Caenorhabditis elegans. Our studies have revealed lipid variants and their metabolic pathways, in specific tissues, impact development and behaviors by regulating specific signaling events. The review also discusses the general research approach, style of lab management, and funding mechanisms that have facilitated the frequent research direction changes in the lab, including the journey into the lipid field.