This paper deals with the global boundedness of a two-competing-species chemotaxis model with indirect signal production in a three-dimensional bounded domain.The current work extends prior results by ZHENG et al.(202...This paper deals with the global boundedness of a two-competing-species chemotaxis model with indirect signal production in a three-dimensional bounded domain.The current work extends prior results by ZHENG et al.(2022)who established global existence and boundedness of classical solution under the parameter constraintsµ_(1)µ_(2)a_(2)≥χ1(4+µ_(2)^(2)a _(2)^(2)),µ_(1)µ_(2)a_(1)≥χ2(4+µ_(1)^(2)a_(1)^( 2)).Our main contribution demonstrates that these technical conditions can be significantly relaxed toµ1≥5χ_(1),µ2≥5χ_(2),thereby expanding the admissible parameter space for solution boundedness.展开更多
A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inp...A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inputs to the pre-sympathetic glutamatergic neural hub,located in the paraventricular nucleus of the hypothalamus(PVN),upon stimulation by angiotensin II(Ang-II).For Ang-II-induced disinhibition,targeting microglial migration had an effect similar to ADAM17 knockout in glutamatergic neurons.Ang-II promoted neuron-mediated chemotaxis of microglia via neuronal CX3CL1 and ADAM17.Inhibiting microglial chemotaxis by targeting CX3CR1 abolished the Ang-II-induced microglial displacement of GABAergic presynaptic terminals and significantly blunted Ang-II’s pressor response.Using conditional and targeted knockout models of ADAM17,an increase in the contact between pre-sympathetic neurons and reactive microglia in the PVN was demonstrated to be neuronal ADAM17-dependent during the developmental stage of salt-sensitive hypertension.Collectively,this study provides evidence that neuronal ADAM17-mediated microglial chemotaxis facilitates the disinhibition of pre-sympathetic glutamatergic tone upon hormonal stimulation.展开更多
Chronic obstructive pulmonary disease(COPD),a disease responsible for early mortality worldwide,is well accepted to be associated with periodontitis epidemiologically.Although both of the diseases are the multi-microb...Chronic obstructive pulmonary disease(COPD),a disease responsible for early mortality worldwide,is well accepted to be associated with periodontitis epidemiologically.Although both of the diseases are the multi-microbial inflammatory disease,the precise underlying mechanisms by which periodontitis influences the progression of COPD remains largely unknown.Here,we established COPD accompanied with periodontitis mouse models and observed the pronounced progress in pulmonary symptoms and histopathology,cha racterized by poorer respiratory function,thicke ned bronchial walls,and increased neutrophils infiltration in lung tissue.Mechanistically,periodontitis pathogen Porphyromonas gingivalis(P.gingivalis)relocated in the lung through the respiratory tract and LPS from P.gingivalis promoted the secretion of chemokines CXCL2 and G-CSF of alveolar epithelial cells through NF-κB and p38 MAPK pathways to recruit neutrophils.Furthermore,exposure to P.gingivalis of infiltrated neutrophils released matrix metallopeptidase-8(MMP-8)and neutrophil elastase(NE),which aggravated airway inflammation and tissue damage.These findings indicated that periodontitis could exacerbate COPD via its pathogen P.gingivalis,which translocated in the lung and stimulated neutrophil chemotaxis and activation in the lung.展开更多
Liver-expressed antimicrobial peptide 2(LEAP2)is a key regulator of innate immune defense in teleosts,yet the molecular basis of its chemotactic function remains largely unidentified.Boleophthalmus pectinirostris MOSP...Liver-expressed antimicrobial peptide 2(LEAP2)is a key regulator of innate immune defense in teleosts,yet the molecular basis of its chemotactic function remains largely unidentified.Boleophthalmus pectinirostris MOSPD2(BpMOSPD2)was previously identified as a candidate receptor for BpLEAP2 in monocytes/macrophages(MO/MΦ).In the present study,BpLEAP2 stimulation was found to trigger a retromer-dependent intracellular trafficking program essential for BpMOSPD2-mediated chemotaxis.Exposure to BpLEAP2 significantly enhanced BpMO/MΦmigration and promoted the accumulation of BpMOSPD2 at the plasma membrane.Subcellular fractionation and immunofluorescence analyses revealed that BpMOSPD2 translocated from the endoplasmic reticulum(ER)to early endosomes upon BpLEAP2 stimulation,followed by redistribution to the cell surface.Blockade of ER export or knockdown of core retromer subunits(BpVPS35,BpVPS26,or BpVPS29)abolished membrane localization and attenuated BpLEAP2-induced migration.Co-immunoprecipitation combined with mass spectrometry confirmed direct binding between BpMOSPD2 and BpVPS35,while domain-mapping indicated that this interaction was not exclusively dependent on MSP or CRAL-TRIO domains.Depletion of individual retromer components led to retention of BpMOSPD2 in early endosomes,establishing the necessity of the retromer complex for receptor recycling.Functionally,disruption of this complex eliminated the pro-migratory activity of BpLEAP2 on BpMO/MΦ.These findings identify the retromer complex as a critical regulator of BpMOSPD2 trafficking and uncover a previously unrecognized mechanism through which BpLEAP2 promotes MO/MΦmigration in teleosts.展开更多
Estuaries are key areas for organic carbon cycling,where polymeric carbohydrates are abundant and chemically diverse.The recycling of these polymers by microbes depends on a variety of carbohydrate-active enzymes(CAZy...Estuaries are key areas for organic carbon cycling,where polymeric carbohydrates are abundant and chemically diverse.The recycling of these polymers by microbes depends on a variety of carbohydrate-active enzymes(CAZymes).However,it remains unclear whether other gene traits,particularly those related to cell motility toward polymeric carbohydrates,are intertwined with carbohydrate depolymerization and niche specialization in estuarine sediment soils.In this study,estuarine sediments were incubated with four prevalent polymeric carbohydrates(laminarin,fucan,cellulose,and chitin) under anaerobic conditions.Based on metagenomic analysis,we identified potential responses to the degradation and utilization of polymeric carbohydrate substrates from the perspectives of CAZymes and sugar transporters.The analysis of metagenomic gene data also revealed a positive correlation between chemotaxis and the abundance of CAZymes genes.Furthermore,metagenomes-assembled genomes(MAGs) that exhibited higher abundance in polysaccharide-treated samples compared to controls also featured elevated copies of genes involved in polysaccharide utilization loci(PULs),chemotaxis,as well as those associated with flagellar or gliding movement.SprB and CTDs associated with gliding proteins genes are essential for type Ⅸ secretion system-mediated secretion of CAZymes and gliding motility in Bacteroidota.The enhanced potential for mobility,coupled with the ability to degrade polymeric carbohydrates,may enable these bacteria to exploit nutrients beyond carbon sources,thereby potentially broadening their ecological niches.展开更多
目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间...目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间的相关性;利用IL-6+粒细胞-巨噬细胞集落刺激因子(GM-CSF)共同诱导人外周血单个核细胞(PBMCs)中MDSCs的生成,流式细胞术检测MDSCs生成比例,CD33磁珠分选MDSCs;收集肺腺癌SPC-A1细胞野生型以及MCTS1敲减和过表达SPC-A1细胞的无血清细胞上清液,利用Transwell小室进行MDSCs的趋化试验并计算趋化指数;羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)标记CD8^(+)T细胞与发生趋化的MDSCs细胞共培养,流式细胞术检测CD8^(+)T细胞的增殖水平;实时荧光定量PCR(qRT-PCR)测定MDSCs相关趋化因子的mRNA水平;流式多因子芯片技术检测细胞上清液中C-X-C基序趋化因子配体1(CXCL1)的含量;Western blot检测janus激酶2(JAK2)的表达水平以及信号转导子和转录激活子1(STAT1)的活化水平。结果肺腺癌组织MCTS1与MDSCs浸润程度呈正相关(Spearmanρ=0.226,P<0.001);与空白对照组比较,IL-6和GM-CSF共同诱导PBMCs后可显著增加MDSCs的比例(4.95±1.03 vs 0.97±0.24,t=6.54,P<0.01);MCTS1过表达的SPC-A1细胞上清液对MDSCs的趋化指数较对照组显著升高(4.88±0.99 vs 2.94±0.27,q=6.29,P<0.01),而经MCTS1敲减的细胞上清液可使MDSCs的趋化指数显著降低(1.50±0.17 vs 2.94±0.27,q=4.69,P<0.05);MCTS1过表达的SPC-A1细胞中CXCL1 mRNA(2.79±0.16 vs 1.00±0.08,q=28.94,P<0.001)和上清液中蛋白质水平(78.20±6.16 vs 37.50±3.31,q=16.83,P<0.001)均显著升高,而敲减MCTS1则可抑制CXCL1 mRNA(0.53±0.03 vs 1.00±0.08,q=7.64,P<0.01)和蛋白质水平(17.33±1.96 vs 37.50±3.31,q=8.34,P<0.01);此外,与对照组比较,MCTS1过表达组JAK2蛋白的表达水平(2.11±0.15 vs 1.00±0.05,q=19.48,P<0.001)和STAT1的活化水平(2.10±0.19 vs 1.00±0.10,q=15.02,P<0.001)显著升高,而MCTS1敲减组JAK2蛋白水平(0.56±0.06 vs 1.00±0.05,q=7.61,P<0.01)和STAT1的活化水平均显著降低(0.46±0.07 vs 1.00±0.05,q=7.45,P<0.01)。结论肺腺癌细胞MCTS1通过JAK2-STAT1信号通路调控CXCL1的表达,并介导MDSCs的趋化。展开更多
In this paper, we use contraction mapping principle, operator-theoretic approach and some uniform estimates to establish local solvability of the parabolic-hyperbolic type chemotaxis system with fixed boundary in 1-di...In this paper, we use contraction mapping principle, operator-theoretic approach and some uniform estimates to establish local solvability of the parabolic-hyperbolic type chemotaxis system with fixed boundary in 1-dimensional domain. In addition, local solvability of the free boundary problem is considered by straightening the free boundary.展开更多
Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,...Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,such as Pb,Cu,Ag,and Cr,would result in severe defects of chemotaxis to water-soluble attractants of NaCl,cAMP,and biotin.Moreover,the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies,relative lengths of sensory endings in ASE neurons,and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants.In addition,the dendrite morphology could be noticeably changed in animals exposed to 150μmol/L of Pb,Cu,and Ag.Furthermore,we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5μmol/L,and in Cu,Ag,and Cr exposed che-1 mutant at concentrations more than 50μmol/L.Therefore,impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.展开更多
基金Supported by the National Natural Science Foundation of China(12301631)the Natural Science Foundation of Qinghai Province(2023-ZJ-949Q)。
文摘This paper deals with the global boundedness of a two-competing-species chemotaxis model with indirect signal production in a three-dimensional bounded domain.The current work extends prior results by ZHENG et al.(2022)who established global existence and boundedness of classical solution under the parameter constraintsµ_(1)µ_(2)a_(2)≥χ1(4+µ_(2)^(2)a _(2)^(2)),µ_(1)µ_(2)a_(1)≥χ2(4+µ_(1)^(2)a_(1)^( 2)).Our main contribution demonstrates that these technical conditions can be significantly relaxed toµ1≥5χ_(1),µ2≥5χ_(2),thereby expanding the admissible parameter space for solution boundedness.
基金supported by the National Natural Science Foundation of China(82100454,32271016,82101586,and 81872563)the National Heart,Lung,Blood,and Sleep Institute(HL163588).
文摘A disintegrin and metalloprotease 17(ADAM17)is a membrane-bound enzyme that cleaves cell-surface proteins.Here,we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inputs to the pre-sympathetic glutamatergic neural hub,located in the paraventricular nucleus of the hypothalamus(PVN),upon stimulation by angiotensin II(Ang-II).For Ang-II-induced disinhibition,targeting microglial migration had an effect similar to ADAM17 knockout in glutamatergic neurons.Ang-II promoted neuron-mediated chemotaxis of microglia via neuronal CX3CL1 and ADAM17.Inhibiting microglial chemotaxis by targeting CX3CR1 abolished the Ang-II-induced microglial displacement of GABAergic presynaptic terminals and significantly blunted Ang-II’s pressor response.Using conditional and targeted knockout models of ADAM17,an increase in the contact between pre-sympathetic neurons and reactive microglia in the PVN was demonstrated to be neuronal ADAM17-dependent during the developmental stage of salt-sensitive hypertension.Collectively,this study provides evidence that neuronal ADAM17-mediated microglial chemotaxis facilitates the disinhibition of pre-sympathetic glutamatergic tone upon hormonal stimulation.
基金supported by National High Level Hospital Clinical Research Funding,grant nos.BJ-2025-122,BJ2023-126CAMS Innovation Fund for Medical Sciences(CIFMS),grant no.2021-I2M-1050National Natural Science Foundation of China,grant no.82170956。
文摘Chronic obstructive pulmonary disease(COPD),a disease responsible for early mortality worldwide,is well accepted to be associated with periodontitis epidemiologically.Although both of the diseases are the multi-microbial inflammatory disease,the precise underlying mechanisms by which periodontitis influences the progression of COPD remains largely unknown.Here,we established COPD accompanied with periodontitis mouse models and observed the pronounced progress in pulmonary symptoms and histopathology,cha racterized by poorer respiratory function,thicke ned bronchial walls,and increased neutrophils infiltration in lung tissue.Mechanistically,periodontitis pathogen Porphyromonas gingivalis(P.gingivalis)relocated in the lung through the respiratory tract and LPS from P.gingivalis promoted the secretion of chemokines CXCL2 and G-CSF of alveolar epithelial cells through NF-κB and p38 MAPK pathways to recruit neutrophils.Furthermore,exposure to P.gingivalis of infiltrated neutrophils released matrix metallopeptidase-8(MMP-8)and neutrophil elastase(NE),which aggravated airway inflammation and tissue damage.These findings indicated that periodontitis could exacerbate COPD via its pathogen P.gingivalis,which translocated in the lung and stimulated neutrophil chemotaxis and activation in the lung.
基金supported by the National Natural Science Foundation of China(32173004)Natural Science Foundation of Zhejiang Province(LZ23C190001)。
文摘Liver-expressed antimicrobial peptide 2(LEAP2)is a key regulator of innate immune defense in teleosts,yet the molecular basis of its chemotactic function remains largely unidentified.Boleophthalmus pectinirostris MOSPD2(BpMOSPD2)was previously identified as a candidate receptor for BpLEAP2 in monocytes/macrophages(MO/MΦ).In the present study,BpLEAP2 stimulation was found to trigger a retromer-dependent intracellular trafficking program essential for BpMOSPD2-mediated chemotaxis.Exposure to BpLEAP2 significantly enhanced BpMO/MΦmigration and promoted the accumulation of BpMOSPD2 at the plasma membrane.Subcellular fractionation and immunofluorescence analyses revealed that BpMOSPD2 translocated from the endoplasmic reticulum(ER)to early endosomes upon BpLEAP2 stimulation,followed by redistribution to the cell surface.Blockade of ER export or knockdown of core retromer subunits(BpVPS35,BpVPS26,or BpVPS29)abolished membrane localization and attenuated BpLEAP2-induced migration.Co-immunoprecipitation combined with mass spectrometry confirmed direct binding between BpMOSPD2 and BpVPS35,while domain-mapping indicated that this interaction was not exclusively dependent on MSP or CRAL-TRIO domains.Depletion of individual retromer components led to retention of BpMOSPD2 in early endosomes,establishing the necessity of the retromer complex for receptor recycling.Functionally,disruption of this complex eliminated the pro-migratory activity of BpLEAP2 on BpMO/MΦ.These findings identify the retromer complex as a critical regulator of BpMOSPD2 trafficking and uncover a previously unrecognized mechanism through which BpLEAP2 promotes MO/MΦmigration in teleosts.
基金supported by the National Natural Science Foundation of China(Nos.42073078,U1901211 and 41876126)the National Key Research and Development Program of China(Nos.2023YFC3905003,2023-67 and 2017FY100700)+4 种基金the Hainan Province Science and Technology Special Fund(ZDYF2023SHFZ172)the Natural Science Foundation of Guangdong Province(Nos.2020A1515011137,2023A1515012004 and 2024A1515011203)Nansha District High-Level Talent Innovation Team Project in 2021(Mangrove Wetland Blue Carbon Sequestration Technology Innovation Team)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA19060204)the Key Tasks Guarantee Special Fund Project for Green-Beautiful Guangdong Ecological Construction in 2024(Precise Restoration and Ecological Function Evaluation of Mangroves).
文摘Estuaries are key areas for organic carbon cycling,where polymeric carbohydrates are abundant and chemically diverse.The recycling of these polymers by microbes depends on a variety of carbohydrate-active enzymes(CAZymes).However,it remains unclear whether other gene traits,particularly those related to cell motility toward polymeric carbohydrates,are intertwined with carbohydrate depolymerization and niche specialization in estuarine sediment soils.In this study,estuarine sediments were incubated with four prevalent polymeric carbohydrates(laminarin,fucan,cellulose,and chitin) under anaerobic conditions.Based on metagenomic analysis,we identified potential responses to the degradation and utilization of polymeric carbohydrate substrates from the perspectives of CAZymes and sugar transporters.The analysis of metagenomic gene data also revealed a positive correlation between chemotaxis and the abundance of CAZymes genes.Furthermore,metagenomes-assembled genomes(MAGs) that exhibited higher abundance in polysaccharide-treated samples compared to controls also featured elevated copies of genes involved in polysaccharide utilization loci(PULs),chemotaxis,as well as those associated with flagellar or gliding movement.SprB and CTDs associated with gliding proteins genes are essential for type Ⅸ secretion system-mediated secretion of CAZymes and gliding motility in Bacteroidota.The enhanced potential for mobility,coupled with the ability to degrade polymeric carbohydrates,may enable these bacteria to exploit nutrients beyond carbon sources,thereby potentially broadening their ecological niches.
文摘目的探讨肺腺癌细胞恶性T细胞扩增序列1(MCTS1)介导骨髓源性抑制细胞(MDSCs)趋化的作用机制。方法利用生物信息学(http://timer.cistrome.org/#tab-8258-2)分析癌症基因组图谱(TCGA)中肺腺癌组织(n=515)MCTS1的表达水平与MDSCs浸润之间的相关性;利用IL-6+粒细胞-巨噬细胞集落刺激因子(GM-CSF)共同诱导人外周血单个核细胞(PBMCs)中MDSCs的生成,流式细胞术检测MDSCs生成比例,CD33磁珠分选MDSCs;收集肺腺癌SPC-A1细胞野生型以及MCTS1敲减和过表达SPC-A1细胞的无血清细胞上清液,利用Transwell小室进行MDSCs的趋化试验并计算趋化指数;羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)标记CD8^(+)T细胞与发生趋化的MDSCs细胞共培养,流式细胞术检测CD8^(+)T细胞的增殖水平;实时荧光定量PCR(qRT-PCR)测定MDSCs相关趋化因子的mRNA水平;流式多因子芯片技术检测细胞上清液中C-X-C基序趋化因子配体1(CXCL1)的含量;Western blot检测janus激酶2(JAK2)的表达水平以及信号转导子和转录激活子1(STAT1)的活化水平。结果肺腺癌组织MCTS1与MDSCs浸润程度呈正相关(Spearmanρ=0.226,P<0.001);与空白对照组比较,IL-6和GM-CSF共同诱导PBMCs后可显著增加MDSCs的比例(4.95±1.03 vs 0.97±0.24,t=6.54,P<0.01);MCTS1过表达的SPC-A1细胞上清液对MDSCs的趋化指数较对照组显著升高(4.88±0.99 vs 2.94±0.27,q=6.29,P<0.01),而经MCTS1敲减的细胞上清液可使MDSCs的趋化指数显著降低(1.50±0.17 vs 2.94±0.27,q=4.69,P<0.05);MCTS1过表达的SPC-A1细胞中CXCL1 mRNA(2.79±0.16 vs 1.00±0.08,q=28.94,P<0.001)和上清液中蛋白质水平(78.20±6.16 vs 37.50±3.31,q=16.83,P<0.001)均显著升高,而敲减MCTS1则可抑制CXCL1 mRNA(0.53±0.03 vs 1.00±0.08,q=7.64,P<0.01)和蛋白质水平(17.33±1.96 vs 37.50±3.31,q=8.34,P<0.01);此外,与对照组比较,MCTS1过表达组JAK2蛋白的表达水平(2.11±0.15 vs 1.00±0.05,q=19.48,P<0.001)和STAT1的活化水平(2.10±0.19 vs 1.00±0.10,q=15.02,P<0.001)显著升高,而MCTS1敲减组JAK2蛋白水平(0.56±0.06 vs 1.00±0.05,q=7.61,P<0.01)和STAT1的活化水平均显著降低(0.46±0.07 vs 1.00±0.05,q=7.45,P<0.01)。结论肺腺癌细胞MCTS1通过JAK2-STAT1信号通路调控CXCL1的表达,并介导MDSCs的趋化。
基金Supported by the National Natural Science Foundation of China(11131005)the Fundamental Research Funds for the Central Universities(2014201020202)
文摘In this paper, we use contraction mapping principle, operator-theoretic approach and some uniform estimates to establish local solvability of the parabolic-hyperbolic type chemotaxis system with fixed boundary in 1-dimensional domain. In addition, local solvability of the free boundary problem is considered by straightening the free boundary.
基金supported by the National Natural Science Foundation of China(No.30771113,30870810)the Program for New Century Excellent Talents in Universityprovided by the Caenorhabdits Genetics Center(funded by the NIH National Center for Research Resource,USA).
文摘Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,such as Pb,Cu,Ag,and Cr,would result in severe defects of chemotaxis to water-soluble attractants of NaCl,cAMP,and biotin.Moreover,the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies,relative lengths of sensory endings in ASE neurons,and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants.In addition,the dendrite morphology could be noticeably changed in animals exposed to 150μmol/L of Pb,Cu,and Ag.Furthermore,we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5μmol/L,and in Cu,Ag,and Cr exposed che-1 mutant at concentrations more than 50μmol/L.Therefore,impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.
