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- Carney Almroth, Bethanie, 1974, et al.
(författare)
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Assessing the effects of textile leachates in fish using multiple testing methods: From gene expression to behavior
- 2021
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 207
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Tidskriftsartikel (refereegranskat)abstract
- The textile industry, while of major importance in the world economy, is a toxic industry utilizing and emitting thousands of chemical substances into the aquatic environment. The aim of this project was to study the potentially harmful effects associated with the leaching of chemical residues from three different types of textiles: sportswear, children’s bath towels, and denim using different fish models (cell lines, fish larvae and juvenile fish). A combination of in vitro and in vivo test systems was used. Numerous biomarkers, ranging from gene expression, cytotoxicity and biochemical analysis to behavior, were measured to detect effects of leached chemicals. Principle findings indicate that leachates from all three types of textiles induced cytotoxicity on fish cell lines (RTgill-W1). Leachates from sportswear and towels induced mortality in zebrafish embryos, and chemical residues from sportswear reduced locomotion responses in developing larval fish. Sportswear leachate increased Cyp1a mRNA expression and EROD activity in liver of exposed brown trout. Leachates from towels induced EROD activity and VTG in rainbow trout, and these effects were mitigated by the temperature of the extraction process. All indicators of toxicity tested showed that exposure to textile leachate can cause adverse reactions in fish. These findings suggested that chemical leaching from textiles from domestic households could pose an ecotoxicological threat to the health of the aquatic environment.
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| 2. |
- Lu, Qiongxuan, et al.
(författare)
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IL-17 undermines longevity and stress tolerance by inhibiting a protective transcriptional network
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aberrant cytokine secretion contributes to the pathogenesis of autoimmune diseases and age-related disorders, but the molecular mechanism underlying this is not entirely clear. Here, we elucidate how interleukin-17 (IL-17) overactivation shortens lifespan and damages defense mechanisms against stress inC. elegans. Our analysis reveals that NHR-49, theC. elegansortholog of human PPARα and HNF4, is the central component in the transcriptional network undermined by increased IL-17 signaling. Both NHR-49 and its coactivator MDT-15 physically interact with the downstream components of IL-17 pathway, and their expression is significantly decreased when IL-17 signaling is enhanced. IL-17 overactivation also induces the expression and nucleus entry of theC. elegansortholog of NF-κB inhibitor NFKI-1/IκBζ to repress the activity of transcriptional coactivator MDT-15 and CBP-1. IL-17 signaling acts on neurons to modulate the activity of NFKI-1/IκBζ and NHR-49. In addition, persistent IL-17 activation decreases the expression of HLH-30/TFEB, leading to the reduced transcription of lysosomal lipase genes in the distal tissues. All these jointly contribute to the increased sensitivity to oxidative stress of animals with enhanced IL-17 signaling. Collectively, our work illustrates a transcription system undermined by IL-17 overactivation in the animals without NF-κB, and provides mechanistic insight into the pathogenesis of abnormal IL-17 secretion.
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| 3. |
- Pu, Longjun, et al.
(författare)
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Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts.
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| 4. |
- Pu, Longjun, et al.
(författare)
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Hypoxia induces food leaving in C. elegans
- 2023
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Ingår i: microPublication Biology. - : California Institute of Technology. - 2578-9430.
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia alters eating behavior in different animals. In C. elegans, hypoxia induces a strong food leaving response. We found that this behavior was independent of the known O 2 response mechanisms including acute O2 sensation and HIF-1 signaling of chronic hypoxia response. Mutating egl-3 and egl-21, encoding the neuropeptide pro-protein convertase and carboxypeptidase, led to defects in hypoxia induced food leaving, suggesting that neuropeptidergic signaling was required for this response. However, we failed to identify any neuropeptide mutants that were severely defective in hypoxia induced food leaving, suggesting that multiple neuropeptides act redundantly to modulate this behavior.
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| 6. |
- Zhao, Lina, 1990-
(författare)
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Oxygen sensing in Caenorhabditis elegans
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sufficient supply of oxygen (O2) to tissue is essential for survival of aerobicanimals. In mammals, there are constant homeostatic regulation mechanisms that act on different time scales to maintain optimal O2 delivery to tissues. The ability to detect and respond to acute oxygen shortages is indispensable to aerobic life. However, the molecular mechanisms and circuits underlying this capacity are poorly understood.We characterize the locomotory response of feeding Caenorhabditis elegans (C. elegans) to 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. Increasing cGMP signaling inhibits escape from 1% O2, and that cGMP activates the protein kinase G, EGL-4, which in turn enhances neuroendocrine secretion to inhibit acute response to 1% O2. A primary source of cGMP is the guanylyl cyclase, GCY-28. In addition, increasing mitochondrial reactive oxygen species (ROS), abrogate acute hypoxia response. Up-regulation of mitochondrial ROS increases cGMP levels, which contribute to the reduced hypoxia response. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute response to hypoxia by C. elegans.In addition, we found that FMRFamide-related peptides FLP-1 plays a role in hypoxia evoked locomotory response. Our data showed that FLP-1 secretion from AVK interneurons acts on AVA and other neurons through DMSR-4, DMSR7, and DMSR-8 GPCR receptors to maintain baseline speed and to promote locomotory response to hypoxia.We also found that hypoxia could induce food leaving behavior in C. elegans. Animals quickly escaped from the bacterial lawn when exposed to 1% O2. The known O2 response mechanisms cannot explain this phenotype, instead, neuropeptidergic signalling seems to be required for this behaviour.It's known that pro-inflammatory cytokine ILC-17.1, the homologue of mammalian IL-17s, act as a neuromodulator involved in hyperoxia sensing in C. elegans. We found that it was not involved in acute hypoxia response. Instead, ILC-17.1 could modulate lifespan and damage defense mechanisms against stress in C. elegans by triggering an inhibitory network to constrain the activity of the nuclear hormone receptor, NHR-49.In summary, our research can provide molecular and neurological understanding of how O2 is sensed by animals. Additionally, it further emphasis C. elegans as a good model to understand oxygen sensing
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