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- Biurrun, Idoia, et al.
(author)
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Benchmarking plant diversity of Palaearctic grasslands and other open habitats
- 2021
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In: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
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Journal article (peer-reviewed)abstract
- Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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- Moparthi, Lavanya, et al.
(author)
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Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin
- 2020
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In: Cell Calcium. - : Elsevier BV. - 0143-4160 .- 1532-1991. ; 90
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Journal article (peer-reviewed)abstract
- Extracellular influx of calcium or release of calcium from intracellular stores have been shown to activate mammalian TRPA1 as well as to sensitize and desensitize TRPA1 electrophilic activation. Calcium binding sites on both intracellular N- and C-termini have been proposed. Here, we demonstrate based on Förster resonance energy transfer (FRET) and bilayer patch-clamp studies, a direct calmodulin-independent action of calcium on the purified human TRPA1 (hTRPA1), causing structural changes and activation without immediate subsequent desensitization of hTRPA1 with and without its N-terminal ankyrin repeat domain (N-ARD). Thus, calcium alone activates hTRPA1 by a direct interaction with binding sites outside the N-ARD.
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| 5. |
- Moparthi, Lavanya, et al.
(author)
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Electrophile-Induced Conformational Switch of the Human TRPA1 Ion Channel Detected by Mass Spectrometry
- 2020
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:18
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Journal article (peer-reviewed)abstract
- The human Transient Receptor Potential A1 (hTRPA1) ion channel, also known as the wasabi receptor, acts as a biosensor of various potentially harmful stimuli. It is activated by a wide range of chemicals, including the electrophilic compound N-methylmaleimide (NMM), but the mechanism of activation is not fully understood. Here, we used mass spectrometry to map and quantify the covalent labeling in hTRPA1 at three different concentrations of NMM. A functional truncated version of hTRPA1 (Delta 1-688 hTRPA1), lacking the large N-terminal ankyrin repeat domain (ARD), was also assessed in the same way. In the full length hTRPA1, the labeling of different cysteines ranged from nil up to 95% already at the lowest concentration of NMM, suggesting large differences in reactivity of the thiols. Most important, the labeling of some cysteine residues increased while others decreased with the concentration of NMM, both in the full length and the truncated protein. These findings indicate a conformational switch of the proteins, possibly associated with activation or desensitization of the ion channel. In addition, several lysines in the transmembrane domain and the proximal N-terminal region were labeled by NMM, raising the possibility that lysines are also key targets for electrophilic activation of hTRPA1.
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| 6. |
- Moparthi, Lavanya, et al.
(author)
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Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel
- 2020
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In: Cell Calcium. - : Elsevier BV. - 0143-4160 .- 1532-1991. ; 91
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Journal article (peer-reviewed)abstract
- The role of mammalian Transient Receptor Potential Ankyrin 1 (TRPA1) as a mechanosensor is controversial. Here, we report that purified human TRPA1 (hTRPA1) with and without its N-terminal ankyrin repeat domain responded with pressure-dependent single-channel current activity when reconstituted into artificial lipid bilayers. The hTRPA1 activity was abolished by the thiol reducing agent TCEP. Thus, depending on its redox state, hTRPA1 is an inherent mechanosensitive ion channel gated by force-from-lipids.
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| 7. |
- Moparthi, Lavanya, et al.
(author)
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The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- TRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, ∆1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas ∆1-854 hTRPA1, also lacking the S1-S4 voltage sensing-like domain (VSLD), gained sensitivity to cold but lost its heat sensitivity. In hTRPA1 intrinsic tryptophan fluorescence studies, cold and heat evoked rearrangement of VSLD and the C-terminus domain distal to the transmembrane pore domain S5-S6 (CTD). In whole-cell electrophysiology experiments, replacement of the CTD located cysteines 1021 and 1025 with alanine modulated hTRPA1 cold responses. It is proposed that hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5-S6 pore region and the VSLD, respectively.
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- Nilsson, Johan, et al.
(author)
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Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity
- 2021
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 213
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Journal article (peer-reviewed)abstract
- Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio.
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| 9. |
- Zhang, Liying, et al.
(author)
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Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from rat and human mast cells. Each ligand causes distinct conformational changes in TRPV2 as revealed by cryo-EM. Although the binding for probenecid remains elusive, C16 associates within the vanilloid pocket. As such, the C16 binding location is distinct from that of cannabidiol, partially overlapping with the binding site of the TRPV2 inhibitor piperlongumine. Taken together, we discover a new cannabinoid binding site in TRPV2 that is under the influence of allosteric control by probenecid. This molecular insight into ligand modulation enhances our understanding of TRPV2 in normal and pathophysiology.
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