RESUMEN
Arthropods maintain ecosystem balance while also contributing to the spread of disease. Plant-derived natural repellents represent an ecological method of pest control, but their direct molecular targets in arthropods remain to be further elucidated. Occupying a critical phylogenetic niche in arthropod evolution, scorpions retain an ancestral genetic profile. Here, using a behavior-guided screening of the Mesobuthus martensii genome, we identified a scorpion transient receptor potential (sTRP1) channel that senses Cymbopogon-derived natural repellents, while remaining insensitive to the synthetic chemical pesticide DEET. Scrutinizing orthologs of sTRP1 in Drosophila melanogaster, we further demonstrated dTRPγ ion channel as a chemosensory receptor of natural repellents to mediate avoidance behavior. This study sheds light on arthropod molecular targets of natural repellents, exemplifying the arthropodplant adaptation. It should also help the rational design of insect control strategy and in conserving biodiversity.
Asunto(s)
Artrópodos , Repelentes de Insectos , Venenos de Escorpión , Animales , Artrópodos/genética , Drosophila melanogaster/genética , Biblioteca de Genes , Repelentes de Insectos/farmacología , Venenos de Escorpión/química , EscorpionesRESUMEN
BACKGROUND: The synthetic chemical 1,4-dioxane is used as industrial solvent, food, and care product additive. 1,4-Dioxane has been noted to influence the nervous system in long-term animal experiments and in humans, but the molecular mechanisms underlying its effects on animals were not previously known. RESULTS: Here, we report that 1,4-dioxane potentiates the capsaicin-sensitive transient receptor potential (TRP) channel TRPV1, thereby causing hyperalgesia in mouse model. This effect was abolished by CRISPR/Cas9-mediated genetic deletion of TRPV1 in sensory neurons, but enhanced under inflammatory conditions. 1,4-Dioxane lowered the temperature threshold for TRPV1 thermal activation and potentiated the channel sensitivity to agonistic stimuli. 1,3-dioxane and tetrahydrofuran which are structurally related to 1,4-dioxane also potentiated TRPV1 activation. The residue M572 in the S4-S5 linker region of TRPV1 was found to be crucial for direct activation of the channel by 1,4-dioxane and its analogs. A single residue mutation M572V abrogated the 1,4-dioxane-evoked currents while largely preserving the capsaicin responses. Our results further demonstrate that this residue exerts a gating effect through hydrophobic interactions and support the existence of discrete domains for multimodal gating of TRPV1 channel. CONCLUSIONS: Our results suggest TRPV1 is a co-receptor for 1,4-dioxane and that this accounts for its ability to dysregulate body nociceptive sensation.
Asunto(s)
Hiperalgesia , Canales Catiónicos TRPV , Animales , Capsaicina/farmacología , Dioxanos , Ratones , Solventes , Canales Catiónicos TRPV/genéticaRESUMEN
Quasi-2D metal halide perovskites are promising candidates for light-emitting applications owing to their large exciton binding energy and strong quantum confinement effect. Usually, quasi-2D perovskites are composed of multiple phases with various numbers of layers (n) of metal halide octahedron sheets, enabling light emission from the lowest-bandgap phase by cascade energy transfer. However, the energy transfer processes are extremely sensitive to the phase distribution and trap density in the quasi-2D perovskite films, and the insufficient energy transfer between different-n phases and the defect-induced traps would result in nonradiative losses. Here, significantly reduced nonradiative losses in the quasi-2D perovskite films are achieved by tailoring the low-dimensional phase components and lowering the density of trap states. Butylammonium bromide (BABr) and potassium thiocyanate (KSCN) are employed to synergistically decrease the nonradiative recombination in the quasi-2D perovskite films of PEABr : CsPbBr3. The incorporation of BABr is found to suppress the formation of the n = 1 phase, while adding KSCN can further reduce the low-n phases, passivate the notorious defects and improve the alignment of the high-n phases. By incorporating appropriate contents of BABr and KSCN, the resultant quasi-2D perovskite films show high photoluminescence quantum yield (PLQY) and highly ordered crystal orientation, which enable not only the green light-emitting diodes (LEDs) with a high external quantum efficiency (EQE) of 16.3%, but also the amplified spontaneous emission (ASE) with a low threshold of 2.6 µJ cm-2. These findings provide a simple and effective strategy to develop high-quality quasi-2D perovskites for LED and laser applications.
RESUMEN
Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages' phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts.
All the cells in our body have a membrane that separates their interior from the outside environment. However, studded across this barrier are numerous ion channels which allow the cell to sense and react to changes in its surroundings. This includes the ion channel TRPV2, which opens in response to mechanical pressure, certain chemical signals, or rising temperature levels. Many types of cell express TRPV2, including cells in the nervous system, muscle, and the immune system. However, despite being extensively studied, it is still not clear how TRPV2 opens and closes upon encountering high temperatures. In particular, previous work suggested that TRPV2 only responds when a cell's surroundings reach around 52°C, which is a much higher temperature than cells inside our body normally encounter, even during a fever. To help resolve this mystery, Mo, Pang et al. studied TRPV2 in neurons responsible for sending sensory information and in immune cells called macrophages which had been extracted from rodents and grown in the laboratory. They found that when the cells were bathed in solutions containing magnesium ions, their TRPV2 channels were more sensitive to a number of different cues, including temperature. Further biochemical experiments showed that magnesium ions do not directly affect TRPV2, but increase the activity of another protein called JAK1. The magnesium ions caused JAK1 to attach specialized structures called phosphorylation tags to TRPV2. This modification (known as phosphorylation) made the channel more sensitive, allowing it to open in response to temperatures as low as 40°C. Mo, Pang et al. found that inhibiting JAK1 reduced the activity of TRPV2. Conversely, inhibiting the enzyme that removes the phosphorylation tags, called PTPN1, increased the channel's activity. They also discovered that when JAK1 was blocked, macrophages were less able to 'eat up' bacteria, which is one of their main roles in the immune system. Taken together these experiments advance our understanding of how TRPV2 becomes active. The balance between the phosphorylation by JAK1 and the dephosphorylation by PTPN1 controls the temperature at which TRPV2 opens. Since TRPV2 contributes to several biological functions, including the development of the nervous system, the maintenance of heart muscles, and inflammation, these findings will be important to scientists in a broad range of fields.
Asunto(s)
Ganglios Espinales , Canales Catiónicos TRPV , Animales , Ganglios Espinales/metabolismo , Fagocitosis , Fosforilación , Ratas , Canales Catiónicos TRPV/metabolismo , Tirosina/metabolismoRESUMEN
Metal halide perovskites have received much attention for their application in light-emitting diodes (LEDs) in the past several years. Rapid progress has been made in efficient green, red, and near-infrared perovskite LEDs. However, the development of blue perovskite LEDs is still lagging far behind. Here, we report efficient sky-blue perovskite LEDs by rearranging low-dimensional phase distribution in quasi-2D perovskites. We incorporated sodium ions into the mixed-Cl/Br quasi-2D perovskites with phenylethylammonium as the organic spacer and cesium lead halide as the inorganic framework. The inclusion of the sodium ion was found to significantly reduce the formation of the n = 1 phase, which was dominated by nonradiative transition, and increase the formation of other small-n phases for efficient exciton energy transfer. By managing the phase distribution, a maximum external quantum efficiency (EQE) of 11.7% was achieved in the sky-blue perovskite LED, with a stable emission peak at 488 nm. Further optimizing the phase distribution and film morphology with Pb content, we demonstrated the sky-blue devices with the average EQE approaching 10%. This strategy of engineering phase distribution of quasi-2D perovskites with a sodium ion could provide a useful way for the fabrication of high-performance blue perovskite LEDs.
RESUMEN
Based on exciplexes as hosts, the monochromatic organic light-emitting diodes (OLEDs) have achieved high power and external quantum efficiencies. However, the high-quality white OLEDs (WOLEDs) with high color rendering index (CRI) have the unsatisfactory efficiencies at high luminance, particularly in terms of power efficiency (PE), resulting in high energy consumption. Here, a new design concept using multiple exciplexes as hosts to match different phosphors has been demonstrated to develop high-performance WOLEDs. It can be seen that the resulting WOLEDs work at a low turn-on voltage of 2.3 V and exhibit the large forward-viewing PE and external quantum efficiency (EQE) of 79 lm W-1 and 22.5%, respectively, without light out-coupling techniques. Significantly, the PE and EQE still remain 48.0 lm W-1 and 21.4% at 1000 cd m-2, showing extremely low efficiency roll-off. The CRI is as high as 81. The keys to success are the selection of the different exciplex hosts matched to different phosphors and the reasonable arrangement of emissive layers, which are beneficial to regulate the exciton distribution and reduce the energy losses.