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1.
Proc Natl Acad Sci U S A ; 119(12): e2113645119, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35294287

RESUMEN

Acute nociception is essential for survival by warning organisms against potential dangers, whereas tissue injury results in a nociceptive hypersensitivity state that is closely associated with debilitating disease conditions, such as chronic pain. Transient receptor potential (Trp) ion channels expressed in nociceptors detect noxious thermal and chemical stimuli to initiate acute nociception. The existing hypersensitivity model suggests that under tissue injury and inflammation, the same Trp channels in nociceptors are sensitized through transcriptional and posttranslational modulation, leading to nociceptive hypersensitivity. Unexpectedly and different from this model, we find that in Drosophila larvae, acute heat nociception and tissue injury-induced hypersensitivity involve distinct cellular and molecular mechanisms. Specifically, TrpA1-D in peripheral sensory neurons mediates acute heat nociception, whereas TrpA1-C in a cluster of larval brain neurons transduces the heat stimulus under the allodynia state. As a result, interfering with synaptic transmission of these brain neurons or genetic targeting of TrpA1-C blocks heat allodynia but not acute heat nociception. TrpA1-C and TrpA1-D are two splicing variants of TrpA1 channels and are coexpressed in these brain neurons. We further show that Gq-phospholipase C signaling, downstream of the proalgesic neuropeptide Tachykinin, differentially modulates these two TrpA1 isoforms in the brain neurons by selectively sensitizing heat responses of TrpA1-C but not TrpA1-D. Together, our studies provide evidence that nociception and noncaptive sensitization could be mediated by distinct sensory neurons and molecular sensors.


Asunto(s)
Nocicepción , Canales de Potencial de Receptor Transitorio , Animales , Drosophila/fisiología , Neuronas , Nocicepción/fisiología , Nociceptores/fisiología , Transductores , Canales de Potencial de Receptor Transitorio/genética
2.
Angew Chem Int Ed Engl ; 63(21): e202400625, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38556897

RESUMEN

Single-metal atomic sites and vacancies can accelerate the transfer of photogenerated electrons and enhance photocatalytic performance in photocatalysis. In this study, a series of nickel hydroxide nanoboards (Ni(OH)x NBs) with different loadings of single-atomic Ru sites (w-SA-Ru/Ni(OH)x) were synthesized via a photoreduction strategy. In such catalysts, single-atomic Ru sites are anchored to the vacancies surrounding the pits. Notably, the SA-Ru/Ni(OH)x with 0.60 wt % Ru loading (0.60-SA-Ru/Ni(OH)x) exhibits the highest catalytic performance (27.6 mmol g-1 h-1) during the photocatalytic reduction of CO2 (CO2RR). Either superfluous (0.64 wt %, 18.9 mmol g-1 h-1; 3.35 wt %, 9.4 mmol-1 h-1) or scarce (0.06 wt %, 15.8 mmol g-1 h-1; 0.29 wt %, 21.95 mmol g-1 h-1; 0.58 wt %, 23.4 mmol g-1 h-1) of Ru sites have negative effect on its catalytic properties. Density functional theory (DFT) calculations combined with experimental results revealed that CO2 can be adsorbed in the pits; single-atomic Ru sites can help with the conversion of as-adsorbed CO2 and lower the energy of *COOH formation accelerating the reaction; the excessive single-atomic Ru sites occupy vacancies that retard the completion of CO2RR.

3.
Int J Mol Sci ; 24(10)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37240123

RESUMEN

Abscisic acid (ABA) plays an important role in the response of plants to drought stress. However, the chemical structure of ABA is unstable, which severely limits its application in agricultural production. Here, we report the identification of a small molecule compound of tetrazolium as an ABA analog (named SLG1) through virtual screening. SLG1 inhibits the seedling growth and promotes drought resistance of Arabidopsis thaliana with higher stability. Yeast two-hybrid and PP2C inhibition assays show that SLG1 acts as a potent activator of multiple ABA receptors in A. thaliana. Results of molecular docking and molecular dynamics show that SLG1 mainly binds to PYL2 and PYL3 through its tetrazolium group and the combination is stable. Together, these results demonstrate that SLG1, as an ABA analogue, protects A. thaliana from drought stress. Moreover, the newly identified tetrazolium group of SLG1 that binds to ABA receptors can be used as a new option for structural modification of ABA analogs.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Resistencia a la Sequía , Simulación del Acoplamiento Molecular , Sequías , Proteínas Portadoras/metabolismo , Regulación de la Expresión Génica de las Plantas , Receptores de Superficie Celular/metabolismo
4.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-31991793

RESUMEN

Circular RNAs (circRNAs) are endogenous noncoding RNAs with covalently closed continuous loop structures that are formed by 3'-5' ligation during splicing. These molecules are involved in diverse physiological and developmental processes in eukaryotic cells. Jasmonic acid (JA) is a critical hormonal regulator of plant growth and defense. However, the roles of circRNAs in the JA regulatory network are unclear. In this study, we performed high-throughput sequencing of Arabidopsis thaliana at 24 h, 48 h, and 96 h after methyl JA (MeJA) treatment. A total of 8588 circRNAs, which were distributed on almost all chromosomes, were identified, and the majority of circRNAs had lengths between 200 and 800 bp. We identified 385 differentially expressed circRNAs (DEcircRNAs) by comparing data between MeJA-treated and untreated samples. Gene Ontology (GO) enrichment analysis of the host genes that produced the DEcircRNAs showed that the DEcircRNAs are mainly involved in response to stimulation and metabolism. Additionally, some DEcircRNAs were predicted to act as miRNA decoys. Eight DEcircRNAs were validated by qRT-PCR with divergent primers, and the junction sites of five DEcircRNAs were validated by PCR analysis and Sanger sequencing. Our results provide insight into the potential roles of circRNAs in the MeJA regulation network.


Asunto(s)
Acetatos/farmacología , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Ciclopentanos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Oxilipinas/farmacología , Reguladores del Crecimiento de las Plantas/farmacología , ARN Circular/genética , Mapeo Cromosómico , Biología Computacional/métodos , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , MicroARNs/genética , ARN Mensajero/genética
5.
Molecules ; 24(8)2019 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-31013599

RESUMEN

Flavonols are important copigments that affect flower petal coloration. Flavonol synthase (FLS) catalyzes the conversion of dihydroflavonols to flavonols. In this study, we identified a FLS gene, MaFLS, expressed in petals of the ornamental monocot Muscari aucheri (grape hyacinth) and analyzed its spatial and temporal expression patterns. qRT-PCR analysis showed that MaFLS was predominantly expressed in the early stages of flower development. We next analyzed the in planta functions of MaFLS. Heterologous expression of MaFLS in Nicotiana tabacum (tobacco) resulted in a reduction in pigmentation in the petals, substantially inhibiting the expression of endogenous tobacco genes involved in anthocyanin biosynthesis (i.e., NtDFR, NtANS, and NtAN2) and upregulating the expression of NtFLS. The total anthocyanin content in the petals of the transformed tobacco plants was dramatically reduced, whereas the total flavonol content was increased. Our study suggests that MaFLS plays a key role in flavonol biosynthesis and flower coloration in grape hyacinth. Moreover, MaFLS may represent a new potential gene for molecular breeding of flower color modification and provide a basis for analyzing the effects of copigmentation on flower coloration in grape hyacinth.


Asunto(s)
Flavonoles/biosíntesis , Flores , Hyacinthus , Oxidorreductasas , Pigmentación/fisiología , Proteínas de Plantas , Antocianinas/genética , Flavonoles/genética , Flores/enzimología , Flores/genética , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación de la Expresión Génica de las Plantas/fisiología , Hyacinthus/enzimología , Hyacinthus/genética , Oxidorreductasas/biosíntesis , Oxidorreductasas/genética , Proteínas de Plantas/biosíntesis , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Nicotiana/enzimología , Nicotiana/genética
6.
Proc Natl Acad Sci U S A ; 111(8): 3164-9, 2014 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-24516124

RESUMEN

In insects, olfactory information received by peripheral olfactory receptor neurons (ORNs) is conveyed from the antennal lobes (ALs) to higher brain regions by olfactory projection neurons (PNs). Despite the knowledge that multiple types of PNs exist, little is known about how these different neuronal pathways work cooperatively. Here we studied the Drosophila GABAergic mediolateral antennocerebral tract PNs (mlPNs), which link ipsilateral AL and lateral horn (LH), in comparison with the cholinergic medial tract PNs (mPNs). We examined the connectivity of mlPNs in ALs and found that most mlPNs received inputs from both ORNs and mPNs and participated in AL network function by forming gap junctions with other AL neurons. Meanwhile, mlPNs might innervate LH neurons downstream of mPNs, exerting a feedforward inhibition. Using dual-color calcium imaging, which enables a simultaneous monitoring of neural activities in two groups of PNs, we found that mlPNs exhibited robust odor responses overlapping with, but broader than, those of mPNs. Moreover, preferentially down-regulation of GABA in most mlPNs caused abnormal courtship and aggressive behaviors in male flies. These findings demonstrate that in Drosophila, olfactory information in opposite polarities are carried coordinately by two parallel and interacted pathways, which could be essential for appropriate behaviors.


Asunto(s)
Encéfalo/fisiología , Drosophila/fisiología , Modelos Neurológicos , Percepción Olfatoria/fisiología , Neuronas Receptoras Olfatorias/fisiología , Conducta Sexual Animal/fisiología , Animales , Animales Modificados Genéticamente , Conectoma , Cruzamientos Genéticos , Neuronas GABAérgicas/fisiología , Microscopía Confocal , Optogenética , Técnicas de Placa-Clamp , Estadísticas no Paramétricas , Estimulación Química , Ácido gamma-Aminobutírico/metabolismo
7.
Opt Express ; 24(8): 8926-39, 2016 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-27137324

RESUMEN

We report in this work the first all-optical wavelength conversion (AOWC) of a mode division multiplexed (MDM) superchannel consisting of 2N modes by dividing the superchannel into N single-mode (SM) tributaries, wavelength converting N SM signals using well developed SM-AOWC techniques, and finally combining the N SM tributaries back to an MDM superchannel at the converted wavelength, inspired by the idea of using SM filtering techniques to filter multimode signals in astronomy. The conversions between multimode and SM are realized by 3D laser-writing photonic lanterns and SM-AOWCs are realized based on polarization insensitive four wave mixing (FWM) configuration in N semiconductor optical amplifiers (SOAs). As a proof of concept demonstration, the conversion of a 6-mode MDM superchannel with each mode modulated with orthogonal frequency division multiplexed (OFDM) quadrature phase-shift keying (QPSK)/16 quadrature amplitude modulation (QAM) signals is demonstrated in this work, indicating that the scheme is transparent to data format, polarization and compatible with multi-carrier signals. Data integrity of the converted superchannel has been verified by using coherent detection and digital signal processing (DSP). Bit error rates (BERs) below the forward error correction (FEC) hard limit (3.8 × 10-3) have been obtained for QPSK modulation at a net bitrate of 104.2 Gbit/s and BERs below the soft decision FEC threshold (1.98 × 10-2) have been achieved for 16-QAM format, giving a total aggregate bit rate of 185.8 Gbit/s when taking 20% coding overhead into account. Add and drop functionalities that usually come along with wavelength conversion in flexible network nodes have also been demonstrated. The working conditions of the SOAs, especially the pump and signal power levels, are critical for the quality of the converted signal and have been thoroughly discussed. The impact of imbalanced FWM conversion efficiency among different SM tributaries has also been analyzed. This work illustrates a promising way to perform all-optical signal processing for MDM superchannels.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38411834

RESUMEN

The increased incidence of hypertension associated with obstructive sleep apnea (OSA) presents significant physical, psychological, and economic challenges. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in both OSA and hypertension, yet the therapeutic potential of PPARγ agonists and antagonists for OSA-related hypertension remains unexplored. Therefore, we constructed a chronic intermittent hypoxia (CIH)-induced hypertension rat model that mimics the pathogenesis of OSA-related hypertension in humans. The model involved administering PPARγ agonist rosiglitazone (RSG), PPARγ antagonist GW9662, or normal saline, followed by regular monitoring of blood pressure and thoracic aorta analysis using staining and electron microscopy. Intriguingly, our results indicated that both RSG and GW9662 appeared to potently counteract CIH-induced hypertension. In silico study suggested that GW9662's antihypertensive effect might mediated through angiotensin II receptor type 1 (AGTR1). Our findings provide insights into the mechanisms of OSA-related hypertension and propose novel therapeutic targets.

9.
Bone Jt Open ; 5(5): 419-425, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767221

RESUMEN

Aims: The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery. Methods: An electronic survey was conducted of practising female orthopaedic surgeons based in the USA through both the Ruth Jackson Society and the online Facebook group "Women of Orthopaedics". Results: The majority of surveyed female orthopaedic surgeons reported being married (76.4%; 285/373) and having children (67.6%; 252/373). In all, 66.5% (247/373) were collegiate athletes; 82.0% (306/373) reported having no female orthopaedic surgeon mentors in undergraduate and medical school. Their mean height is 65.8 inches and average weight is 147.3 lbs. Conclusion: The majority of female orthopaedic surgeons did not have female mentorship during their training. Additionally, biometrically, their build is similar to that of the average American woman.

10.
J Clin Invest ; 134(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557496

RESUMEN

Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8+ memory T cells. These data indicate anti-PD-1 CAR T cells depleted PD-1+ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.


Asunto(s)
Linfocitos T CD4-Positivos , Receptores Quiméricos de Antígenos , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Linfocitos T CD4-Positivos/inmunología , Centro Germinal/inmunología , Infecciones por VIH/terapia , Macaca mulatta/metabolismo , Receptor de Muerte Celular Programada 1 , Receptores Quiméricos de Antígenos/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/terapia
11.
Eur J Neurosci ; 38(1): 2057-64, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23590241

RESUMEN

Mechanotransduction is the basis of several sensory modalities, including touch, hearing, proprioception and gravity sensation. Despite its importance to sensory processing and behavior, the molecular mechanisms underlying mechanotransduction remain to be fully understood. In particular, the identity of the ion channels serving mechanotransduction is still unknown in many species. Drosophila melanogaster nompC (no mechanoreceptor potential C) has been shown to be essential for mechanotransduction in flies, yet there is no direct evidence demonstrating that NOMPC is indeed a mechanotransducing ion channel in Drosophila. To dissect the functional roles of NOMPC in mechanotransduction, we found that NOMPC-dependent transient adapting mechanoreceptor current (MRC) in the external bristle sensory organ was also chloride dependent. However, this chloride-dependent current was not necessary for spike generation. Furthermore, ectopic expression of wild-type NOMPC conferred mechanosensitivity on the interneurons in the antennal lobe (AL) and cation-mediated inward mechanocurrent was recorded, while a point mutation in the putative selective filter region of NOMPC failed to produce the mechanocurrent in the AL interneurons. These functional studies imply that NOMPC is likely to be a crucial component of mechanotransducers that accounts for mechanotransductions in mechanosensory neurons of Drosophila.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiología , Mecanorreceptores/fisiología , Canales de Potencial de Receptor Transitorio/metabolismo , Potenciales de Acción , Animales , Cloruros/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Interneuronas/metabolismo , Interneuronas/fisiología , Mecanorreceptores/metabolismo , Mecanotransducción Celular , Mutación , Canales de Potencial de Receptor Transitorio/genética
12.
Micromachines (Basel) ; 14(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37893297

RESUMEN

In Tb-Dy-Fe alloy systems, Tb0.29Dy0.71Fe1.95 alloy shows giant magnetostrictive properties under low magnetic fields, thus having great potential for transducer and sensor applications. In this work, the lattice parameters of Tb0.29Dy0.71Fe1.95 compounds as a function of a magnetic field were investigated using in situ X-ray diffraction under an applied magnetic field. The results showed that the c-axis elongation of the rhombohedral unit cell was the dominant contributor to magnetostriction at a low magnetic field (0-500 Oe). As the magnetic field intensity increased from 500 Oe to 1500 Oe, although the magnetostrictive coefficient continued to increase, the lattice constant did not change, which indicated that the elongated c-axis of the rhombohedral unit cell rotated in the direction of the magnetic field. This rotation mainly contributed to the magnetostriction phenomenon at magnetic fields of above 500 Oe. The structural origin of the magnetostriction performance of these materials was attributed to the increase in rhombohedral lattice parameters and the rotation of the extension axis of the rhombohedral lattice.

13.
Micromachines (Basel) ; 14(12)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38138335

RESUMEN

In Tb-Dy-Fe alloy systems, Tb0.29Dy0.71Fe1.95 alloy shows giant magnetostrictive properties under low magnetic fields, thus having great potential for transducers, microsensors, and other applications. The C15 cubic crystal structure of Tb-Dy-Fe has long been thought to be the source of giant magnetostriction. It is surprising that such a highly symmetrical crystal structure exhibits such a large magnetostrictive strain. In this work, the lattice parameters of Tb0.29Dy0.71Fe1.95 magnetostrictive materials were studied by processing atomic-resolution images. The selected area diffraction patterns show a face-centered cubic structure, but the fast Fourier transform diagram shows that the cubic structure has obvious distortion. The lattice parameters obtained by geometric phase analysis (GPA) and Gaussian model-based fitting and calculation show that the lattice constants a, b, and c are not strictly equal, and small disturbance of the lattice constants occurs based on the cubic structure. The actual crystal structure of the Tb-Dy-Fe material is a slightly disturbed cubic structure. This variation in the crystal lattice is mainly caused by the inhomogeneous composition and may be related to the giant magnetostrictive properties of Tb-Dy-Fe alloy.

14.
Food Chem X ; 20: 100932, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37868367

RESUMEN

The characteristic of typical base liquor is crucial in controlling ultimate quality of Jiang-flavor Baijiu. This study investigates the flavor compounds of three typical base liquors (Jiangxiang, Chuntian, and Jiaodixiang) by LLE/LLME/HS-SPME, gas chromatography-mass spectrometry (GC-MS), gas chromatography-flame ionization detection (GC-FID), sensory analysis, and odor activity value (OAV). Of the 201 main volatile compounds identified, 37 significant compounds distinguished the three typical base liquors. Acid (441.72 ±â€¯0.17 mg/L), alcohol (5388.88 ±â€¯0.55 mg/L), and ester compounds (8181.64 ±â€¯0.15 mg/L) were respectively marked in Jiangxiang, Chuntian, and Jiaodixiang typical base liquors. Orthogonal partial least squares discriminant analysis (OPLS-DA), correlation analysis, and aroma recombination showed that butyric acid (OAV: 102.23), butyl 2-methylbutyrate (OAV: 6045.59), and ethyl caproate (OAV: 418.37) were significantly correlated with sweet, fruity, pit mud, jiang, and ethanol aromas. It identifies the primary constituents that affect flavor variations in the three typical base liquors and provides guidance for investigations on the flavor formation of Jiang-flavor Baijiu.

15.
Sci Adv ; 9(21): eadc9660, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37224252

RESUMEN

Adult stem cells are essential for tissue maintenance and repair. Although genetic pathways for controlling adult stem cells are extensively investigated in various tissues, much less is known about how mechanosensing could regulate adult stem cells and tissue growth. Here, we demonstrate that shear stress sensing regulates intestine stem cell proliferation and epithelial cell number in adult Drosophila. Ca2+ imaging in ex vivo midguts shows that shear stress, but not other mechanical forces, specifically activates enteroendocrine cells among all epithelial cell types. This activation is mediated by transient receptor potential A1 (TrpA1), a Ca2+-permeable channel expressed in enteroendocrine cells. Furthermore, specific disruption of shear stress, but not chemical, sensitivity of TrpA1 markedly reduces proliferation of intestinal stem cells and midgut cell number. Therefore, we propose that shear stress may act as a natural mechanical stimulation to activate TrpA1 in enteroendocrine cells, which, in turn, regulates intestine stem cell behavior.


Asunto(s)
Células Madre Adultas , Proteínas de Drosophila , Drosophila , Canales Iónicos , Animales , Proliferación Celular , Intestinos/citología , Estrés Mecánico , Canales Iónicos/metabolismo , Proteínas de Drosophila/metabolismo
16.
Dev Cell ; 58(8): 660-676.e7, 2023 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-37028426

RESUMEN

How glia control axon regeneration remains incompletely understood. Here, we investigate glial regulation of regenerative ability differences of closely related Drosophila larval sensory neuron subtypes. Axotomy elicits Ca2+ signals in ensheathing glia, which activates regenerative neurons through the gliotransmitter adenosine and mounts axon regenerative programs. However, non-regenerative neurons do not respond to glial stimulation or adenosine. Such neuronal subtype-specific responses result from specific expressions of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes axon regeneration of regenerative neurons, and ectopic adenosine receptor expression in non-regenerative neurons suffices to activate regenerative programs and induce axon regeneration. Furthermore, stimulating gliotransmission or activating the mammalian ortholog of Drosophila adenosine receptors in retinal ganglion cells (RGCs) promotes axon regrowth after optic nerve crush in adult mice. Altogether, our findings demonstrate that gliotransmission orchestrates neuronal subtype-specific axon regeneration in Drosophila and suggest that targeting gliotransmission or adenosine signaling is a strategy for mammalian central nervous system repair.


Asunto(s)
Adenosina , Axones , Ratones , Animales , Axones/metabolismo , Adenosina/metabolismo , Regeneración Nerviosa/fisiología , Células Ganglionares de la Retina/metabolismo , Drosophila , Mamíferos
17.
Neuron ; 110(22): 3727-3742.e8, 2022 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-36087585

RESUMEN

Mechanical nociception is essential for animal survival. However, the forces involved in nociceptor activation and the underlying mechanotransduction mechanisms remain elusive. Here, we address these problems by investigating nocifensive behavior in Drosophila larvae. We show that strong poking stimulates nociceptors with a mixture of forces including shear stress and stretch. Unexpectedly, nociceptors are selectively activated by shear stress, but not stretch. Both the shear stress responses of nociceptors and nocifensive behavior require transient receptor potential A1 (TrpA1), which is specifically expressed in nociceptors. We further demonstrate that expression of mammalian or Drosophila TrpA1 in heterologous cells confers responses to shear stress but not stretch. Finally, shear stress activates TrpA1 in a membrane-delimited manner, through modulation of membrane fluidity. Together, our study reveals TrpA1 as an evolutionarily conserved mechanosensitive channel specifically activated by shear stress and suggests a critical role of shear stress in activating nociceptors to drive mechanical nociception.


Asunto(s)
Nociceptores , Canales de Potencial de Receptor Transitorio , Animales , Nociceptores/metabolismo , Drosophila/metabolismo , Nocicepción/fisiología , Mecanotransducción Celular , Canal Catiónico TRPA1/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Mamíferos/metabolismo
18.
Front Plant Sci ; 13: 1088278, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36714693

RESUMEN

Roots are the main organs through which plants absorb water and nutrients. As the key phytohormone involved in root growth, auxin functions in plant environmental responses by modulating auxin synthesis, distribution and polar transport. The Arabidopsis thaliana trehalose-6-phosphate phosphatase gene AtTPPI can improve root architecture, and tppi1 mutants have significantly shortened primary roots. However, the mechanism underlying the short roots of the tppi1 mutant and the upstream signaling pathway and downstream genes regulated by AtTPPI are unclear. Here, we demonstrated that the AtTPPI gene could promote auxin accumulation in AtTPPI-overexpressing plants. By comparing the transcriptomic data of tppi1 and wild-type roots, we found several upregulations of auxin-related genes, including GH3.3, GH3.9 and GH3.12, may play an important role in the AtTPPI gene-mediated auxin transport signaling pathway, ultimately leading to changes in auxin content and primary root length. Moreover, increased AtTPPI expression can regulate primary root growth and lateral root elongation under different concentration of nitrate conditions. Overall, constitutive expression of AtTPPI increased auxin contents and improved lateral root elongation, constituting a new method for improving the nitrogen utilization efficiency of plants.

19.
J Biol Chem ; 285(36): 27737-44, 2010 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-20595388

RESUMEN

Abnormal activation of calpain is implicated in synaptic dysfunction and participates in neuronal death in Alzheimer disease (AD) and other neurological disorders. Pharmacological inhibition of calpain has been shown to improve memory and synaptic transmission in the mouse model of AD. However, the role and mechanism of calpain in AD progression remain elusive. Here we demonstrate a role of calpain in the neuropathology in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, an established mouse model of AD. We found that overexpression of endogenous calpain inhibitor calpastatin (CAST) under the control of the calcium/calmodulin-dependent protein kinase II promoter in APP/PS1 mice caused a remarkable decrease of amyloid plaque burdens and prevented Tau phosphorylation and the loss of synapses. Furthermore, CAST overexpression prevented the decrease in the phosphorylation of the memory-related molecules CREB and ERK in the brain of APP/PS1 mice and improved spatial learning and memory. Interestingly, treatment of cultured primary neurons with amyloid-beta (Abeta) peptides caused an increase in the level of beta-site APP-cleaving enzyme 1 (BACE1), the key enzyme responsible for APP processing and Abeta production. This effect was inhibited by CAST overexpression. Consistently, overexpression of calpain in heterologous APP expressing cells up-regulated the level of BACE1 and increased Abeta production. Finally, CAST transgene prevented the increase of BACE1 in APP/PS1 mice. Thus, calpain activation plays an important role in APP processing and plaque formation, probably by regulating the expression of BACE1.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Calpaína/metabolismo , Regulación Enzimológica de la Expresión Génica , Placa Amiloide/metabolismo , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Precursor de Proteína beta-Amiloide/genética , Animales , Proteínas de Unión al Calcio/metabolismo , Muerte Celular , Línea Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Activación Enzimática , Femenino , Humanos , Masculino , Memoria , Ratones , Ratones Transgénicos , Fosforilación , Placa Amiloide/enzimología , Placa Amiloide/patología , Presenilina-1/genética , Sinapsis/metabolismo , Regulación hacia Arriba , Proteínas tau/metabolismo
20.
Environ Sci Pollut Res Int ; 28(1): 1061-1071, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32827120

RESUMEN

Biochar (BC) has been widely used to remove heavy metals from wastewater. However, due to the hydrophobicity of BC and the lack of its surface functional groups, the effect of metal ions adsorption onto BC is limited. In order to improve the adsorption efficiency, L-cysteine was used to modify biochar derived from pomelo peel (PP) to regulate surface structure. The characteristics of BC and cysteine/biochar composite (cys/BC) were analyzed by various characterization methods. Results showed that the hydrophilicity of biochar was enhanced, and the number of surface functional groups was increased, resulting to strong adsorption ability of Ag(I) (618.9 mg/g), Pb(II) (274.5 mg/g), and As(V) (34.7 mg/g) for cys/BC, which increased approximately by 15%, 35%, and 29% compared with that of BC, respectively. The adsorption process of Pb(II) onto cys/BC was fitted better by the Freundlich isotherm model and for Ag(I) and As(V) by the Langmuir isotherm model. Moreover, the adsorption kinetics followed pseudo-second-order equation and the adsorption process was controlled by the intraparticle diffusion for Ag(I), Pb(II), and As(V) adsorption onto cys/BC. In addition, the adsorption capacities of cys/BC for Ag(I), Pb(II), and As(V) decreased slightly after five adsorption/desorption cycles. Finally, the multiple adsorption mechanisms including functional groups, pore adsorption, surface complexation, and cations-π were analyzed. The paper demonstrated that the cys/BC composite could be reused as effective adsorbents for removing contaminants in the environment.


Asunto(s)
Cisteína , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico , Cinética , Contaminantes Químicos del Agua/análisis
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