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Light and brassinosteroids (BR) are indispensable for plant growth and control cell division in the apical meristem. However, how external light signals cooperate with internal brassinosteroids to program root meristem development remains elusive. We reveal that the photoreceptor phytochrome B (phyB) guides the scaffold protein RACK1 to coordinate BR signaling for maintaining root meristematic activity. phyB and RACK1 promote early root meristem development. Mechanistically, RACK1 could reinforce the phyB-SPA1 association by interacting with both phyB and SPA1, which indirectly affects COP1-dependent RACK1 degradation, resulting in the accumulation of RACK1 in roots. Subsequently, RACK1 interacts with BES1 to repress its DNA-binding activity toward the target gene CYCD3;1, leading to the release of BES1-mediated inhibition of CYCD3;1 transcription, and hence the promotion of root meristem development. Our study provides mechanistic insights into the regulation of root meristem development by combination of light and phytohormones signals through the photoreceptors and scaffold proteins.
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Plants deploy versatile scaffold proteins to intricately modulate complex cell signaling. Among these, RACK1A (Receptors for Activated C Kinase 1A) stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling pathways. However, the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely unclear. Here, we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling pathways. RACK1A interacts with PHYTOCHROME INTERACTING FACTOR (PIF)3, enhances PIF3 binding to the promoter of BBX11 and down-regulates its transcription. Furthermore, RACK1A associates with ELONGATED HYPOCOTYL 5 (HY5) to repress HY5 biochemical activity toward target genes, ultimately contributing to hypocotyl elongation. In darkness, RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC (COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome system. Our findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation, ensuring proper skoto- and photo-morphogenic development.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Hipocótilo , Receptores de Quinase C Ativada , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Receptores de Quinase C Ativada/metabolismo , Receptores de Quinase C Ativada/genética , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Luz , Transdução de Sinais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Transdução de Sinal Luminoso , FosforilaçãoRESUMO
Plants have adopted versatile scaffold proteins to facilitate the crosstalk between multiple signaling pathways. Leaf senescence is a well-programmed developmental stage that is coordinated by various external and internal signals. However, the functions of plant scaffold proteins in response to senescence signals are not well understood. Here, we report that the scaffold protein RACK1A (RECEPTOR FOR ACTIVATED C KINASE 1A) participates in leaf senescence mediated by ethylene signaling via the coordination of the EIN3-miR164-ORE1 transcriptional regulatory cascade. RACK1A is a novel positive regulator of ethylene-mediated leaf senescence. The rack1a mutant exhibits delayed leaf senescence, while transgenic lines overexpressing RACK1A display early leaf senescence. Moreover, RACK1A promotes EIN3 (ETHYLENE INSENSITIVE 3) protein accumulation, and directly interacts with EIN3 to enhance its DNA-binding activity. Together, they then associate with the miR164 promoter to inhibit its transcription, leading to the release of the inhibition on downstream ORE1 (ORESARA 1) transcription and the promotion of leaf senescence. This study reveals a mechanistic framework by which RACK1A promotes leaf senescence via the EIN3-miR164-ORE1 transcriptional cascade, and provides a paradigm for how scaffold proteins finely tune phytohormone signaling to control plant development.
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Proteínas de Arabidopsis , Arabidopsis , Receptores de Quinase C Ativada , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Senescência Vegetal , Receptores de Quinase C Ativada/genética , Receptores de Quinase C Ativada/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Plant hormone abscisic acid (ABA) is essential for regulating plant growth and various stress responses. ABA-mediated signaling depends on local ABA levels rather than the overall cellular ABA concentration. While cellular concentration of ABA can be detected using Förster resonance energy transfer (FRET)-based ABA probes, direct imaging of subcellular ABA levels remains unsolved. Here, we modified the previously reported ABAleon2.1 and generated a new ABA sensor, named ABAleon2.1_Tao3. Via transient expression in tobacco (Nicotiana tabacum) protoplasts, we targeted ABAleon2.1_Tao3s to the endoplasmic reticulum (ER) membrane with the ABA sensing unit facing the cytosol and the ER, respectively, through a nanobody-epitope-mediated protein interaction. Combining FRET with fluorescence lifetime imaging microscopy, ABA-triggered-specific increases in the fluorescence lifetime of the donor mTurquoise in the ABAleon2.1_Tao3 were detected in both transient assays and stably transformed Arabidopsis plants. In tobacco protoplasts, ER membrane-targeted ABAleon2.1_Tao3s showed a generally higher basal level of ABA in the ER than that in the cytosol and ER-specific alterations in the level of ABA upon environmental cues. In ABAleon2.1_Tao3-transformed Arabidopsis roots, mannitol triggered increases in cytosolic ABA in the division zone and increases in ER ABA in the elongation and maturation zone within 1 h after treatment, both of which were abolished in the bg1-2 mutant, suggesting the requirement for BG1 in osmotic stress-triggered early ABA induction in Arabidopsis roots. These data demonstrate that ABAleon2.1_Tao3s can be used to monitor ABA levels in the cytosol and the ER, providing key information on stress-induced changes in the level of ABA in different subcellular compartments.
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Ácido Abscísico/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Nicotiana/química , Nicotiana/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Estresse Fisiológico/fisiologia , Ácido Abscísico/análise , Transferência Ressonante de Energia de Fluorescência/métodos , Microscopia de Fluorescência/métodos , Reguladores de Crescimento de Plantas/análise , Protoplastos/metabolismoRESUMO
Proton decay is a smoking gun signature of grand unified theories (GUTs). Searches by Super-Kamiokande have resulted in stringent limits on the GUT symmetry-breaking scale. The large-scale multipurpose neutrino experiments DUNE, Hyper-Kamiokande, and JUNO will either discover proton decay or further push the symmetry-breaking scale above 10^{16} GeV. Another possible observational consequence of GUTs is the formation of a cosmic string network produced during the breaking of the GUT to the standard model gauge group. The evolution of such a string network in the expanding Universe produces a stochastic background of gravitational waves which will be tested by a number of gravitational wave detectors over a wide frequency range. We demonstrate the nontrivial complementarity between the observation of proton decay and gravitational waves produced from cosmic strings in determining SO(10) GUT-breaking chains. We show that such observations could exclude SO(10) breaking via flipped SU(5)×U(1) or standard SU(5), while breaking via a Pati-Salam intermediate symmetry, or standard SU(5)×U(1), may be favored if a large separation of energy scales associated with proton decay and cosmic strings is indicated. We note that recent results by the NANOGrav experiment have been interpreted as evidence for cosmic strings at a scale of â¼10^{14} GeV. This would strongly point toward the existence of GUTs, with SO(10) being the prime candidate. We show that the combination with already available constraints from proton decay allows us to identify preferred symmetry-breaking routes to the standard model.
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MAIN CONCLUSION: Carbonic anhydrases CA1 and CA4 attenuate plant immunity and can contribute to altered disease resistance levels in response to changing atmospheric CO2 conditions. ß-Carbonic anhydrases (CAs) play an important role in CO2 metabolism and plant development, but have also been implicated in plant immunity. Here we show that the bacterial pathogen Pseudomonas syringae and application of the microbe-associated molecular pattern (MAMP) flg22 repress CA1 and CA4 gene expression in Arabidopsis thaliana. Using the CA double-mutant ca1ca4, we provide evidence that CA1 and CA4 play an attenuating role in pathogen- and flg22-triggered immune responses. In line with this, ca1ca4 plants exhibited enhanced resistance against P. syringae, which was accompanied by an increased expression of the defense-related genes FRK1 and ICS1. Under low atmospheric CO2 conditions (150 ppm), when CA activity is typically low, the levels of CA1 transcription and resistance to P. syringae in wild-type Col-0 were similar to those observed in ca1ca4. However, under ambient (400 ppm) and elevated (800 ppm) atmospheric CO2 conditions, CA1 transcription was enhanced and resistance to P. syringae reduced. Together, these results suggest that CA1 and CA4 attenuate plant immunity and that differential CA gene expression in response to changing atmospheric CO2 conditions contribute to altered disease resistance levels.
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Proteínas de Arabidopsis/metabolismo , Dióxido de Carbono/metabolismo , Anidrases Carbônicas/metabolismo , Doenças das Plantas , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Anidrases Carbônicas/genética , Resistência à Doença , Imunidade Vegetal , Pseudomonas syringae/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
PURPOSE: To investigate the mediators of health-related quality of life (HR-QoL) in colorectal cancer (CRC) patients and effect on overall survival. METHODS: We analyzed baseline (within 1 year of diagnosis) SF-12v1 questionnaire data from 3734 CRC patients and assessed the differences in mental composite scores (MCS) and physical composite scores (PCS) by socio-demographics and risks of poor HR-QoL by these factors. Hazard ratios were generated using univariate Cox regression for MCS and PCS dichotomized using the normalized scoring-based mean of 50 and survival estimates generated using the Kaplan-Meier method. RESULTS: Differences in MCS and PCS were identified by sex, age, education level, alcohol use, tobacco use, and stage. Race, marital status, and cancer site differed only by PCS. Being female, never married, former alcohol user, or with stage IV disease significantly increased risk of a poor HR-QoL, with magnitudes of risk from 1.25- to 1.97-fold. Higher education level had a protective effect (MCS: P trend = 2.32 × 10-7; PCS: P trend = 5.62 × 10-14). Hispanics and African-Americans had a 1.35- and 1.57-fold risk of poor PCS, and increase in age had a protective effect for risk of poor MCS (P trend = 1.84 × 10-7). Poor MCS or PCS were associated with poor prognosis and decreased survival at 5 years (HRMCS 1.57, 95 % CI 1.41-1.76 and HRPCS 2.38, 95 % CI 2.08-2.72), and both remained significant when adjusting for age, gender, race, education level, tumor stage, and tumor site. CONCLUSIONS: Our findings identify potential mediators for HR-QoL and suggest that baseline HR-QoL assessment may be prognostic for CRC.
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Neoplasias Colorretais/psicologia , Perfil de Impacto da Doença , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Taxa de SobrevidaRESUMO
ATP-binding cassette (ABC) transporters are integral membrane proteins that have evolved diverse functions fulfilled via the transport of various substrates. In Arabidopsis, the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress responses. In this study, we revealed that two Arabidopsis ABCG transporters, ABCG16 and ABCG25, engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester (ABA-GE), respectively. We first revealed that ABCG16 contributes to osmotic stress tolerance via ABA signaling. More specifically, ABCG16 induces cellular ABA efflux in both yeast and plant cells. Using FRET analysis, we showed that ABCG16 forms obligatory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA, undergoing notable conformational changes. Furthermore, we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum (ER) membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco cells. The specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhibitory role of these two ABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER membrane. Our endomembrane-specific analysis of the FRET signals derived from the homo- or heterodimerized ABCG complexes allowed us to link endomembrane-biased dimerization to the translocation of distinct substrates by ABCG transporters, providing a prototypic framework for understanding the omnipotence of ABCG transporters in plant development and stress responses.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Dimerização , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Desenvolvimento Vegetal , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana/metabolismoRESUMO
Cellular hormone homeostasis is essential for precise spatial and temporal signaling responses and plant fitness. Abscisic acid (ABA) plays pivotal roles in orchestrating various developmental and stress responses and confers fitness benefits over ecological and evolutionary timescales in terrestrial plants. Cellular ABA level is regulated by complex processes, including biosynthesis, catabolism, and transport. AtABCG25 is the first ABA exporter identified through genetic screening and affects diverse ABA responses. Resolving the structural basis of ABA export by ABCG25 is critical for further manipulations of ABA homeostasis and plant fitness. We used cryo-electron microscopy to elucidate the structural dynamics of AtABCG25 and successfully characterized different states, including apo AtABCG25, ABA-bound AtABCG25, and ATP-bound AtABCG25 (E232Q). Notably, AtABCG25 forms a homodimer that features a deep, slit-like cavity in the transmembrane domain, and we precisely characterized the critical residues in the cavity where ABA binds. ATP binding triggers closure of the nucleotide-binding domains and conformational transitions in the transmembrane domains. We show that AtABCG25 belongs to a conserved ABCG subfamily that originated during the evolution of angiosperms. This subfamily neofunctionalized to regulate seed germination via the endosperm, in concert with the evolution of this angiosperm-specific, embryo-nourishing tissue. Collectively, these findings provide valuable insights into the intricate substrate recognition and transport mechanisms of the ABA exporter AtABCG25, paving the way for genetic manipulation of ABA homeostasis and plant fitness.
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Proteínas de Arabidopsis , Arabidopsis , Magnoliopsida , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Microscopia Crioeletrônica , Trifosfato de Adenosina/metabolismoRESUMO
The Ras GTPase-activating protein SH3 domain-binding protein (G3BP) belongs to the highly conserved family of RNA-binding proteins, which has been well-investigated in humans and animals. However, limited study of plant G3BP has been reported, and the precise biological function of the G3BP family has not been elucidated yet. In this study, the Arabidopsis G3BP family, comprising seven members, was comparatively analyzed. Transcriptome analysis showed that most G3BP genes are ubiquitously expressed in various tissues/organs. Transient expression analysis revealed that all G3BPs were presented in the cytoplasm, among which G3BP6 was additionally found in the nucleus. Further study revealed a conserved NLS motif required for the nuclear localization of G3BP6. Additionally, phenotypic analysis revealed that loss-of-function g3bp6 presented late-flowering phenotypes. RNA-sequencing analysis and qRT-PCR assays demonstrated that the expressions of abundant floral genes were significantly altered in g3bp6 plants. We also discovered that overexpression of G3BP6 in the nucleus, rather than in the cytoplasm, propelled bolting. Furthermore, we revealed that the scaffold protein Receptor for Activated C Kinase 1 (RACK1) interacted with and modulated the nuclear localization of G3BP6. Altogether, this study sheds new light on G3BP6 and its specific role in regulating the flowering transition in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Humanos , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Receptores de Quinase C Ativada/genéticaRESUMO
In this study, the impacts of loin ham with sorbitol-mediated curing on its physicochemical properties and bacterial community composition during fermentation and ripening were investigated. The salt content, pH, and water activity (aw) were lower in the sorbitol group than in the control group throughout the fermentation and ripening stages (P < 0.05). In addition, the L* values were higher in the sorbitol group (P < 0.05). Additionally, microbial diversity diminished in all groups as the fermentation and ripening process proceeded, with Lactobacillus turning into the dominant genus in the control group and Staphylococcus and Lactobacillus becoming dominant in the sorbitol group. Pearson's correlation analysis confirmed that the physicochemical properties have been significantly correlated with the bacterial community. In conclusion, sorbitol-mediated curing not only facilitates salt reduction while prolonging the storage period of loin ham, but also improves the distribution of bacterial community in loin ham and enhances its quality.
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Polyhydroxy alcohol-mediated curing has great potential for producing low-salt cured meat products. This study investigated the mass transfer kinetics and the one-way diffusion simulation of sodium chloride (NaCl) during the curing process. Furthermore, Fick's second law determined the NaCl diffusion coefficient (De) of xylitol-mediated cured pork tenderloin. The results demonstrated that adding xylitol could reduce the De of NaCl. The De of NaCl, calculated using the one-way model, was 1.29 × 10-9 m2·s-1, 1.22 × 10-9 m2·s-1, 1.2 × 10-9 m2·s-1, and 1.15 × 10-9 m2·s-1 when the amount of xylitol added was 0%, 4%, 8%, and 12% (w/w), respectively. This result agrees with the predicted values from the power function time-varying model. Moreover, a three-dimensional simulating model of mass transfers constructed using COMSOL Multiphysics was developed to evaluate the NaCl diffusion in pork tenderloin during the curing process. This model has high accuracy and can be used to describe the diffusion of NaCl in curing. Overall, this study provided a foundation for NaCl diffusion and distribution during the curing process.
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Stimulator of interferon genes (STING) plays a vital role in the human innate immune system. Aberrant expression of STING has been proven to be associated with several diseases, such as STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and systemic lupus erythematosus. Therefore, inhibition of the STING signaling pathway can also be expected to provide effective therapeutic strategies for treating specific inflammatory and autoimmune diseases. However, the development of STING inhibitors is still in its infancy. There is still a need for additional efforts toward the discovery of new skeletons and more potent lead compounds for STING inhibition to meet clinical demand. In this review, we provide a summary of STING inhibitors, classified by different structural skeletons, reported in patents published from 2019 to July 2022. In addition, we also focus on the STING inhibitors, representative structures, biological activity, and mechanisms of action.
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Stimulator of interferon gene (STING) is a critical adaptor protein that has a pivotal role in triggering inherent immune responses to infection. STING-linked interferon production has been involved in anti-inflammation, anti-infection, and antitumor immunity. Herein, a series of amidobenzimidazole analogues as STING agonists were profiled for potency and drug-like properties. By structure-based modification and optimization based on mono-aminobenzimidazole (ABZI), analogues with nanomolar STING agonistic activities were obtained. Among them, compounds D59 and D61 significantly increased the transcription of IFN-ß and proinflammatory cytokine CXCL10, as well as dramatically induced the phosphorylation of STING downstream proteins in THP1 cells. Furthermore, compound D61 exhibited favorable pharmacokinetic properties and metabolic stabilities. In a CT-26 syngeneic mice-bearing tumor model, D61 effectively inhibited tumor growth with good tolerance when administered via intratumoral, intravenous, intraperitoneal, and oral routes. This research on orally bioavailable amidobenzimidazole analogues expands the diversity of chemical structures of agonists for STING-mediated immunotherapy.
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Neoplasias , Receptores de Interferon , Animais , Camundongos , Fosforilação , InterferonsRESUMO
This study focused on how different concentrations of tea branch liquid smoke (TLS) in the curing solution impacted the physicochemical properties and antioxidant properties of pork tenderloin. Five experimental (1.25 mL/kg, 2.5 mL/kg, 5 mL/kg, 10 mL/kg, 20 mL/kg) and blank groups set up over 4 days, and it was found that the physicochemical indexes, antioxidant capacity, thermal stability and protein network structure of the cured meat using 5 mL/kg of liquid smoke were excellent than the other groups used (P < 0.05). However, concentrations at 20 mL/kg accelerated protein oxidation. Low frequency nuclear magnetic resonance (LFNHR) revealed that TLS also improved the water holding capacity of the cured meat by increasing the percentage of bound water. Additionally, the correlation analysis demonstrated that the inoxidizability of myofibrillar protein was significantly related to cooking loss and water distribution, which were adjusted by changing the usage of liquid smoke.
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ABCB1 and ABCG2 are the important ATP-binding cassette (ABC) transporters associated with multidrug resistance (MDR). Herein, we designed a series of imidazo[1,2-a]pyridine derivatives as dual-target inhibitors of ABCB1 and ABCG2 through the scaffold hopping strategy. Compound Y22 displayed potential efflux function inhibitory toward both ABCB1 and ABCG2 (reversal fold: ABCB1 = 8.35 and ABCG2 = 2.71) without obvious cytotoxicity. Y22 also enhanced the potency of antiproliferative drugs in vitro. Mechanistic studies demonstrated that Y22 slightly suppressed ATPase activity but did not affect the protein expression of ABCB1 or ABCG2. Notably, Y22 exhibited negligible CYP3A4 inhibition and enhanced the antiproliferative activity of adriamycin in vivo by restoring the sensitivity of resistant cells. Thus, Y22 may be effective clinically in combination with common chemotherapy agents. In summary, Y22 is a potential dual-target inhibitor that reverses MDR by blocking the efflux function of ABCB1 and ABCG2.
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Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Antineoplásicos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Piridinas/farmacologia , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , HumanosRESUMO
Abscisic acid (ABA) is a critical phytohormone involved in multifaceted processes in plant metabolism and growth under both stressed and nonstressed conditions. Its accumulation in various tissues and cells has long been established as a biomarker for plant stress responses. To date, a comprehensive understanding of ABA distribution and dynamics at subcellular resolution in response to environmental cues is still lacking. Here, we modified the previously developed ABA sensor ABAleon2.1_Tao3 (Tao3) and targeted it to different organelles including the endoplasmic reticulum (ER), chloroplast/plastid, and nucleus through the addition of corresponding signal peptides. Together with the cytosolic Tao3, we show distinct ABA distribution patterns in different tobacco cells with the chloroplast showing a lower level of ABA in both cell types. In a tobacco mesophyll cell, organellar ABA displayed specific alterations depending on osmotic stimulus, with ABA levels being generally enhanced under a lower and higher concentration of salt and mannitol treatment, respectively. In Arabidopsis roots, cells from both the meristem and elongation zone accumulated ABA considerably in the cytoplasm upon mannitol treatment, while the plastid and nuclear ABA was generally reduced dependent upon specific cell types. In Arabidopsis leaf tissue, subcellular ABA seemed to be less responsive when stressed, with notable increases of ER ABA in epidermal cells and a reduction of nuclear ABA in guard cells. Together, our results present a detailed characterization of stimulus-dependent cell type-specific organellar ABA responses in tobacco and Arabidopsis plants, supporting a highly coordinated regulatory network for mediating subcellular ABA homeostasis during plant adaptation processes.
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Ácido Abscísico , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Manitol , Organelas/metabolismo , Nicotiana/metabolismoRESUMO
Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-restricted member of the serine/threonine Ste20-related protein kinases, is a negative regulator of the T cell receptor, B cell receptor, and dendritic cells. Loss of HPK1 kinase function increases cytokine secretion and enhances T cell signaling, virus clearance, and tumor growth inhibition. Therefore, HPK1 is considered a promising target for tumor immunotherapy. Several HPK1 inhibitors have been reported to regulate T cell function. In addition, HPK1-targeting PROTACs, which can induce the degradation of HPK1, have also been developed. Here, we provide an overview of research concerning HPK1 protein structure, function, and inhibitors and propose perspectives and insights for the future development of agents targeting HPK1.
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Química Farmacêutica , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Proteínas Serina-Treonina Quinases , Transdução de SinaisRESUMO
Considering the hazards of high salt intake and the current status of research on low-sodium meat products, this study was to analyze the effect of ultrasound combined with glycerol-mediated low-sodium salt curing on the quality of pork tenderloin by analyzing the salt content, water activity (aw), cooking loss, and texture. The results of scanning electron microscope (SEM) analysis, Raman spectroscopy, ultraviolet fluorescence, and surface hydrophobicity were proposed to reveal the mechanism of the effect of combined ultrasound and glycerol-mediated low sodium salt curing on the quality characteristics of pork tenderloin. The results showed that the co-mediated curing could reduce salt content, aw, and cooking loss (p < 0.05), improve texture and enhance product quality. Compared with the control group, the co-mediated curing increased the solubility of the myofibrillar protein, improved the surface hydrophobicity of the protein, increased the content of reactive sulfhydryl groups (p < 0.05), and changed the protein structure. The SEM results showed that the products treated using a co-mediated curing process had a more detailed and uniform pore distribution. These findings provide new insights into the quality of ultrasonic-treated and glycerol-mediated low-salt cured meat products.
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This study investigated the mechanism of glycerol, xylitol, and sorbitol-mediated curing of cured minced pork tenderloin. The use of polyhydroxy alcohol during mediated curing significantly reduced the salt content (p < 0.01) and water activity (aw) of the cured pork tenderloin. Low-field nuclear magnetic resonance (LFNMR) revealed that 1 % glycerol, 1 % xylitol, 1 % sorbitol, and 10 % glycerol-mediated curing decreased water mobility, and improved water holding capacity (WHC), and produced uniform dense microstructures. Raman spectroscopy and molecular docking indicated that polyhydroxy alcohols formed hydrogen bonds with myosin, as well as hydrogen bonds with free water molecules to convert free water into bound water to reduce aw, and altered the hydrophobic environment of myosin surface to reduce structural damage caused by high salt content. In conclusion, using polyhydroxy alcohol to mediate curing can effectively reduce the salt content of cured meat and provide a theoretical basis for its application in the cured meat industry.