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BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0
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Doença da Artéria Coronariana , Calcificação Vascular , Humanos , Diálise Renal/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Hormônio Paratireóideo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia , Peptídeos , Fosfatase AlcalinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Kadsura coccinea (Lem.) A. C. Smith is an ethnomedicine used to treat abnormal menstruation, menopausal syndrome, and female infertility among the Dong Nationality in China. AIM OF THE STUDY: Our study aimed to identify the volatile oil profiles of the K. coccinea fruit and elucidate their estrogenic activity. MATERIALS AND METHODS: The peel volatile oil (PeO), pulp volatile oil (PuO), and seed volatile oil (SeO) of K. coccinea were extracted using hydrodistillation and qualitatively analyzed using gas chromatography-mass spectrometry (GC-MS). Estrogenic activity was evaluated in vitro using cell assay and in vivo using immature female rats. Serum 17ß-Estradiol (E2) and follicle-stimulating hormone (FSH) levels were detected using ELISA. RESULTS: In total, 46 PeO, 27 PuO, and 42 SeO components representing 89.96%, 90.19%, and 97% of the total composition, respectively, were identified. The compounds with the highest content in PeO, PuO, and SeO were ß-caryophyllene, γ-amorphene, and n-hexadecanoic acid, respectively. PeO induced proliferation of MCF-7 cells with an EC50 of 7.40 µg/mL. Subcutaneous administration of 10 mg/kg PeO significantly increased the weight of the uteri in immature female rats, with no effect on serum E2 and FSH levels. PeO acted as an agonist of ERα and ERß. PuO and SeO showed no estrogenic activity. CONCLUSION: The chemical compositions of PeO, PuO, and SeO of K. coccinea are different. PeO is the main effective fraction for estrogenic activities, providing a new source of phytoestrogen for the treatment of menopausal symptoms.
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Kadsura , Óleos Voláteis , Feminino , Ratos , Animais , Frutas , Kadsura/química , Fitoestrógenos/farmacologia , Estrona , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Hormônio FoliculoestimulanteRESUMO
Objective: To explore the relationship of hypertriglyceridemic waist phenotype (HTWP) with initial neurological severity and etiologic subtypes in patients with acute ischemic stroke. Methods: The data for this study were collected from hospitalized patients within 72 h of acute ischemic stroke onset at the Department of Neurology of the Affiliated Hospital of Beihua University from 1 July 2020 to 30 June 2022. The initial neurological severity was assessed by the National Institute of Health Stroke Scale (NIHSS) on the day of admission: NIHSS <6 was defined as mild stroke, and NIHSS ≥6 as moderate to severe stroke. HTWP was defined by fasting serum triglycerides ≥1.7 mmol/L and waist circumference ≥90 cm in men and ≥80 cm in women. Differentiation of etiologic subtypes was based on the method reported in the Trial of Org 10 172 in Acute Stroke Treatment. Multivariate logistic regression analysis was used to analyze the association of HTWP with initial neurological severity and etiologic subtypes. Results: The study included 431 patients. Compared with the normal waist-normal blood triglyceride group, patients with HTWP had reduced risks of moderate to severe stroke [odds ratio (OR): 0.384, 95% confidence interval (CI): 0.170-0.869; P = 0.022]. In addition, the risk of small-artery occlusion stroke was 2.318 times higher in the HTWP group than in the normal triglyceride-normal waist (NWNT) group (OR: 2.318, 95% CI: 1.244-4.319; P = 0.008). Conclusion: Initial neurological severity was less severe in patients with HTWP, and HTWP was associated with an increased risk of small-artery occlusion stroke.
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Cintura Hipertrigliceridêmica , AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Cintura Hipertrigliceridêmica/complicações , AVC Isquêmico/complicações , Fatores de Risco , Acidente Vascular Cerebral/complicações , Triglicerídeos , FenótipoRESUMO
Primary aldosteronism (PA) is a disease characterized by hypertension and hypokalemia due to the excessive aldosterone secretion from the adrenal cortex, which leads to the retention of both water and sodium, and the inhibition of the renin-angiotensin system as well. Familial hyperaldosteronism type II (FH-II) is known as an autosomal dominant hereditary disease, which is a scarce cause of PA. In this report, we cllected the clinical data of a patient with repeated hypertension and hypokalemia of uncertain diagnosis since 2014. Nevertheless, we discovered by genetic sequencing in 2021 that the CLCN2 and WFS1 gene mutation of the patient, whose mother belongs to heterozygote genotype and father belongs to wild-type genotype. Combined with a series of endocrine function tests and imaging studies, the patient was finally certified her suffering from FH-II and WFS1 gene mutation. By summarizing and analyzing the characteristics and genetic test results of this case, we recommended gene sequencing for patients with PA whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.
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Hiperaldosteronismo , Hipertensão , Hipopotassemia , Humanos , Feminino , Hipopotassemia/complicações , Hipopotassemia/genética , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Hiperaldosteronismo/terapia , Testes Genéticos , Mutação , Hipertensão/genéticaRESUMO
Maternal-to-filial nutrition transfer is central to grain development and yield. nitrate transporter 1/peptide transporter (NRT1-PTR)-type transporters typically transport nitrate, peptides, and ions. Here, we report the identification of a maize (Zea mays) NRT1-PTR-type transporter that transports sucrose and glucose. The activity of this sugar transporter, named Sucrose and Glucose Carrier 1 (SUGCAR1), was systematically verified by tracer-labeled sugar uptake and serial electrophysiological studies including two-electrode voltage-clamp, non-invasive microelectrode ion flux estimation assays in Xenopus laevis oocytes and patch clamping in HEK293T cells. ZmSUGCAR1 is specifically expressed in the basal endosperm transfer layer and loss-of-function mutation of ZmSUGCAR1 caused significantly decreased sucrose and glucose contents and subsequent shrinkage of maize kernels. Notably, the ZmSUGCAR1 orthologs SbSUGCAR1 (from Sorghum bicolor) and TaSUGCAR1 (from Triticum aestivum) displayed similar sugar transport activities in oocytes, supporting the functional conservation of SUGCAR1 in closely related cereal species. Thus, the discovery of ZmSUGCAR1 uncovers a type of sugar transporter essential for grain development and opens potential avenues for genetic improvement of seed-filling and yield in maize and other grain crops.
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Grão Comestível , Glucose , Transportadores de Nitrato , Transportador 1 de Peptídeos , Proteínas de Plantas , Sacarose , Zea mays , Humanos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Glucose/metabolismo , Células HEK293 , Transportadores de Nitrato/genética , Transportadores de Nitrato/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sacarose/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Transportador 1 de Peptídeos/genética , Transportador 1 de Peptídeos/metabolismo , Transporte BiológicoRESUMO
Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Citocinas/genética , Expressão Gênica , Humanos , Vírus da Influenza A Subtipo H1N1/genética , MicrogliaRESUMO
Stomatal closure is an important process to prevent water loss in plants response to drought stress, which is finely modulated by ion channels together with their regulators in guard cells, especially the S-type anion channel AtSLAC1 in Arabidopsis. However, the functional characterization and regulation analyses of anion channels in gramineous crops, such as in maize guard cells are still limited. In this study, we identified an S-type anion channel ZmSLAC1 that was preferentially expressed in maize guard cells and involved in stomatal closure under drought stress. We found that two Ca2+ -dependent protein kinases ZmCPK35 and ZmCPK37 were expressed in maize guard cells and localized on the plasma membrane. Lesion of ZmCPK37 resulted in drought-sensitive phenotypes. Mutation of ZmSLAC1 and ZmCPK37 impaired ABA-activated S-type anion currents in maize guard cells, while the S-type anion currents were increased in the guard cells of ZmCPK35- and ZmCPK37-overexpression lines. Electrophysiological characterization in maize guard cells and Xenopus oocytes indicated that ZmCPK35 and ZmCPK37 could activate ZmSLAC1-mediated Cl- and NO3- currents. The maize inbred and hybrid lines overexpressing ZmCPK35 and ZmCPK37 exhibited enhanced tolerance and increased yield under drought conditions. In conclusion, our results demonstrate that ZmSLAC1 plays crucial roles in stomatal closure in maize, whose activity is regulated by ZmCPK35 and ZmCPK37. Elevation of ZmCPK35 and ZmCPK37 expression levels is a feasible way to improve maize drought tolerance as well as reduce yield loss under drought stress.
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Secas , Proteínas de Membrana/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Quinases , Zea mays , Ácido Abscísico/metabolismo , Ânions/metabolismo , Estômatos de Plantas/fisiologia , Proteínas Quinases/metabolismo , Zea mays/enzimologia , Zea mays/genéticaRESUMO
BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have revolutionized the therapeutic strategy for anemia in chronic kidney disease. However, some cases are resistant or hyporesponsive to ESAs. Roxadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Here, we describe a hemodialysis patient with refractory anemia who did not respond to traditional treatments and depended on blood transfusion for more than 1 year. After applying Roxadustat, the patient's anemia improved significantly. CASE SUMMARY: A 44-year-old man was diagnosed with uremia accompanied by severe anemia with a hemoglobin (Hb) level ranging from 30-40 g/L. His anemia did not improve after sufficient dialysis or high doses of active ESAs; other causes of anemia were excluded. The patient required approximately 600-1000 mL of red blood cell suspension every 15-30 d for more than 1 year. After accepting Roxadustat therapy, the patient's anemia symptoms improved significantly; his Hb level gradually increased to 50 g/L, and no further blood transfusions were administered. His Hb level reached 69 g/L by the 34th week. Although a Hb level of 60-70 g/L cannot be considered satisfactory, he no longer required blood transfusions and his quality of life was substantially improved. Roxadustat showed good efficacy and safety in this case. CONCLUSION: Roxadustat represents an innovative and effective agent for the clinical treatment of renal anemia caused by multiple complex factors.
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Organismal homeostasis of the essential ion K+ requires sensing of its availability, efficient uptake, and defined distribution. Understanding plant K+ nutrition is essential to advance sustainable agriculture, but the mechanisms underlying K+ sensing and the orchestration of downstream responses have remained largely elusive. Here, we report where plants sense K+ deprivation and how this translates into spatially defined ROS signals to govern specific downstream responses. We define the organ-scale K+ pattern of roots and identify a postmeristematic K+-sensing niche (KSN) where rapid K+ decline and Ca2+ signals coincide. Moreover, we outline a bifurcating low-K+-signaling axis of CIF peptide-activated SGN3-LKS4/SGN1 receptor complexes that convey low-K+-triggered phosphorylation of the NADPH oxidases RBOHC, RBOHD, and RBOHF. The resulting ROS signals simultaneously convey HAK5 K+ uptake-transporter induction and accelerated Casparian strip maturation. Collectively, these mechanisms synchronize developmental differentiation and transcriptome reprogramming for maintaining K+ homeostasis and optimizing nutrient foraging by roots.
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Adaptação Fisiológica , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Homeostase , Nutrientes/metabolismo , Raízes de Plantas/metabolismo , Potássio/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Complexo do Signalossomo COP9/genética , Complexo do Signalossomo COP9/metabolismo , Cálcio/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , TranscriptomaRESUMO
Potassium and nitrogen are essential mineral elements for plant growth and development. The protein kinase LKS1/CIPK23 is involved in both K+ and NH4+ uptake in Arabidopsis root. The transcripts of LKS1 can be induced by low K+ (0.1 mM) and high NH4+ (30 mM); however, the molecular mechanism is still unknown. In this study, we isolated the transcription factor STOP1 that positively regulates LKS1 transcription in Arabidopsis responses to both low-K+ and high-NH4+ stresses. STOP1 proteins can directly bind to the LKS1 promoter, promoting its transcription. The stop1 mutants displayed a leaf chlorosis phenotype similar to lks1 mutant when grown on low-K+ and high-NH4+ medium. On the other hand, STOP1 overexpressing plants exhibited a similar tolerant phenotype to LKS1 overexpressing plants. The transcript level of STOP1 was only upregulated by low K+ rather than high NH4+; however, the accumulation of STOP1 protein in the nucleus was required for the upregulation of LKS1 transcripts in both low-K+ and high-NH4+ responses. Our data demonstrate that STOP1 positively regulates LKS1 transcription under low-K+ and high-NH4+ conditions; therefore, LKS1 promotes K+ uptake and inhibits NH4+ uptake. The STOP1/LKS1 pathway plays crucial roles in K+ and NH4+ homeostasis, which coordinates potassium and nitrogen balance in plants in response to external fluctuating nutrient levels.
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Compostos de Amônio/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/fisiologia , Potássio/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismo , Transcrição Gênica , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Modelos Biológicos , Mutação/genética , Raízes de Plantas/metabolismo , Potássio/farmacologia , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Protoplastos/efeitos dos fármacos , Protoplastos/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Transcrição Gênica/efeitos dos fármacosRESUMO
Nitrogen (N), potassium (K), and phosphorus (P) are essential macronutrients for plant growth and development, and their availability affects crop yield. Compared with N, the relatively low availability of K and P in soils limits crop production and thus threatens food security and agricultural sustainability. Improvement of plant nutrient utilization efficiency provides a potential route to overcome the effects of K and P deficiencies. Investigation of the molecular mechanisms underlying how plants sense, absorb, transport, and use K and P is an important prerequisite to improve crop nutrient utilization efficiency. In this review, we summarize current understanding of K and P transport and signaling in plants, mainly taking Arabidopsis thaliana and rice (Oryza sativa) as examples. We also discuss the mechanisms coordinating transport of N and K, as well as P and N.
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Arabidopsis/metabolismo , Fósforo/metabolismo , Potássio/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
Protein kinase-mediated phosphorylation modulates the absorption of many nutrients in plants. CALCIUM-DEPENDENT PROTEIN KINASES (CPKs) are key players in plant signaling to translate calcium signals into diverse physiological responses. However, the regulatory role of CPKs in ammonium uptake remains largely unknown. Here, using methylammonium (MeA) toxicity screening, CPK32 was identified as a positive regulator of ammonium uptake in roots. CPK32 specifically interacted with AMMONIUM TRANSPORTER 1;1 (AMT1;1) and phosphorylated AMT1;1 at the non-conserved serine residue Ser450 in the C-terminal domain. Functional analysis in Xenopus oocytes showed that co-expression of CPK32 and AMT1;1 significantly enhanced the AMT1;1-mediated inward ammonium currents. In transgenic plants, the phosphomimic variant AMT1;1S450E, but not the non-phosphorylatable variant AMT1;1S450A, fully complemented the MeA insensitivity and restored high-affinity 15NH4+ uptake in both amt1;1 and cpk32 mutants. Moreover, in the CPK32 knockout background, AMT1;1 lost its ammonium transport activity entirely. These results indicate that CPK32 is a crucial positive regulator of ammonium uptake in roots and the ammonium transport activity of AMT1;1 is dependent on CPK32-mediated phosphorylation.
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Compostos de Amônio , Arabidopsis , Proteínas de Transporte de Cátions , Compostos de Amônio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica de Plantas , Fosforilação , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Proteínas Quinases , Compostos de Amônio Quaternário/metabolismoRESUMO
Potassium (K) is essential for plant growth and development. Here, we show that the KUP/HAK/KT K+ transporter KUP9 controls primary root growth in Arabidopsis thaliana. Under low-K+ conditions, kup9 mutants displayed a short-root phenotype that resulted from reduced numbers of root cells. KUP9 was highly expressed in roots and specifically expressed in quiescent center (QC) cells in root tips. The QC acts to maintain root meristem activity, and low-K+ conditions induced QC cell division in kup9 mutants, resulting in impaired root meristem activity. The short-root phenotype and enhanced QC cell division in kup9 mutants could be rescued by exogenous auxin treatment or by specifically increasing auxin levels in QC cells, suggesting that KUP9 affects auxin homeostasis in QC cells. Further studies showed that KUP9 mainly localized to the endoplasmic reticulum (ER), where it mediated K+ and auxin efflux from the ER lumen to the cytoplasm in QC cells under low-K+ conditions. These results demonstrate that KUP9 maintains Arabidopsis root meristem activity and root growth by regulating K+ and auxin homeostasis in response to low-K+ stress.
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Proteínas de Arabidopsis , Arabidopsis , Ácidos Indolacéticos , Meristema/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Potássio , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , HomeostaseRESUMO
The yeast ATP-dependent chromatin remodeling enzyme Fun30 has been shown to regulate heterochromatin silencing, DNA repair, transcription, and chromatin organization. Although chromatin structure has been proposed to influence splice site recognition and regulation, whether ATP-dependent chromatin remodeling enzyme plays a role in regulating splicing is not known. In this study, we find that pre-mRNA splicing efficiency is impaired and the recruitment of spliceosome is compromised in Fun30-depleted cells. In addition, Fun30 is enriched in the gene body of individual intron-containing genes. Moreover, we show that pre-mRNA splicing efficiency is dependent on the chromatin remodeling activity of Fun30. The function of Fun30 in splicing is further supported by the observation that, Smarcad1, the mammalian homolog of Fun30, regulates alternative splicing. Taken together, these results provide evidence for a novel role of Fun30 in regulating splicing.
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Trifosfato de Adenosina/metabolismo , Cromatina/metabolismo , DNA Helicases/metabolismo , Splicing de RNA/genética , RNA Mensageiro , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Fatores de Transcrição/metabolismo , Animais , DNA Helicases/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genéticaRESUMO
Nitrate is one of the main inorganic nitrogen sources for plants. Nitrate absorption from soils is achieved through the combined activities of specific nitrate transporters. Nitrate transporter 2.1 (NRT2.1) is the major component of the root high-affinity nitrate transport system in Arabidopsis thaliana. Studies to date have mainly focused on transcriptional control of NRT2.1. Here, we show that NRT2.1 protein stability is also regulated in response to nitrogen nutrition availability. When seedlings were transferred to nitrate-limited conditions, the apparent half-life of NRT2.1 in roots increased from 3 to 9 h. This stabilization of NRT2.1 protein occurred rapidly, even prior to the transcriptional stimulation of NRT2.1. Furthermore, we revealed that phosphorylation at serine 28 (Ser28) of NRT2.1 is involved in regulating the stability of this protein. Substitution of Ser28 by alanine resulted in unstable NRT2.1, and this loss-of-phosphorylation mutant (NRT2.1S28A ) failed to complement the growth-restricted phenotype of the nrt2.1 mutant when a low concentration of nitrate was the sole nitrogen source. These results demonstrate that phosphorylation at Ser28 is crucial for NRT2.1 protein stabilization and accumulation in response to nitrate limitation.
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Proteínas de Transporte de Ânions/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Nitratos/metabolismo , Fosfosserina/metabolismo , Proteínas de Transporte de Ânions/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Meia-Vida , Mutação/genética , Nitratos/farmacologia , Fenótipo , Fosforilação/efeitos dos fármacos , Plantas Geneticamente Modificadas , Estabilidade Proteica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
It is found that catechol inhibits the oxidase-mimicking activity of chitosan-protected platinum nanoparticles (Chit-PtNPs) by competing with the substrate for the active site of the Ch-PtNPs. The inhibition mechanism of catechol is different from that of ascorbic acid in that it neither reacts with O2â¢- nor reduces the oxidized 3,3',5,5'-tetramethylbenzidine (TMB). Tyrosinase (TYRase) catalyzes the oxidation of catechol, thus restoring the activity of oxidase-mimicking Chit-PtNPs. By combining the Chit-PtNP, catechol, and TYRase interactions with the oxidation of TMB to form a yellow diamine (maximal absorbance at 450 nm), a colorimetric analytical method was developed for TYRase determination and inhibitor screening. The assay works in the 0.5 to 2.5 U·mL-1 TYRase activity range, and the limit of detection is 0.5 U·mL-1. In our perception, this new assay represents a powerful approach for determination of TYRase activity in biological samples. Graphical abstract Schematic representation of a colorimetric method for tyrosinase (TYRase) detection and inhibitor screening. It is based on the fact that catechol can inhibit the oxidase-like activity of chitosan-stabilized platinum nanoparticles (Ch-PtNPs) by competing with the substrate for the active sites and TYRase can catalyze the oxidation of catechol.
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Materiais Biomiméticos/química , Catecóis/farmacologia , Quitosana/química , Colorimetria/métodos , Nanopartículas Metálicas/química , Monofenol Mono-Oxigenase/metabolismo , Platina/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Oxirredutases/metabolismoRESUMO
Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by the remodeling of small pulmonary arteries. The aberrant proliferation of pulmonary arterial smooth muscle cells (PASMCs) is the primary feature of PAH. MicroRNA (miR)132 has been demonstrated to inhibit the proliferation of vascular smooth muscle cells and repress neointimal formation. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a direct target of miR132 that has been revealed to be involved in the development of PAH. However, the role of miR132 in PAH remains unclear. The present study demonstrated that miR132 expression was upregulated in monocrotalineinduced PAH rats and plateletderived growth factorinduced PASMCs. In addition, treatment of PASMCs with miR132 mimics inhibited their proliferation, whereas miR132 inhibition exhibited the opposite effects. Furthermore, miR132 mimics promoted cell migration and maintained the PASMC contractile phenotype. Finally, the expression levels of PTEN were significantly decreased in PAH and PASMCs treated with miR132 mimics. Taken collectively, the data suggested that miR132 regulated PASMC function via PTEN and that it may be used as a potential target for the treatment of PAH.
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Movimento Celular , Proliferação de Células , Hipertensão Pulmonar/patologia , MicroRNAs/genética , Músculo Liso Vascular/patologia , PTEN Fosfo-Hidrolase/metabolismo , Artéria Pulmonar/patologia , Animais , Apoptose , Células Cultivadas , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Masculino , Monocrotalina/toxicidade , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , PTEN Fosfo-Hidrolase/genética , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
[This corrects the article DOI: 10.1371/journal.pgen.1005833.].
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Potassium and nitrogen are essential nutrients for plant growth and development. Plants can sense potassium nitrate (K+/NO3 -) levels in soils, and accordingly they adjust root-to-shoot K+/NO3 - transport to balance the distribution of these ions between roots and shoots. In this study, we show that the transcription factorMYB59 maintains this balance by regulating the transcription of the Arabidopsis (Arabidopsis thaliana) Nitrate Transporter1.5 (NRT1.5)/ Nitrate Transporter/Peptide Transporter Family7.3 (NPF7.3) in response to low K+ (LK) stress. The myb59 mutant showed a yellow-shoot sensitive phenotype when grown on LK medium. Both the transcript and protein levels of NPF7.3 were remarkably reduced in the myb59 mutant. LK stress repressed transcript levels of both MYB59 and NPF7.3 The npf7.3 and myb59 mutants, as well as the npf7.3 myb59 double mutant, showed similar LK-sensitive phenotypes. Ion content analyses indicated that root-to-shoot K+/NO3 - transport was significantly reduced in these mutants under LK conditions. Moreover, chromatin immunoprecipitation and electrophoresis mobility shift assay assays confirmed that MYB59 bound directly to the NPF7.3 promoter. Expression of NPF7.3 in root vasculature driven by the PHOSPHATE 1 promoter rescued the sensitive phenotype of both npf7.3 and myb59 mutants. Together, these data demonstrate that MYB59 responds to LK stress and directs root-to-shoot K+/NO3 - transport by regulating the expression of NPF7.3 in Arabidopsis roots.
Assuntos
Proteínas de Transporte de Ânions/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Membrana Transportadoras/metabolismo , Nitratos/metabolismo , Compostos de Potássio/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Transporte de Ânions/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Mutação , Fenótipo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/fisiologia , Potássio/metabolismo , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS: The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.