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1.
Bioorg Med Chem Lett ; : 127862, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33609659

RESUMEN

Autoimmune and inflammatory diseases place a huge burden on the healthcare system. Small molecule (SM) therapeutics provide much needed complementary treatment options for these diseases. This digest series highlights the latest progress in the discovery and development of safe and efficacious SMs to treat autoimmune and inflammatory diseases with each part representing a class of SMs, namely: 1) protein kinases; 2) nucleic acid-sensing pathways; and 3) soluble ligands and receptors on cell surfaces. In this first part of the series, the focus is on kinase inhibitors that emerged between 2018 and 2020, and which exhibit increased target and tissue selectivity with the aim of increasing their therapeutic index.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33596179

RESUMEN

Because of the rapid and serious nature of acute cardiovascular disease (CVD) especially ST segment elevation myocardial infarction (STEMI), a leading cause of death worldwide, prompt diagnosis and treatment is of crucial importance to reduce both mortality and morbidity. During a pandemic such as coronavirus disease-2019 (COVID-19), it is critical to balance cardiovascular emergencies with infectious risk. In this work, we recommend using wearable device based mobile health (mHealth) as an early screening and real-time monitoring tool to address this balance and facilitate remote monitoring to tackle this unprecedented challenge. This recommendation may help to improve the efficiency and effectiveness of acute CVD patient management while reducing infection risk.

3.
J Neuroimmunol ; 353: 577487, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33578311

RESUMEN

Complement component 3 (C3) had been proved to be involved in the pathogenesis and exacerbation of both myasthenia gravis (MG) patients and experimental autoimmune myasthenia gravis (EAMG) models. We evaluated the underlying association between five SNPs (rs344555, rs7951, rs3745568, rs366510 and rs163913) in C3 gene and Chinese adult MG patients. Our study consisted of 409 adult MG patients and 487 healthy controls. Subgroups were classified by gender, onset age, thymoma, anti-AChR antibody, onset muscle involvement (ocular/generalized) and severity (Oosterhuis score at the maximal severity during the initial two years after the onset of MG). We found significant differences in allele frequencies between MG and the control group, between various MG subgroups and the control group in rs344555 and rs3745568. There were significant differences in genotype frequencies between MG group and the control group, between MG subgroups and the control group under the codominant and additive inheritance models in rs344555 and rs3745568. No association was found between the frequencies of these SNPs and the severity of MG. We also used a comprehensive classification which was close to the clinical scenario to minimize the interaction among clinical features. In rs344555, the T allele frequency in thymoma (-) AChR-Ab (+) subgroup was significantly higher than that in the control group. Our results indicated that rs344555 was associated with the susceptibility of Chinese adult MG patients; rs3745568 was probably associated with the susceptibility of Chinese adult MG patients. No association was found between the frequencies of these SNPs and the severity of MG.

4.
Dev Sci ; : e13096, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33544950

RESUMEN

Scientific research on how children learn to tell lies has existed for more than a century. Earlier studies mainly focused on moral, social, and situational factors contributing to the development of lying. Researchers have only begun to explore the cognitive correlations of children's lying in the last two decades. Cognitive theories suggest that theory of mind (ToM) and executive function (EF) should be closely related to the development of lying since lying is, in essence, ToM and EF in action. Yet, findings from empirical studies are mixed. To address this issue, the current meta-analysis reviewed all prior literature that examined the relations between children's lying and ToM and/or between children's lying and EF. In total, 47 papers consisting of 5099 participants between 2 and 19 years of age were included, which yielded 74 effect sizes for ToM and 94 effect sizes for EF. Statistically significant but relatively small effects were found between children's lying and ToM (r = .17) and between lying and EF (r = .13). Further, EF's correlation with children's initial lies was significantly smaller than its correlation with their ability to maintain lies. This comprehensive meta-analysis provides a clear picture of the associations between children's ToM/EF and their lying behavior and confirms that ToM and EF indeed play a positive role in children's lying and its development.

5.
Cancer Sci ; 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33540491

RESUMEN

Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC) especially in BRAF-like PTC by analyzing TCGA database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5 specific antagonist TC LPA5 4 treatment inhibited CGTH-W3, TPC-1, B-CPAP and BHT-101 cells proliferation, CGTH-W3 and TPC-1 cells migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH-W3 xenograft growth in nude mice. We also found that LPAR5 specific antagonists TC LPA5 4, PI3K inhibitor Wortmannin or mTOR inhibitor Rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH-W3 and TPC-1 cells. Stimulating CGTH-W3 cells transfected with pEGFPC1-Grp1-PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)-triphosphate, which indicates that PI3K was activated by LPA directly. The p110ß-siRNA instead of p110α-siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110ß. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or PI3K/Akt signal may be the novel therapeutic strategy for treating thyroid cancer.

6.
Infect Dis Poverty ; 10(1): 8, 2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33468247

RESUMEN

BACKGROUND: The detection of drug-resistant tuberculosis (DR-TB) is a major health concern in China. We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province, analyse their impact, and highlight policy implications for improving the prevention and control of DR-TB. METHODS: We selected six prefectures from south, central and north Jiangsu Province. We reviewed policy documents between 2008 and 2019, and extracted routine TB patient registration data from the TB Information Management System (TBIMS) between 2013 and 2019. We used the High-quality Health System Framework to structure the analysis. We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection. RESULTS: Three prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) and the Bill & Melinda Gates Foundation (Gates Foundation). By 2017, all prefectures in Jiangsu had implemented provincial level DR-TB policies, such as use of rapid molecular tests (RMT), and expanded drug susceptibility testing (DST) for populations at risk of DR-TB. The percentage of pulmonary TB cases confirmed by bacteriology increased from 30.0% in 2013 to over 50.0% in all prefectures by 2019, indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy. At the same time, the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially, indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB. Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support. However, the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices. CONCLUSIONS: The introduction of new diagnostics, including RMT, have improved the detection of DR-TB. Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB. Additionally, the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.

7.
J Adv Nurs ; 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33432661

RESUMEN

AIMS: To investigate practice patterns in exit-site care and identify the risk factors for exit-site infection. DESIGN: A quantitative cross-sectional design. METHODS: Data were collected in 12 peritoneal dialysis (PD) centres in 2018. Daily exit-site care practice patterns and exit-site status of patients receiving PD were assessed through interviews and questionnaires. RESULTS/FINDINGS: Most of the 1,204 patients adhered with the protocols about main aspects of exit-site care, such as cleansing agents selection, frequency of cleansing, catheter fixation, and following the catheter protective measures. However, their adherence levels on hand hygiene, mask wearing, observing exit site, examining secretion, and communicating with PD staff were rather low. Eighty-four patients' exit sites were evaluated as problematic exit site (PES). And 186 patients had catheter-related infection (CRI) history. After multivariable logistic regression analysis, diabetes (OR = 1.631), traction bleeding history (OR = 2.697), antibiotic agents use (OR = 2.460), compliance on mask wearing (OR = 0.794), and observing exit site (OR = 0.806) were influencing factors of CRI history. Traction bleeding history (OR = 2.436), CRI history (OR = 10.280), and effective communication (OR = 0.808) with PD staff were influencing factors for PES. CONCLUSIONS: The adherence levels on different aspects of exit-site care were varied in patients having PD. Their self-care behaviours did correlate with the exit-site status. IMPACT: The adherence level of patients' exit-site care practice needs attention of medical staff. Further studies about the optimal procedure in exit-site care were warranted.

8.
Org Biomol Chem ; 19(7): 1541-1545, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33503103

RESUMEN

Three novel jatrophane diterpenes, cyclojatrophanes A-C (1-3), were isolated from the seeds of Euphorbia peplus. Compounds 1-3 featured an unprecedented 5/5/5/11 tetracyclic ring system incorporating ditetrahydropyran rings. Their structures including their absolute configurations were established by extensive spectroscopic analysis, X-ray crystallographic experiments and chemical transformations. In addition, these compounds could significantly activate the lysosomal-autophagy pathway.

9.
Eur J Med Chem ; 212: 113097, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33385836

RESUMEN

Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5-NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1-H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1-H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1-H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.

10.
J Exp Child Psychol ; 201: 104990, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32977115

RESUMEN

Past research shows that parental mental state talk (MST) is closely associated with children's theory-of-mind (ToM) understanding. The current study extends previous work by investigating whether parental MST is also associated with children's ToM in action (i.e., lying). A total of 90 Singaporean 3- to 5-year-olds participated in this study with their parents. Parental MST was measured using a storytelling task with a wordless picture book. Mediation analysis revealed an indirect effect: Children's ToM understanding served as a mediator in the path between parental MST and children's lying, whereas there was no significant direct effect of parental MST on children's lying. This study is the first to focus on the relation between parental MST and ToM in an applied setting. Our findings suggest that parental MST can help children to develop sociocognitive skills, which in turn can help children to gain the insight that lying may be used as a strategy for personal gain.

11.
Phytochemistry ; 182: 112597, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33341030

RESUMEN

Seven pairs of undescribed enantiomeric bis-coumarins, (±)-dievodialetins A-G, were separated from the roots of Evodia lepta Merr. Two coumarin nuclei were linked via a 1,4-dimethyl4-vinylcyclohexene moiety in (±)-dievodialetins C-G. The structures of the undescribed compounds, including their absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. In the biosynthetic pathways, these bis-coumarins were presumably derived from the precursors demethylsuberosin and 3-(3-methylbut-2-enyl)umbelliferone via a [4 + 2] Diels-Alder reaction. Besides, all compounds exhibited neuroprotective effects by inhibiting acetylcholinesterase (AChE) activity with IC50 values ranging from 7.3 to 12.1 nM and they also suppressed oxidative stress (MDA and SOD) and neuroinflammation (IL-1ß and IL-6).


Asunto(s)
Evodia , Rutaceae , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Cumarinas/farmacología , Estructura Molecular , Raíces de Plantas/metabolismo , Rutaceae/metabolismo
12.
Biomed Pharmacother ; 134: 111107, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33341059

RESUMEN

The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immunosuppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4+ and CD8+ lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.

13.
J Hazard Mater ; 401: 123724, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33113726

RESUMEN

Organophosphates (OPs) are highly toxic compounds, with widespread application in agricultural and chemical industries, whose introduction into the environment poses serious hazards to humans and ecological systems. To assess and ultimately mitigate these hazards, this study predicted the acute toxicity of OPs according to their chemical structure and administration route. The acute toxicity data of 161 OPs in two species via six different administration routes were manually collected and used to develop a series of quantitative structure-toxicity relationship (QSTR) models with robust and practical predictive abilities. The random forest algorithm was used to develop the models, employing both quantum chemical and two-dimensional descriptors according to OECD guidelines. Correlation results and feature similarities indicated that whereas acute toxicity data from rats and mice via the same administration route were combinable for modeling, data from different routes were not. Six QSTR models for each route in a single species and two QSTR models for a single route in the two species were constructed, achieving practical predictive performance. Despite significant variances in their datasets, the prediction models could predict the acute toxicity of novel or unknown OPs, realize rapid assessment, and provide guidance for regulatory decisions to reduce the hazards of OPs.

15.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(4): 306-311, 2020 Jul.
Artículo en Chino | MEDLINE | ID: mdl-33167088

RESUMEN

OBJECTIVE: To study the effects of acorus tatarinowii Schott and its active ingredient-alpha-asarone on learning and memory, free radical metabolism and nNOS/NO signal in hippocampus of rats with fatigue movement. METHODS: Eighty SD male rats were randomly divided into eight groups: control group(A), exercise group(B), exercise + alpha-asarone low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H),with ten rats in each group. The rats in group C, D and E were administered with alpha-asarone at the doses of 0.10, 0.50 and 1.00 mg.kg-1.WT-1 by ig. The rats in group F, G and H were administered with the extracts of Acorus tatarinowii Schott of at the doses of 0.12, 1.20 and 4.80 g.kg-1.WT-1 by ig. Learning and memory of rats were tested by the method of water maze experiment, and the activities of SOD and NOS, the contents of MDA were detected by the biochemical methods, and the expression levels of nNOS protein in hippocampus of rats were tested by the method of Western blot in at the end of the experiment. RESULTS: The escape latency and MDA content in hippocampus of rats in groups E and H were lower than those in groups B, C, D, F and G and the numbers of Plateau crossing, SOD and NOS activities and the expression levels of nNOS protein in hippocampus of rats were higher than those in groups B, C, D, F and G(P<0.01). The activities of SOD in hippocampus of rats in groups A, E and H were A>E>H, whereas the contents of MDA were opposite (P<0.01); the activities of NOS and the expression levels of nNOS protein in hippocampus of group E were lower than those of groups A and H (P<0.01 or P<0.05), but there was no significant difference between groups A and H (P>0.05). There were no significant difference in escape latency and numbers of crossing platform among groups A, E and H (P>0.05). CONCLUSION: Acorus tatarinowii Schott and alpha-asarone can significantly improve learning and memory of rats with fatigue movement. The mechanism is related to reclaiming the imbalance of free radical metabolism and up-regulating nNOS/NO signal in hippocampus of the rats.

16.
Phytochemistry ; 181: 112566, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33197743

RESUMEN

Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC50 values of 4.97-33.28 µM, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC50 values of 4.45-7.49 µM.

17.
Database (Oxford) ; 20202020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33216897

RESUMEN

Rattus norvegicus, or the rat, has been widely used as animal models for a diversity of human diseases in the last 150 years. The rat, as a disease model, has the advantage of relatively large body size and highly similar physiology to humans. In drug discovery, rat models are routinely used in drug efficacy and toxicity assessments. To facilitate molecular pharmacology studies in rats, we present the predicted rat interactome database (PRID), which is a database of high-quality predicted functional gene interactions with balanced sensitivity and specificity. PRID integrates functional gene association data from 10 public databases and infers 305 939 putative functional associations, which are expected to include 13.02% of all rat protein interactions, and 52.59% of these function associations may represent protein interactions. This set of functional interactions may not only facilitate hypothesis formulation in molecular mechanism studies, but also serve as a reference interactome for users to perform gene set linkage analysis (GSLA), which is a web-based tool to infer the potential functional impacts of a set of changed genes observed in transcriptomics analyses. In a case study, we show that GSLA based on PRID may provide more precise and informative annotations for investigators to understand the physiological mechanisms underlying a phenotype and lead investigators to testable hypotheses for further studies. Widely used functional annotation tools such as Gene Ontology (GO) analysis, and Database for Annotation, Visualization and Integrated Discovery (DAVID) did not provide similar insights. Database URL: http://rat.biomedtzc.cn.

18.
Ann Transl Med ; 8(19): 1230, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33178762

RESUMEN

Background: The global mortality rate for coronavirus disease 2019 (COVID-19) is 3.68%, but the mortality rate for critically ill patients is as high as 50%. Therefore, the exploration of prognostic predictors for patients with COVID-19 is vital for prompt clinical intervention. Our study aims to explore the predictive value of hematological parameters in the prognosis of patients with severe COVID-19. Methods: Ninety-eight patients who were diagnosed with COVID-19 at Jingzhou Central Hospital and Central Hospital of Wuhan, Hubei Province, were included in this study. Results: The median age of the patients was 59 [28-80] years; the median age of patients with a good prognosis was 56 [28-79] years, and the median age of patients with a poor outcome was 67 [35-80] years. The patients in the poor outcome group were older than the patients in the good outcome group (P<0.05). The comparison of hematological parameters showed that lymphocyte count (Lym#), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were significantly lower in the poor outcome group than in the good outcome group (P<0.05). Further, the red cell volume distribution width-CV (RDW-CV) and red cell volume distribution width-SD (RDW-SD) were significantly higher in the poor outcome group than in the good outcome group (P<0.0001). Receiver operating characteristic (ROC) curves showed RDW-SD, with an area under the ROC curve (AUC) of 0.870 [95% confidence interval (CI) 0.796-0.943], was the most significant single parameter for predicting the prognosis of severe patients. When the cut-off value was 42.15, the sensitivity and specificity of RDW-SD for predicting the prognosis of severe patients were 73.1% and 80.2%, respectively. Reticulocyte (RET) channel results showed the RET level was significantly higher in critical patients than in moderate patients and severe patients (P<0.05), which may be one cause of the elevated RDW in patients with a poor outcome. Conclusions: In this study, the hematological parameters of COVID-19 patients were statistically analyzed. RDW was found to be a prognostic predictor for patients with severe COVID-19, and the increase in RET may contribute to elevated RDW.

19.
Brain Topogr ; 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33135142

RESUMEN

Previous studies showed that the cortical reward system plays an important role in deceptive behavior. However, how the reward system activates during the whole course of dishonest behavior and how it affects dishonest decisions remain unclear. The current study investigated these questions. One hundred and two participants were included in the final analysis. They completed two tasks: monetary incentive delay (MID) task and an honesty task. The MID task served as the localizer task and the honesty task was used to measure participants' deceptive behaviors. Participants' spontaneous responses in the honesty task were categorized into three conditions: Correct-Truth condition (tell the truth after guessing correctly), Incorrect-Truth condition (tell the truth after guessing incorrectly), and Incorrect-Lie condition (tell lies after guessing incorrectly). To reduce contamination from neighboring functional regions as well as to increase sensitivity to small effects (Powell et al., Devel Sci 21:e12595, 2018), we adopted the individual functional channel of interest (fCOI) approach to analyze the data. Specially, we identified the channels of interest in the MID task in individual participants and then applied them to the honesty task. The result suggested that the reward system showed different activation patterns during different phases: In the pre-decision phase, the reward system was activated with the winning of the reward. During the decision and feedback phase, the reward system was activated when people made the decisions to be dishonest and when they evaluated the outcome of their decisions. Furthermore, the result showed that neural activity of the reward system toward the outcome of their decision was related to subsequent dishonest behaviors. Thus, the present study confirmed the important role of the reward system in deception. These results can also shed light on how one could use neuroimaging techniques to perform lie-detection.

20.
Theor Appl Genet ; 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33140169

RESUMEN

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

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