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1.
Artigo em Inglês | MEDLINE | ID: mdl-31473923

RESUMO

Little is known regarding the effects of environmental mercury (Hg) exposure on liver dysfunction in adolescents. We aimed to explore the association between Hg exposure and the risk of nonalcoholic fatty liver disease (NAFLD) in the adolescent population. The cross-sectional associations between blood Hg concentrations and serum alanine aminotransferase (ALT) levels, a surrogate for suspected NAFLD, were evaluated using data from adolescents (aged 12-17 years old) who participated in the National Health and Nutrition Examination Survey (NHANES), 1999-2014. A final sample of 6389 adolescents was analysed. Elevated ALT was defined as > 25 IU/L and > 22 IU/L for boys and girls ≤ 17 years old, respectively. Odds ratios (ORs) of Hg levels in association with serum ALT levels were estimated using a logistic regression after adjusting for gender, age, ethnicity, serum cotinine, body mass index, the poverty income ratio, and NHANES cycles. The median blood Hg level was 0.73 ± 0.91 µg/L amongst US adolescents. In the adjusted model, the ORs of elevated ALT levels of those in the 4th quartile were higher amongst non-Hispanic white adolescents (OR = 1.76, 95% CI 1.20, 2.59; P = 0.035) and those who were normal or underweight (OR = 1.41, 95% CI 1.08, 1.85; P = 0.020). No association was observed for the other variables. Our results indicate that the positive association between blood Hg exposure and the risk of NAFLD in US adolescents is the highest amongst non-Hispanic white and those who are normal or underweight, regardless of ethnicity. More research is necessary to confirm this association and to clarify the potential mechanisms.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 452-456, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484605

RESUMO

To analyze the clinical features and prognosis of ulcerative colitis(UC)complicated with acute massive lower gastrointestinal bleeding(LGIB). Methods Eleven patients hospitalized in Peking Union Medical College Hospital from January 2006 to December 2017 for treatment of UC,suffering from acute massive LGIB,were enrolled and descriptively analyzed. Results The proportion of UC patients with acute massive LGIB was 0.7% among all 1486 UC patients hospitalized during the study period.The disease was moderately or severely active in these 11 patients,among whom 9 patients(81.8%)had chronic relapsing pancolitis.Cytomegalovirus infection was present in 5 patients,among whom 4 patients received antiviral treatments.All the 11 patients received treatments including food and water fasting,rehydration,blood transfusion,and use of somatostatin.Four patients received emergency surgical treatment after the first episode of massive bleeding,and 3 of them suffered from re-bleeding after the surgery.Among the remaining seven patients,two underwent emergency total colectomy+subtotal rectectomy+ileostomy and three received elective total resection of colon and rectum or total colectomy+subtotal rectectomy+ileostomy.Thus,9 patients underwent emergency surgery,1 patient did not receive surgey during follow-up,and 1 patient was lost to follow-up. Conclusions Acute massive LGIB is a manifestation of active UC and can be associated with poor prognosis.Optimized perioperative management is important for improving the outcomes of such patients.

3.
Environ Sci Technol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486635

RESUMO

Historically, beehive coke ovens (BCOs) have been extensively operated in China and emit large quantities of pollutants, including primary PM2.5, secondary PM2.5 precursors, and other climate forcers. Although the ovens were legally banned in 1996 by the Coal Law, the process of phasing them out took over a decade to accomplish. Based on historical operation data derived from remote sensing images, temporal trends and the spatial distribution of the emissions of various pollutants from BCOs were compiled and used to model the resulting perturbation in ambient PM2.5, population exposure, and PM2.5-associated adverse health impacts. Historically, PM2.5 originating from BCOs affected a vast region across China, peaked approximately 1996, and decreased afterwards until the ovens' final elimination in 2011. According to the results of a supply-demand model, emissions from the BCOs would have continued to increase after 1996 if they had not been banned. As a result, national average PM2.5 attributable to BCOs in 2014 would have been more than three times as great as in 1996. It was estimated that the cumulative number of premature deaths associated with BCOs-originating PM2.5 from 1982 to 2014 was as high as 365,000 (95% confidence interval 259,000-402,000). The number would have nearly tripled if BCOs had not been banned and halved if the banning had been implemented immediately after the regulation was in force, suggesting the importance of legislation implementation.

4.
Genes (Basel) ; 10(9)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480272

RESUMO

ZmPGP1, involved in the polar auxin transport, has been shown to be associated with plant height, leaf angle, yield traits, and root development in maize. To explore natural variation and domestication selection of ZmPGP1, we re-sequenced the ZmPGP1 gene in 349 inbred lines, 68 landraces, and 32 teosintes. Sequence polymorphisms, nucleotide diversity, and neutral tests revealed that ZmPGP1 might be selected during domestication and improvement processes. Marker-trait association analysis in inbred lines identified 11 variants significantly associated with 4 plant architecture and 5 ear traits. SNP1473 was the most significant variant for kernel length and ear grain weight. The frequency of an increased allele T was 40.6% in teosintes, and it was enriched to 60.3% and 89.1% during maize domestication and improvement. This result revealed that ZmPGP1 may be selected in the domestication and improvement process, and significant variants could be used to develop functional markers to improve plant architecture and ear traits in maize.

5.
Sensors (Basel) ; 19(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480359

RESUMO

With the development of the Internet-of-Things (IoT) technology, the applications of gas sensors in the fields of smart homes, wearable devices, and smart mobile terminals have developed by leaps and bounds. In such complex sensing scenarios, the gas sensor shows the defects of cross sensitivity and low selectivity. Therefore, smart gas sensing methods have been proposed to address these issues by adding sensor arrays, signal processing, and machine learning techniques to traditional gas sensing technologies. This review introduces the reader to the overall framework of smart gas sensing technology, including three key points; gas sensor arrays made of different materials, signal processing for drift compensation and feature extraction, and gas pattern recognition including Support Vector Machine (SVM), Artificial Neural Network (ANN), and other techniques. The implementation, evaluation, and comparison of the proposed solutions in each step have been summarized covering most of the relevant recently published studies. This review also highlights the challenges facing smart gas sensing technology represented by repeatability and reusability, circuit integration and miniaturization, and real-time sensing. Besides, the proposed solutions, which show the future directions of smart gas sensing, are explored. Finally, the recommendations for smart gas sensing based on brain-like sensing are provided in this paper.

6.
J Biol Chem ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481466

RESUMO

Polyunsaturated fatty acids (PUFAs) such as α-linolenic acid (ALA, 18:3Δ9cis,12cis,15cis ) have high nutritional and industrial values. In oilseed crops, PUFAs are synthesized on phosphatidylcholine (PC) and accumulated in triacylglycerol (TAG). Therefore, exploring the mechanisms that route PC-derived PUFA to TAG is essential for understanding and improving PUFA production. The seed oil of flax (Linum usitatissimum) is enriched in ALA, and this plant has many lipid biosynthetic enzymes that prefer ALA-containing substrates. In this study, using membrane yeast two-hybrid and bimolecular fluorescence complementation assays, we probed recombinant flax transferase enzymes, previously shown to contribute to PUFA enrichment of TAG, for physical interactions with each other under in vivo conditions. We found that diacylglycerol acyltransferases, which catalyze the final reaction in acyl-CoA-dependent TAG biosynthesis, interact with the acyl-editing enzymes phosphatidylcholine: diacylglycerol cholinephosphotransferase and lysophosphatidylcholine acyltransferase. Physical interactions among the acyl-editing enzymes were also identified. These findings reveal the presence of an assembly of interacting transferases that may facilitate the channeling of PUFA from PC to TAG in flax and possibly also in other oleaginous plants that produce seeds enriched in PC-modified fatty acids.

7.
Environ Res ; 178: 108666, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31472363

RESUMO

Studies have shown that persistent organic pollutants (POPs) can have various health effects. However, little is known about the effects of multiple chemicals with possible common sources of exposure on walking speed, a proxy index reflecting lower limb neuromuscular function and physical function. We simultaneously applied multiple linear and nonlinear statistical models to explore the complex exposure-response relationship between a mixture of 22 selected POPs and walking speed. A total of 14 polychlorinated biphenyls (PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 5 polychlorinated dibenzofurans (PCDFs) were measured in the serum of participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. Walking speed was measured during a physical examination. Linear regression (LR), least absolute shrinkage and selection operator (LASSO), and group LASSO were used to evaluate the linearity of mixtures, while restricted cubic spline (RCS) regression, random forest (RF), and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Potential confounders were adjusted in the above models. A total of 436 subjects were included in our final analysis. The results of the LR model did not identify any POP exposure that was significantly associated with walking speed. The LASSO results revealed an inverse association of one PCDD congener and two PCDF congeners with walking speed, while the group LASSO analysis identified PCDFs at the exposure level and at the group level. In the RCS analysis, two PCB congeners presented significant overall associations with walking speed. The PCB congener PCB194 showed statistically significant effects on the outcome (P = 0.01) when a permutation-based RF was used. The BKMR analysis suggested that PCBs and PCDFs (probabilities = 0.887 and 0.909, respectively) are potentially associated with walking speed. Complex statistical models, such as RCS regression, RF and BKMR models, can detect the nonlinear and nonadditive relationships between PCBs and walking speed, while LASSO and group LASSO can identify only the linear relationships between PCDFs and walking speed. Fully considering the influence of collinearity in each method during modelling can increase the comprehensiveness and reliability of conclusions in studies of multiple chemicals.

8.
Lipids ; 54(9): 571-579, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478204

RESUMO

Phospholipid:diacylglycerol acyltransferase (PDAT) catalyzes the acyl-CoA-independent triacylglycerol (TAG) biosynthesis in plants and oleaginous microorganisms and thus is a key target in lipid research. The conventional in vitro PDAT activity assay involves the use of radiolabeled substrates, which, however, are expensive and demand strict regulation. In this study, a reliable fluorescence-based method using nitrobenzoxadiazole-labeled diacylglycerol (NBD-DAG) as an alternative substrate was established and subsequently used to characterize the enzyme activity and kinetics of a recombinant Arabidopsis thaliana PDAT1 (AtPDAT1). We also demonstrate that the highly toxic benzene used in typical PDAT assays can be substituted with diethyl ether without affecting the formation rate of NBD-TAG. Overall, this method works well with a broad range of PDAT protein content and shows linear correlation with the conventional method with radiolabeled substrates, and thus may be applicable to PDAT from various plant and microorganism species.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31514150

RESUMO

Deep learning has recently gained more and more popularity, because of its high accuracy and wide range of coverage. In particular, deep learning is widely used in the medical field. Because in the field of image classification and biological applications, the accuracy of deep learning is very high. Unfortunately, even under the collaborative deep learning, there is still serious risk of information leakage. Moreover, the risk of information leakage in the medical field is greater and the harm is even greater. For example, medical treatment data may be leaked to third-party organizations. When these important medical data is illegally used by for-profit organizations or obtained by criminals, it will not only lead to the disclosure of personal privacy information, but also cause serious economic losses to the victims. However, the victim cannot delete the leaked information by itself or limit the scope and use of the information that has been leaked. Therefore, the adverse effects are unimaginable. This paper mainly studies the information protection methods under GAN model attack, in order to find a better way to prevent attacks and effectively protect information.

10.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502559

RESUMO

Stable transgenic rice line (named KRSV-1) with strong resistance against rice stripe virus was generated using the gene sequence of disease-specific protein by RNA interference. Comprehensive safety assessment of transgenic plants has turned into a significant field of genetic modification food safety. In this study, a safety assessment of KRSV-1 was carried out in a stepwise approach. The molecular analysis exhibited that KRSV-1 harbored one copy number of transgene, which was integrated into the intergenic non-coding region of chromosome 2 associated with inter-chromosomal translocations of 1.6-kb segments of chromosome 8. Then, transcriptomics and proteomics analyses were carried out to detect the unintended effects as a result of the integration of the transgene. Although 650 dramatically differentially expressed genes (DDEGs) and 357 differentially expressed proteins were detected between KRSV-1 and wild-type (WT) by transcriptomics and proteomics analyses, no harmful members in the form of toxic proteins and allergens were observed. Encouragingly, the nutritional compositions of seeds from KRSV-1 were comparable with WT seeds. The results of this entire study of molecular analysis, transcriptome and proteome profile of KRSV-1 revealed that no detrimental changes in the form of toxic proteins and allergens were detected in the transgenic rice line due to the integration of the transgene.

11.
J Biomed Mater Res A ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498962

RESUMO

Platelet-rich plasma (PRP) is rich in a variety of growth factors and play an important role in the proliferation and differentiation of mesenchymal stem cells (MSCs). It has been reported that the preparation of freeze-dried platelets (LyPRP) from platelets could be an effective strategy to preserve the bioactivity of platelets for a long time. In this study, the osteogenic induction effects of PRP and LyPRP on MSCs were evaluated. The rabbit arterial blood was drawing to preparation of PRP by secondary centrifugation. Whole blood was prepared by lyophilization buffer to prepare LyPRP, which were activated by chloride and their surface morphology was observed. It was observed by SEM that platelets were evenly distributed on the surface of PRP and LyPRP. Growth factors were slowly released from PRP and LyPRP during the first seven days and detected by ELISA kit. Cell proliferation assays and FDA/PI staining demonstrated that PRP and LyPRP could promote cell proliferation. PRP and LyPRP were also shown to promote osteogenic differentiation of MSCs in vitro by osteogenesis characteristic staining and qPCR quantitative detection of osteogenic related gene expression. Both PRP and LyPRP could promote the proliferation and osteogenic differentiation of MSCs effectively. Moreover, PRP exhibited a better osteogenic induction effect on MSC than LyPRP. This article is protected by copyright. All rights reserved.

12.
J Hematol Oncol ; 12(1): 88, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481121

RESUMO

BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

13.
Foodborne Pathog Dis ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31478765

RESUMO

In the field of the detection of pathogens responsible for infectious diarrhea, multiplex nucleic acids detection technology has attracted attention due to its ability to simultaneously screen a wide range of pathogens, its simplicity to operate and a faster turnaround time. We conducted a three-center evaluation that compared the BioFire FilmArray gastrointestinal panel (FA GI) and real-time polymerase chain reaction (PCR) assays for the detection of pathogens from 462 clinical diarrhea specimens, and characterized the distribution of various pathogens that were analyzed. The sensitivity of FA GI was 100% for 13 pathogens and 93.8-98.3% for 4 pathogens, but low for Salmonella (60.5%) and adenovirus (88.9%). The sensitivity per pathogen of real-time PCR assays was lower than that observed with FA GI. The specificity of FA GI and real-time PCR assays per pathogen was greater than 94.5% and 99%, respectively. FA GI and real-time PCR assays detected ≥1 pathogen in 339 (73.4%) and 297 (64.3%) samples, respectively, and 324 (70.1%) samples were considered as positive according to the reference standard. Multiple pathogens were detected in 37.2% and 24.9% of samples by FA GI and real-time PCR assays, respectively. Norovirus GI/GII and Campylobacter were less associated with coinfections. The positive rates of some pathogens varied among the three regions of China. Molecular methods can help squickly identify the cause of diarrhea and provide valuable information for early diagnosis and optimal patient therapy.

14.
J Phys Chem Lett ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31515995

RESUMO

Predicting thermometric performance for diverse materials will facilitate the selection and design of nanothermometers to meet complex environment and specific signal output with saving a lot of time and expense. Herein we explore and unveil the thermal coupled thermometric performance of Er3+/Yb3+ co-doped a set of host lattices via the chemical bond theory of complex crystals. The unknown B and ΔE values of the thermometry are accurately estimated by the chemical bond parameters, further deepening our cognition of the correlation between luminescence properties of Er3+ ions and microscopic crystal structure. This allows us to precisely forecast the thermal coupled thermometric performance of Er3+ for varying host lattices in advance.

15.
Prostate ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31497879

RESUMO

BACKGROUND: Family history (FH) of prostate cancer (PCa) in Chinese population is poorly understood. The objective of this study is to evaluate the association between FH and PCa in a Chinese biopsy cohort. METHODS: Consecutive patients who received 10 to 12 core systematic prostate biopsies from April 2013 to October 2018 in three medical centers were enrolled in this study. Demographic information and clinical information were obtained through prebiopsy questionnaire, including cancer FH, age, and total prostate-specific antigen (tPSA). RESULTS: Of 2321 patients, 83 (3.6%) were reported a FH of PCa. The positive biopsy rate in these patients was 54.2%, significantly higher than the patients without the family history of PCa (42.6%; relative risk [RR] = 1.27; P = .024). In patients with positive FH of breast cancer gene (BRCA)-related cancers (breast, ovarian, and prostate cancer, n = 154), 74 (48.1%) were diagnosed as PCa, higher than those without FH (42.7%; RR = 1.13; P = .112). Multivariate logistic regression analysis (after adjusting for age and tPSA values) showed that there was 2.1-fold increased risk of PCa in patients with positive FH of PCa (P = .005), and 1.6-fold increased risk in patients with positive FH of BRCA-related cancers (P = .019). However, there was no significant association between FH of PCa or BRCA-related cancer and high-grade PCa after adjusting age and tPSA level (P = .404 for PCa, P = 0.991 for BRCA-related cancers). CONCLUSIONS: Patients with positive FH of PCa had 2.1-fold higher risk of PCa, and patients with positive FH of BRCA-related cancers had 1.6-fold higher risk in this biopsy cohort of Chinese population. Patients with positive FH of PCa or BRCA-related cancers would have earlier age at onset of PCa.

16.
Cell Res ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444468

RESUMO

The transient elevation of cytoplasmic calcium is essential for pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). However, the calcium channels responsible for this process have remained unknown. Here, we show that rice CDS1 (CELL DEATH and SUSCEPTIBLE to BLAST 1) encoding OsCNGC9, a cyclic nucleotide-gated channel protein, positively regulates the resistance to rice blast disease. We show that OsCNGC9 mediates PAMP-induced Ca2+ influx and that this event is critical for PAMPs-triggered ROS burst and induction of PTI-related defense gene expression. We further show that a PTI-related receptor-like cytoplasmic kinase OsRLCK185 physically interacts with and phosphorylates OsCNGC9 to activate its channel activity. Our results suggest a signaling cascade linking pattern recognition to calcium channel activation, which is required for initiation of PTI and disease resistance in rice.

17.
J Cell Biochem ; 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31448453

RESUMO

Accumulating studies have implicated that long noncoding RNA (lncRNA) plays a vital role in lung cancer. However, little is known of the role of lncRNA highly upregulated in liver cancer (HULC) in the pathogenesis of lung squamous cell carcinoma (LSCC). In this study, we investigated the modifying effects and underlying mechanisms of lncRNA HULC in LSCC. Significantly decreased level of lncRNA HULC was observed in LSCC samples compared with adjacent tissues. Besides, the expression of lncRNA HULC was negatively associated with protein tyrosine phosphatase receptor type O (PTPRO) in LSCC. Moreover, lncRNA HULC could promote the proliferation of LSCC cells by downregulating the expression PTPRO dependent on the phosphorylation and activation of nuclear factor-κB (NF-κB). The present study firstly shows strong evidence supporting a critical role of lncRNA HULC in promoting LSCC by regulating PTPRO/NF-κB signaling pathway, which provides new promising biomarkers for LSCC.

18.
FASEB J ; : fj201900693R, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451050

RESUMO

Reactive oxygen species (ROS) can act as second messengers in various signaling pathways, and abnormal oxidation contributes to multiple diseases, including cancer. Detecting and quantifying protein oxidation is crucial for a detailed understanding of reduction-oxidation reaction (redox) signaling. We developed an Activated Thiol Sepharose-based proteomic (ATSP) approach to quantify reversible protein oxidation. ATSP can enrich H2O2-sensitive thiol peptides, which are more likely to contain reactive cysteines involved in redox signaling. We applied our approach to analyze hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a type of kidney cancer that harbors fumarate hydratase (FH)-inactivating mutations and has elevated ROS levels. Multiple proteins were oxidized in FH-deficient cells, including many metabolic proteins such as the pyruvate kinase M2 isoform (PKM2). Treatment of HLRCC cells with dimethyl fumarate or PKM2 activators altered PKM2 oxidation levels. Finally, we found that ATSP could detect Src homology region 2 domain-containing phosphatase-2 and PKM2 oxidation in cells stimulated with platelet-derived growth factor. This newly developed redox proteomics workflow can detect reversible oxidation of reactive cysteines and can be employed to analyze multiple physiologic and pathologic conditions.-Xu, Y., Andrade, J., Ueberheide, B., Neel, B. G. Activated Thiol Sepharose-based proteomic approach to quantify reversible protein oxidation.

19.
J Biol Chem ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439667

RESUMO

De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway involves highly endergonic biochemical reactions that must be fine-tuned with energy homeostasis. Previous studies have shown that CTP:phosphocholine cytidylyltransferase (CCT) is an important regulatory enzyme in this pathway, and its activity can be controlled at both transcriptional and post-translational levels. Here, we identified an important additional mechanism regulating plant CCT1 activity. Comparative analysis revealed that Arabidopsis CCT1 (AtCCT1) contains catalytic and membrane-binding domains that are homologous to those of rat CCT1. In contrast, the C-terminal phosphorylation domain important for stringent regulation of rat CCT1 was apparently missing in AtCCT1. Instead, we found that AtCCT1 contains a putative consensus site (Ser-187) for modification by sucrose nonfermenting 1-related protein kinase 1 (SnRK1 or KIN10/SnRK1.1), involved in energy homeostasis. Phos-tag SDS-PAGE coupled with MS analysis disclosed that SnRK1 indeed phosphorylates AtCCT1 at Ser-187, and we found that AtCCT1 phosphorylation substantially reduces its activity by as much as 70%. A Ser187Ala variant exhibited decreased activity, indicating the importance of Ser-187 in catalysis, and this variant was less susceptible to SnRK1-mediated inhibition. Protein truncation and liposome-binding studies indicated that SnRK1-mediated AtCCT1 phosphorylation directly affects the catalytic domain rather than interfering with phosphatidate-mediated AtCCT1 activation. Overexpression of the AtCCT1 catalytic domain in Nicotiana benthamiana leaves increased PC content, and SnRK1 co-expression reduced this effect. Taken together, our results suggest that SnRK1 mediates the phosphorylation and concomitant inhibition of AtCCT1, revealing an additional mode of regulation for this key enzyme in plant PC biosynthesis.

20.
Brain Behav ; : e01382, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429525

RESUMO

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Hemorrhagic transformation (HT) is a serious complication of ischemic cerebral infarction and can be intensified by therapeutic interventions for acute ischemic stroke (AIS). The purpose of our research was to explore the predictive effect of NLR for HT in patients with AIS and to determine the best predictive value. METHODS: PubMed, Web of Science, EMBASE, MEDLINE, Cochrane, and Google Scholar were searched. The primary endpoint was HT, and subgroup analysis was performed. Review Manager software version 5.3 was used to statistically analyze the outcomes. RESULTS: A total of seven studies including 3,726 patients met the inclusion criteria. The pooled odds ratio (OR) value of the high NLR that predicted HT in AIS patients was 1.53 (95% CI, 1.21-1.92; p = .0003). In addition, 1.10 (95% CI, 1.05-1.15; p < .0001) was the pooled OR of the high NLR associated with increased 3-month mortality in patients with AIS. In the subgroup analysis with an NLR cutoff value of 7.5-11, the correlation between NLR above the cutoff value and the rate of HT in patients with AIS was statistically significant (OR, 7.93; 95% CI, 2.25-27.95; p = .001). CONCLUSION: A high NLR can predict HT and 3-month mortality in patients with AIS. Regardless of the country of origin and the sampling time, an NLR with a cutoff value of 7.5-11 was independently associated with HT in AIS patients.

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